Low skeletal muscle mass assessed directly from the 3rd cervical vertebra can predict pharyngocutaneous fistula risk after total laryngectomy in the male population

xlomafota13 shared this article with you from Inoreader Low skeletal muscle mass assessed directly from the 3rd cervical vertebra can predict pharyngocutaneous fistula risk after total laryngectomy in the male population Via http://link.springer.com/journal/405,European archives of oto-rhino-laryngology,The European Federation of Oto-Rhino-Laryngological Societies (EUFOS) : affiliated with the German Society for Oto-Rhino Eur Arch Otorhinolaryngol. 2021 Oct 19. doi: 10.1007/s00405-021-07127-3. Online ahead of print. ABSTRACT PURPOSE: Skeletal muscle mass (SMM) loss and sarcopenia have been identified as risk factors for postoperative complications. The aim of this study was to investigate the relationship between pharyngocutaneous fistula (PCF) formation after total laryngectomy (TL) and SMM assessed from a computed tomography image of the 3rd cervical vertebra (C3). METHODS: Retrospective study of 86 male patients who underwent TL between 2013 and 2019 in a single institution. We excluded women from the analysis due to our limited sample. SMM was determined from cross-sectional muscle area (CSMA) measurement at C3 using the ImageJ software. Results were compared with those for the skeletal muscle mass index (SMMI) calculated from the estimated measure at 3rd lumbar vertebra (L3). RESULTS: PCF formation occurred in 21/86 patients. According to the CSMA at a C3 cut-off of 35.5cm2, of 18 patients (20.9%) with low SMM, 9 developed PCFs (50.0%). Among patients with normal SMM (n = 68, 79.1%), 12 developed PCFs (17.6%). The CSMA at C3 was the only variable significantly associated with PCF risk, which was 4.7 times greater in patients with low SMM (p = 0.007). Sarcopenia was more frequent in underweight patients (p = 0.0001), patients undergoing extended surgeries (p = 0.003), or presenting preoperative anaemia (p = 0.009) or hypoalbuminemia (p = 0.027). CONCLUSION: Measuring the CSMA at C3 obtained results equivalent to those obtained by calculating the SMMI at L3, suggesting that direct SMM assessment from C3 is a useful approach to evaluating PCF formation risk after TL. PMID:34665301 | DOI:10.1007/s00405-021-07127-3 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Valproic acid during pregnancy decrease the number of spermatogenic cells and testicular volume in the offspring of mice: Stereological quantification

xlomafota13 shared this article with you from Inoreader Valproic acid during pregnancy decrease the number of spermatogenic cells and testicular volume in the offspring of mice: Stereological quantification Via Cellular and Molecular Biology Histol Histopathol. 2021 Oct 19:18380. doi: 10.14670/HH-18-380. Online ahead of print. ABSTRACT Valproic acid (VPA) is a drug used to treat epilepsy, bipolar disorders and headaches. As a secondary effect, this antiepileptic drug can cause a decrease in androgens and gonadotropins, and dose-dependent testicular defects, such as reduction of testicular weights, sperm motility and degeneration of the seminiferous tubules. In offspring exposed to VPA, its effects have not been evaluated, so the study aimed to determine the morphological effects of the use of VPA along testicular development in mice. 30 adult female BALB/c mice were crossed and divided by age, with embryos of 12.5 days post coitum (dpc), fetuses of 17.5 dpc and male mice 6 weeks postnatal. In each case, the pregnant mouse received 600 mg/kg of VPA, making up the VPA groups, or 0.3 mL of 0.9% physiological solution for the control groups, from the beginning to the end of th e pregnancy, orally.t. A morpho-quantitative analysis was carried out on the gonadal development of the male offspring. In the groups treated with VPA, at all ages studied they had lower testicular volume. At 12.5 dpc, they showed less testicular development in the form of sex cords, with fewer gonocytes and somatic cells. At 17.5 dpc, they presented greater interstitial space, fewer spermatogonial, sustentacular Sertoli, peritubular and interstitial Leydig cells. At 6 weeks postnatal, they presented fewer spermatogonia, pachytene spermatocytes, elongated spermatids, sustentacular Sertoli and interstitial Leydig cells, with statistically significant differences. In conclusion, prenatal exposure to VPA causes histopathological alterations in the offspring of mice in testicular development, from the embryonic stage to 6 weeks postnatal. PMID:34664708 | DOI:10.14670/HH-18-380 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study

