The systemic inflammation response index predicts the survival of patients with clinical T1‐2N0 oral squamous cell carcinoma

xloma.fota13 shared this article with you from Inoreader The systemic inflammation response index predicts the survival of patients with clinical T1‐2N0 oral squamous cell carcinoma Via Oral Diseases Abstract Objective The systemic inflammation response index (SIRI) is an independent prognostic factor for many malignant tumors. However, the value of this factor in patients with clinical T1‐2N0 (cT1‐2N0) oral squamous cell carcinoma (OSCC) is still unclear. Methods We calculated SIRI of 235 cT1‐2N0 OSCC patients from 2013 to 2017. Multivariate cox regression analysis was applied to verify the prognostic significance of SIRI. Kaplan‐Meier curves were plotted to analyze the overall survival (OS) and disease‐specific survival (DSS) for cT1‐2N0 OSCC patients. Results According to the optimal cutoff point of SIRI, we divided cT1‐2N0 OSCC patients into high SIRI group (SIRI ≥ 1.3) and low SIRI group (SIRI < 1.3). SIRI was an independent prognostic indicator for OS (HR = 2.87; 95% CI = 1.35‐6.10; P = 0.006) and DSS (HR = 2.17; 95% CI = 1.10‐4.27; P = 0.025). High SIRI had a significantly poorer OS (P = 0.001) and DSS (P = 0.007) in survival analysis than the low SIRI. Moreover, the prognostic value of SIRI was significantly stronger than neutrophil‐to‐lymphocyte ratio (NLR) and monocyte‐to‐lymphocyte ratio (MLR). Conclusions Preoperative SIRI can be regarded as a meaningful indicator for poor survival of cT1‐2N0 OSCC patients, and it is a promising tool to formulate the best individualized treatment for high‐risk patients. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Age‐related dental phenotypes and tooth characteristics of FAM83H‐associated hypocalcified amelogenesis imperfect

xloma.fota13 shared this article with you from Inoreader Age‐related dental phenotypes and tooth characteristics of FAM83H‐associated hypocalcified amelogenesis imperfect Via Oral Diseases Abstract Objectives Autosomal‐dominant hypocalcified amelogenesis imperfecta (ADHCAI) shows phenotypic heterogeneity. Our aim was to characterise the ADHCAI phenotypes, tooth properties, and genotypes. Methods Three unrelated ADHCAI probands and seven additional affected members of the three families were recruited. Mutations were identified by exome and Sanger sequencing, and haplotypes by SNP array. Tooth colour, roughness, density, nanohardness, minerals, and ultrastructure were investigated. Results Ten participants were heterozygous for the FAM83H mutation c.1387C>T (p.Gln463*). All shared a 3.43 Mbp region on chromosome 8q24.3 encompassing the FAM83H variant, indicating a common ancestry. The c.1387C>T was estimated to be 23.8 generations or 600 years. The FAM83H enamel had higher roughness and lower lightness, density, nanohardness, and calcium and phosphorus levels than controls. Blunted enamel rods, wide interrod spaces, and disorganized dentinoenamel junctions were observed. Evaluating the patients with the same mutation and reviewing others with different mutations in FAM83H revealed that the FAM83H heterogeneous phenotypes are age‐influenced. Tooth colour and surface texture change with aging. Conclusions FAM83H enamel demonstrated decreased lightness, density, hardness, calcium, phosphorus, and defective ultrastructure. We have identified that the phenotypic variation in FAM83H‐associated ADHCAI is age‐related. Awareness of the correlation between age and clinical features of FAM83H‐ADHCAI can help dentists make an accurate diagnosis. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Efficacy and safety of sorafenib plus vitamin K treatment for hepatocellular carcinoma: A phase II, randomized study

