Κυριακή 14 Νοεμβρίου 2021

Demographic, anthropometric, and metabolic characteristics of obstructive sleep apnea patients from Romania before the COVID-19 pandemic

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Exp Ther Med. 2021 Dec;22(6):1487. doi: 10.3892/etm.2021.10922. Epub 2021 Oct 26.

ABSTRACT

Obstructive sleep apnea (OSA) syndrome is one of the major pathologies of modern life, with multiple etiologies intertwining: the increase in life expectancy, facial and dental changes, metabolic syndrome, and others. The current diagnosis is based on sleep studies, flexible endoscopy, imaging studies and a complete differential diagnosis from other possible pathologies. We present a retrospective study of 80 cases with OSA managed in 2019 prior to the beginning of the COVID-19 pandemic. We analyzed various demographic, anthropometric and metabolic data recorded in our study group. Some of the results, such as high levels of cholesterol and triglycerides, were consistent with worldwide literature. However, regarding the anthropometric data, we underline a general decrease in height in the Romanian population. In addition, demographic data have ch anged in the last decade due to the work immigration in the European Union. This data will be used in a future analysis for comparison with variables recorded from cases with OSA during the COVID-19 pandemic. Current cases with OSA are not a priority for healthcare systems, and patients avoid referral to a specialist as much as possible.

PMID:34765028 | PMC:PMC8576615 | DOI:10.3892/etm.2021.10922

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Environmental allergens house dust mite-induced asthma is associated with ferroptosis in the lungs

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Exp Ther Med. 2021 Dec;22(6):1483. doi: 10.3892/etm.2021.10918. Epub 2021 Oct 26.

ABSTRACT

Previous studies have indicated that allergens such as house dust mites (HDM) in the environment can induce allergic asthma. Ferroptosis is a newly discovered form of regulatory cell death characterized by aberrant lipid peroxidation and the accumulation of reactive oxygen species (ROS) in cells. However, whether ferroptosis participates in the pathological process of asthma remains to be elucidated. The present study used a HDM-induced mouse asthma model to determine the effect of HDM exposure on allergic asthma and its underlying mechanisms. Female BALB/c mice were intranasally exposed to HDM to induce allergic asthma. Airway hyperresponsiveness (AHR), lung inflammation, mucus secretion, IgE levels, cytokine levels and inflammatory cell counts in bronchoalveolar lavage fluid (BALF) were investigated. In addition, the morphological changes of mi tochondria, ROS levels, glutathione (GSH) levels and changes in ferroptosis pathway proteins were also determined in murine lungs. As a result, HDM exposure significantly increased AHR, inflammatory cell infiltration and mucus secretion around the airways. Furthermore, elevated IgE levels in the BALF, lung eosinophilia and a concomitant increase in IL-13 and IL-5 levels in BALF were observed. HDM inhalation increased ROS and decreased GSH levels in the lungs. HDM inhalation induced dysmorphic small mitochondria with decreased crista, as well as condensed, ruptured outer membranes. Western blotting demonstrated that the activities of glutathione peroxidase 4 and catalytic subunit solute carrier family 7 member 11 were significantly decreased, and that protein expression levels of acyl-CoA synthetase long-chain family member 4 and 15 lipoxygenase 1 were upregulated compared with mice in the normal control group. Overall, these results indicated that the AHR, airway inflammation, lipid peroxidation and ROS levels increased in HDM-induced asthma, and that HDM inhalation induced ferroptosis in the lungs, which helped to form an improved understanding of the pathogenesis of allergic asthma.

PMID:34765024 | PMC:PMC8576623 | DOI:10.3892/etm.2021.10918

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Epigenetic approaches for cervical neoplasia screening (Review)

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Exp Ther Med. 2021 Dec;22(6):1481. doi: 10.3892/etm.2021.10916. Epub 2021 Oct 25.

ABSTRACT

Human papillomavirus (HPV) infection is the leading cause of cervical cancer. The Papanicolaou cytology test is the usually employed type of screening for this infection; however, its sensibility is limited. Only a small percentage of women infected with high-risk HPV develop cervical cancer with an array of genetic and epigenetic modifications. Thus, it is necessary to develop rapid, reproducible and minimally invasive technologies for screening. DNA methylation has gained attention as an alternative method for molecular diagnosis and prognosis in HPV infection. The aim of the present review was to highlight the potential of DNA methylation in cervical neoplasia screening for clinical applications. It was observed that the methylation human and viral genes was correlated with high-grade lesions and cancer. Methylation biomarkers have shown a goo d capacity to discriminate between high-grade lesions with a transformative potential and cervical cancer, being able to detect these modifications at an early stage. With further research, the epigenetic profiles and subtypes of the tumors could be elaborated, which would aid in therapy selection by opening avenues in personalized precision medicine. Response to therapy could also be evaluated through such methods and the accessibility of liquid biopsies would allow a constant monitoring of the patient's status without invasive sampling techniques.

