1
Anticancer Res




. 2020 Jun;40(6):3097-3108. doi: 10.21873/anticanres.14291.
Interaction Between CCL18 and GPR30 Differs From the Interaction Between Estradiol and GPR30
Roland Schmidt-Wolf 1, Gernot Zissel 2
Affiliations expand
PMID: 32487604
DOI: 10.21873/anticanres.14291

Abstract


Background/aim: C-C motif chemokine ligand 18 (CCL18) is overexpressed in the microenvironment of tumors, promotes invasion and metastasis and is thus important for the therapeutic outcome of many tumor entities. The Gs-coupled seven-transmembrane receptor GPR30 is known as both a CCL18 and an estrogen receptor; its activation by estradiol leads to a transactivation of membrane-tethered pro-heparin-binding EGF-like growth factor and the MAPK/ERK pathway. We examined whether this signaling pathway remains the same under CCL18 stimulation, as opposed to estradiol stimulation.

Materials and methods: We investigated the effects of CCL18 on the lung cancer cell line A549, that show low GPR30 expression and the breast cancer cell lines MCF-7, that has high GPR30 expression and MDA-MB-231. These cells were stimulated in different media with CCL18 and then analyzed by qPCR, In-Cell Western®, western blot and ELISA.

Results: Many similarities on the effect of CCL18 on the already known estradiol-activated signaling pathway via the G protein-coupled estrogen receptor GPR30 were identified. GPR30 is involved in the expression of matrix metalloproteinases (MMPs), which may play a role in the transactivation of ERK-1/-2 via the cleavage of membrane-bound HB-EGF, via Src-related tyrosine kinases and Gβγ-subunits. With increasing CCL18 concentration, the expression of MMP7 decreased in A549 cells. With decreasing estrogen content of the medium, there was an increasing effect of CCL18 on the inhibition of the relative expression of MMP7. Inhibition of GPR30 with G15 also resulted in a decrease in the relative expression of MMP7, irrespective of the subsequent stimulation with CCL18. This is a rather unexpected result, because the estrogen estradiol and CCL18 both activate GPR30. MCF-7 cells which express more GPR30 did not show any dependence of the relative MMP7 expression on CCL18 except in estrogen-free FCS medium. CCL18 induced an increased relative ERK activation in In-Cell western (ICW) at A549 cells. Stimulation with CCL18 caused decreased ERK activation with simultaneous inhibition of adenylate cyclase in MCF-7. However, stimulation with CCL18 and simultaneous inhibition of cyclooxygenase in MCF-7 resulted in increased ERK activation. In A549, stimulation with CCL18 and co-incubation with dbcAMP resulted in decreased ERK activation in both ICW and Western blot.

Conclusion: In summary, the Gs-coupled receptor GPR30 plays an important role in the signaling pathway of CCL18. CCL18 and estradiol may not lead to the same signaling pathway after activating GPR30.

Keywords: Ccl18 protein; cancer; epithelial-mesenchymal transition (EMT); gpr30; metastasis.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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2
Anticancer Res




. 2020 Jun;40(6):3147-3153. doi: 10.21873/anticanres.14296.
Six Candidate miRNAs Associated With Early Relapse in Pediatric B-Cell Acute Lymphoblastic Leukemia
Ernest K Amankwah 1 2, Meenakshi Devidas 3, David T Teachey 4, Karen R Rabin 5, Patrick A Brown 6 7
Affiliations expand
PMID: 32487609
DOI: 10.21873/anticanres.14296

Abstract


Background/aim: Few studies have evaluated the role of miRNAs in pediatric acute lymphoblastic leukemia (ALL) relapse and a consensus of a clinically significant miRNA signature is yet to be identified. In this study, we evaluated miRNAs associated with pediatric B-ALL early relapse in two independent sample sets.

Materials and methods: We performed global miRNA profiling on diagnostic bone marrow specimens from six early relapse (≤3 years after diagnosis) and six age- and cytogenetics-matched prolonged remission (≥4 years) patients (first set) and an independent set of 14 early relapse and 14 matched prolonged remission specimens (second set).

Results: Twelve and 39 top differentially expressed miRNAs were observed in the first and second sets, respectively; however, there was no overlap between the top candidates. In post-hoc analyses six miRNAs (miR-101-3p, miR-4774-5p, miR-1324, miR-631, miR-4699-5p and miR-922) among the top candidates in the second, but not the first set, were consistently upregulated in early relapse compared to remission specimens in both first (fold change=1.13-2.19, q<0.38) and second (fold change=1.48-4.78, all q<0.05) sets. Four (miR-631, mir-101-3p, miR-922 and miR-1324) of these miRNAs have been previously implicated in key functional oncogenic pathways in adult cancers.

Conclusion: This study suggests that six candidate miRNAs, not previously implicated in pediatric ALL, are associated with early relapse in pediatric B-ALL. Validation and investigation of mechanistic roles of these miRNAs in a larger cohort are warranted, so that they may be used as prognostic markers for early relapse of pediatric B-ALL.

Keywords: ALL; Pediatric; epigenetic; miRNA; relapse.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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3
Anticancer Res




. 2020 Jun;40(6):3129-3138. doi: 10.21873/anticanres.14294.
Paclitaxel, Carboplatin and 1,25-D3 Inhibit Proliferation of Ovarian Cancer Cells In Vitro
Tea Kuittinen 1, Päivi Rovio 2, Tiina Luukkaala 3 4, Marita Laurila 5, Seija Grénman 6 7, Anne Kallioniemi 8 9, Johanna Mäenpää 8
Affiliations expand
PMID: 32487607
DOI: 10.21873/anticanres.14294

Abstract


Background/aim: The combination of paclitaxel and carboplatin is the standard chemotherapy for ovarian cancer. Previous studies have implied that vitamin D (1,25-D3) may have growth inhibitory effects in ovarian cancer. This study aimed to investigate the effect of paclitaxel, carboplatin and 1,25-D3 on the growth of ovarian cancer cells in vitro, based on the hypothesis that 1,25-D3 might potentiate the effect of paclitaxel and/or carboplatin.

Materials and methods: Three non-commercial ovarian carcinoma cell lines UT-OV-1(mucinous), UT-OV-3B (serous) and UT-OV-4 (endometrioid) were exposed to different concentrations of 1,25-D3, paclitaxel and carboplatin, respectively. The cell viability was measured using a Crystal violet assay kit. The cellular vitamin D receptor (VDR) mRNA levels were measured by qRT-PCR using the LightCycler equipment.

Results: The growth-inhibitory effect of the combination of paclitaxel and carboplatin was 56% in UT-OV-1, 33% in UT-OV-3B and 47% in UT-OV-4 cells. Single 1,25-D3 (10 μM) inhibited the growth of UT-OV-3B and UT-OV-4 by 23% and 28%, respectively, whereas no effect was seen in UT-OV-1 cells. These results are in line with the finding that the expression of VDR was high in UT-OV-3B and UT-OV-4, but very low in UT-OV-1. The combination of 1,25-D3, paclitaxel and carboplatin resulted in 61%, 46% and 58% growth reduction in UT-OV-1, UT-OV-3B and UT-OV-4 cells, respectively. The additive effect of 1,25-D3 was 21% in UT-OV-4, 20% in UT-OV-3B and 12% in UT-OV-1 cell line.

Conclusion: The results imply that combining 1,25-D3 with paclitaxel and carboplatin may potentiate their growth inhibitory effect on ovarian cancer cells with high VDR expression.

Keywords: 1,25-D3; VDR; Vitamin D; carboplatin; growth inhibition; in vitro; ovarian cancer; paclitaxel.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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4
Anticancer Res




. 2020 Jun;40(6):3325-3331. doi: 10.21873/anticanres.14315.
Melanoma Risk Estimation Based on Objective Measures as a Complement to Self-Assessment
Adam Carlsson 1, Magnus Falk 2
Affiliations expand
PMID: 32487628
DOI: 10.21873/anticanres.14315

Abstract


Background/aim: A variety of self-tests addressing individual skin cancer risk are available online. These are generally based on self-estimated measures, such as self-rated skin sensitivity to sun exposure, affecting its reliability. The aim of this study was to investigate whether the addition of objective variables, by means of ultraviolet (UV) sensitivity phototesting and nevi count, could be of contributory value for the composition of a comprehensive risk score for skin cancer, and whether the use of such a score could contribute to change of behavior in the sun after assessment of individual risk.

Patients and methods: A sample of 70 voluntary participants, all university students, were recruited for the study. The participants rated their sun exposure habits by filling out the Sun Exposure and Protection Index (SEPI) questionnaire, and their skin UV-sensitivity was decided both by self-estimation, using Fitzpatricks's skin type scale, and objectively, by the performance of a UV-sensitivity phototest. Finally, the number of pigmented nevi on the lower arm was counted both by the participants themselves and by a trained observer. A cumulated skin cancer risk score was calculated on the basis on these three variables (sun habits, UV-sensitivity and nevi count), and the outcome compared whether based on the participants' self-assessments or on the objective assessment. The individual risk score, based on objective measures, along with a tailored sun protection advice, was communicated to the participants, and after three weeks they once again filled-out the SEPI part addressing propensity to increase sun protection.

Results: The results showed good correlation between the self-assessed and trained observer performed nevi count, but poor agreement between self-estimated and objectively measured skin UV-sensitivity. For the cumulative risk score, the self-performed score was on average slightly lower than its reference, but no systematic difference could be observed. At follow-up, high-risk individuals showed a significant decrease in total SEPI score (p<0.05).

Conclusion: Objective assessment of nevi count and skin UV-sensitivity might be of significant value when estimating individual skin cancer risk, in order to communicate tailored sun protection advice.

Keywords: Malignant melanoma; questionnaire; sun habits; tailored advice; ultraviolet radiation.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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5
Anticancer Res




. 2020 Jun;40(6):3307-3314. doi: 10.21873/anticanres.14313.
Race Does Not Affect Survival in Patients With Prostate Cancer Treated With Radiation Therapy
Joyson Kodiyan 1, Mark Ashamalla 2, Adel Guirguis 2, Hani Ashamalla 2
Affiliations expand
PMID: 32487626
DOI: 10.21873/anticanres.14313

Abstract


Background/aim: Recent evidence has shown that African American men with prostate cancer may have more radiosensitive disease with greater overall survival (OS) with radiotherapy compared to Caucasian men. We compared OS in African American and Caucasian men receiving radiotherapy utilizing the National Cancer Database.

Patients and methods: African American or Caucasian men with N0M0 prostate adenocarcinoma diagnosed between 2004 and 2013 were selected and grouped into favorable and unfavorable risk based on clinical T-stage, clinical Gleason score, and prostate-specific antigen. Patients with favorable risk received brachytherapy or dose-escalated external beam radiation (EBRT); those with unfavorable risk received EBRT plus anti-androgen therapy with/without brachytherapy. African American and Caucasian men in each subgroup were propensity score-matched and analyzed for survival. Sensitivity analysis used treatment-race and age-race interaction terms.

Results: 27,150 patients met the inclusion criteria, with a median age of 68 (range=38-90) years and median follow-up of 59.93 (range=48-142.62) months. OS was equivalent between African American and Caucasian race in favorable risk [log-rank p=0.82; hazard ratio (HR)=0.928; 95% confidence intervaI (CI)=0.583-1.477, p=0.753] and unfavorable-risk subgroups (log-rank p=0.87, HR=1.078, 95% CI=0.843-1.379, p=0.550). No significant interaction existed between treatment and race for either cohort but there was a significant interaction between race and age in those with unfavorable risk (HR=1.046, 95% CI=1.009-1.084, p=0.015), with greater OS in those of Caucasian race ≤60 years (HR=0.320, 95% CI=0.137-0.752, p=0.009).

Conclusion: African American and Caucasian men have similar survival when treated with risk-appropriate definitive radiotherapy. However, younger (age ≤60 years) African American men with unfavorable risk have poorer survival than their Caucasian counterparts and may harbor a significantly different biology of disease.

Keywords: Prostate; race; radiation; survival.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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6
Review
Anticancer Res




. 2020 Jun;40(6):3039-3047. doi: 10.21873/anticanres.14284.
The Role of MSCs in the Tumor Microenvironment and Tumor Progression
Sung Yong Ahn 1
Affiliations expand
PMID: 32487597
DOI: 10.21873/anticanres.14284

Abstract


Over the past few decades, longevity without disease has become an important topic worldwide. However, as life expectancy increases, the number of patients with cancer is also increasing. Tumor progression is related to interactions between tumor cells and mesenchymal stem cells (MSCs) in the tumor microenvironment. MSCs are multipotent stromal cells known to be present in a variety of locations in the body, including bones, cartilage, fat, muscles, and dental pulp. MSCs migrate toward inflamed areas during pathological immune responses. MSCs also migrate toward tumor stroma and participate in tumor progression. MSCs can contribute to tumor progression by interacting with tumor cells via paracrine signaling and differentiate into diverse cell types. This also enables MSCs to make direct contact with tumor cells in tumor stroma. Interactions between tumor cells and MSCs enhance tumorigenic and metastatic potential, in addition to stimulating epithelial to mesenchymal transition. Herein, we reviewed the research associated with the tumor-enhancing role of MSCs in tumor progression, from primary tumor growth to distant tumor metastasis.

Keywords: Mesenchymal stem cells; review; tumor microenvironment; tumor progression.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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7
Anticancer Res




. 2020 Jun;40(6):3411-3415. doi: 10.21873/anticanres.14325.
National Comprehensive Analysis of Characteristics of Acral Lentiginous Melanoma
Maria T Huayllani 1, David J Restrepo 1, Daniel Boczar 1, Francisco R Avila 1, Sanjay P Bagaria 2, Aaron C Spaulding 3, Brian D Rinker 1, Antonio J Forte 4
Affiliations expand
PMID: 32487638
DOI: 10.21873/anticanres.14325

Abstract


Background/aim: Acral lentiginous melanoma (ALM) is the least common subtype of cutaneous melanoma and typically occurs on the palms, soles, and nails. Tumor characteristics and disease severity in the US population are not well understood. Our aim was to analyze the characteristics of ALM of the extremities.

Patients and methods: We queried the National Cancer Database to identify patients with the diagnosis of ALM and common malignant melanoma located in the extremities (CMME). We compared demographic, tumor, and treatment characteristics between patients with ALM and those with CMME. Statistical analysis was performed with chi-squared test and multivariate logistic regression models.

Results: We identified 5,203 patients with ALM and 118,485 with CMME. When compared with patients with CMME, those with ALM were more likely to be older than 80. years at diagnosis [odds ratio (OR)=2.85, 95% confidence intervaI (CI)=2.12-3.82; p<0.001], have stage III disease (OR=4.22, 95% CI=1.47-12.16; p=0.01), and have ulceration (OR=1.52, 95% CI=1.33-1.74; p<0.001). Moreover, patients with ALM were less likely to have a mitotic count of 1/mm2 or greater (OR=0.57, 95% CI=0.48-0.67; p<0.001). No statistical difference was found for sex, lymph node involvement, regression, and use of surgery, radiotherapy, and immunotherapy between groups.

Conclusion: Age, disease stage, ulceration, and mitotic count are independent factors associated with ALM. Knowledge of the disease characteristics may allow for better diagnosis and understanding of disease pathophysiology.