xloma.fota13 shared this article with you from Inoreader Efficacy and safety of sorafenib plus vitamin K treatment for hepatocellular carcinoma: A phase II, randomized study Via Cancer Medicine Vitamin K dosing during sorafenib treatment against HCC showed higher ORR and prolonged PFS significantly. The vitamin K dosing might enhance the antitumor action of sorafenib by suppressing des‐γ‐carboxy prothrombin, which is a factor that promotes angiogenesis and tumor growth. Abstract The previous retrospective study suggested that dosing vitamin K may enhance the anticancer action of sorafenib against hepatocellular carcinoma. To confirm it, we performed a phase II, randomized, open‐label study. Patients with hepatocellular carcinoma were randomly assigned to receive sorafenib + vitamin K2 (menatetrenone, 45 mg daily, orally) or sorafenib only. Between 1 May 2012 and 1 May 2016, 68 patients were screened. Forty‐four eligible patients were assigned at a 1:1 ratio to each cohort. The objective response rate in the vitamin K‐dosed group was significantly higher than that in the sorafenib only group (27.3% vs 4.5%, respectively; p = 0.039). The median time of progression‐free survival was significantly extended in the vitamin K‐dosed group compared with the sorafenib only group (4.9 months vs 2.7 months, respectively; hazard ratio (HR), 0.44; 95% confidence interval (CI): 0.21–0.89; p = 0.018). Although there was no significant difference between the two groups in the median time of overall survival, patients in the vitamin K‐dosed group with a complete response or partial response achieved a significantly extended median time of overall survival compared with the other patients in the vitamin K‐dosed group or the patients in the sorafenib only group (26.1 months vs 9.0 months; HR, 0.34; 95% CI: 0.11–0.95; p = 0.046 or 11.5 months; HR, 0.16; 95% CI: 0.034–0.70; p = 0.006, respectively). Dosing vitamin K could augment the anticancer action of sorafenib against HCC. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Circ_0008305‐mediated miR‐660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis

xloma.fota13 shared this article with you from Inoreader Circ_0008305‐mediated miR‐660/BAG5 axis contributes to hepatocellular carcinoma tumorigenesis Via Cancer Medicine circ_0008305 was greatly increased in HCC tissues and cells. circ_0008305 can act as a sponge of miR‐660. miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). Abstract Increasing circRNAs have attracted a lot of attention because of their significant biological effects in many diseases. It has been reported that circ_0008305 can modulate lung cancer progression. However, the association between circ_0008305 and hepatocellular carcinoma (HCC) needs to be well explored. In this current research, we studied the molecular function and potential mechanism of circ_0008305 in HCC progression. First, it was demonstrated that circ_0008305 was greatly increased in HCC tissues and cells. Moreover, we observed silencing circ_0008305 markedly repressed HCC cells in vitro growth and reduced tumor growth in vivo. Additionally, it was identified that circ_0008305 can act as a sponge of miR‐660 while miR‐660 targeted Bcl‐2‐associated athanogene 5 (BAG5). BAG5 belongs to a member of BAG family and it is involved in multiple diseases. We reported that circ_0008305 contributed to the inhibition of miR‐660, which resulted in an upregulated expression of BA G5 in HCC. Subsequently, rescue assays were conducted and it was indicated that loss of BAG5 reversed the effects of miR‐660 inhibitors on HCC partially. To sum up, it was illustrated by our study that circ_0008305‐mediated miR‐660‐5p/BAG5 axis triggered HCC progression, which could provide a novel insight on the underlying mechanism of HCC progression. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases

