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Αλέξανδρος Γ. Σφακιανάκης

Sunday, February 13, 2022

Human telomerase reverse transcriptase protein expression is associated with survival in patients with oral squamous cell carcinoma

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Int J Clin Exp Pathol. 2022 Jan 15;15(1):29-37. eCollection 2022.

ABSTRACT

Despite improvements in diagnosis and treatment, the 5-year survival of oral squamous cell carcinoma (OSCC), no matter the location, remains low, averaging 50%. Telomerase is expressed in 85% of malignancies and may play an important role in human carcinogenesis. Its catalytic component is human telomerase reverse transcriptase (hTERT), which has been thought, but not proven, to be involved in survival with OSCC. We investigated whether hTERT protein was a prognostic factor in OSCC by evaluating its association with clinicopathologic findings and OSCC survival. We found that in comparison to patients with high hTERT expression, patients with low hTERT expression survived significantly longer, including a longer 5-year overall survival. In addition, overall survival was significantly correlated to hTERT expression and the histologic grade and N status of the tumo r. Disease-free survival was significantly related to hTERT expression, the histologic grade and N status of the tumor, and mode of invasion. These results suggest that hTERT protein is involved in cervical lymph node metastasis, that its levels may be increased during carcinogenesis, and that it may influence tumor invasion. We believe that this study is the first to demonstrate that OSCC with high hTERT expression carries a worse prognosis than cases with low hTERT expression.

PMID:35145581 | PMC:PMC8822205

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Comparison of manual and automated digital image analysis systems for quantification of cellular protein expression

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Histol Histopathol. 2022 Feb 11:18434. doi: 10.14670/HH-18-434. Online ahead of print.

ABSTRACT

OBJECTIVE: Quantifying protein expression in immunohistochemically stained histological slides is an important tool for oncologic research. The use of computer-aided evaluation of IHC-stained slides significantly contributes to objectify measurements. Manual digital image analysis (mDIA) requires a user-dependent annotation of the region of interest (ROI). Others have built-in machine learning algorithms with automated digital image analysis (aDIA) and can detect the ROIs automatically. We aimed to investigate the agreement between the results obtained by aDIA and those derived from mDIA systems.

METHODS: We quantified chromogenic intensity (CI) and calculated the positive index (PI) in cohorts of tissue microarrays (TMA) using mDIA and aDIA. To consider the different distributions of staining within cellular sub-compartments and diffe rent tumor architecture our study encompassed nuclear and cytoplasmatic stainings in adenocarcinomas and squamous cell carcinomas.

RESULTS: Within all cohorts, we were able to show a high correlation between mDIA and aDIA for the CI (p<0.001) along with high agreement for the PI. Moreover, we were able to show that the cell detections of the programs were comparable as well and both proved to be reliable when compared to manual counting.

CONCLUSION: mDIA and aDIA show a high correlation in acquired IHC data. Both proved to be suitable to stratify patients for evaluation with clinical data. As both produce the same level of information, aDIA might be preferable as it is time-saving, can easily be reproduced, and enables regular and efficient output in large studies in a reasonable time period.

PMID:35146728 | DOI:10.14670/HH-18-434

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Understanding Public Perceptions Regarding Cochlear Implant Surgery in Adults

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Otol Neurotol. 2022 Mar 1;43(3):e331-e336. doi: 10.1097/MAO.0000000000003439.

ABSTRACT

BACKGROUND AND OBJECTIVE: Approximately 6% of adults eligible for cochlear implantation (CI) undergo surgery. This study aims to understand how general perceptions about CI contribute to barriers causing this low utilization rate.

METHODS: Participants completed an online survey regarding their perceptions about cochlear implantation. They were asked to rank CIQOL-10 Global priorities and corresponding risk tolerance for minor complications (changes in taste, vertigo) and major complications (infections requiring hospitalization, meningitis, reimplantation, facial paralysis, and cerebrospinal fluid [CSF] leak).

