ST3GAL2 knock-down decreases tumoral character of colorectal cancer cells in vitro and in vivo

xlomafota13 shared this article with you from Inoreader ST3GAL2 knock-down decreases tumoral character of colorectal cancer cells in vitro and in vivo Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):280-302. eCollection 2022. ABSTRACT Tumor cells have a modified glycosylation profile that promotes their evolution and/or their maintenance in the tumor. Sialylation is a type of glycosylation that is often altered in cancers. RNA-Seq database analysis revealed that the sialyltransferase gene ST3GAL2 is significantly overexpressed at all stages of colorectal cancer (CRC). ST3GAL2 sialylates both glycoproteins and glycolipids. The aim of this work was to investigate the involvement of ST3GAL2 in CRC. Using the HT29 tumor cell line derived from a stage II of CRC, we decreased the expression of ST3GAL2 by specific shRNA, and then characterized these cells by performing functional tests. We found that ST3GAL2 knock down (KD) significantly decreases tumor cell proliferation, cell migration and invasiveness properties in vitro. The cell cycle of these cells is affected with a ch ange in cell cycle distribution and an increase of cell apoptosis. The effect of ST3GAL2 KD was then studied in vivo, following xenografts into nude mice, in which the tumor progression was significantly reduced. This work demonstrates that ST3GAL2 is a major player in the behavior of colorectal tumor cells, by modifying the sialylation state of glycoproteins and glycolipids which remain to be specifically identified. PMID:35141018 | PMC:PMC8822282 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Trends in Subglottic Stenosis Management: Resource Utilization and Pediatric Otolaryngology Training

xlomafota13 shared this article with you from Inoreader Trends in Subglottic Stenosis Management: Resource Utilization and Pediatric Otolaryngology Training Via The Laryngoscope Objectives/Hypothesis The role for endoscopic management in children with subglottic stenosis (SGS) has grown, but there are no data on resource utilization or the impact on surgical training in pediatric otolaryngology. This study hypothesizes that this shift has increased resource utilization and has impacted surgical training by shifting the focus toward more endoscopic techniques. Study Design Retrospective database review. Methods The Kids' Inpatient Database for 2003, 2006, 2009, and 2012 was queried for admissions with the diagnosis of SGS. Surgical caseload was studied using the Accreditation Council for Graduate Medical Education Accreditation data system for 2010 to 2017. Results Admissions with SGS remained constant between 2003 and 2012. Hospital charges per admission did not change between 2003 and 2009 but increased in 2012. Tracheostomy decreased from 10.5% of admissions in 2003 to 6.8% in 2012. The percentage requiring repair of the larynx did not change; other operations on the larynx increased from 4.5% in 2003 to 11.6% in 2012. The median number of laryngoplasties performed per trainee decreased from 14 to nine between 2010 and 2017, whereas the number of laryngoscopy with intervention procedures increased from 34 to 56. Conclusions The evolution of SGS management appears to have led to a decrease in tracheostomy and an increase in certain procedures that may include endoscopic procedures. Recently, there has been a shift in airway surgical training, with trainees logging less open laryngotracheoplasty and more interventional laryngoscopy. Although these trends cannot be directly linked, the changes in trainee surgical experience may be justified by the decrease in larger open procedures and associated resource utilization. Level of Evidence 2c Laryngoscope, 132:S1–S9, 2022 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Analysis of Xinjiang HPV16 L1 gene polymorphisms: a newly developed, low-cost enzyme-linked immunosorbent assay

xlomafota13 shared this article with you from Inoreader Analysis of Xinjiang HPV16 L1 gene polymorphisms: a newly developed, low-cost enzyme-linked immunosorbent assay Via International Journal of Clinical and Experimental Pathology Int J Clin Exp Pathol. 2022 Jan 15;15(1):1-10. eCollection 2022. ABSTRACT BACKGROUND: Xinjiang, China shows the world's highest incidence and mortality rates of cervical cancer. Due to limited conditions available for medical examination, hybrid capture 2 (HC2) and other detection methods are used rarely, and early screening for human papillomavirus (HPV) cannot be carried out. Therefore, we established a double-antibody sandwich (DAS)-enzyme-linked immunosorbent assay (ELISA) based on a polymorphism of the Xinjiang HPV16 L1 strain (KU721788). METHODS: According to the conserved sequence and specific epitope of Xinjiang strain HPV16 L1, we prepared two anti-HPV16 L1 monoclonal antibodies and combined them to construct a DAS-ELISA. Detection conditions for the DAS-ELISA were optimized, and HC2 was used as the control to verify the specificity, repeatability and coincidence detection of the DAS-ELISA. RESULTS: The optimized c onditions for the DAS-ELISA were: dilution of the capture antibody was 1:100; the enzyme-labelled antibody was 1:10; the sample reaction time was 45 min; the enzyme-labelled antibody was applied for 40 min, and the substrate color development time was 15 min. The quality of the DAS-ELISA for the detection of HPV 16 was very high, and there was no significant difference when compared with HC2. CONCLUSION: The DAS-ELISA developed on the basis of the Xinjiang strain (KU721788) polymorphism possesses the advantages of a detection rate similar to that for the HC2 assay currently used clinically, but it is more convenient operationally and at lower cost. DAS-ELISA is thus easier to implement for cervical cancer screening in economically depressed areas. PMID:35145578 | PMC:PMC8822206 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Human telomerase reverse transcriptase protein expression is associated with survival in patients with oral squamous cell carcinoma Via International Journal of Clinical and Experimental Pathology 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Understanding Public Perceptions Regarding Cochlear Implant Surgery in Adults

xlomafota13 shared this article with you from Inoreader Understanding Public Perceptions Regarding Cochlear Implant Surgery in Adults Via leak of cerebrospinal fluid 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Selected by bioinformatics and molecular docking analysis, Dhea and 2–14,15-Eg are effective against cholangiocarcinoma Via Head and neck cancers 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. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Vertical rectus abdominis myocutaneous flap to reconstruct thigh and groin defects: A retrospective cohort and systematic review Via Journal of plastic, reconstructive & aesthetic surgery : JPRAS 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