xloma.fota13 shared this article with you from Inoreader Real world outcomes of combination and timing of immunotherapy with radiotherapy for melanoma with brain metastases Via Cancer Medicine In our study of the National Cancer Data Base (NCBD), addition of immunotherapy to radiation therapy improves survival in patients with melanoma with brain metastases when added to SBRT or WBRT, with the best survival observed for IT with SBRT. Concurrrent versus Noncurrent immunotherapy combined with radiation had no significantly different survival. Abstract Introduction Immunotherapy (IT) and radiotherapy (RT) have improved overall survival in patients with melanoma with brain metastasis (MBM). We examined the real‐world survival impact of IT and RT combination and timing strategies. Materials and Methods From the facility‐based National Cancer Database (NCDB) data set, 3008 cases of MBM were identified between 2011 and 2015. Six treatment cohorts were identified: stereotactic radiosurgery (SRS) + IT, SRS alone, whole brain radiotherapy (WBRT) + IT, WBRT alone, IT alone, and none. Concurrent therapy was defined as IT given within 28 days before or after RT; nonconcurrent defined as IT administered within 28–90 days of RT. The co‐primary outcomes were propensity score‐adjusted overall survival by treatment regimen and overall survival by RT and IT timing. Results Median overall survival (mOS) was performed for each treatment category; SRS +IT 15.77 m; (95%CI 12.13–21.29), SRS alone (9.33 m; 95%CI: 8.0–11.3), IT alone (7.29 m; 95%CI: 5.35–12.91), WBRT +IT (4.89 m; 95%CI: 3.65–5.92), No RT or IT (3.29 m; 95%CI: 2.96–3.75), and WBRT alone (3.12 m; 95%CI 2.79–3.52). By propensity score matching, mOS for SRS +IT (15.5 m; 95%CI: 11.5–20.2) was greater than SRS alone (10.1 m; 95%CI: 8.4–11.8) (p = 0.010), and median survival for WBRT +IT (4.6 m; 95%CI: 3.4–5.6) was greater than WBRT alone (2.9 m; 95%CI: 2.5–3.5) (p < 0.001). In the SRS +IT group, 24‐month landmark survival was 47% (95%CI; 42–52) for concurrent versus 37% (95%CI; 30–44) for nonconcurrent (p = 0.40). Conclusion Those who received IT in addition to WBRT and SRS experienced longer survival compared to RT modalities alone, while those receiving concurrent SRS and IT trended toward improved survival versus nonconcurrent therapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Targeting YAP‐p62 signaling axis suppresses the EGFR‐TKI‐resistant lung adenocarcinoma

xloma.fota13 shared this article with you from Inoreader Targeting YAP‐p62 signaling axis suppresses the EGFR‐TKI‐resistant lung adenocarcinoma Via Cancer Medicine The accumulated p62 by autophagy inhibitor, chloroquine has oncogenic functions in EGFR‐TKI resistant lung adenocarcinoma. Hippo effector YAP regulates p62 transcription through ERK, and YAP inhibition significantly suppresses the expression of p62. We suggest that targeting YAP‐p62 signaling axis can be useful to overcome the EGFR‐TKI resistance in lung adenocarcinoma. Abstract Background Despite the progress of advanced target therapeutic agents and immune checkpoint inhibitors, EGFR‐TKI resistance is still one of the biggest obstacles in treating lung cancer. Clinical studies with autophagy inhibitors are actively underway to overcome drug resistance. Methods We used PC9, PC9/GR, and HCC827/GR cell lines to evaluate the activation of autophagy and EGFR‐TKI resistance. Chloroquine was applied as an autophagic blocker and verteporfin was utilized as a YAP inhibitor. Results In this study, we tried to reveal the effect of autophagy adaptor p62 which is accumulated by autophagy inhibitor in EGFR‐TKI‐resistant lung adenocarcinoma. We identified that p62 has oncogenic functions that induce cell proliferation and invasion of EGFR‐TKI‐resistant lung adenocarcinoma. Interestingly, we found for the first time that YAP regulates p62 transcription through ERK, and YAP inhibition can suppress the expression of oncogenic p62. We also confirmed that the expressions of p62 and YAP have a positive correlation in EGFR‐mutant lung adenocarcinoma patients. To block cell survival via perturbing YAP‐p62 axis, we treated EGFR‐TKI‐resistant lung cancer cells with YAP inhibitor verteporfin. Remarkably, verteporfin effectively caused the death of EGFR‐TKI‐resistant lung cancer cells by decreasing the expressions of p62 with oncogenic function, YAP, and its target PD‐L1. So, the cumulative effect of oncogenic p62 should be considered when using autophag y inhibitors, especially drugs that act at the last stage of autophagy such as chloroquine and bafilomycin A1. Conclusion Finally, we suggest that targeting YAP‐p62 signaling axis can be useful to suppress the EGFR‐TKI‐resistant lung cancer. Therefore, drug repurposing of verteporfin for lung cancer treatment may be valuable to consider because it can inhibit critical targets: p62, YAP, and PD‐L1 at the same time. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Plasmodium falciparum FIKK9.1 is a monomeric serine–threonine protein kinase with features to exploit as a drug target