xlomafota13 shared this article with you from Inoreader Prognostic factors in children and adolescents with differentiated thyroid carcinoma treated with total thyroidectomy and RAI: a real-life multicentric study Via radioactive iodine Eur J Nucl Med Mol Imaging. 2021 Oct 19. doi: 10.1007/s00259-021-05586-8. Online ahead of print. ABSTRACT PURPOSE: This multicentric study aimed to investigate the main prognostic factors associated with treatment response at 1 year after radioactive iodine therapy (RAIT) and the last disease status in pediatric patients affected by differentiated thyroid carcinoma (DTC). MATERIALS AND METHODS: In the period 1990-2020, all consecutive patients ≤ 18 years from six different c enters were retrospectively included. Patients were classified as low, intermediate, and high risk for persistence/recurrence. The response to RAIT was evaluated and scored 1 year later according to 2015 ATA guidelines. Moreover, at the last follow-up, the disease status was evaluated and dichotomized as no evidence of disease (NED) or persistent disease. RESULTS: Two hundred and eighty-five patients (197 female, 88 male; mean age 14.4 years) were recruited. All, except nine, underwent near-total thyroidectomy followed by RAIT. One-year after first RAIT, 146/276 (53%) patients had excellent response, 37/276 (14%) indeterminate response, and 91/276 (33%) incomplete response. One-year after RAIT, children with excellent response had significantly lower stimulated thyroglobulin (sTg) compared to not excellent group (median sTg 4.4 ng/ml vs 52.5 ng/ml, p < 0.001). ROC curve showed sTg higher than 27.2 ng/ml as the most accurate to predict 1-year treatment response. After a medi an follow-up of 133 months, NED was present in 241 cases (87%) while persistent disease in 35 (13%). At multivariate analysis, sTg and 1-year treatment response categories were both significantly associated with the last disease status (p value 0.023 and < 0.001). CONCLUSIONS: In pediatric DTC, sTg is significantly associated with 1-year treatment response and final outcome. However, 1-year response is the principal prognostic factor able to predict pediatric DTCs outcome. PMID:34664092 | DOI:10.1007/s00259-021-05586-8 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Tumor Microenvironment-Associated Pericyte Populations May Impact Therapeutic Response in Thyroid Cancer

xlomafota13 shared this article with you from Inoreader Tumor Microenvironment-Associated Pericyte Populations May Impact Therapeutic Response in Thyroid Cancer Via radioactive iodine Adv Exp Med Biol. 2021;1329:253-269. doi: 10.1007/978-3-030-73119-9_14. ABSTRACT Thyroid cancer is the most common endocrine malignancy, and aggressive radioactive iodine refractory thyroid carcinomas still lack an effective treatment. A deeper understanding of tumor heterogeneity and microenvironment will be critical to establishing new therapeutic approaches. One of the important influencing factors of tumor heterogeneity is the diversity of cells in the tumor microenvironment. A mong these are pericytes, which play an important role in blood vessel stability and angiogenesis, as well as tumor growth and metastasis. Pericytes also have stem cell-like properties and are a heterogeneous cell population, and their lineage, which has been challenging to define, may impact tumor resistance at different tumor stages. Pericytes are also important stroma cell types in the angiogenic microenvironment which express tyrosine-kinase (TK) pathways (e.g., PDGFR-β). Although TK inhibitors (TKI) and BRAFV600E inhibitors are currently used in the clinic for thyroid cancer, their efficacy is not durable and drug resistance often develops. Characterizing the range of distinct pericyte populations and distinguishing them from other perivascular cell types may enable the identification of their specific functions in the thyroid carcinoma vasculature. This remains an essential step in developing new therapeutic strategies. Also, assessing whether thyroid tumors hold i mmature and/or mature vasculature with pericyte populations coverage may be key to predicting tumor response to either targeted or anti-angiogenesis therapies. It is also critical to apply different markers in order to identify pericyte populations and characterize their cell lineage. This chapter provides an overview of pericyte ontogenesis and the lineages of diverse cell populations. We also discuss the role(s) and targeting of pericytes in thyroid carcinoma, as well as their potential impact on precision targeted therapies and drug resistance. PMID:34664244 | DOI:10.1007/978-3-030-73119-9_14 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Support Vector Machine-based Spontaneous Intracranial Hypotension Detection on Brain MRI