Keywords: Acral lentiginous melanoma; National Cancer Database; malignant melanoma; tumor characteristics.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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8
Anticancer Res




. 2020 Jun;40(6):3459-3468. doi: 10.21873/anticanres.14332.
Correlation of Iodine Quantification and FDG Uptake in Early Therapy Response Assessment of Non-small Cell Lung Cancer: Possible Benefit of Dual-energy CT Scan as an Integral Part of PET/CT Examination
Jan Baxa 1, Jaroslav Ludvik 2, Martin Sedlmair 3, Thomas Flohr 3, Bernhard Schmidt 3, Petr Hošek 4, Milos Pesek 5, Martin Svatoň 5, Jiri Ferda 2
Affiliations expand
PMID: 32487645
DOI: 10.21873/anticanres.14332

Abstract


Aim: To compare iodine-related and fluorine-18 fluorodeoxyglucose (18F-FDG) parameters during staging of lung cancer as well as during early follow-up, while investigating potential use and possible substitutability in the assessment of therapeutic response or prediction.

Patients and methods: Patients (n=45) with confirmed lung cancer underwent 18F-FDG positron-emission tomography (PET) using single-source dual-energy computed tomography was performed for staging and early follow-up. Correlation of FDG uptake and iodine-related parameters was assessed and comparison with therapy response was performed.

Results: A strong correlation was found between the volumetric FDG parameters metabolic tumour volume (MTV) and total lesion glycolysis (TLG) and iodine uptake (IU) in staging (IU vs. MTV: rs=0.894; p<0.001 and IU vs. TLG: rs=0.874; p<0.001) and follow-up (IU vs. MTV: rs=0.934, p<0.001 and IU vs. TLG: rs=0.935, p<0.001). We also found significant correlation of change in these values between timepoints. We observed a significant correlation of IU, MTV and TLG with early therapy response and IU was found as a possible strong predictor.

Conclusion: Strong correlation of IU and volume-based FDG parameters was proved in staging, follow-up and change during therapy. Potential role of IU in prediction of early therapy-response was identified. Our study suggests a significant benefit of using the dual-energy computed tomography as a part of 18F-FDG PET/CT in patients with lung cancer.

Keywords: Multidetector computed tomography; dual-energy; fluorodeoxyglucose; iodine; lung cancer; positron-emission tomography.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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9
Anticancer Res




. 2020 Jun;40(6):3071-3080. doi: 10.21873/anticanres.14288.
Retinoids Augment Thiazolidinedione PPARγ Activation in Oral Cancer Cells
Raul Rosas 1, Seth Buryska 2, Robert Silver 3, Beverly Wuertz 4, Frank Ondrey 2
Affiliations expand
PMID: 32487601
DOI: 10.21873/anticanres.14288

Abstract


Background/aim: Head and neck squamous cell carcinoma affects nearly 500,000 people annually. Augmenting PPARγ functional activation is linked with multiple anti-carcinogenic processes in aerodigestive cell lines and animal models. PPARγ/RXRα heterodimers may be key partners in this activation.

Materials and methods: CA 9-22 and NA cell lines were treated with the PPARγ agonist ciglitazone and/or the RXRα agonist 9-cis-retinoic acid. PPARγ functional activation, cellular proliferation, apoptosis activity, and phenotype were subsequently analyzed.

Results: Ciglitazone and 9-cis-retinoic acid independently activated PPARγ and down-regulated the carcinogenic phenotype in vitro. Combination treatment significantly augmented these effects, further decreasing proliferation (p<0.0001), and increasing PPARγ functional activation (p<0.0001), apoptosis (p<0.05), and adipocyte differentiation markers (p<0.0001).

Conclusion: The efficacy of the combination of ciglitazone and 9-cis-retinoic acid afforded lowering treatment concentrations while maintaining desired therapeutic outcomes, optimistically supporting the feasibility and practicality of this novel treatment option.

Keywords: 9-cis-retinoic acid; PPARγ; ciglitazone; head and neck squamous carcinoma; retinoids; thiazolidinedione.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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10
Anticancer Res




. 2020 Jun;40(6):3119-3128. doi: 10.21873/anticanres.14293.
Knockdown of Myoferlin Suppresses Migration and Invasion in Clear-Cell Renal-Cell Carcinoma
Alexander Cox 1, Chenming Zhao 2, Yuri Tolkach 3, Daniel Nettersheim 4, Doris Schmidt 2, Glen Kristiansen 3, Stefan C Mueller 2, Manuel Ritter 2, Stefan Hauser 2, Joerg Ellinger 2
Affiliations expand
PMID: 32487606
DOI: 10.21873/anticanres.14293

Abstract


Background/aim: Myoferlin (MYOF) has emerged as an oncogenic protein in various human cancer types. This study was conducted to investigate comprehensively the expression and functional properties of MYOF in clear-cell renal-cell carcinoma (ccRCC) with respect to its value as diagnostic biomarker and therapeutic target.

Materials and methods: mRNA and protein expression of MYOF were assessed by quantitative polymerase chain reaction and immunohistochemistry. siRNA-mediated knockdown of MYOF was performed in the RCC cell line ACHN followed by proliferation, migration and invasion assays.

Results: MYOF mRNA and protein expression were significantly up-regulated in ccRCC. Higher mRNA levels were measured in advanced tumors. MYOF protein expression was increased in tumors with higher histological grades, and those with positive lymph node and surgical margin status. MYOF knockdown led to reduction of migration and invasion in ACHN cells, whereas expression of angiogenesis-associated genes tyrosine-protein kinase receptor-2 (TIE2), angiopoietin 2 (ANG2) and caveolin-1 (CAV1) was up-regulated following knockdown.

Conclusion: MYOF may serve as a diagnostic biomarker of tumor progression and a potential therapeutic target in ccRCC.

Keywords: Biomarker; immunohistochemistry; knockdown; myoferlin; renal cell carcinoma.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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11
Published Erratum
Anticancer Res




. 2020 Jun;40(6):3589.
Erratum
No authors listed
PMID: 32487662

Erratum for
Genetic Variations of VEGFA Gene Are Associated With Infiltration of Adjacent Tissues and the Clinical Outcome of Patients With Nasopharyngeal Carcinoma.
Psoma E, Koliou GA, Dimitrakopoulos FI, Papadopoulou K, Rontogianni D, Bobos M, Visvikis A, Kosmidis PA, Fountzilas G, Constantinidis J, Kalogera-Fountzila A.Anticancer Res. 2020 Feb;40(2):677-688. doi: 10.21873/anticanres.13997.PMID: 32014908
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12
Anticancer Res




. 2020 Jun;40(6):3527-3534. doi: 10.21873/anticanres.14341.
Diagnostic Reliability, Accuracy and Safety of Ultrasound-guided Biopsy and Ascites Puncture in Primarily Inoperable Ovarian Tumours
Pavel Vlasak 1, Jiri Bouda 1, Jan Kostun 1, Denis Berezovskiy 1, Michal Zikan 2, Vit Weinberger 3, Ondrej Ondic 4, Zdenek Rusavy 1, Radek Kucera 5, Ondrej Topolcan 5, Zdenek Novotny 1, Jiri Presl 6
Affiliations expand
PMID: 32487654
DOI: 10.21873/anticanres.14341

Abstract


Background/aim: To compare the diagnostic reliability, accuracy and safety of ultrasound-guided biopsy (Tru-Cut biopsy) and ascites puncture in patients with a primarily inoperable malignant ovarian tumor.

Patients and methods: This is a retrospective analysis of the studied methods in consecutively examined patients and a prospective validation of these methods. 79 women with a suspected primarily inoperable ovarian tumor underwent Tru-Cut biopsies and were included in the ultrasound-guided biopsy group. In addition, 55 patients after ascites puncture were enrolled in the comparison group. Both procedures were performed in 48 patients for the prospective validation.

Results: Significant differences in favour of ultrasound-guided biopsy were found in all studied variables (malignancy confirmation 72.9% vs. 95.8%, tumor origin 52.1% vs. 89.6%, histologic subtype 43.8% vs. 85.4% and accuracy, i.e. agreement of preoperative and definitive diagnosis 43.7% vs. 95.4%).

Conclusion: Ultrasound-guided biopsy is an accurate, reliable, safe and minimally invasive method. Owing to the high reliability and accuracy, it has the capacity to replace ascites puncture with cytologic examination or a more invasive method (laparoscopy, laparotomy) for adequate tumor sampling.

Keywords: Tru-Cut biopsy; ascites; ovarian cancer; puncture.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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13
Anticancer Res




. 2020 Jun;40(6):3395-3400. doi: 10.21873/anticanres.14323.
Tumor-infiltrating Lymphocyte Score Based on FDG PET/CT for Predicting the Effect of Neoadjuvant Chemotherapy in Breast Cancer
Shinsuke Sasada 1, Yuri Kimura 2, Akiko Emi 2, Norio Masumoto 2, Takayuki Kadoya 2, Koji Arihiro 3, Morihito Okada 2
Affiliations expand
PMID: 32487636
DOI: 10.21873/anticanres.14323

Abstract


Aim: To investigate whether tumor-infiltrating lymphocyte (TIL) scoring based on 18F-fluorodeoxyglucose positron-emission tomography/computed tomography (FDG PET/CT) can predict the pathological response to neoadjuvant chemotherapy.

Patients and methods: A total of 261 patients with breast cancer underwent complete resection after neoadjuvant chemotherapy. PET-TIL score was calculated using tumor size, Ki-67 labeling index, and maximum standardized uptake value (SUVmax) on FDG PET/CT. The efficacy of the PET-TIL score in predicting the pathological complete response (pCR) was retrospectively evaluated.

Results: pCR rates were 11.4%, 58.6%, and 38.8% in luminal, human epidermal growth factor receptor 2 (HER2)-positive, and triple-negative breast cancer, respectively. The corresponding median PET-TIL scores were 28, 37, and 45. pCR rates were 20.0% and 44.2% in the low and high PET-TIL score groups, respectively (p<0.001). HER2-positive and triple-negative subtypes and high PET-TIL score were independent predictors for pCR.

Conclusion: PET-TIL score can predict pCR after neoadjuvant chemotherapy in breast cancer.

Keywords: Breast cancer; PET; SUV; neoadjuvant chemotherapy; pathological complete response; tumor-infiltrating lymphocyte.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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14
Anticancer Res




. 2020 Jun;40(6):3513-3517. doi: 10.21873/anticanres.14339.
Pattern of Local Failure and Its Risk Factors of Locally Advanced Non-small Cell Lung Cancer Treated With Concurrent Chemo-radiotherapy
Takanori Abe 1, Nao Kobayashi 2, Tomomi Aoshika 2, Yasuhiro Ryuno 2, Satoshi Saito 2, Mitsunobu Igari 2, Ryuta Hirai 2, Y U Kumazaki 2, Y U Miura 3, Kyoichi Kaira 3, Hiroshi Kagamu 3, Shin-Ei Noda 2, Shingo Kato 2
Affiliations expand
PMID: 32487652
DOI: 10.21873/anticanres.14339

Abstract


Background/aim: The treatment outcome of locally advanced non-small cell lung cancer (LA-NSCLC) has been improved over the past years but local failure is still common for these patients. The purpose of this study is to analyze the pattern of local failure and its risk factor of concurrent chemo-radiotherapy (CCRT) for locally advanced LA-NSCLC.

Patients and methods: We evaluated 77 patients treated with CCRT for LA-NSCLC from July 2007 to December 2017 at our institution. Most of the patients were treated with 60 Gy in 30 fractions of radiotherapy and concurrent chemotherapy. The median follow-up time was 26 months.

Results: Among the 77 patients, 50 developed progressive disease during follow-up, including 14 with only local recurrence (LR), 10 with only distant metastasis and 26 with both. Of the 14 patients with only LR, 12 had primary tumor recurrence and 2 had recurrence in lymph nodes. A primary tumor volume of 50 cm3 was identified as the optimal cut-off value that was significantly correlated with primary tumor recurrence and overall survival.

Conclusion: Primary tumor recurrence without lymph node and distant metastasis was observed in 12 patients (16%). Primary tumor volume of 50 cm3 was the optimal cut-off value for the prediction of primary tumor recurrence.

Keywords: Local failure; concurrent chemo-radiotherapy; locally advanced non-small cell lung cancer.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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15
Anticancer Res




. 2020 Jun;40(6):3579-3587. doi: 10.21873/anticanres.14348.
Neoadjuvant Treatment in Upper Rectal Cancer Does Not Improve Oncologic Outcomes But Increases Postoperative Morbidity
Nicolas Tabchouri 1, Yassine Eid 2, Gilles Manceau 3, Alice Frontali 4, Zaher Lakkis 5, Ephrem Salame 1, Thierry Lecomte 6, Sophie Chapet 7, Gilles Calais 7, Bruno Heyd 5, Mehdi Karoui 3, Arnaud Alves 2, Yves Panis 4, Mehdi Ouaissi 8
Affiliations expand
PMID: 32487661
DOI: 10.21873/anticanres.14348

Abstract


Background/aim: Neoadjuvant chemoradiation/radiation therapy in locally advanced (LA) upper rectal adenocarcinoma management remains unclear. The aim of this study was to compare outcomes between neoadjuvant chemoradiation therapy (CRT) and upfront surgery (US).

Patients and methods: A total of 127 patients were retrospectively included from 5 centers (79 treated with US and 48 with CRT). CRT and US groups were compared in terms of postoperative complications and long-term oncological and functional results.

Results: Total mesorectal excision (TME) was more frequent in CRT (58% vs. 20% in US, p<0.001). CRT was associated with more overall and severe postoperative complications (60% vs. 30%, p<0.001 and 17% vs. 1%, p=0.002, respectively), and was the only risk factor [OR=18.8 (2.2-160.2), p=0.007]. Five-year overall survival and 5-year recurrence-free survival were similar between CRT and US (96% vs. 91% p=0.256 and 85.4% vs. 85%, p=0.495). The functional results were similar between the two groups.

Conclusion: CRT did not improve long-term oncological outcomes in patients with LA upper rectal adenocarcinoma, but increased postoperative complications compared with US.

Keywords: Upper rectal cancer; chemoradiation therapy; long-term functional results; neoadjuvant treatment; recurrence-free and overall survival.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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16
Anticancer Res




. 2020 Jun;40(6):3239-3246. doi: 10.21873/anticanres.14305.
NCAPH Is Required for Proliferation, Migration and Invasion of Non-small-cell Lung Cancer Cells
Byeol Kim 1, Seok Won Kim 2, Ji-Yeon Lim 1, Seon-Joo Park 3
Affiliations expand
PMID: 32487618
DOI: 10.21873/anticanres.14305

Abstract


Background/aim: Non-structural maintenance of chromosomes condensin I complex subunit H (NCAPH) is implicated in correct chromosome condensation and segregation during mitosis. However, the functional role of NCAPH in the pathogenesis of non-small-cell lung cancer (NSCLC) remains unclear. The aim of this study was to elucidate the role of NCAPH in NSCLC cells.

Materials and methods: A549 and H1299 NSCLC cells were transfected with small-interfering RNA (siRNA) against NCAPH. Subsequently, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, colony-formation assay and flow cytometry analysis were performed to reveal the role of NCAPH in NSCLC cells. In addition, migration and invasion assay were also performed.