PMID:34765022 | PMC:PMC8576616 | DOI:10.3892/etm.2021.10916

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Heat-induced antigen retrieval in fluorescence in situ hybridization: An effective approach enhancing signal intensity in poor-quality FFPE sections

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Exp Ther Med. 2021 Dec;22(6):1480. doi: 10.3892/etm.2021.10915. Epub 2021 Oct 25.

ABSTRACT

Fluorescence in situ hybridization (FISH) serves as an ancillary tool for assessing chromosomal abnormalities and is important in differential diagnoses and treatment decisions. In clinical practice, pathologists encounter unsatisfactory formalin-fixed paraffin-embedded (FFPE) sections exhibiting weak fluorescence signals, mostly due to inappropriate tissue processing or preservation, leading to interpretation difficulties. For the present study, FFPE samples for which conventional FISH failed were collected. Instead of a pretreatment step using a commercial kit, heat-induced antigen retrieval (HIAR) was introduced using either citrate buffer or Tris-EDTA buffer, while the subsequent experimental workflow remained unchanged. After HIAR-assisted FISH, the hybridization efficiency and signal intensity were markedly enhanced and no difference in signal adequacy was observed when comparing the effect of the two AR solutions. The present study demonstrated that HIAR is a reliable tool for FISH, particularly for poor-quality FFPE sections yielding weak or no fluorescence signals in the conventional analysis.

PMID:34765021 | PMC:PMC8576618 | DOI:10.3892/etm.2021.10915

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FOXO1: a pivotal pioneer factor in oral squamous cell carcinoma

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Am J Cancer Res. 2021 Oct 15;11(10):4700-4710. eCollection 2021.

ABSTRACT

The transcription factor FOXO1 regulates cell cycle progression, apoptosis and oxidative stress. Interestingly, numerous studies have implicated their positive role in tumor suppression, angiogenesis and metastasis in oral squamous cell carcinoma (OSCC). Distinct post-transcriptional and post-translational modifications actuate the physiological role of FOXO1 in OSCC. Here, we evaluate the role of FOXO1 proteins in OSCC, their fundamental structure and the major players involved in FOXO1 regulation and how they are Pharmacologically modulated in OSCC. Finally, their role in regulating epithelial-mesenchymal transition (EMT), autophagy, stress tolerance and stemness, which would significantly aid in novel potential oversight for future research and thus developing strategies to prevent or reverse OSCC.

PMID:34765288 | PMC:PMC8569351

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Long-term oncologic outcomes of breast conserving surgery with propofol-based total intravenous anesthesia or volatile inhalational general anesthesia without propofol: a propensity score-matched, population-based cohort study

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Am J Cancer Res. 2021 Oct 15;11(10):4966-4980. eCollection 2021.

ABSTRACT

To estimate oncologic outcomes (overall survival [OS], locoregional recurrence [LRR], and distant metastasis [DM]) in patients with breast intraductal carcinoma (IDC) receiving breast conserving surgery (BCS) under propofol-based total intravenous anesthesia (TIVA) or volatile inhalational (INHA) general anesthesia (GA) without propofol. Patients with breast IDC receiving BCS were recruited through propensity score matching and categorized by anesthesia techniques into propofol-based TIVA-GA and non-propofol-based INHA-GA groups, respectively. Cox regression analysis was performed to calculate hazard ratios and 95% confidence intervals (CIs). In multivariate Cox regression analysis, the adjusted hazard ratio (aHR; 95% CI) of all-cause mortality for TIVA-GA with propofol compared with INHA-GA without propofol was 0.94 (0.83-1.31). The aHR (95% CI) of LRR for TIVA- GA with propofol group compared with INHA-GA without propofol was 0.77 (0.58-0.87). The aHR (95% CI) of DM for TIVA-GA with propofol compared with INHA-GA without propofol was 0.91 (0.82-1.24). Propofol-based TIVA-GA might be beneficial for reducing LRR in women with breast IDC receiving BCS compared with non-propofol-based INHA-GA.