xlomafota13 shared this article with you from Inoreader Support Vector Machine-based Spontaneous Intracranial Hypotension Detection on Brain MRI Via leak of cerebrospinal fluid Clin Neuroradiol. 2021 Oct 19. doi: 10.1007/s00062-021-01099-x. Online ahead of print. ABSTRACT BACKGROUND AND PURPOSE: To develop a fully automatic algorithm for the magnetic resonance imaging (MRI) identification of patients with spontaneous intracranial hypotension (SIH). MATERIAL AND METHODS: A support vector machine (SVM) was trained with structured reports of 140 patients with clinically suspected SIH. Venous sinuses and basal cisterns were segmented on contrast-enhanced T1-weighted MPRAGE (Magnetization Prepared-Rapid Gradient Echo) sequences using a convolutional neural network (CNN). For the segmented sinuses and cisterns, 56 radiomic features were extracted, which served as input data for the SVM. The algorithm was validated with an independent cohort of 34 patients with proven cerebrospinal fluid (CSF) leaks and 27 patients who had MPRAGE scans for unrelated reasons. RESULTS: The venous sinuses and the suprasellar ciste rn had the best discriminative power to separate SIH and non-SIH patients. On a combined score with 2 points, mean SVM score was 1.41 (±0.60) for the SIH and 0.30 (±0.53) for the non-SIH patients (p < 0.001). Area under the curve (AUC) was 0.91. CONCLUSION: A fully automatic algorithm analyzing a single MRI sequence separates SIH and non-SIH patients with a high diagnostic accuracy. It may help to consider the need of invasive diagnostics and transfer to a SIH center. PMID:34665277 | DOI:10.1007/s00062-021-01099-x View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Rethinking Low-Risk Papillary Thyroid Cancers < 1cm (Papillary Microcarcinomas): An Evidence Review for Recalibrating Diagnostic Thresholds and/or Alternative Labels

xlomafota13 shared this article with you from Inoreader Rethinking Low-Risk Papillary Thyroid Cancers < 1cm (Papillary Microcarcinomas): An Evidence Review for Recalibrating Diagnostic Thresholds and/or Alternative Labels Via liebertpub1 Thyroid, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

DNA Methylation Patterns in the HLA-DPB1 and PDCD1LG2 Gene Regions in Patients with Autoimmune Thyroiditis from Different Water Iodine Areas

xlomafota13 shared this article with you from Inoreader DNA Methylation Patterns in the HLA-DPB1 and PDCD1LG2 Gene Regions in Patients with Autoimmune Thyroiditis from Different Water Iodine Areas Via liebertpub1 Thyroid, Ahead of Print. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Repurposing of posaconazole as a hedgehog/SMO signaling inhibitor for embryonal rhabdomyosarcoma therapy

xlomafota13 shared this article with you from Inoreader Repurposing of posaconazole as a hedgehog/SMO signaling inhibitor for embryonal rhabdomyosarcoma therapy Via American Journal of Cancer Research Am J Cancer Res. 2021 Sep 15;11(9):4528-4540. eCollection 2021. ABSTRACT Posaconazole (POS) is a novel antifungal agent, which has been repurposed as an anti-tumor drug for its potential inhibition of Hedgehog signaling pathway. Hedgehog pathway is reported to be abnormally activated in embryonal rhabdomyosarcoma (ERMS), this study aimed to reveal whether POS could inhibit Hedgehog signaling pathway in ERMS. Following POS treatment, XTT viability assay was used to determine the cell proliferation of ERMS cell lines. Protein changes related to Hedgehog signaling, cell cycle and autophagy were detected by Western blot. The cell cycle distribution was analyzed by flow cytometry. Moreover, a subcutaneous tumor mouse model of ERMS was established to assess the anti-tumor effect of POS. POS was found to inhibit tumor progression by inducing G0/G1 arrest and autophagy of RD, RMS-YM, and KYM-1 cells dose-dependently. Western blot demonstrated that POS downregulated the expressions of SMO, Gli1, c-Myc, CDK4, and CDK6, while upregulated the expressions of autophagy-related proteins. Immunofluorescence microscopy revealed a significant increase of LC3B puncta in POS-treated ERMS cells. Furthermore, POS treatment led to a significant inhibition of tumor growth in mice bearing ERMS. Our findings could provide a theoretical basis and have important clinical implications in developing POS as a promising agent against ERMS by targeting Hedgehog pathway. PMID:34659903 | PMC:PMC8493378 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Current methodologies to detect circulating tumor cells: a focus on ovarian cancer