Results: NCAPH knockdown inhibited cell proliferation, induced cell-cycle arrest at G2/M phase, and prevented colony formation, migration and invasion by NSCLC cells.

Conclusion: NCAPH is involved in NSCLC progression and development, and may be a potential therapeutic target for NSCLC treatment.

Keywords: NCAPH; NSCLC; cell cycle; chromosome; condensin.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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17
Anticancer Res




. 2020 Jun;40(6):3435-3444. doi: 10.21873/anticanres.14329.
Clinical Utility of Combined Circulating Tumor Cell and Circulating Tumor DNA Assays for Diagnosis of Primary Lung Cancer
Seong Mi Moon 1 2, Ji-Ho Kim 3, Seong Keun Kim 4, Seonwoo Kim 5, Hyuk-Jung Kwon 3, Jin-Sik Bae 3, Sunghoon Lee 3, Hye Seon Lee 4, Mi-Young Choi 4, Byung Hee Jeon 4, Byeong-Ho Jeong 1, Kyungjong Lee 1, Hong Kwan Kim 6, Jhingook Kim 6, Sang-Won Um 7
Affiliations expand
PMID: 32487642
DOI: 10.21873/anticanres.14329

Abstract


Background/aim: Although it has been suggested that circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) might be used in a complementary manner in lung cancer diagnosis, limited confirmatory data are available. In this prospective study, we evaluated the diagnostic performance of each assay separately and in combination.

Patients and methods: From March 2018 to January 2019, patients with suspected primary lung cancer, who underwent routine lung cancer work-up and peripheral blood sampling, were prospectively enrolled in the study. Epithelial cell adhesion molecule and cytokeratin served as markers of CTCs. In terms of ctDNA analysis, single-nucleotide variants were evaluated via next-generation sequencing.

Results: We analyzed 111 patients, including 99 with primary lung cancer and 12 with benign pulmonary disease. The median number of CTCs in 10 ml of blood was 3. The most frequently detected single nucleotide variants of ctDNA were TP53, CDKN2A, and EGFR. The diagnostic sensitivity of conventional tumor marker (combination of carcinoembryonic antigen/CYFRA 21-1/neuron-specific enolase) was 66.7%, while those of the ctDNA and CTC assays were 72.7% and 65.7%, respectively. The sensitivity of the CTC/ctDNA combination (95.0%) was significantly greater than those of the CTC (p<0.001), ctDNA (p<0.001), or conventional tumor marker (p<0.001) alone. Subgroup analysis revealed that the sensitivity of the combination assay was greater than those of the CTC or ctDNA assays alone, regardless of tumor stage or histopathology type.

Conclusion: The CTC/ctDNA combination assay enhanced the sensitivity of primary lung cancer diagnosis. The combination assay strategy may be clinically useful and could enhance the early detection of lung cancer (ClinicalTrials.gov number: NCT03479099).

Keywords: Liquid biopsy; circulating tumor DNA; circulating tumor cell; diagnosis; primary lung cancer.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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18
Anticancer Res




. 2020 Jun;40(6):3469-3476. doi: 10.21873/anticanres.14333.
Comparison Between Biweekly and Weekly Cetuximab in Patients With Metastatic Colorectal Cancer: A Meta-analysis
Akihisa Matsuda 1, Takeshi Yamada 2, Supaschin Jamjittrong 3, Seiichi Shinji 2, Ryo Ohta 2, Hiromichi Sonoda 2, Tunyaporn Kamonvarapitak 3, Kumiko Sekiguchi 4, Masao Miyashita 4, Hideyuki Suzuki 4, Hiroshi Yoshida 3
Affiliations expand
PMID: 32487646
DOI: 10.21873/anticanres.14333

Abstract


Background/aim: Although weekly administration of cetuximab is the standard regimen in patients with metastatic colorectal cancer (mCRC), the efficacy and safety of a biweekly regimen is a pending issue. We conducted this meta-analysis to compare the efficacy and safety of a biweekly vs. a weekly regimen of cetuximab in the treatment of mCRC.

Patients and methods: We conducted a comprehensive electronic literature search up to January 2020 to identify studies directly comparing the efficacy and safety of biweekly cetuximab administration and conventional weekly administration in patients with mCRC. We then performed a meta-analysis using random-effects models to calculate risk ratios and mean differences with 95% confidence intervals.

Results: Four studies with a total of 381 patients were included in this meta-analysis. The meta-analysis showed that biweekly administration conferred equivalent efficacy, including objective response rate, disease-control rate, progression-free survival, and overall survival, as well as safety, including skin toxicity, gastrointestinal toxicity, and hematologic toxicity, compared with weekly administration in patients with mCRC.

Conclusion: Results from this meta-analysis support the administration of biweekly instead of weekly cetuximab, which is beneficial for both patients and health resources.

Keywords: Cetuximab; biweekly; metastatic colorectal cancer; weekly.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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19
Anticancer Res




. 2020 Jun;40(6):3139-3145. doi: 10.21873/anticanres.14295.
Anti-infectious and Anti-tumor Activities of β-Glucans
Vaclav Vetvicka 1, Jana Vetvickova 2
Affiliations expand
PMID: 32487608
DOI: 10.21873/anticanres.14295

Abstract


Background/aim: The aim of this study was to directly compare the anti-infectious and anti-cancer effects of five commercially available glucans.

Materials and methods: We used five different glucans isolated from algae, yeast, bacteria, oat, and mushroom. We compared their effects on the stimulation of phagocytosis of blood cells, on the secretion of IL-2, and on the inhibition of melanoma and breast and lung cancers. In addition, we evaluated the effects of glucan supplementation on two experimental models of infection.

Results: Most of the tested glucans stimulated phagocytosis and IL-2 secretion, reduced cancer growth, and ameliorated some effects of experimental infections.

Conclusion: Glucans can produce significant pleiotropic effects, but the activity varies among individual samples.

Keywords: Glucan; IL-2; cancer; infection; phagocytosis.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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20
Anticancer Res




. 2020 Jun;40(6):3379-3386. doi: 10.21873/anticanres.14321.
The Role of Radiotherapy for Patients With Thyroid Cancer in the Modern Era
Laith Samhouri 1, Jan Kriz 1, Khaled Elsayad 1, Mohammed Channaoui 1, Andreas Pascher 2, Burkhard Riemann 3, Rainer Wiewrodt 4, Uwe Haverkamp 1, Sergiu Scobioala 1, Hans Theodor Eich 5
Affiliations expand
PMID: 32487634
DOI: 10.21873/anticanres.14321

Abstract


Background/aim: Thyroid cancer (TC) is a relatively rare malignancy. The mainstay treatment is surgery followed by radioactive iodine (RAI) and medical systemic treatments. The role of external beam radiotherapy (EBRT) in TC is controversial regarding the survival benefits. The aim of this study was to analyse the effectiveness of EBRT for different forms of TC in different stages.

Patients and methods: Between January 1990 and 2016, 75 patients underwent 255 radiotherapy (RT) courses at our Institution. Local control (LC) and progression-free survival (PFS) were analyzed.

Results: The cohort consisted of 22 patients who received curative RT and 53 patients who received RT in a palliative setting. The estimated 5-year LC for the curative group was 92±8% and the palliative group 78±7%. The estimated 5-year PFS for the curative group was 27±9% and for palliative group 31±6%.

Conclusion: The addition of RT in TC seems to be safe and effective. Our analysis showed an excellent local control (median >15 years) regardless of the treatment setting.

Keywords: Thyroid cancer; curative; palliative setting; stereotactic radiotherapy.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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21
Anticancer Res




. 2020 Jun;40(6):3091-3096. doi: 10.21873/anticanres.14290.
Oncogenic miRNAs Identified in Tear Exosomes From Metastatic Breast Cancer Patients
Sachiko Inubushi 1 2 3, Hiroki Kawaguchi 1, Sachiko Mizumoto 4, Tomonari Kunihisa 4, Motoi Baba 4, Yukiya Kitayama 5, Toshifumi Takeuchi 5, Robert M Hoffman 2 3, Ryohei Sasaki 6
Affiliations expand
PMID: 32487603
DOI: 10.21873/anticanres.14290

Abstract


Background/aim: Exosomes are produced by normal and cancer cells. Exosomes are found in the serum of cancer patients and have been used for diagnosis and prognosis. Recently tears from non-cancer patients have been found to contain exosomes. In the present report we describe tears from advanced breast-cancer patients.

Materials and methods: We found oncogenic miRNAs in the exosomes isolated from tear fluids obtained from five patients with metastatic breast cancer and compared them with tear exosomes form eight healthy volunteers.

Results: Tear exosomes had a significantly higher quantity of exosome markers than serum exosomes (CD9, CD63). Tear exosomes were subjected to quantitative reverse-transcription polymerase reaction (qRT-PCR), and western blot analysis to elucidate the status of miRNAs, previously reported in serum from patients with metastatic breast cancer. qRT-PCR and western-blot analysis revealed that breast-cancer-specific miR-21 and miR-200c were highly expressed in tear exosomes from metastatic breast cancer patients in contrast to tear exosomes from healthy volunteers.

Conclusion: Tear exosomes can be a potential source of diagnostic and prognostic biomarkers for metastatic breast cancer, and possibly other cancers or diseases.

Keywords: Exosomes; biomarkers; breast cancer; extracellular vesicles; miRNA; tears.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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22
Anticancer Res




. 2020 Jun;40(6):3297-3306. doi: 10.21873/anticanres.14312.
An Animal Model of Colorectal Cancer Liver Metastasis With a High Metastasis Rate and Clonal Dynamics
Ki Beom Bae 1 2, Sun-Hee Kim 3 2 4, Mi Seon Kang 5, Dong-Hyun Kim 6
Affiliations expand
PMID: 32487625
DOI: 10.21873/anticanres.14312

Abstract


Background: Various animal models have been introduced into the study of liver metastasis of colorectal cancer, but they have not been compared under the same conditions. The aim of this study was to identify an optimized mouse model that showed a high rate of hepatic metastasis and expression of clonal dynamics.

Materials and methods: Athymic nude mice (n=30) were divided into two equal groups for the creation of a splenic injection model (SIM) and surgically orthotopic implantation model (SOIM) of liver metastasis of colorectal cancer using HCT116 cells. Hepatic metastasis was confirmed by gross and microscopic examinations. Expression of MET transcriptional regulator MACC1 (MACC1) in colon cancer cell lines and metastatic tumors in the group with a higher liver metastasis rate was confirmed by quantitative reverse-transcription-polymerase chain reaction.

Results: The observation time was significantly shorter for SIM than for SOIM (33.0±6.8 vs. 41.2±7.2 days, p<0.001). The rate of hepatic metastasis was significantly higher in SIM than in SOIM (76.9% vs. 38.4%, p=0.038). MACC1 was expressed in Colo201, HCT116, HT29, LS513, SW620, and WiDr cells but not in SW480 cells. All hepatic metastases in SIM mice expressed MACC1, and metastatic HCT116 cells had significantly greater expression than did the original HCT116 cells (p<0.001).

Conclusion: With a higher rate of hepatic metastasis with clonal dynamics in a shorter observation time than the SOIM, SIM appears to be a good animal model for identifying new targets and in drug development for colorectal cancer liver metastasis. SOIM should also be considered for the study of the full steps of metastasis.

Keywords: Colorectal cancer; animal model; clonal dynamics; liver metastasis; orthotopic implantation; splenic injection.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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23
Anticancer Res




. 2020 Jun;40(6):3287-3296. doi: 10.21873/anticanres.14311.
Tranilast Inhibits TGF-β1-induced Epithelial-mesenchymal Transition and Invasion/Metastasis via the Suppression of Smad4 in Human Lung Cancer Cell Lines
Koji Takahashi 1, Toshi Menju 2, Shigeto Nishikawa 1, Ryo Miyata 1, Satona Tanaka 1, Yojiro Yutaka 1, Yoshito Yamada 1, Daisuke Nakajima 1, Masatsugu Hamaji 1, Akihiro Ohsumi 1, Toyofumi Fengshi Chen-Yoshikawa 3, Toshihiko Sato 1, Makoto Sonobe 4, Hiroshi Date 1
Affiliations expand
PMID: 32487624
DOI: 10.21873/anticanres.14311

Abstract


Background/aim: Transforming growth factor β1 (TGF-β1) is an important epithelial-mesenchymal transition (EMT) activator that regulates the expression of E-cadherin and vimentin through Smad signalling. Tranilast is an anti-allergic drug that inhibits TGF-β1, and is used in the treatment of keloids and hypertrophic scars. We investigated whether tranilast inhibits TGF-β1-induced EMT and invasiveness in human non-small cell lung cancer cell lines.

Materials and methods: We examined the effects of tranilast treatment on EMT markers, TGF-β1/Smad signalling, and cell invasiveness in A549 and PC14 cells. Tumours from a mouse orthotopic lung cancer model with or without tranilast treatment were also immunohistochemically evaluated.

Results: Tranilast increased E-cadherin expression via Smad4 suppression and inhibited cell invasion in TGF-β1-stimulated cells. Tranilast treatment of the in vivo mouse model reduced the pleural dissemination of cancer cells and suppressed vimentin and Smad4 expression.

Conclusion: Tranilast inhibited TGF-β1-induced EMT and cellular invasion/metastasis by suppressing Smad4 expression in cancer cells.

Keywords: EMT; Smad4; TGF-β1; tranilast.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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24
Anticancer Res




. 2020 Jun;40(6):3535-3542. doi: 10.21873/anticanres.14342.
Inflammation Caused by Surgical Stress Has a Negative Impact on the Long-term Survival Outcomes in Patients With Colorectal Cancer
Masatsune Shibutani 1, Shigetomi Nakao 2, Kiyoshi Maeda 2, Hisashi Nagahara 2, Tatsunari Fukuoka 2, Yasuhito Iseki 2, Kosei Hirakawa 2, Masaichi Ohira 2
Affiliations expand
PMID: 32487655
DOI: 10.21873/anticanres.14342

Abstract


Background/aim: Inflammation is known to promote the progression of cancer, and there is increasing evidence that inflammation caused by the antitumor response of the host and post-operative infectious complications worsens the prognosis for colorectal cancer. However, the impact of post-operative inflammation caused by surgical stress on long-term survival is unclear.

Patients and methods: A total of 274 patients who underwent curative operation for stage II/III colorectal cancer were enrolled and assessed for the serum C-reactive protein (CRP) levels on postoperative day (POD) 1 and 7 and postoperative infectious complications.

Results: The high POD-1 CRP group had a significantly lower relapse-free and overall survival rate than the low POD-1 CRP group. Similarly, the high POD-7 CRP group had a significantly lower relapse-free and overall survival rate than the low POD-7 CRP group. Sub-group analysis limited to patients without postoperative infectious complications indicated that the high POD-7 CRP group tended to have a lower relapse-free survival rate and a significantly lower overall survival rate than the low POD-7 CRP group.

Conclusion: Inflammation caused by postoperative infectious complications and by surgical stress worsens long-term survival outcomes after a curative operation for colorectal cancer.