RESULTS: A total of 615 responses (female 55%, mean age 39 years [range 20-78]) were included. Respondents identified issues with insurance (46%) and fear of undergoing surgery (21%) as barriers preventing eligible adults from receiving C I. Regarding surgical risk, respondents significantly underestimated rates of minor complications (p < 0.0001) and almost all major complications (all p < 0.0001) while overestimating rates of serious infections and need for reimplantation (both p < 0.005). The ability to hear strangers in noisy environments was identified as the highest priority for CI (26%). Individuals who knew someone with a cochlear implantation were willing to tolerate higher rates of all minor and major complications (all p < 0.05). Healthcare workers were similarly willing to tolerate significantly higher rates of meningitis, facial paralysis, and CSF leak to achieve their highest priority (all p < 0.05).

CONCLUSIONS: Respondents identify insurance coverage and fear of surgery as primary reasons for low utilization of adult CI in the United States. However, healthcare workers or those who knew someone with a cochlear implantation indicated significantly higher rates of risk tolerance to achieve their highest quality of life priorities, indicating the potential that the benefits of cochlear implantation are underappreciated in the general population.

PMID:35147605 | DOI:10.1097/MAO.0000000000003439

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Irradiated fibroblasts increase interleukin-6 expression and induce migration of head and neck squamous cell carcinoma

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by Shinsuke Suzuki, Satoshi Toyoma, Yohei Kawasaki, Takechiyo Yamada

Background

Cytotoxic effects of radiation play an important role in the treatment of head and neck cancer. However, irradiation is known to lead to the migration of various cancer cells, including those of head and neck cancer. Recently, fibroblasts in the cancer microenvironment have been reported to be involved in this mechanism. Nevertheless, the mechanism underlying migration of head and neck cancer cells remains unclear. Herein, we aimed to elucidate this migration mechanism induced by irradiation in terms of the interaction of head and neck cancer cells with fibroblasts.

Methods

We used the head and neck squamous cell carcinoma (HNSCC) cell lines SAS and FaDu as well as fibroblast cell lines. These cells were irradiated and their viability was compared. In fibroblasts, changes in interleukin-6 (IL-6) secretion caused by irradiation were measured by enzyme-linked immunosorbent assay (ELISA). The cell migration ability of cancer cells was evaluated via a migration assay using a semipermeable membrane. HNSCC cells were cocultured with irradiated and nonirradiated fibroblasts, and their migration ability under each condition was compared. We also examined the effect of IL-6 on the migration of HNSCC cells. Furthermore, to investigate the effect of fibroblast-derived IL-6 on the migration ability of HNSCC cells, we conducted a coculture study using IL-6 neutralizing antibody.

Results

Irradiation reduced the survival of HNSCC cells, whereas fibroblasts were resistant to irradiation. Irradiation also increased IL-6 secretion by fibroblasts. Migration of HNSCC cells was enhanced by coculture with fibroblasts and further enhanced by coculture with irradiated fibroblasts. We also confirmed that the migration of HNSCC cells was induced by IL-6. The enhanced migration of cancer cells caused by coculturing with fibroblasts was canceled by the IL-6 neutralizing antibody.

Conclusion

These results show that fibroblasts survive irradiation and indu ce the migration ability of HNSCC cells through increased secretion of IL-6.

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Selected by bioinformatics and molecular docking analysis, Dhea and 2–14,15-Eg are effective against cholangiocarcinoma

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by Lei Qin, Jun Kuai, Fang Yang, Lu Yang, Peisheng Sun, Lanfang Zhang, Guangpeng Li

Object

To identify novel targets for the diagnosis, treatment and prognosis of cholangiocarcinoma, we screen ideal lead compounds and preclinical drug candidates with MYC inhibitory effect from the ZINC database, and verify the therapeutic effect of Dhea and 2–14,15-Eg on cholangiocarcinoma.

Methods

The gene expression profiles of GSE132305, GSE89749, and GSE45001 were obtained respectively from the Gene Expression Omnibus database. The DEGs were identified by comparing the gene expression profiles of cholangiocarcinoma and normal tissues. GO, KEGG analysis and PPI network analyses were performed. LibDock, ADME and toxicity prediction, molecular docking and molecular dynamics simulations were used to identify potential inhibitors of MYC. Moreover, in vitro, MTT assay, colony-forming assay, the scratch assay and Western blotting were performed to verify the therapeutic effect of Dhea and 2–14,15-Eg.