xlomafota13 shared this article with you from Inoreader Current methodologies to detect circulating tumor cells: a focus on ovarian cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Sep 15;11(9):4111-4126. eCollection 2021. ABSTRACT Identification of circulating tumor cells (CTC) in liquid biopsies opens a window of opportunities for the optimization of clinical management of oncologic patients. In ovarian cancer (OC), which involves atypical routes of metastatic spread, CTC analyses may also offer novel insights about the mechanisms behind malignant progression of the disease. However, current methodologies struggle to precisely define CTC number in the peripheral blood of OC patients, and the isolation of viable cells for further characterization is still challenging. The biggest limitation is the lack of methodological standardization for OC CTC detection, preventing comprehensive definition of their clinical potential required for the transfer to practice. Here we describe and compare methods for CTC analysis that have been implemented for OC thus far, discussing pros, cons and improvemen ts needed. We identify biophysical separation approaches as optimal for CTC enrichment. On the other hand, the identification of specific tumor antigens or gene transcripts, despite displaying drawbacks related to tumor heterogeneity, still remains the best approach for OC CTC detection. PMID:34659879 | PMC:PMC8493391 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Anti-cancer effects of Hederoside C, a pentacyclic triterpene saponin, through the intrinsic apoptosis and STAT3 signaling pathways in osteosarcoma

xlomafota13 shared this article with you from Inoreader Anti-cancer effects of Hederoside C, a pentacyclic triterpene saponin, through the intrinsic apoptosis and STAT3 signaling pathways in osteosarcoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Sep 15;11(9):4541-4550. eCollection 2021. ABSTRACT Natural compounds have emerged as an approach in cancer therapy. Pulsatilla koreana Nakai is used as a traditional medicinal plant that found throughout China and Korea. However, anti-cancer effects of Hederoside C (HedC) isolated from P. koreana has not been investigated in osteosarcoma. The present study aimed to demonstrate anti-cancer functions of HedC against human osteosarcoma cells. Herein, we found that HedC suppressed the proliferation of MG63 cells and U2OS cells in the dose- and time-dependent manner, and caused intrinsic apoptosis pathways as evidenced by morphological changes, TUNEL-positive cells, cleaved-PARP, and cleaved-caspase 9 and 3. HedC increased p53, Bax, and p21, whereas HedC reduced Bcl-2. HedC-mediated apoptosis was accompanied by decreases in the mitogen-activated protein kinases (MAPKs) and STAT3 phosphorylation. Wound hea ling and Boyden chamber assays also showed the anti-metastatic effects of HedC by suppressing migration and invasion. In addition, the anti-cancer effects of HedC were observed in in vivo xenograft mice model, and HedC treatment induced the decreased PCNA and p-STAT3 as well as the increased p53 and cleaved caspase-3. Taken together, our results provide evidence that HedC might be an attractive therapeutic strategy against osteosarcoma. PMID:34659904 | PMC:PMC8493407 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Capsaicin exerts therapeutic effects by targeting tNOX-SIRT1 axis and augmenting ROS-dependent autophagy in melanoma cancer cells

xlomafota13 shared this article with you from Inoreader Capsaicin exerts therapeutic effects by targeting tNOX-SIRT1 axis and augmenting ROS-dependent autophagy in melanoma cancer cells Via American Journal of Cancer Research Am J Cancer Res. 2021 Sep 15;11(9):4199-4219. eCollection 2021. ABSTRACT Although considered a sporadic type of skin cancer, malignant melanoma has regularly increased internationally and is a major cause of cancer-associated death worldwide. The treatment options for malignant melanoma are very limited. Accumulating data suggest that the natural compound, capsaicin, exhibits preferential anticancer properties to act as a nutraceutical agent. Here, we explored the underlying molecular events involved in the inhibitory effect of capsaicin on melanoma growth. The cellular thermal shift assay (CETSA), isothermal dose-response fingerprint curves (ITDRFCETSA), and CETSA-pulse proteolysis were utilized to confirm the direct binding of capsaicin with the tumor-associated NADH oxidase, tNOX (ENOX2) in melanoma cells. We also assessed the cellular impact of capsaicin-targeting of tNOX on A375 cells by flow cytometry and protein analy sis. The essential role of tNOX in tumor- and melanoma-growth limiting abilities of capsaicin was evaluated in C57BL/6 mice. Our data show that capsaicin directly engaged with cellular tNOX to inhibit its enzymatic activity and enhance protein degradation capacity. The inhibition of tNOX by capsaicin was accompanied by the attenuation of SIRT1, a NAD+-dependent deacetylase. The suppression of tNOX and SIRT1 then enhanced ULK1 acetylation and induced ROS-dependent autophagy in melanoma cells. Capsaicin treatment of mice implanted with melanoma cancer cells suppressed tumor growth by down-regulating tNOX and SIRT1, which was also seen in an in vivo xenograft study with tNOX-depleted melanoma cells. Taken together, our findings suggest that tNOX expression is important for the growth of melanoma cancer cells both in vitro and in vivo, and that inhibition of the tNOX-SIRT1 axis contributes to inducting ROS-dependent autophagy in melanoma cells. PMID :34659883 | PMC:PMC8493390 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.