Keywords: Inflammation; colorectal cancer; surgical stress; survival.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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25
Anticancer Res




. 2020 Jun;40(6):3155-3161. doi: 10.21873/anticanres.14297.
Sirtuin 1 Activation Suppresses the Growth of T-lymphoblastic Leukemia Cells by Inhibiting NOTCH and NF-κB Pathways
Salwa M Okasha 1, Mai Itoh 1, Shuji Tohda 2
Affiliations expand
PMID: 32487610
DOI: 10.21873/anticanres.14297

Abstract


Background/aim: The deacetylase sirtuin1 (SIRT1) inhibits tumor suppressor p53 and may promote tumorigenesis; however, SIRT1 effects on leukemia cells are controversial. The aim of this study was to clarify the activity of SIRT1 in leukemia cells.

Materials and methods: The effects of SIRT1 inhibition or activation and SIRT1 knockdown or overexpression were examined in two T cell acute lymphoblastic leukemia (T-ALL) cell lines carrying NOTCH1 mutations and three acute myeloid leukemia (AML) cell lines.

Results: The growth of T-ALL cells was promoted by SIRT1 inhibition and SIRT1 knockdown but was reduced by SIRT1 activation and overexpression; however, no effects were observed in AML cells. SIRT1 activation decreased NOTCH, NF-κB, and mTOR signaling and inhibited p53, suggesting that the possible mechanisms of T-ALL growth suppression by SIRT1 are independent of p53.

Conclusion: SIRT1 activators acting through the down-regulation of NOTCH, NF-κB, and mTOR pathways can be novel targeted drugs for NOTCH1-mutated T-ALLs.

Keywords: NF-κB; NOTCH; Sirtuin1; leukemia; p53.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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26
Review
Anticancer Res




. 2020 Jun;40(6):3013-3030. doi: 10.21873/anticanres.14282.
Second-line Treatment in Advanced Biliary Tract Cancer: Today and Tomorrow
Alessandro Rizzo 1, Angela Dalia Ricci 2, Nastassja Tober 2, Maria Concetta Nigro 2, Mirta Mosca 2, Andrea Palloni 2, Francesca Abbati 2, Giorgio Frega 2, Stefania DE Lorenzo 2, Simona Tavolari 2, Giovanni Brandi 2
Affiliations expand
PMID: 32487595
DOI: 10.21873/anticanres.14282

Abstract


Biliary tract cancer (BTC) patients usually have poor prognosis. Whereas combination chemotherapy has been shown to improve survival in the frontline setting, second-line treatment is subject to a lot of debate in the scientific community. Recent data of the ABC-06 trial has provided slight evidence for the use of second-line chemotherapy after progression on cisplatin plus gemcitabine combination. In this study, mFOLFOX plus active symptom control (ASC) improved overall survival (OS) after progression on cisplatin-gemcitabine combination compared with ASC alone, with an increase in 6- and 12-month OS rate. Although genomic studies have paved the way for a new age in cancer management, the "Precision Medicine Era" in BTC is still limited to intrahepatic cholangiocarcinoma and primarily focused on isocitrate dehydrogenase (IDH) and fibroblast growth factor receptor (FGFR) targeted therapies. We herein review recent published data regarding the use of second-line treatment after failure of standard first-line therapies in BTC patients, with a particular focus on ongoing active and recruiting clinical trials.

Keywords: Biliary tract cancer; chemotherapy; cholangiocarcinoma; review; second-line; targeted therapy.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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27
Anticancer Res




. 2020 Jun;40(6):3169-3190. doi: 10.21873/anticanres.14299.
Investigation of the Involvement of Parkin in Parkinson's Disease and Cancer by Monitoring the Changes in SH-SY5Y Cells at the Nuclear Proteome Level
Abula Ayimugu 1, Mehmet Sarihan 2, Murat Kasap 3, Gurler Akpinar 2
Affiliations expand
PMID: 32487612
DOI: 10.21873/anticanres.14299

Abstract


Background/aim: During the last two decades, Parkinson's disease (PD)-associated genes have been associated with cancer; however, a shared pathogenic mechanism has yet to be discovered. Parkin, an E3 ubiquitin ligase that is involved in early-onset Parkinson's disease, has also been reported to exert tumor suppressor activity. However, the details about the role of Parkin in cancer remain unknown. The present study aimed at identifying differentially regulated nuclear proteins and nuclear phosphoproteins whose levels were affected by Parkin expression.

Materials and methods: SHS-SY5Y cells expressing either wild-type Parkin or its mutant under tetracycline control were used in this study; cells not expressing Parkin served as control. Nuclear proteins were enriched from Parkin-expressing and control cells to perform a comparative proteomics study using two-dimensional gel electrophoresis (2D) coupled to matrix assisted laser desorption/ionisation-time of flight (MALDI-TOF/TOF) mass spectrometry analysis. Changes in phosphoproteome and nuclear phosphoproteome were also studied by staining the 2D gels with ProQ diamond phosphoprotein stain. The identified proteins were subjected to bioinformatics analysis to elucidate the reactomes and relevant pathways.

Results: Six nuclear proteins, namely NCL, DDIT3, PARP1, HMGB1, TCTP and TPI were shown to be differentially regulated in cells expressing Parkin protein. Regulations in phosphorylation levels of ENPL, PRDX4, ECHM, ALDOA SET, DHSA, RCC1 and DULRD were also detected. Bioinformatics analysis of differentially regulated proteins highlighted the involvement of Parkin in DNA repair.

Conclusion: Several nuclear protein candidates whose expression or phosphorylation levels were altered in cells expressing Parkin. Bioinformatics analysis of these proteins indicated that the nuclear form of Parkin may play a significant role in DNA repair and contribute to prevention of tumorogenesis via maintaining DNA integrity.

Keywords: 2D gel electrophoresis; Parkin; neuroblastoma cancer; nuclear proteome; phosphoproteome.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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28
Anticancer Res




. 2020 Jun;40(6):3505-3512. doi: 10.21873/anticanres.14338.
Clinical Significance of Nucleoli Cytomorphology Assessment in Patients With Uveal Melanoma
Tomasz Berus 1, Anna Markiewicz 2, Przemysław Biecek 3, Jolanta Orłowska-Heitzman 4, Agnieszka Hałoń 5, Bożena Romanowska-Dixon 2, Piotr Donizy 5
Affiliations expand
PMID: 32487651
DOI: 10.21873/anticanres.14338

Abstract


Aim: To assess the prognostic significance of nucleolar morphological parameters in a large cohort of patients with uveal melanoma.

Patients and methods: The presence, size and number of nucleoli of cancer cells were assessed in haematoxylin and eosin (HE)-stained slides of 164 formalin-fixed paraffin-embedded primary uveal melanoma tissue specimens. The results were correlated with clinicopathological features and patient survival.

Results: The presence of macronucleoli and multiple nucleoli significantly correlated with the epithelioid type of uveal melanoma, high mitotic rate, and marked pleomorphism. There was a positive correlation between the presence of macronucleoli as well as the number of nucleoli and the largest tumour basal diameter. The increased nucleolus count in tumour cells positively correlated with primary tumour (pT) staging. The presence of both prominent and multiple nucleoli was associated with significantly reduced overall and disease-free survival.

Conclusion: Histological assessment of nucleolar morphology in routine HE staining would be a helpful low-cost method to obtain reliable prognostic information.

Keywords: H&E staining; Nucleolus; prognosis; uveal melanoma.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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29
Review
Anticancer Res




. 2020 Jun;40(6):3049-3053. doi: 10.21873/anticanres.14285.
Tumor Handling of Early-stage Cervical Cancer: A Literature Analysis of Villoglandular Adenocarcinoma of the Cervix
Anna Dietl 1, Konrad Aumann 2, Matthias W Beckmann 3
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PMID: 32487598
DOI: 10.21873/anticanres.14285

Abstract


Background/aim: Recent studies have demonstrated the inferior overall survival outcomes of patients with early-stage cervical cancer who undergo minimally invasive surgery (MIS). One possible explanation for these unexpected results is intraoperative tumor manipulation.

Materials and methods: Considering this hypothesis, we have reviewed the literature on the oncological outcomes of patients with villoglandular adenocarcinoma (VGA) of the cervix, an uncommon variant of cervical cancer that has an excellent prognosis.

Results: VGA generally presents as an exophytic mass arising from the endocervix. In a systematic review, we identified 221 patients treated surgically for VGA (FIGO stage Ia-Ib1). Of these, 11 developed recurrence, and four died. The recurrence sites in 8 cases were the pelvis (n=3), vaginal cuff (n=3), episiotomy scar (n=1), and cervix (n=1). Furthermore, 23 VGA-patients were treated by MIS, four experienced recurrence, and one died. Three intraabdominal metastases after MIS were reported.

Conclusion: Excessive tumor-handling during MIS or manipulations, e.g. cervix-dilation (during delivery), can worsen the otherwise excellent prognosis.

Keywords: Early-stage cervical cancer; minimal handling; minimal invasive surgery; review; villoglandular adenocarcinoma of the uterine cervix.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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30
Anticancer Res




. 2020 Jun;40(6):3315-3323. doi: 10.21873/anticanres.14314.
Efficacy of Adjuvant Combination Therapy With Trastuzumab and Chemotherapy in HER2-positive Early Breast Cancer: A Single Institutional Cohort Study From Clinical Practice
Masahiro Okamoto 1, Wakako Tajiri 1, Hiroki Ueo 1, Takanobu Masuda 1, Hideki Ijichi 1, Chinami Koga 1, Yoshiaki Nakamura 1, Kenichi Taguchi 2, Shinji Ohno 3, Eriko Tokunaga 4
Affiliations expand
PMID: 32487627
DOI: 10.21873/anticanres.14314

Abstract


Background/aim: To evaluate the improvement in the prognosis by adjuvant trastuzumab in clinical practice and the risk factors for distant recurrence, we retrospectively investigated the prognosis of HER2-positive early breast cancer in our department before and after the introduction of adjuvant trastuzumab.

Patients and methods: Cohorts A and B included 161 and 182 cases, respectively, who underwent surgery before (2000-2007) and after (2008-2015) the introduction of adjuvant trastuzumab.

Results: The rates of relapse-free and distant metastasis-free survival were significantly better in cohort B than in cohort A. The risk factors of distant recurrence found in cohort A, such as the presence of lymph node metastasis, lymphatic invasion, and a low histological grade, did not increase the risk in cohort B.

Conclusion: Many risk factors seemed to have been negated by adjuvant trastuzumab administration. Therefore, further escalation of adjuvant treatment should be carefully considered.

Keywords: Breast cancer; HER2; trastuzumab.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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31
Anticancer Res




. 2020 Jun;40(6):3571-3577. doi: 10.21873/anticanres.14347.
Effectiveness of Photodynamic Screening Using 5-Aminolevulinic Acid for the Diagnosis of Pancreatic Cancer
Tsukasa Ikeura 1, Yuichi Hori 2, Toshiyuki Mitsuyama 2, Hideaki Miyoshi 2, Masaaki Shimatani 2, Kazushige Uchida 3, Makoto Takaoka 2, Urara Ota 4, Atsuko Kamiya 4, Kiwamu Takahashi 4, Masahiro Ishizuka 4, Masaki Kaibori 5, Kazuichi Okazaki 2
Affiliations expand
PMID: 32487660
DOI: 10.21873/anticanres.14347

Abstract


Background/aim: We evaluated urinary levels of porphyrin metabolites, such as uroporphyrin (UP) and coproporphyrin (CP), after 5-Aminolevulinic acid (ALA) administration in patients with or without pancreatic cancer (PaC).

Patients and methods: Sixty-seven subjects with PaC, 11 with pancreatitis, and 9 with normal pancreas (NP) were enrolled. Urine samples from all subjects were collected prior to ALA administration and at more than 4 hours after ALA administration. We measured the urinary levels of UP and CP by high-performance liquid chromatography analysis.

Results: The PaC group showed significantly higher UP levels compared to NP groups (104.9 nmol/g Cre vs. 53.4 nmol/g Cre, p=0.014). Moreover, PaC patients with long-term survival had significantly lower urinary levels of UP at diagnosis (98.8 nmol/gCre) than the short-term survival group (125.2 nmol/gCre) (p=0.042).

Conclusion: The urinary levels of UP after ALA administration might serve as a promising biomarker for diagnosis and prognosis prediction of PaC.

Keywords: 5-aminolevulinic acid; Pancreatic cancer; biomarker; photodynamic screening.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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32
Anticancer Res




. 2020 Jun;40(6):3543-3550. doi: 10.21873/anticanres.14343.
Tumor-to-nipple Distance Should Not Preclude Nipple-sparing Mastectomy in Breast Cancer Patients. Personal Experience and Literature Review
Piero Fregatti 1 2, Marco Gipponi 3, Gabriele Zoppoli 4, Matteo Lambertini 5, Eva Blondeaux 2, Liliana Belgioia 6, Raffaele Derosa 1, Federica Murelli 1 2, Francesca Depaoli 7, Marcello Ceppi 8, Alessandro Garlaschi 9, Daniele Friedman 1 2
Affiliations expand
PMID: 32487656
DOI: 10.21873/anticanres.14343

Abstract


Background/aim: A retrospective study was performed in 246 breast cancer patients to define whether tumor-to-nipple distance (TND) assessment by breast MRI may select patients eligible to nipple-sparing mastectomy (NSM) as compared to permanent section assessment of retroareolar margin.

Patients and methods: Pre- and post-operative parameters including imaging data, histology of the primary tumor, biologic prognostic factors, and adjuvant regimens were retrieved; patients with close/positive retroareolar margins underwent nipple or NAC excision. The primary endpoint was loco-regional recurrence (LRR).

Results: Patients with TND ≤2 cm had a significantly higher rate of invasive ductal carcinoma (p<0.003) and excision margins less than 2 mm (p<0.000). Eleven retroareolar specimens were positive at definitive pathology; final re-excision specimen examination showed residual disease in seven patients (63.6%). At a median follow-up of 31 to 33 months, no NAC recurrence did occur; disease-free survival was more than 96%, and LRR was homogeneously distributed among TND subgroups.

Conclusion: Therapeutic NSM is a safe procedure independently of TND assessed at preoperative breast MRI. Permanent section assessment of retroareolar tissue is more accurate and cost-effective than frozen section. Furthermore, delayed nipple and/or NAC excision did not impair local disease control.

Keywords: Breast cancer; breast MRI; nipple-sparing mastectomy.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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33
Anticancer Res




. 2020 Jun;40(6):3401-3410. doi: 10.21873/anticanres.14324.
Hydro-MDCT for Gastric Adenocarcinoma Staging. A Comparative Study With Surgical and Histopathological Findings for Selecting Patients for Echo-endoscopy
Marco DI Girolamo 1, Francesco Carbonetti 2, Paolo Bonome 2, Andrea Grossi 2, Federica Mazzuca 3, Luigi Masoni 4
Affiliations expand
PMID: 32487637
DOI: 10.21873/anticanres.14324

Abstract


Background/aim: In local staging of gastric adenocarcinoma CT is the modality of choice. Less frequently used in a few selected patients is echo-endoscopy. Aim of this study was to evaluate the accuracy of hydro-multidetector-computed tomography (hydro-MDCT) in the evaluation of gastric adenocarcinomas with subsequent surgical and histopathological correlation to select cases for echo-endoscopy.