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

xlomafota13 shared this article with you from Inoreader Impact of Medicaid Expansion on Rhinologic Cancer Presentation, Treatment, and Outcomes Via The Laryngoscope 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 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Two‐Incision Approach for Hypoglossal Nerve Stimulator Placement: A Single Institution Assessment

xlomafota13 shared this article with you from Inoreader Two‐Incision Approach for Hypoglossal Nerve Stimulator Placement: A Single Institution Assessment Via The Laryngoscope Objective(s) Upper airway stimulator (UAS) placement is a treatment for obstructive sleep apnea (OSA) with few complications and low morbidity. UAS placement has traditionally been performed using a three-incision approach, however, it has been implanted using a two-incision approach. This approach could significantly decrease operation time without a difference in postoperative complications, demonstrating its safety and feasibility for UAS placement. The objective was to assess operative time and complication rate in the two-incision approach for UAS placement compared to the three-incision approach. Study Design Retrospectively reviewed. Methods Patients who underwent UAS placement using the two- or three-incision approach at a single academic institution from November 2014 to June 2021 were retrospectively reviewed. The two-incision approach did not include the incision at the mid-axillary line. Main outcome measures included operation time and complication rates. Results Three-hundred forty-eight patients underwent UAS placement. The three-incision approach demonstrated an average operation time of 143.3 minutes whereas the two-incision approach averaged 129.4 minutes (P < .001). There was no significant difference in rate of postoperative complications between the two- and three-incision cohorts including pneumothorax (0% vs. 0.4%, P > .99), patient-reported discomfort (5.6% vs. 6.5%, P > .99), activity restriction (0% vs. 1.4%, P > .50), and incisional pain (0.0% vs. 1.0%, P > .99). No patients experienced incision site bleeding or infection. The two-incision approach was associated with decreased rate of revision surgery (0.0% vs. 5.4%, P = .048). Conclusion The UAS two-incision approach proved to have a significantly shorter operative time without an increase in complications as compared to the three-incision approach. This approach is a safe and feasible option. Level of Evidence III Laryngoscope, 2022 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Management of postradiation late hemorrhage following treatment for HPV‐positive oropharyngeal squamous cell carcinoma

xlomafota13 shared this article with you from Inoreader Management of postradiation late hemorrhage following treatment for HPV‐positive oropharyngeal squamous cell carcinoma Via Head & Neck Abstract Background Acute oropharyngeal hemorrhage is a serious complication for patients with oropharyngeal squamous cell carcinoma (OPSCC), particularly in patients with a history of radiation therapy (RT). Methods Retrospective case series from at a tertiary care center for treated patients with HPV-positive OPSCC presenting with oropharyngeal hemorrhage. Results Median time from completion of chemoradiation to first hemorrhagic event was 186 days (range 66–1466 days). Seven patients (58%) required intervention to secure their airway. All patients were evaluated for endovascular intervention, six (50%) were embolized. Eight patients (67%) had a second hemorrhagic event; median time to second bleed was 22 days (range 3–90 days). Conclusions Acute oropharyngeal hemorrhage is a sequelae following treatment for HPV-positive OPSCC. The majority of bleeds occurred within a year of completion of treatment. While more research is needed to determine optimal treatment paradigms, endovascular intervention should be considered, even if noninvasive imaging does not demonstrate active bleeding. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Exploiting induced vulnerability to overcome PARPi resistance and clonal heterogeneity in BRCA mutant triple-negative inflammatory breast cancer

xlomafota13 shared this article with you from Inoreader Exploiting induced vulnerability to overcome PARPi resistance and clonal heterogeneity in BRCA mutant triple-negative inflammatory breast cancer Via American Journal of Cancer Research Am J Cancer Res. 2022 Jan 15;12(1):337-354. eCollection 2022. ABSTRACT Acquired resistance and clonal heterogeneity are critical challenges in cancer treatment, and the lack of effective computational tools hampers the discovery of new treatments to overcome resistance. Using high-throughput transcriptomic databases of compound perturbation profiles, we have developed a bioinformatic strategy for identifying candidate drugs to overcome resistance with combinatorial therapy. We devised this strategy during an investigation into the acquired resistance against PARP inhibitors (PARPi) in a triple-negative inflammatory breast cancer cell line. In this study, we derived multiple PARPi-resistant clones and characterized their transcriptomic adaptations compared to the parental clone. The transcriptomes of the resistant clones showed substantial heterogeneity, highlighting the importance of characterizing multiple clones from the same tumour. Surprisingly, we found that these transcriptomic changes may not actually confer PARPi resistance, but they may nevertheless induce a shared secondary vulnerability. By modeling our data in relation to transcriptomic perturbation profiles of compounds, we uncovered deficiencies in Ras signaling that resulted from transcriptional adaptation to long-term PARPi treatment across multiple resistant clones. Due to these induced deficiencies, we predicted that the resistant clones would be sensitive to pharmacological reinforcement of PARPi-induced transcriptional adaptation. We then experimentally validated this predicted vulnerability that is shared by multiple resistant clones. Our results thus provide a promising paradigm for integrating transcriptomic data with compound perturbation profiles in order to identify drugs that can exploit an induced vulnerability and overcome therapeutic resistance, thus providing another strategy towards precision oncology. PMID:35141022 | PMC:PMC8822293 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.