PMID:34765304 | PMC:PMC8569355

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PD-1 antibody camrelizumab for Epstein-Barr virus-positive metastatic gastric cancer: a single-arm, open-label, phase 2 trial

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Am J Cancer Res. 2021 Oct 15;11(10):5006-5015. eCollection 2021.

ABSTRACT

Gastric cancer (GC) patients with Epstein-Barr virus (EBV) positivity have demonstrated promising response with immunotherapy. We assessed the efficacy and safety of camrelizumab as salvage treatment in EBV-positive mGC. In this single-arm, phase 2 prospective clinical trial (NCT03755440), stage IV EBV-positive GC patients who failed/could not tolerate previous lines of chemotherapy were given intravenous camrelizumab 200 mg every 2 weeks until disease progression or unacceptable toxicity. The primary endpoint was objective response rate. Secondary endpoints were progression-free survival (PFS), overall survival (OS), disease control rate (DCR), duration of response, and toxicity. Exploratory analysis included the associations between treatment response and tumor mutation burden (TMB), programmed cell death ligand-1 (PD-L1) expression. Six eligible patients were enrolled in the first stage of the study. No patient achieved an objective response; thus, the study did not proceed to the second stage. The DCR was 67% (4/6). The median PFS rate was 2.2 months (95% CI: 1.5-not reached [NR]) and median OS was 6.8 months (95% CI: 1.7-NR). All treatment-related adverse events were grade 1-2, with reactive cutaneous capillary endothelial proliferation (n=4 [67%]) being the most commonly observed event. The only patient with PD-L1 combined positive score >1 had disease progression. Two stable disease and one disease progression were observed in three patients with TMB >10 Mut/Mb. EBV positivity may not be a good predictor for response to camrelizumab in mGC. Newer biomarkers are needed to identify EBV-positive mGC respondents who might benefit from immunotherapy.

PMID:34765307 | PMC:PMC8569350

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Multiple functions of the DEAD-box RNA helicase, DDX5 (p68), make DDX5 a superior oncogenic biomarker and target for targeted cancer therapy

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Am J Cancer Res. 2021 Oct 15;11(10):5190-5213. eCollection 2021.

ABSTRACT

DDX5 (p68) is a well-known multifunctional DEAD-box RNA helicase and a transcription cofactor. Since its initial discovery more than three decades ago, DDX5 is gradually recognized as a potential biomarker and target for the treatment of various cancer types. Studies over the years significantly expanded our understanding of the functional diversity of DDX5 in various cancer types and extended our knowledge of its Mechanism of Action (MOA). This provides a rationale for the development of novel cancer therapeutics by using DDX5 as a biomarker and a therapeutic target. However, while most of the published studies have found DDX5 to be an oncogenic target and a cancer treatment-resistant biomarker, a few studies have reported that in certain scenarios, DDX5 may act as a tumor suppressor. After careful review of all the available relevant studies in the literature, we found that the multiple functions of DDX5 make it both a superior independent oncogenic biomarker and target for targeted cancer therapy. In this article, we will summarize the relevant studies on DDX5 in literature with a careful analysis and discussion of any inconsistencies encountered, and then provide our conclusions with respect to understanding the MOA of FL118, a novel small molecule. We hope that such a review will stimulate further discussion on this topic and assist in developing better strategies to treat cancer by using DDX5 as both an oncogenic biomarker and therapeutic target.

PMID:34765320 | PMC:PMC8569338

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Cumulative obesity exposure increases the risk of kidney cancer: a longitudinal nationwide cohort study

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Am J Cancer Res. 2021 Oct 15;11(10):5016-5026. eCollection 2021.