Patients and methods: A total of 65 patients with gastric adenocarcinomas, diagnosed by endoscopy and biopsy, underwent contrast-enhanced hydro-MDCT with subsequent tumor, nodes, metastases (TNM) classification. The distension of the gastric lumen was obtained after the oral administration of 500 ml of water.

Results: Hydro-MDCT always detected gastric cancer and in 49/65 patients the assessment of T-parameter was identical to the histopathological results (accuracy: 75%). We found overstaging in 12 and understaging in 4 cases. N-parameter with MDCT was in agreement with histo-pathology in 69%of patients; in metastatic disease hydro-MDCT had an accuracy of 99%. Hydro-MDCT has proven to be a reliable diagnostic technique in evaluating gastric cancer T3-T4 stages in comparison to T1 and T2: in defining T2-stage we found the highest number of errors (37%).

Conclusion: Hydro-MDCT is a reliable technique in the preoperative staging of gastric adenocarcinoma. Echo-endoscopy could be particularly useful in doubtful cases to evaluate the muscularis propria infiltration (T2 vs. T3) and characterize the peri-gastric lymph nodes.

Keywords: Stomach neoplasms; contrast media; echo-endoscopy; multidetector computed tomography; neoplasm staging.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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34
Review
Anticancer Res




. 2020 Jun;40(6):3031-3037. doi: 10.21873/anticanres.14283.
Is Perineural Invasion a Novel Prognostic Factor Useful to Tailor Adjuvant Treatment in Patients Treated With Primary Surgery for Cervical and Vulvar Carcinoma?
Angiolo Gadducci 1, Sabina Pistolesi 2, Stefania Cosio 3, Antonio Giuseppe Naccarato 2
Affiliations expand
PMID: 32487596
DOI: 10.21873/anticanres.14283

Abstract


Perineural invasion (PNI) is detected in 7.0-35.1% of cervical carcinomas. This histological finding correlates with cervical invasion, lymph-vascular space invasion (LVSI), tumor size, positive resection margins, parametrial invasion, node metastases and advanced stage. Some authors have reported that PNI has no prognostic relevance, others have found that PNI is related to disease-free survival or overall survival (OS) at univariate analysis, and others have observed that it is an independent poor prognostic factor for OS. The evaluation of PNI status should be included in the decision-making process for planning adjuvant treatment. PNI has been found in 7.6-52.4% of vulvar carcinomas. This feature, which is strongly associated with depth of invasion, LVSI, tumor size, advanced stage and nodal involvement, is an independent prognostic variable for the risk of recurrence and death in most series. PNI should be evaluated routinely in histopathology reports of vulvar carcinoma and could help clinicians to tailor adjuvant treatment.

Keywords: Perineural invasion; adjuvant therapy; cervical cancer; review; surgery; vulvar cancer.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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35
Anticancer Res




. 2020 Jun;40(6):3255-3264. doi: 10.21873/anticanres.14307.
EBV Rta-induced IL-6 Promotes Migration of Bystander Tumor Cells Through IL-6R/JAK/STAT3 Pathway In Vitro
Kuo-Lung Tung 1, Yen-Ting Wu 2, Cheng Liu 1 3, Sheng-Chieh Lin 1, Chin-Han Wu 1, Shih-Yi Wu 2, Yao Chang 4, Yu-Yan Lan 5
Affiliations expand
PMID: 32487620
DOI: 10.21873/anticanres.14307

Abstract


Background/aim: Rta, a transactivator of Epstein-Barr virus, is associated with progression of nasopharyngel carcinoma (NPC); however, its mechanism of contribution to the pathogenesis of NPC remains unclear. Interleukin-6 (IL-6), a tumor promoter, is detected in NPC. This in vitro study examined whether and how Rta promotes NPC progression by up-regulating IL-6.

Materials and methods: Semiquantitative reverse transcription-polymerase chain reaction (RT-PCR), quantitative real-time PCR, ELISA, immunoblotting assays, reporter gene assays, and transwell migration assays were performed.

Results: In NPC cells, Rta up-regulated IL-6 expression at the mRNA and protein levels, and the Rta's C-terminus was essential for promoter activation and expression of IL-6. The induction of IL-6 by Rta also required activation of extracellular signal-regulated kinase 1/2 and activator protein-1. Furthermore, IL-6 secreted from Rta-expressing NPC cells promoted migration of Rta-negative NPC cells by activating IL-6 receptor/Janus kinase/signal transducer and activator of transcription 3 pathway.

Conclusion: Rta contributes to progression of NPC cells through induction of IL-6 in vitro.

Keywords: Epstein-Barr virus; Rta; cell migration; interleukin-6; nasopharyngeal carcinoma.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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36
Anticancer Res




. 2020 Jun;40(6):3333-3343. doi: 10.21873/anticanres.14316.
Symptomatic Intraosseous Vascular Malformation of Infraorbital Rim: A Case Report With Literature Survey
Reinhard E Friedrich 1, Ulrich Grzyska 2, Felix K Kohlrusch 3, Simon VON Kroge 4, Tobias Vollkommer 3, Andreas M Luebke 5
Affiliations expand
PMID: 32487629
DOI: 10.21873/anticanres.14316

Abstract


Background/aim: Intraosseous orbital hemangiomas or vascular malformations (VM) are rare. This report is intended to complement the experience of diagnosing and treating a rare vascular lesion at this site. Special attention is paid to three-dimensional imaging and the morphological distinction between the two entities in this location.

Case report: A 54-year-old female was examined and surgically treated for an exophytic firm mass of the infraorbital, which had become palpable as a hard mass due to growth in size. At first, a bone tumor, for example, an osteoma, was suspected. Intraoperatively, an osseous expansion with distinct fenestrations of the newly grown bone's surface, was detected. The lesion was firmly attaching to the orbital rim. The densely vascularized tumor was well defined to the soft tissues but had grown in continuity from the orbital floor and rim. Vascularized cavities caused the tumor to have a slightly reddish color. The histological examination confirmed the suspicion of the lesion's vascular origin. The lesion's immunohistochemical expression profile approved the final diagnosis of intraosseous VM.

Conclusion: The symptoms of intraosseous vascular lesions of the orbit are determined by location and size. Modern imaging techniques facilitate the estimation of tumor-like expansion of lesions. However, the imaging characteristics of intraosseous vascular lesions are very variable. The symptoms of the patient presented herein show that growth phases of a vascular orbital malformation can occur in later stages of life and are initially indistinguishable from a neoplasm. In individual cases, patient care necessitates advanced diagnostic measures to establish the diagnosis and determine surgical therapy.

Keywords: 3D reconstruction; Vascular malformation; bone mineral density; cone beam computed tomography; differential diagnosis; haemangioma; immunohistochemistry; intraosseous; orbit.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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37
Anticancer Res




. 2020 Jun;40(6):3429-3434. doi: 10.21873/anticanres.14328.
Seizures Prior to Whole-brain Irradiation for Metastatic Disease: Prevalence, Risk Factors and Association With Survival
Dirk Rades 1, Jaspar Witteler 2, Liesa Dziggel 2, Troels W Kjaer 3, Soeren Tvilsted 4, Steven E Schild 5
Affiliations expand
PMID: 32487641
DOI: 10.21873/anticanres.14328

Abstract


Background/aim: Seizures are a serious condition for patients with brain metastases. Prevalence, risk factors and a potential association of seizures with survival prior to whole-brain irradiation (WBI) for cerebral metastases were retrospectively investigated.

Patients and methods: In 1,934 patients, the prevalence of pre-treatment seizures (pre-WBI) was determined. Seven pre-treatment characteristics were evaluated for associations with seizures. Ten characteristics including pre-treatment symptoms (none vs. seizures only vs. seizures+others vs. others only) and seizures (yes vs. no) were analyzed for survival.

Results: In 251 patients (13.0%), pre-treatment seizures were documented. The occurrence of seizures was significantly associated with 1-3 brain metastases and lack of extra-cerebral spread. On multivariate analysis, age, gender, performance score, number of metastases and extra-cerebral spread were significantly associated with survival; pre-treatment symptoms and seizures showed associations on univariate but not on multivariate analyses.

Conclusion: Few brain metastases and lack of extra-cerebral spread were independent risk factors for pre-treatment seizures. Seizures appeared positively associated with survival.

Keywords: Seizures; brain metastases; prevalence; risk factors; survival; whole-brain irradiation.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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38
Anticancer Res




. 2020 Jun;40(6):3559-3564. doi: 10.21873/anticanres.14345.
Epithelial-Mesenchymal Transition Status of Circulating Tumor Cells Is Associated With Tumor Relapse in Head and Neck Squamous Cell Carcinoma
Hiroe Tada 1, Hideyuki Takahashi 1, Shota Ida 1, Yurino Nagata 1, Kazuaki Chikamatsu 2
Affiliations expand
PMID: 32487658
DOI: 10.21873/anticanres.14345

Abstract


Background/aim: We aimed to elucidate the clinical implication of the epithelial-mesenchymal plasticity of circulating tumor cells (CTCs) in patients with head and neck squamous cell carcinoma (HNSCC).

Patients and methods: CTCs isolated from 44 patients with non-recurrent/metastatic HNSCC and 42 with recurrent/metastatic (R/M) HNSCC were classified into four epithelial-mesenchymal transition (EMT) statuses based on the expression of epithelial (keratin 19) and mesenchymal (vimentin) markers and the relationships between EMT status in CTCs and clinical factors were investigated.

Results: E+M- CTC phenotype was more frequent in patients without recurrence/metastasis (p=0.0468) and was also more frequent in those with a complete response (p=0.0346). The E+M+ phenotype constituted the major proportion of the CTCs detected in patients with R/M HNSCC (p=0.0374).

Conclusion: CTCs may play unique roles at various stages of metastasis through transitioning from epithelial to mesenchymal phenotypes.

Keywords: Epithelial–mesenchymal transition; circulating tumor cell; head and neck squamous cell carcinoma; metastasis; recurrence.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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39
Anticancer Res




. 2020 Jun;40(6):3445-3451. doi: 10.21873/anticanres.14330.
Umbilical Defunctioning Ileostomy for Rectal Cancer Results in Reduced Risk for Incisional Hernia
Ken Eto 1, Makoto Kosuge 2, Masahisa Ohkuma 2, Daisuke Ito 2, Yasuhiro Takeda 2, Saori Yatabe 2, Hiroshi Sugano 2, Naoki Takada 2, Tomotaka Kumamoto 2, Katsuhiko Yanaga 2
Affiliations expand
PMID: 32487643
DOI: 10.21873/anticanres.14330

Abstract


Background/aim: Umbilical defunctioning ileostomy (UDI) spares one incision, which may reduce the overall incidence of incisional hernia. Our aim was to evaluate the occurrence and risk factors of incisional hernias between UDI and conventional defunctioning ileostomy (CDI) after ileostomy closure.

Patients and methods: Incidence of incisional hernia after ileostomy closure was compared between UDI (n=51) and CDI (n=86) groups. Risk factors for incisional hernia were also considered through a retrospective analysis.

Results: The overall incidence of incisional hernia was 5.9% in the UDI group, which was significantly lower than the 22.1% (7.0% at the midline incision and 15.1% at the stoma site) in the CDI group (p=0.012). Multivariate analysis showed higher BMI (p=0.035) and CDI (p=0.031) as risk factors for developing incisional hernias overall.

Conclusion: UDI results in fewer incisional hernias than CDI and seems to be superior to CDI from the standpoint of overall incidence of incisional hernias.

Keywords: Umbilical defunctioning ileostomy; incisional hernia; laparoscopic surgery; rectal cancer.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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40
Anticancer Res




. 2020 Jun;40(6):3209-3220. doi: 10.21873/anticanres.14302.
Tannic Acid Inhibits Non-small Cell Lung Cancer (NSCLC) Stemness by Inducing G 0/G 1 Cell Cycle Arrest and Intrinsic Apoptosis
Nipin Sp 1, Dong Young Kang 1, Doh Hoon Kim 1, Ji-Seung Yoo 2, Eun Seong Jo 1, Alexis Rugamba 1, Kyoung-Jin Jang 3, Young Mok Yang 3
Affiliations expand
PMID: 32487615
DOI: 10.21873/anticanres.14302

Abstract


Background/aim: Non-small cell lung cancer (NSCLC) is one among the most common cancers worldwide. Recently, dietary phytochemicals have been reported as an attractive approach to improve the symptoms of NSCLC patients. Tannic acid is a natural polyphenol, which is known to have anticancer effects on in vitro models of breast, gingival and colon cancer. However, the molecular mechanisms associated with the actions of tannic acid on A549 human lung cancer cells have not been elucidated.

Materials and methods: In this study, we analyzed the effect of tannic acid on A549 cells and their underlying mechanisms using western blotting, flow cytometry, invasion assay and tumorsphere formation assay.

Results: Tannic acid treatment suppressed the viability of A549 cells through cell cycle arrest and induction of the intrinsic pathways of apoptosis. In addition, the various malignant phenotypes of A549 cells including invasion, migration, and stemness were inhibited by tannic acid treatment.

Conclusion: Tannic acid could be used as an effective inhibitor of lung cancer progression.

Keywords: G0/G1 cell cycle arrest; Lung cancer; intrinsic apoptosis; tannic acid.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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41
Anticancer Res




. 2020 Jun;40(6):3221-3229. doi: 10.21873/anticanres.14303.
Possible Diagnostic Application of CXCL12 and CXCR4 as Tumor Markers in Breast Cancer Patients
Emilia Dąbrowska 1, Andrzej Przylipiak 2, Monika Zajkowska 3, Barbara M Piskor 2, Iwona Sidorkiewicz 4, Maciej Szmitkowski 3, Slawomir Lawicki 5
Affiliations expand
PMID: 32487616
DOI: 10.21873/anticanres.14303

Abstract


Background/aim: Chemokines are cytokines involved not only in inflammatory but also in inappropriate response of the immune system in breast cancer (BC) progression. We examined the diagnostic usefulness of CXCL12, CXCR4 and CA 15-3 in BC patients, based on ROC curve analysis.

Materials and methods: The study group consisted of 100 patients with BC; the control group consisted of 35 women with benign breast disease and 35 healthy patients. The median concentration of chemokines was measured by ELISA and that of CA 15-3 by chemiluminescent microparticle immunoassay.

Results: The concentrations of CXCL12 and CXCR4 in the BC group were significantly higher than those in the control groups. The AUC value of CXCL12 (0.7502) was the highest of all the chemokines measured in the BC patients.

Conclusion: There may be a link between CXCL12, CXCR4 and BC that can assist in the diagnosis, markedly when combined with CA 15-3.

Keywords: Breast cancer; C-X-C motif chemokine ligand 12; C-X-C motif chemokine receptor 4; tumor marker.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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42
Anticancer Res




. 2020 Jun;40(6):3109-3118. doi: 10.21873/anticanres.14292.
New Pancreatic Cancer Biomarkers eIF1, eIF2D, eIF3C and eIF6 Play a Major Role in Translational Control in Ductal Adenocarcinoma
Nicole Golob-Schwarzl 1 2, Philip Puchas 1, Margit Gogg-Kamerer 1, Wilko Weichert 3, Benjamin Göppert 4, Johannes Haybaeck 5 6
Affiliations expand
PMID: 32487605
DOI: 10.21873/anticanres.14292

Abstract


Background/aim: Pancreatic cancer is one of the deadliest forms of cancer and ranks among the leading causes of cancer-related death worldwide. The most common histological type is ductal adenocarcinoma (PDAC), accounting for approximately 95% of cases. Deregulation of protein synthesis has been found to be closely related to cancer. The rate-limiting step of translation is initiation, which is regulated by a broad range of eukaryotic translation initiation factors (eIFs).