Results

PPI network analysis showed that ALB, MYC, APOB, IGF1 and KNG1 were hub genes, of which MYC was mainly studied in this study. A battery of computer-aided virtual techniques showed that Dhea and 2–14,15-Eg have lower rodent carcinogenicity, Ames mutagenicity, developmental toxicity potential, and high tolerance to cytochrome P4502D6, as well as could exist stably in natural circumstances. In vitro assays showed that Dhea and 2–14,15-Eg inhibited cholangiocarcinoma cellular viability, proliferation, and migration inhibiting expression of MYC.

Conclusion

This study suggested that Dhea and 2–14,15-Eg were novel potential inhibitors of MYC targeting, as well as are a promising drug in dealing with cholangiocarcinoma and have a perspective application.

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Vertical rectus abdominis myocutaneous flap to reconstruct thigh and groin defects: A retrospective cohort and systematic review

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J Plast Reconstr Aesthet Surg. 2022 Jan 19:S1748-6815(22)00028-6. doi: 10.1016/j.bjps.2022.01.015. Online ahead of print.

ABSTRACT

BACKGROUND: The vertical rectus abdominis myocutaneous (VRAM) flap is one of the options for soft-tissue reconstruction in the groin and thigh. The aim of this study is to evaluate the clinical outcomes, risk factors for complications, and the utility of using mesh to prevent abdominal hernia.

METHODS: A retrospective review of patients who underwent VRAM flap reconstruction to reconstruct proximal thigh and groin defects from 1997 to 2018 was performed. Data regarding patient demographics, surgical characteristics, and postoperative outcomes were collected. Proportional hazard regression analysis was performed to assess the association of the risk of recipient site complications. A systematic review was performed to assess the outcomes and summarize the evidence from published studies.

RESULTS: Fifty-three patients were identified and included in this study. In most of the cases, the procedures were performed after tumor resection (77%) and in the rest of the cases, they were performed for chronic complicated wounds (23%). Twenty-five (47.2%) patients developed complications. Intraoperative and postoperative radiotherapy, chronic kidney disease, history of prior tumor resection, and reconstructions of chronic complicated wounds were associated with an increased risk of recipient site complications. A systematic review identified 9 articles, for a total of 189 reconstructions. The pooled complications and failure rates were 31.2% and 2.1%, respectively. Stratified analysis showed that the rate of abdominal hernia was similar in patients with mesh (16.7%) and in patients with primary closure only (15.1%; p = 0.761).

CONCLUSION: Defects in the groin or proximal thigh can be treated successfully with the VRAM flap. Although wound complications and hernia rates are high, the reconstruction failure rate is low.

PMID:35148978 | DOI:10.1016/j.bjps.2022.01.015

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Impact of Medicaid Expansion on Rhinologic Cancer Presentation, Treatment, and Outcomes

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Objective

The United States Patient Protection and Affordable Care Act allocated funds for states to expand Medicaid coverage. However, several states declined expansion. We aim to determine whether Medicaid expansion is associated with healthcare coverage, cancer stage at diagnosis, treatment, and survival among patients with rhinologic cancer.

Study design

Cohort study.

Methods

Patients diagnosed with primary rhinologic malignancies between 2007 to 2016 were extracted from the National Cancer Institute Surveillance, Epidemiology, End Results (SEER) registry. Patients were grouped by diagnosis before and after 2014 (when Medicaid expansion became effective) and whether their state had expanded Medicaid. Multivariable logistic regression controlling for age, sex, race, ethnicity, and income/education was utilized to examine associations between Medicaid expansion/insurance status and stage at diagnosis, treatment, and survival. Overall and disease-specific survival were examined using Kaplan–Meier analysis.

Results

Analysis included 10,164 patients. The proportion of uninsured patients decreased after 2014 (2.4%) compared to before 2014 (4.8%, P < .001). After 2014, patients in nonexpanded states were more likely to be diagnosed with advanced stage disease compared to patients in expanded states (N = 2,364; OR = 1.27, 95% CI 1.01–1.60). Being uninsured in any state was associated with advanced stage disease at diagnosis (OR = 1.75, 95% CI 1.41–2.22) and increased risk of disease-specific death (HR = 1.54, 95% CI 1.32–1.82). Survival measures were not associated with diagnosis before versus after 2014 or Medicaid expansion.

Conclusions

Patients lacking insurance or residing in nonexpanded states may be more likely to present with advanced stage rhinologic cancer. Longitudinal studies should validate these findings.

Level of Evidence

Level 3 Laryngoscope, 2022

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