xloma.fota13 shared this article with you from Inoreader Plasmodium falciparum FIKK9.1 is a monomeric serine–threonine protein kinase with features to exploit as a drug target Via Chemical Biology & Drug Design FIKK‐9.1 kinase is monomeric with a native molecular weight of 60 ± 1.6 kDa. The C‐terminal domain of protein has a well‐defined pocket to bind ATP. FIKK protein binds ATP with a K d of 45.6 ± 2.4 µM. FIKK‐9.1 has 23 pockets to serve potential docking sites for substrates. Peptide P277 is fitting nicely into the binding pocket. FIKK‐9.1 is phosphorylating spectrin, ankyrin, band 3 in the IRBC. FIKK 9.1 can be exploited in drug discovery and diagnostics. Abstract FIKK‐9.1 is essential for parasite survival, but its structural and biochemical characterization will enable us to understand its role in the parasite life cycle. The recombinant FIKK9.1 kinase is monomeric with a native molecular weight of 60 ± 1.6 kDa. Structural characterization of FIKK9.1 kinase reveals that it consists of two domains: N‐terminal FHA like domain and C‐terminal kinase domain. The C‐terminal domain has a well‐defined pocket, but it displayed RMSD deviation of 1.38–3.2 Å from host kinases. ITC analysis indicates that ATP binds to the protein with a K d of 45.6 ± 2.4 µM. Mutational studies confirm the role of Val‐244, Met‐245, Lys‐320, 324, and Glu‐366 for ATP binding. Co‐localization studies revealed FIKK9.1 in the parasite cytosol with a component trafficked to the apicoplast and also to IRBC. FIKK9.1 has 23 pockets to serve as potential docking sites for substrates. Correlation analysis of peptides from the combinatorial library concluded that peptide P277 (MFDFHYTLGPMWGTL) was fitting nicely into the binding pocket. The peptide P277 picked up candidates from parasite and key players from RBC cytoskeleton. Interestingly, FIKK9.1 is phosphorylating spectrin, ankyrin, and band‐3 from RBC cytoskeleton. Our study highlights the structural and biochemical features of FIKK9.1 to exploit it as a drug target. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Administrative coding in electronic health care record‐based research of NAFLD: an expert panel consensus statement

xloma.fota13 shared this article with you from Inoreader Administrative coding in electronic health care record‐based research of NAFLD: an expert panel consensus statement Via Hepatology Abstract Background and aims Electronic health record (EHR)‐based research allows the capture of large amounts of data, which is necessary in nonalcoholic fatty liver disease (NAFLD), where the risk of clinical liver outcomes is generally low. The lack of consensus on which International Classification of Disease (ICD) codes should be used as exposures and outcomes limits comparability and generalizability of results across studies. We aimed to establish consensus among a panel of experts on ICD codes that could become the reference standard and provide guidance around common methodological issues. Approach and results Researchers with an interest in EHR‐based NAFLD research were invited to collectively define which administrative codes are most appropriate for documenting exposures and outcomes. We used a modified Delphi approach to reach consensus on several commonly encountered methodological challenges in the field. After two rounds of revision, a high level of agreement (>67%) was reached on all items considered. Full consensus was achieved on a comprehensive list of administrative codes to be considered for inclusion and exclusion criteria in defining exposures and outcomes in EHR‐based NAFLD research. We also provide suggestions on how to approach commonly encountered methodological issues and identify areas for future research. Conclusions This expert panel consensus statement can help harmonize and improve generalizability of EHR‐based NAFLD research. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.