Patients and methods: Human PDAC samples were biochemically analyzed for the expression of various eIF subunits on the protein level (immunohistochemistry, immunoblot analyses) in 174 cases of PDAC in comparison with non-neoplastic pancreatic tissue (n=10).

Results: Our investigation revealed a significant down-regulation of four specific eIF subunits, namely eIF1, eIF2D, eIF3C and eIF6. Concomitantly, the protein (immunoblot) levels of eIF1, eIF2D, eIF3C and eIF6 were reduced in PDAC samples as compared with non-neoplastic pancreatic tissue.

Conclusion: Members of the eIF family are of relevance in pancreatic tumor biology and may play a major role in translational control in PDAC. Consequently, they might be useful as potential new biomarkers and therapeutic targets in PDAC.

Keywords: PI3K/AKT/mTOR pathway; Pancreatic cancer; biomarker; eukaryotic translation initiation factors.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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43
Anticancer Res




. 2020 Jun;40(6):3387-3393. doi: 10.21873/anticanres.14322.
Fractionated Stereotactic Sequential Boost in a Selected Cohort of Glioblastoma Patients: A Mono-institutional Analysis
Alessandro Marchionni 1, Isabella Palumbo 2, Giampaolo Montesi 3, Vittorio Bini 4, Claudio Zucchetti 5, Nunzia Cenci 6, Pietro Chiarini 7, Stefano Saccia 8, Cynthia Aristei 9, Marco Lupattelli 8
Affiliations expand
PMID: 32487635
DOI: 10.21873/anticanres.14322

Abstract


Aim: To retrospectively assess toxicity and survival in 15 selected Glioblastoma patients treated with a sequential fractionated stereotactic radiotherapy (FSRT) boost after chemo-radiotherapy (CHT-RT) and compare their survival outcomes with a control group.

Patients and methods: Toxicity was assessed with the CTCAE 3.0 scale. The Kaplan-Meier method was used to design survival curves, log-rank test for bivariate analysis and Cox proportional hazard regression model for multivariate analysis.

Results: The median follow-up was 16 months (range=5-60). One case of headache and one of radionecrosis (RN) occurred. Median overall survival (OS) was 25 months in the boost group vs. 14 in the no-boost group (p=0.004). Median progression-free survival (PFS) was 15 months in the boost group versus 8 in the no-boost group (p=0.046). At multivariate analysis FSRT boost resulted significantly associated with OS and PFS.

Conclusion: In our series a sequential FSRT boost resulted in safe outcomes and significantly associated with survival.

Keywords: Glioblastoma; boost; fractionated stereotactic radiotherapy; survival; toxicity.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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44
Anticancer Res




. 2020 Jun;40(6):3453-3457. doi: 10.21873/anticanres.14331.
Occurrence of Glioma in Pregnant Patients: An Institutional Case Series and Review of the Literature
Pawan Singh 1, Emmanuel Mantilla 2, Josie Sewell 3, Kimmo J Hatanpaa 4, Edward Pan 5
Affiliations expand
PMID: 32487644
DOI: 10.21873/anticanres.14331

Abstract


Background/aim: Gliomas present a uniquely challenging clinical situation in the context of pregnancy, with no standard recommendations. This case series aimed to describe the treatment regimen and outcomes of five pregnant patients with gliomas.

Patients and methods: This is a retrospective study. A patient database from electronic medical records was evaluated to identify pregnant patients with gliomas treated at our institution between 2008-2018.

Results: Five study patients who were pregnant with gliomas were identified. Of these, 4 were diagnosed during pregnancy, while 1 was diagnosed prior to her pregnancy. One patient had grade 2 astrocytoma, 1 had grade 3 anaplastic astrocytoma, and 3 had grade 4 glioblastomas (GBM). All patients received surgery, and one patient received radiation therapy without concurrent chemotherapy during her pregnancy. All delivered healthy babies. Three of the 5 patients remain alive, and 2 of the 5 were progression-free at the last follow-up.

Conclusion: Treatment plans must be specifically tailored to the individual patient based on the glioma grade, the mother's desire to continue the pregnancy, and the risks of delaying treatment until after pregnancy. Additional studies need to be performed to definitively establish uniform guidelines for the treatment of pregnant patients with glioma.

Keywords: IDH mutated; Pregnancy; glioma; radiation.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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45
Review
Anticancer Res




. 2020 Jun;40(6):3055-3063. doi: 10.21873/anticanres.14286.
PARP Inhibitors as Therapeutic Options for Tyrosine Kinase-dependent Leukemia: A Review
Caio Bezerra Machado 1, Emerson Lucena DA Silva 1, Manoel Odorico DE Moraes Filho 1, Maria Elisabete Amaral DE Moraes 1, Caroline Aquino Moreira-Nunes 2
Affiliations expand
PMID: 32487599
DOI: 10.21873/anticanres.14286

Abstract


The idea of utilizing poly-ADP-ribose polymerase inhibitors (PARPi) as therapeutics for cancer has grown in popularity since its original approval for clinical usage in treatment of BRCA DNA repair-associated-mutated ovarian cancer. In this study, we evaluated experimental data regarding in vitro studies utilizing PARPi as a treatment for tyrosine kinase (TK)-dependent leukemia. Studies from 2015 to 2019 were compiled and the ones with most relevant TK pathways and PARP inhibition were analyzed. PARPi showed activity against many leukemia cell lines and samples from patients with primary leukemia, especially when combined with other signaling pathway inhibitor drugs, improving upon the hypothesis that the utilization of PARPi has potential as a new therapeutic approach in treatment of primary leukemia and TK-dependent leukemia.

Keywords: Leukemia; PARP inhibitors; review; tyrosine kinase.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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46
Anticancer Res




. 2020 Jun;40(6):3355-3360. doi: 10.21873/anticanres.14318.
Classification Model to Estimate MIB-1 (Ki 67) Proliferation Index in NSCLC Patients Evaluated With 18 F-FDG-PET/CT
Barbara Palumbo 1, Rosanna Capozzi 2, Francesco Bianconi 3, Mario Luca Fravolini 4, Silvia Cascianelli 4, Salvatore Gerardo Messina 5, Guido Bellezza 6, Angelo Sidoni 6, Francesco Puma 2, Mark Ragusa 7
Affiliations expand
PMID: 32487631
DOI: 10.21873/anticanres.14318

Abstract


Background/aim: Proliferation biomarkers such as MIB-1 are strong predictors of clinical outcome and response to therapy in patients with non-small-cell lung cancer, but they require histological examination. In this work, we present a classification model to predict MIB-1 expression based on clinical parameters from positron emission tomography.

Patients and methods: We retrospectively evaluated 78 patients with histology-proven non-small-cell lung cancer (NSCLC) who underwent 18F-FDG-PET/CT for clinical examination. We stratified the population into a low and high proliferation group using MIB-1=25% as cut-off value. We built a predictive model based on binary classification trees to estimate the group label from the maximum standardized uptake value (SUVmax) and lesion diameter.

Results: The proposed model showed ability to predict the correct proliferation group with overall accuracy >82% (78% and 86% for the low- and high-proliferation group, respectively).

Conclusion: Our results indicate that radiotracer activity evaluated via SUVmax and lesion diameter are correlated with tumour proliferation index MIB-1.

Keywords: 18F-FDG PET/CT; MIB-1; artificial intelligence; non-small-cell lung cancer.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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47
Anticancer Res




. 2020 Jun;40(6):3551-3557. doi: 10.21873/anticanres.14344.
Risk Factors for Postoperative Deep Infection After Malignant Bone Tumor Surgery of the Extremities
Mickhael Bang Langit 1 2, Shinji Miwa 1, Norio Yamamoto 3, Katsuhiro Hayashi 1, Akihiko Takeuchi 1, Kentaro Igarashi 1, Kaoru Tada 1, Takashi Higuchi 1, Hirotaka Yonezawa 1, Sei Morinaga 1, Yoshihiro Araki 1, Yohei Asano 1, Hiroyuki Tsuchiya 1
Affiliations expand
PMID: 32487657
DOI: 10.21873/anticanres.14344

Abstract


Background/aim: Previous studies have identified pelvic tumors as a risk factor for surgical site infections (SSI). However, risk factors for extremity tumors are still unclear. This study investigated risk factors for postoperative deep infection in malignant bone tumors of the extremities.

Patients and methods: Data from 238 patients with 256 malignant bone tumor surgeries were reviewed. Univariate analysis and multiple logistic regression determined risk factors for deep infection.

Results: Deep infection was found in 23 of 256 cases (9.0%). Tibial tumor (OR=6.04; 95%CI=2.14-17.05; p<0.001) and operative time ≥5 hours (OR=3.25; 95%CI=1.15-9.23; p=0.027) were independent risk factors for deep infection.

Conclusion: Tibial tumor and operative time ≥5 hours are independent risk factors for deep infection after surgery of malignant bone tumor of extremities. Strategies to minimize risk of infection in the tibia and decreasing operative time should be implemented, along with other measures to decrease SSI.

Keywords: Bone tumor; extremity; multivariate analysis; postoperative deep infection; risk factor.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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48
Anticancer Res




. 2020 Jun;40(6):3081-3089. doi: 10.21873/anticanres.14289.
Lack of Correlation Between Immunohistochemical Expression of SPARC and Invasion in Different Grades of Meningiomas
Harcharan K Rooprai 1, Andrew J Martin 2, Andrew King 3, Usha D Appadu 1, Richard W Gullan 4, Nick W M Thomas 1, Geoffrey J Pilkington 5 6
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PMID: 32487602
DOI: 10.21873/anticanres.14289

Abstract


Background: Grade I meningiomas are generally benign and non-invasive whereas Grade II (atypical) and Grade III (malignant) meningiomas tend to be invasive with a high risk of recurrence. SPARC, secreted protein, acidic and rich in cysteine, is a multifunctional glycoprotein which has been proposed to be a potential diagnostic marker of invasive meningiomas. There has been increased reporting of atypical meningiomas since the current World Health Organization (WHO) included brain invasion as a grading criterion for classification of these particular meningiomas.

Materials and methods: The aim of this study was to re-evaluate any correlation between immunohistochemical expression of SPARC in 34 meningiomas of various grades using the current classification (2016). We had previously classified these cases using the 2002 WHO criteria.

Results: There is no correlation between expression of SPARC and invasion in different grades of meningioma.

Conclusion: SPARC does not appear to be a good predictor of invasion in meningiomas.

Keywords: SPARC; immunohistochemistry; invasion; malignant; meningioma; recurrence.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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49
Anticancer Res




. 2020 Jun;40(6):3247-3254. doi: 10.21873/anticanres.14306.
Cell Cycle Dysregulation Is Associated With 5-Fluorouracil Resistance in Gastric Cancer Cells
DA Som Kim 1, Kyoungmi Min 1, Suk Kyeong Lee 2
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PMID: 32487619
DOI: 10.21873/anticanres.14306

Abstract


Background/aim: 5-Fluorouracil (5-FU) is an anticancer drug commonly used to treat gastric cancer; however, continuous 5-FU chemotherapy causes drug resistance.

Materials and methods: We established five sublines of 5-FU-resistant AGS gastric cancer cells to investigate changes that may have occurred in the development of 5-FU resistance. Drug resistance to other chemotherapeutic reagents, proliferation, cell-cycle changes, and wound healing ability were assessed for each subline.

Results: Retarded cell growth, G0/G1 phase arrest, up-regulation of p57, and down-regulation of cyclin D1 were commonly observed in all five sublines. Resistance to paclitaxel and cisplatin was also observed in most of the sublines.

Conclusion: Our data support the notion that G0/G1 arrest due to changes in p57 and cyclin D1 expression may confer drug resistance, while EMT seems non-essential to 5-FU resistance in AGS gastric carcinoma cells.

Keywords: 5-FU; Drug resistance; EMT; cell cycle; cyclin D1; gastric cancer; p57.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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50
Anticancer Res




. 2020 Jun;40(6):3423-3427. doi: 10.21873/anticanres.14327.
Mosaic Neurofibromatosis Type 1 With Multiple Cutaneous Diffuse and Plexiform Neurofibromas of the Lower Leg
Reinhard E Friedrich 1, Christian Hagel 2, Felix K Kohlrusch 3, Ina Schanze 4, Ilse Wieland 4, Martin Zenker 4
Affiliations expand
PMID: 32487640
DOI: 10.21873/anticanres.14327

Abstract


Background: Neurofibromatosis type 1 (NF1) is an autosomal dominant hereditary disease with complete penetrance and a very variable phenotype. Recent research has shown that postzygotic NF1 gene mutations occur to a far greater extent than previously thought. The phenotype of affected individuals reflects the time of somatic mutation and the phenotype is correspondingly diverse. This report describes histological and genetic findings in a case of mosaic NF1, the clinical control of which documents almost stationary skin findings over a period of 9 years.

Case report: The 55-year-old female first presented for advice on a strip of nodular skin tumours of the calf skin. She had no hallmarks of NF1. It was only 9 years later that she had the skin tumours removed, all of which were partially diffuse and partially plexiform neurofibroma. The genetic examination showed an atypical large deletion of the NF1 gene in the skin tumours, but not in overlying skin or blood.

Conclusion: Segmental NF1 is a distinct type of mosaic/somatic NF1 mutation. The phenotype of diffuse and plexiform skin neurofibromas can resemble cutaneous neurofibroma. Surgical therapy for segmental neurofibromatosis does not differ from the concepts for treating nerve sheath tumours in NF1 patients with a germline NF1 mutation.

Keywords: Neurofbromatosis type 1; mosaicism; plexiform neurofibroma; tumour predisposition syndrome.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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51
Anticancer Res




. 2020 Jun;40(6):3277-3285. doi: 10.21873/anticanres.14310.
Induction Chemotherapy in Hypopharyngeal Cancer: Influence of DNA Repair Gene Polymorphisms
Hitoshi Hirakawa 1, Taro Ikegami 2, Satoe Azechi 2, Shinya Agena 2, Jin Uezato 2, Hidetoshi Kinjyo 2, Yukashi Yamashita 2, Asanori Kiyuna 2, Katsunori Tanaka 2, Shunsuke Kondo 2, Hiroyuki Maeda 2, Mikio Suzuki 2, Akira Ganaha 2 3
Affiliations expand
PMID: 32487623
DOI: 10.21873/anticanres.14310

Abstract


Background/aim: The aim was to clarify whether DNA repair gene polymorphisms can be used to predict response to cisplatin, 5-fluorouracil, and docetaxel (TPF) as induction chemotherapy (ICT) in Japanese patients with hypopharyngeal cancer (HPC).