ABSTRACT

Obesity is one of the most important prognostic factors of kidney cancer. However, little is known regarding the cumulative impacts of obesity on kidney cancer risk. We aimed to analyze the dose- and time-dependent impact of obesity on kidney cancer risk using the Korean National Health Insurance System database. This longitudinal nationwide cohort study used data from the Korean National Health Insurance System database between 2012 and 2013. In total, 3,102,240 participants who received annual health examination more than four times consecutively were included in the final analysis. The primary endpoint was newly diagnosed kidney cancer according to the dose- and time-dependent impact of obesity. Dose-dependent impact was measured using body mass index (BMI) and waist circumference (WC), and time-dependent impact was measured using general and abdominal cumulat ive obesity exposure (gCOE and aCOE). COE was defined as the number of years since obesity diagnosis during the exposure period. We identified 1,831 participants with newly diagnosed kidney cancer (median follow-up: 4.3 years). The hazard ratios (HRs) for kidney cancer increased significantly alongside BMI and WC. The HRs for kidney cancer increased significantly in the higher gCOE groups (P for trend <0.001) as follows: 1 (1.33, 95% confidence intervals: 1.10-1.60), 2 (1.33, 1.08-1.63), 3 (1.55, 1.30-1.85), and 4 (1.82, 1.64-2.03) years. Similar trends were observed for aCOE (P for trend <0.001) as follows: 1 (1.42, 1.23-1.64), 2 (1.71, 1.46-2.02), 3 (1.76, 1.48-2.08), and 4 (2.11, 1.84-2.42) years. Risks of kidney cancer related to COE were much more pronounced in participants with the following characteristics: younger than 65 years old, male gender, diabetes, hypertension, and dyslipidemia. Longer COE was associated with an increased risk of kidney cancer in the Korean population. Participants with prolonged obesity and metabolic syndrome need active surveillance for kidney cancer.

PMID:34765308 | PMC:PMC8569344

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Sensitization of breast cancer to Herceptin by redox active nanoparticles

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Am J Cancer Res. 2021 Oct 15;11(10):4884-4899. eCollection 2021.

ABSTRACT

Herceptin-resistant tumor relapse remains a major clinical issue responsible for the poor prognosis of HER2+ breast cancer. Understanding the underlying mechanisms and finding a therapeutic solution are of paramount urgency to improve the patient management. Here we report that anticancer redox active cerium oxide nanoparticles (CONPs) can potently sensitize the cancer cells to the cytotoxicity of Herceptin. By comparing between Herceptin-sensitive and Herceptin-resistant human breast cancer cell lines under normoxic as well as hypoxic culture conditions, we found that in the presence of CONPs, Herceptin can kill the Herceptin-resistant cells equally effectively as it kills the Herceptin-sensitive cells under the hypoxic, but not normoxic, culture conditions by inhibiting the cell viability, survival and proliferation. Signaling analysis reveals that u nder the normoxic conditions, the levels of hypoxia induced factor 1α as well as vascular endothelial growth factor are higher in the Herceptin-resistant cells than that in the Herceptin-sensitive cells and are strongly induced once the culture is switched to the hypoxic conditions, which can be potently suppressed by CONPs. Treatment with CONPs plus Herceptin significantly slows down the primary tumor growth and lung metastasis of the Herceptin-resistant cells in a xenograft mouse model of orthotopic breast cancer through inhibiting the cell proliferation and survival as well as tumor angiogenesis. These results shed new lights on the mechanisms underlying the Herceptin resistance of the HER2+ breast cancer and provide insights into introducing CONPs-like agents to Herceptin-based therapy to improve treatment outcomes.

PMID:34765298 | PMC:PMC8569362

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Postoperative complications and open gastrectomy affect non-cancer-related death and shorten life expectancy in elderly patients with gastric cancer

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Am J Cancer Res. 2021 Oct 15;11(10):5038-5044. eCollection 2021.

ABSTRACT

Postoperative complications contribute to recurrences and poor long-term outcomes for gastric cancer patients, especially among the elderly. However, the prognostic effect of postoperative complications on non-cancer-related death in elderly patients with gastric cancer has not been reported. Two hundred and twenty elderly (> 75 years of age) patients with stage I gastric cancer were retrospectively identified from consecutive admissions between 1995 and 2020. Non-cancer-related death following gastrectomy occurred in 13.6% (30/220) of patients. Non-cancer-related death was associated with respiratory disease in 46.7% (14/30) of cases. Although there was no association with any preoperative comorbidities, postoperative complications [P < 0.001, HR 4.16 (95% CI: 1.91-9.02)] and open gastrectomy [P=0.002, HR 3.87 (95% CI: 1.54-9.66)] were indepe ndently associated with a poorer prognosis for non-cancer-related death. Poor nutritional status [P=0.028, OR 4.25 (95% CI: 1.17-15.4)] was an independent risk factor for postoperative complications. Postoperative complications shortened life expectancy from 8.8 years to 6.1 years. Specifically, postoperative complications shortened life expectancy from 6.7 years to 3.9 years in elderly patients over 80 years of age. Postoperative complications and open gastrectomy affected the incidence of non-cancer-related death among elderly patients with gastric cancer, primarily attributed to respiratory disease. Efforts should be made to perform minimally invasive surgery, improve preoperative nutrition, and avoid postoperative complications.

PMID:34765310 | PMC:PMC8569366

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