Materials and methods: DNA repair gene polymorphisms (rs3212986, rs1799793, rs13181, and rs25487) were analyzed in 117 HPC patients and 125 control subjects by PCR-restriction fragment length polymorphism. Forty-one HPC patients who received TPF-based ICT, followed by surgery or chemoradiotherapy/radiotherapy were analyzed for ICT response, laryngeal preservation, and survival outcome.

Results: ICT responders (29 cases) had significantly better overall survival than ICT non-responders (12 cases; 86.0% vs. 37.0%, respectively, p<0.01 by log-rank test) and better laryngeal preservation rates. The DNA repair gene polymorphisms were not related to ICT response.

Conclusion: ICT is beneficial for chemoselection of HPC patients, but a role for DNA repair gene polymorphisms in ICT response was not confirmed.

Keywords: DNA repair gene; Japanese; hypopharyngeal cancer; overall survival; single nucleotide polymorphism.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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52
Anticancer Res




. 2020 Jun;40(6):3491-3497. doi: 10.21873/anticanres.14336.
Classification of Abnormal Findings on Ring-type Dedicated Breast PET for the Detection of Breast Cancer
Shinsuke Sasada 1, Norio Masumoto 2, Yuri Kimura 2, Akiko Emi 2, Takayuki Kadoya 2, Morihito Okada 2
Affiliations expand
PMID: 32487649
DOI: 10.21873/anticanres.14336

Abstract


Aim: To investigate the usefulness of classification of ring-type dedicated breast positron-emission tomography (dbPET) findings in detection of breast cancer.

Patients and methods: A total of 709 patients with breast cancer underwent dbPET before treatment. Each finding was morphologically categorized as a focus (uptake size ≤5 mm), mass (>5 mm), or non-mass (multiple uptakes not belonging to a three-dimensional mass or without distinct mass features). Non-mass uptakes were additionally classified as linear, focal, segmental, regional, or diffuse distributions. Lesion-to-background ratios were calculated.

Results: Among 910 abnormal findings, 700 (76.9%) were malignant and 210 (23.1%) were benign. Morphologically, 198 (21.8%) lesions were foci, 431 (47.4%) were masses, and 281 (30.9%) were non-masses. In multivariate analysis, mass, focal and segmental distributions of non-mass lesions and high lesion-to-background ratio were significantly related to breast cancer (all p<0.001).

Conclusion: Classification of abnormal findings on dbPET using morphology and lesion-to-background ratio were useful to detect breast cancer.

Keywords: Breast cancer; FDG; abnormal uptake; classification; dedicated breast PET.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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53
Anticancer Res




. 2020 Jun;40(6):3345-3354. doi: 10.21873/anticanres.14317.
Validation of Systemic and Local Tumour Immune Response to Eribulin Chemotherapy in the Treatment of Breast Cancer
Shinichiro Kashiwagi 1, Yuka Asano 2, Wataru Goto 2, Koji Takada 2, Tamami Morisaki 2, Rika Kouhashi 2, Akimichi Yabumoto 2, Sayaka Tanaka 3, Tsutomu Takashima 2, Masahiko Ohsawa 3, Kosei Hirakawa 2 4, Masaichi Ohira 2 4
Affiliations expand
PMID: 32487630
DOI: 10.21873/anticanres.14317

Abstract


Background/aim: In addition to its cytocidal effects as a microtubule dynamics inhibitor, eribulin mesylate (eribulin) regulates the tumour microenvironment. We examined the clinical significance of tumour infiltrating lymphocytes (TILs) and transforming growth factor-β (TGF-β), which are local markers of host immunity, and of the neutrophil-lymphocyte ratio (NLR) and absolute lymphocyte count (ALC), which are systemic markers.

Patients and methods: We administered eribulin chemotherapy to 106 patients with locally advanced or metastatic breast cancer. Of these, 21 had their lesions resected.

Results: The response to eribulin was significantly associated with ALC (p=0.007). The expression of pSmad2 (an indicator of activation of TGF-β downstream signaling) was significantly decreased before and after eribulin chemotherapy (p<0.001). Moreover, a baseline ALC ≥ 1,500 /μl was observed in a significantly high number of patients with pSmad2 negative conversion (p<0.001).

Conclusion: Eribulin improved the tumour immune microenvironment by decreasing TGF-β expression. This demonstrated that local change can be evaluated based on ALC.

Keywords: ALC; Breast cancer; TGF-β; TILs; eribulin; tumour microenvironment.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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54
Anticancer Res




. 2020 Jun;40(6):3191-3201. doi: 10.21873/anticanres.14300.
Galectin-8 Favors VEGF-Induced Angiogenesis: In Vitro Study in Human Umbilical Vein Endothelial Cells and In Vivo Study in Chick Chorioallantoic Membrane
Lenka Varinská 1 2, Lenka Fáber 1, Eva Petrovová 3, Ludmila Balážová 4, Eleonóra Ivančová 5, Michal Kolář 6, Peter Gál 7 8 9
Affiliations expand
PMID: 32487613
DOI: 10.21873/anticanres.14300

Abstract


Background/aim: Although it has been accepted that the tandem repeat galectin-8 (Gal-8) is linked to angiogenesis, the underlying mechanisms in endothelial cells has remained poorly understood. In this study we aimed to investigate the effect of Gal-8 on selected biological processes linked to angiogenesis in in vitro and in vivo models.

Materials and methods: In detail, we assessed how exogenously added human recombinant Gal-8 (with or without vascular endothelial growth factor - VEGF) affects selected steps involved in vessel formation in human umbilical vein endothelial cells (HUVECs) as well as using the chick chorioallantoic membrane (CAM) assay. Gene expression profiling of HUVECs was performed to extend the scope of our investigation.

Results: Our findings demonstrate that Gal-8 in combination with VEGF enhanced cell proliferation and migration, two cellular events linked to angiogenesis. However, Gal-8 alone did not exhibit any significant effects on cell proliferation or on cell migration. The molecular analysis revealed that Gal-8 in the presence of VEGF influenced cytokine-cytokine receptor interactions, HIF-1 and PI3K/AKT signaling pathways. Gal-8 alone also targeted cytokine-cytokine receptor interactions, but with a different expression profile as well as a modulated focal adhesion and TNF signaling.

Conclusion: Gal-8 promotes a pro-angiogenic phenotype possibly in a synergistic manner with VEGF.

Keywords: Tumor growth; glycobiology; sugar code; vessel sprouting; wound healing.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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55
Anticancer Res




. 2020 Jun;40(6):3361-3370. doi: 10.21873/anticanres.14319.
Spleen Volume as a Predictive Biomarker for Thrombocytopenia and Liver Dysfunction After Oxaliplatin-based Chemotherapy
Takashi Miyata 1, Hiroyuki Takamura 2, Ryosuke Kin 1, Hisashi Nishiki 1, Akifumi Hashimoto 1, Yoritaka Fujii 1, Seiko Miura 1, Jun Fujita 1, Daisuke Kaida 1, Yasuto Tomita 1, Naohiko Nakamura 1, Hideto Fujita 1, Shinichi Kinami 1, Nobuhiko Ueda 1, Takeo Kosaka 1
Affiliations expand
PMID: 32487632
DOI: 10.21873/anticanres.14319

Abstract


Background/aim: We evaluated whether splenic volume (SV) predicts sinusoidal obstruction syndrome (SOS) in colorectal cancer (CRC) patients receiving capecitabine plus oxaliplatin (CapeOX) therapy.

Patients and methods: In this retrospective study, we measured SV in 41 patients receiving adjuvant CapeOX for CRC at five different time points. We compared the clinical data of the 18 patients who experienced ≥30% increases in SV immediately after vs. before CapeOX (group A) with data for the remaining 23 patients (group B).

Results: Platelet numbers decreased and the levels of hepatobiliary enzymes increased significantly 1 year after CapeOX compared with before CapeOX in group A. However, in group B, significantly decreased platelet numbers and significantly increased aspartate transaminase levels were confirmed only immediately after CapeOX, with no significant subsequent changes.

Conclusion: SV was significantly associated with thrombocytopenia and liver dysfunction in CRC patients, and predicted SOS.

Keywords: Spleen volume; oxaliplatin; sinusoidal obstruction syndrome.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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56
Review
Anticancer Res




. 2020 Jun;40(6):3065-3069. doi: 10.21873/anticanres.14287.
Surgical Versus Conservative Treatment for Endometrial Cancer in Women of Reproductive Age: Incidence of Urinary Tract Symptoms
Antonios Koutras 1, Angelis Peteinaris 2, Spyridon Davakis 3, Georgios Kalinterakis 4, Ioannis Tsilikis 5, Nikolaos Garmpis 3, Prokopis-Andreas Zotos 6, Athanasios Chionis 1, Dimitrios Schizas 3, Ioannis Karavokyros 3, Nikolaos Thomakos 7, Emmanuel Kontomanolis 8, Athanasios Syllaios 9
Affiliations expand
PMID: 32487600
DOI: 10.21873/anticanres.14287

Abstract


Endometrial cancer is the most common gynecologic malignancy. The mainstay of treatment for endometrial cancer is total hysterectomy with bilateral salpingo-oophorectomy. Radiation and chemotherapy accompanied with progestins can also play a significant role in treatment. Lower urinary tract symptoms (LUTS) following therapy for endometrial cancer are an extremely difficult and challenging condition that deteriorates patients' quality of life. Current literature remains rather scarce regarding LUTS after therapy for endometrial cancer. This review aimed to investigate the incidence of LUTS in endometrial cancer treatment.

Keywords: Endometrial cancer; chemoradiotherapy; progestins; surgical treatment; urinary tract symptoms.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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57
Anticancer Res




. 2020 Jun;40(6):3417-3421. doi: 10.21873/anticanres.14326.
Intraluminal Brachytherapy in Unresectable Extrahepatic Biliary Duct Cancer: An Italian Pooled Analysis
Rosa Autorino 1, Silvia Bisiello 2, Brigida Pappalardi 3, Vanessa Privitera 1, Milly Buwenge 2, Federica Piccolo 4, Carlotta Masciocchi 5, Luca Tagliaferri 1, Gabriella Macchia 6, Clelia Delle Curti 4, Marco Luppatteli 7, Annamaria Cerrotta 4, Alessio Giuseppe Morganti 2, Vincenzo Valentini 1, Giancarlo Mattiucci 1
Affiliations expand
PMID: 32487639
DOI: 10.21873/anticanres.14326

Abstract


Background/aim: To evaluate the outcome of patients with unresectable extrahepatic cholangiocarcinoma (CC) treated with external-beam radiotherapy (EBRT) and concurrent chemotherapy (CT) with or without intraluminal brachytherapy (ILBT) boost or with definitive ILBT.

Patients and methods: A pooled analysis of patients with non-metastatic unresectable CC was performed. They were treated in three different institution with EBRT plus CT with or without an ILBT boost. Some patients received only ILBT with curative dose.

Results: Seventy-three patients were included in the analysis. Thirty-nine patients (53%) received EBRT treatment with ILBT boost (18 patients with CT during EBRT), while 28 patients (38%) were treated with EBRT (CT in 26 patients) and 6 patients (8.2%) with definitive ILBT (2 patients with CT). CT was administered including either the use of gemcitabine or 5-fluorouracil. With a median follow-up of 16 month (range=1-94 months), median overall survival (OS) was 16 months. Overall median LC was 16 months and patients who underwent ILBT had a better local control (LC) (p=0.018).

Conclusion: The role of ILBT in unresectable CC is not yet supported by robust evidence in the literature. However, within this limit, preliminary results seem to suggest an improved local control in patients treated with ILBT, almost comparable to the ones of standard chemo-radiotherapy (CRT).

Keywords: Radiotherapy; biliary tract cancers; brachytherapy; chemoradiation; cholangiocarcinoma.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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58
Anticancer Res




. 2020 Jun;40(6):3163-3167. doi: 10.21873/anticanres.14298.
Oncological Safety of Ultrasonically Activated Surgical Devices During Gastric Cancer Surgery
Takeshi Kubota 1, Katsutoshi Shoda 2, Soichiro Ogawa 2, Tatsuya Matsumoto 2, Hidemasa Kubo 2, Masayuki Yubakami 2, Takuma Ohashi 2, Toshiyuki Kosuga 2, Hirotaka Konishi 2, Atsushi Shiozaki 2, Tomohiro Arita 2, Hiroki Shimizu 2, Yusuke Yamamoto 2, Ryo Morimura 2, Hisashi Ikoma 2, Yoshiaki Kuriu 2, Hitoshi Fujiwara 2, Kazuma Okamoto 2, Eigo Otsuji 2
Affiliations expand
PMID: 32487611
DOI: 10.21873/anticanres.14298

Abstract


Background/aim: Ultrasonically activated surgical devices (USADs) have become indispensable instruments for gastrointestinal surgery. In this study, we investigated the oncological safety of the use of USADs.

Materials and methods: We harvested and cultivated the splashes and mist scattered from an USAD when cutting MKN45-derived cancer nodules. Seven days later, we observed viable cancer cells and the total number of cells was counted. The histopathology of the nodules cut by the USAD was also examined.

Results: The existence of viable cancer cells was confirmed by ex vivo cell culture. The number of viable cancer cells was reduced by slow grasping of the USAD. The surface of cancerous tissue cut by the USAD was partially heat-denatured, however, there were some parts in which cancerous tissue was exposed on the surface.

Conclusion: Surgeons should recognize the possibility that cancer cells may be scattered by USAD use.

Keywords: Ultrasonically-activated surgical device; dissemination; gastric cancer.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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59
Anticancer Res




. 2020 Jun;40(6):3519-3526. doi: 10.21873/anticanres.14340.
Clinical Features of Treatment-related Neuroendocrine Prostate Cancer: A Case Series
Kotaro Suzuki 1, Tomoaki Terakawa 2, Naoe Jimbo 3, Rena Inaba 3, Yuzo Nakano 1, Masato Fujisawa 1
Affiliations expand
PMID: 32487653
DOI: 10.21873/anticanres.14340

Abstract


Background/aim: The development of treatment-related neuroendocrine prostate cancer (t-NEPC) is an increasing clinical concern. The objectives were to clarify the clinical features of t-NEPC.

Patients and methods: A total of 9 patients with histologically confirmed t-NEPC were reviewed.

Results: Of these 9 patients, 2 patients were diagnosed with t-NEPC by a histological examination without elevation in blood tumor marker levels. Immunohistochemistry revealed an acquired Rb loss in 5 patients. All patients were treated with platinum-based chemotherapy as first-line treatment and 6 patients received concurrent radiation therapy (RT). The median cancer-specific survival was 14.4 months, and 7 patients achieved an objective response. Patients with tumor-infiltrating CD8+ lymphocyte (CD8+-TILs) showed better response than those without CD8+-TILs.

Conclusion: We described the clinical features of histologically confirmed t-NEPC. In addition to the importance of biopsy, we showed that platinum-based chemotherapy plus RT had a favorable cytoreductive effect. Further clinical recognition and studies are needed.

Keywords: Neuroendocrine differentiation; neuron-specific enolase; platinum-based chemotherapy; small-cell prostate cancer; treatment-related neuroendocrine prostate cancer.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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60
Anticancer Res




. 2020 Jun;40(6):3265-3270. doi: 10.21873/anticanres.14308.
Investigation of the Effects of MicroRNA-221 Expression Levels in Glioblastoma Multiforme Tumors
Selcuk Ozdogan 1, Cumhur Kaan Yaltirik 2, Seda Gulec Yilmaz 3, Fatma Tuba Akdeniz 3, Kadir Sumerkent 4, Ali Haluk Duzkalir 5, Ugur Ture 2, Turgay Isbir 6
Affiliations expand
PMID: 32487621
DOI: 10.21873/anticanres.14308

Abstract


Background/aim: The aim of our study was to examine miRNA-221 as a candidate biomarker to define prognosis and/or classification for glial tumors.

Materials and methods: This study included 39 patients who underwent glial tumor surgery and 40 healthy individuals as the control group. miRNA expression levels were determined by real-time polymerase chain reaction (RT-PCR). Receiver operating characteristic curve analysis was used for analyzing the predictive ability of miRNA-221.

Results: The levels of miRNA-221 expression were determined by comparing the ΔCT values of miRNAs and the internal control. When the expression levels of miRNA-221 were compared according to the ΔCT method, miRNA-221 was found to be significantly increased in the patient group compared to the control group (p<0.0001).

Conclusion: Increased expression levels of miRNA-221 could be a biomarker for glial tumors.

Keywords: Glial tumors; biomarker; glioblastoma; miRNA-221; microRNA.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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61
Anticancer Res




. 2020 Jun;40(6):3499-3504. doi: 10.21873/anticanres.14337.
Occurrence of Seizures Prior to Single-fraction Radiosurgery or Multi-fraction Stereotactic Radiotherapy in Patients With Very Few Brain Metastases
Dirk Rades 1, Jaspar Witteler 2, Troels W Kjaer 3, Soeren Tvilsted 4, Steven E Schild 5
Affiliations expand
PMID: 32487650
DOI: 10.21873/anticanres.14337

Abstract


Background/aim: Seizures represent a major problem for patients with brain metastases. This study evaluated the role of seizures in patients receiving single-fraction radiosurgery (SRS) or multi-fraction stereotactic radiotherapy (FSRT).

Patients and methods: This retrospective study included 195 patients receiving SRS (n=164) or FSRT (n=31) alone for one to three brain metastases. The prevalence of pre-SRS/FSRT seizures and correlations with pre-treatment factors were investigated. These factors plus pre-SRS/FSRT seizures were assessed in regard to survival.

Results: Thirty-three patients had pre-SRS/FSRT seizures (prevalence=16.9%). Seizures were significantly correlated with age ≤61 years. Trends were observed for seizures being more frequent in those with NSCLC and those without extra-cranial metastatic spread. On multivariate analysis, significant associations with improved survival were found for Karnofsky performance score ≥80%, breast cancer, and an interval from diagnosis of malignant disease to SRS/FSRT ≥21 months.

Conclusion: Younger age, NSCLC and absence of extra-cranial spread appeared to be risk factors for seizures prior to SRS/FSRT. Having seizures prior to SRS/FSRT showed no association with survival.

Keywords: Brain metastases; radiosurgery; seizures; stereotactic radiotherapy.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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62
Anticancer Res




. 2020 Jun;40(6):3565-3570. doi: 10.21873/anticanres.14346.
A Phase II Study of Neoadjuvant Chemotherapy Followed by Extended Field Concurrent Chemoradiotherapy for Para-aortic Lymph Node Positive Cervical Cancer
Yuko Shimoji 1, Yutaka Nagai 1, Takafumi Toita 2, Takuro Ariga 2, Joichi Heianna 2, Tadaharu Nakasone 1, Yusuke Taira 1, Yoshihisa Arakaki 1, Tomoko Nakamoto 1, Takuma Ooyama 1, Wataru Kudaka 1, Itomi Kaneshima 1, Kumiko Nishihira 1, Keiko Mekaru 1, Yoichi Aoki 3
Affiliations expand
PMID: 32487659
DOI: 10.21873/anticanres.14346

Abstract


Background/aim: We conducted a phase II study of neoadjuvant chemotherapy followed by extended field concurrent chemoradiotherapy in patients with cervical cancer with para-aortic node metastasis.

Patients and methods: Thirty-seven women with stage IB1-IVA cervical cancer were enrolled.

Results: The median age was 52 years. Thirty-four patients other than 3 progressive disease, proceeded to extended field concurrent chemoradiotherapy. The 3-year overall survival and progression-free survival rates were 70.1% and 48.5%, respectively. The 3-year overall survival according to stages was significantly worse in stage IIIB. Twelve of the 17 patients with stage IIIB died of the disease.

Conclusion: Neoadjuvant chemotherapy followed by extended field concurrent chemoradiotherapy may improve the prognosis of patients with stages IB and II cervical cancer with positive para-aortic node. However, new strategies should be investigated to improve a poor prognosis in stage IIIB disease with positive para-aortic node.

Keywords: Cervical cancer; extended-field concurrent chemoradiotherapy; neoadjuvant chemotherapy; para-aortic node metastasis; phase II study.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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63
Anticancer Res




. 2020 Jun;40(6):3203-3208. doi: 10.21873/anticanres.14301.
Characteristics of Gastric Carcinomas With High ERCC1 Expression and the Prognostic Value of ERCC1 Expression
Jung Wook Yang 1 2, Jeong-Hee Lee 1 2 3, Jong Sil Lee 1 2 3, Dong Chul Kim 1 2 3, Dae Hyun Song 1 3 4, Se Min Jang 4, Hyo Jung An 4, Hyun Min Koh 4, Minhye Kim 2, Ji Min Na 2, Sang-Ho Jeong 5, Young-Joon Lee 5, Gyung Hyuck Ko 6 2 3
Affiliations expand
PMID: 32487614
DOI: 10.21873/anticanres.14301

Abstract


Background/aim: We aimed to evaluate the characteristics of gastric carcinoma with high excision repair cross complementing 1 (ERCC1) expression and the prognostic value of ERCC1 expression.

Materials and methods: ERCC1 expression was evaluated by immunohistochemistry in 309 surgically resected gastric carcinoma specimens using a tissue microarray. Cancer-related survival was analysed using competing risk analysis.

Results: Compared to ERCC1-low gastric carcinomas, ERCC1-high gastric carcinomas showed less local invasion (p=0.0013), lower N stage (p=0.0302), earlier pTNM stage (p=0.0003), and less frequent recurrence (p=0002). Patients with ERCC1-high gastric carcinoma showed lower cumulative incidence function estimate of cancer-related death [3.37; 95% confidence intervaI (CI)=0.89-8.75] than did those with ERCC1-low gastric carcinoma (17.12; 95% CI=12.24-22.69; p-value by Gray's test=0.0012). Adjusted proportional sub-distribution hazard ratio for cancer-related death in the patients with ERCC1-high tumour was 0.272 (95% CI=0.084-0.878; p=0.0295).

Conclusion: High ERCC1 expression may be an independent positive prognostic marker for gastric carcinoma.

Keywords: ERCC1; Stomach; cisplatin; human gastric carcinoma.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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64
Anticancer Res




. 2020 Jun;40(6):3271-3276. doi: 10.21873/anticanres.14309.
The Putative Glyoxalase 1 Inhibitor Piceatannol Exhibits Both Anxiolytic-like and Antitumor Effects in Mice
Kazumi Yoshizawa 1, Mizuho Tabuchi 2, Saki Ukai 2, Hidetaka Suzuki 2 3, Yohei Kawano 4, Ryoko Takasawa 5
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PMID: 32487622
DOI: 10.21873/anticanres.14309

Abstract


Background/aim: This study aimed to determine the anxiolytic effect of a putative glyoxalase 1 inhibitor, piceatannol, as well as its antitumor activities on the stress-induced tumor growth of Lewis lung carcinoma.

Materials and methods: The anxiolytic activities of piceatannol (1-30 mg/kg) were assessed using the elevated plus maze (EPM) test. We also evaluated the pharmacological modulation of stress-induced tumor growth; the mice were treated with piceatannol (3 and 30 mg/kg) from the 10th day till the 19th day after administration of the LLC cells.

Results: At the low dose (3 mg/kg), piceatannol significantly increased the time spent in the open arms of the EPM test when compared with the vehicle. At higher doses (30 mg/kg), it significantly suppressed the stress-induced enhancement of tumor growth.

Conclusion: A low dose of piceatannol exerts an anxiolytic effect, and high doses have an antitumor effect.

Keywords: Glyoxalase 1; antitumor effect; anxiolytic effect; piceatannol.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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65
Anticancer Res




. 2020 Jun;40(6):3477-3484. doi: 10.21873/anticanres.14334.
Impact of Implementing the Paris System for Reporting Urinary Cytology: A Single-institutional Experience With Emphasis on Diagnostic Yield of High-grade Urothelial Carcinoma and Low-grade Urothelial Neoplasm
Hyun Hee Koh 1, Moon Jung Lee 1, Noh Jin Park 1, Hyun-Soo Kim 2, Young Lyun Oh 2
Affiliations expand
PMID: 32487647
DOI: 10.21873/anticanres.14334

Abstract


Background/aim: The Paris System (TPS) has recently been proposed as a method to standardize urinary cytology reporting. In this study, we evaluated the impact of implementing TPS compared to the traditional reporting system.

Patients and methods: In total, 299 urine samples were reclassified according to TPS. We examined correlations between cytological and histological diagnoses, and calculated probabilities for detecting high-grade urothelial carcinoma (HGUC).

Results: TPS resulted in a decrease in the proportion of cases diagnosed as atypical urothelial cell (AUC) (43% to 31%). Among the AUC cases, the proportion of histologically confirmed HGUC cases rose (75% to 80%), as did the proportion of low-grade urothelial neoplasms (57% to 71%). All probabilities for detecting HGUC significantly increased using TPS.

Conclusion: TPS improved the diagnostic yield of urinary cytology. The implementation of TPS is expected to be a major step towards standardizing urinary cytology reporting and providing clear information to clinicians.

Keywords: Urine; atypical urothelial cell; cytology; high-grade urothelial carcinoma; low-grade urothelial neoplasm; the Paris System.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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66
Anticancer Res




. 2020 Jun;40(6):3231-3237. doi: 10.21873/anticanres.14304.
KHYG-1 Cells With EGFRvIII-specific CAR Induced a Pseudoprogression-like Feature in Subcutaneous Tumours Derived From Glioblastoma-like Cells
Tsutomu Nakazawa 1 2, Toshiharu Murakami 3, Atsushi Natsume 4, Fumihiko Nishimura 3, Takayuki Morimoto 3, Ryosuke Matsuda 3, Mitsutoshi Nakamura 3 5, Shuichi Yamada 3, Ichiro Nakagawa 3, Young-Soo Park 3, Yasushi Motoyama 3, Takahiro Tsujimura 5, Toshihiko Wakabayashi 4, Hiroyuki Nakase 3
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PMID: 32487617
DOI: 10.21873/anticanres.14304

Abstract


Background/aim: We previously established a novel type of epidermal growth factor receptor variant III (EGFRvIII)-specific chimeric antigen receptor (CAR)-expressing natural killer (NK) cell line, designated EvCAR-KHYG-1, which inhibited the growth of glioblastoma (GBM) cells in vitro via apoptosis.

Materials and methods: We investigated the cytokine-producing effect of EvCAR-KHYG-1 cells on GBM-like cell lines and their antitumour effect using in vivo xenograft assays.

Results: EvCAR-KHYG-1 cells produced interleukin-2, interferon-γ, and tumour necrosis factor-α on EGFRvIII-expressing U87MG cells. In vivo xenograft assays showed that EvCAR-KHYG-1 cells did not reduce the volume of subcutaneous tumours derived from EGFRvIII-expressing U87MG cells but did reduce tumour cell occupancy.

Conclusion: EvCAR-KHYG-1 cells led to expression of cellular immunity-related cytokines on EGFRvIII-expressing U87MG in vitro but did not inhibit tumour progression due to the induction of a pseudo progression-like pathological feature. Future studies investigating the effect of different conditions in vivo are required to study the inhibition of tumour progression in GBM.

Keywords: Chimeric antigen receptor; epidermal growth factor receptor variant III; glioblastoma; natural killer cells.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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67
Anticancer Res




. 2020 Jun;40(6):3371-3377. doi: 10.21873/anticanres.14320.
The Lymphocyte-to-monocyte Ratio Is an Independent Prognostic Indicator in Pancreatic Head Cancer That Correlates With Obstructive Jaundice
Masahiro Takeuchi 1 2, Masahiro Mitsuyoshi 3 2, Kumiko Yoshida 3, Masahiko Onoda 3, Michinori Iwamura 3, Akira Furutani 3, Kazuaki Kawano 3, Tomoe Katoh 3
Affiliations expand
PMID: 32487633
DOI: 10.21873/anticanres.14320

Abstract


Background/aim: Several indicators of systemic inflammation have been reported to predict the outcomes of patients with malignant tumors but have not been fully investigated. The aim of this study was to evaluate whether the preoperative lymphocyte-to-monocyte ratio (LMR) can predict the outcomes of patients with pancreatic head cancer.

Patients and methods: We studied 32 patients who underwent curative surgery for pancreatic head cancer in our hospital between 2006 and 2016. Patients were classified into high and low groups according to their LMR.

Results: The low LMR group had a significantly lower survival rate than the high LMR group (p=0.0313). A multivariate analysis showed that the pretreatment LMR (p=0.01) was an independent risk factor for cancer-related death. The LMR was correlated with obstructive jaundice (p=0.001).

Conclusion: Preoperative LMR is a significant predictor of the outcome after pancreaticoduodenectomy in patients with pancreatic head cancer.

Keywords: Pancreatic head cancer; lymphocyte-to-monocyte ratio; obstructive jaundice; prognosis.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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68
Anticancer Res




. 2020 Jun;40(6):3485-3489. doi: 10.21873/anticanres.14335.
Cytoplasmic Expression of AXL Is Associated With High Risk of Postoperative Relapse of Conventional Renal Cell Carcinoma
Lehel Peterfi 1, Thea Bjercke 1, Maria V Yusenko 2, Gyula Kovacs 1 3, Daniel Banyai 4
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PMID: 32487648
DOI: 10.21873/anticanres.14335

Abstract


Background/aim: Despite early detection by widespread use of abdominal imaging more than 40% of patients with conventional renal cell carcinoma (RCC) will die due to metastatic disease. Small kinase inhibitors for AXL receptor tyrosine kinase may delay the progression of metastatic cRCC.

Patients and methods: We analysed AXL expression by immunohistochemistry on tissue multi arrays of 691 conventional RCC without metastasis at the time of nephrectomy.

Results: The Kaplan-Meier survival analysis indicated a poor disease-specific survival rates for patients with tumour showing cytoplasmic AXL staining, whereas expression on the cell membrane is associated with excellent disease outcome. Multivariate Cox regression analysis identified cytoplasmic AXL expression as an independent prognostic factor indicating a five-times higher risk of postoperative tumour progression (RR=5.048; 95% CI=2.391-10.657; p<0.001).

Conclusion: Detecting cytoplasmic expression of AXL can be used to define a subset of conventional RCC with high risk of progression, thus identifying patients for more aggressive surveillance and adjuvant AXL inhibitor treatment as early as possible.

Keywords: AXL expression; Conventional RCC; immunohistochemistry; tumor progression.

Copyright© 2020, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.
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