Genetically predicted high circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 increase the risks of soft tissue sarcoma

xlomafota13 shared this article with you from Inoreader Genetically predicted high circulating insulin-like growth factor-1 and insulin-like growth factor binding protein-3 increase the risks of soft tissue sarcoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3980-3989. eCollection 2021. ABSTRACT Insulin growth factor-1 (IGF-1) plays important roles in carcinogenesis. Previous studies have linked circulating IGF-1 and its main binding protein, insulin-like growth factor-binding protein-3 (IGFBP-3), to cancer risks. However, no study has been conducted in soft tissue sarcoma (STS). In this study, we investigated the relationship of genetically predicted circulating IGF-1 and IGFBP-3 with STS risks. Recent large genome-wide association studies (GWAS) have identified 413 single nucleotide polymorphisms (SNPs) associated with IGF-1 and 4 SNPs associated with IGFBP-3. We genotyped these SNPs in 821 patients and 851 healthy controls. We constructed weighted genetic risk scores (GRS) to predict circulating IGF-1 and IGFBP-3. We determined the associations of individual SNPs and GRS with the risks of STS using multivariate logistic regression analysis. We found hi gh genetically predicted circulating IGF-1 and IGFBP-3 were both associated with increased STS risks. Dichotomized at the median values of IGF-1 and IGFBP-3 in controls, individuals with high level of IGF-1 exhibited a 27% increased risk of STS (odds ratio [OR]=1.27, 95% confidence interval [CI]=1.04-1.54, P=0.017), whereas the OR for high IGFBP-3 was 1.45 (95% CI=1.20-1.77, P<0.001). Interestingly, the significant association between IGFBP-3 and STS risk was only evident in women (OR=1.88, 95% CI=1.42-2.49, P<0.001), but not in men (OR=1.00, 95% CI=0.75-1.33, P=0.992). In stratified analyses by major STS subtypes, the strongest associations were observed in angiosarcoma for IGF-1, leiomyosarcoma for IGFBP-3, and gastrointestinal stromal tumors for IGFBP-3 in women. In conclusion, high circulating IGF-1 and IGFBP-3 levels were both associated with increased STS risks. PMID:34522462 | PMC:PMC8414386 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis

xlomafota13 shared this article with you from Inoreader Downregulation of NEAT1 sensitizes gemcitabine-resistant pancreatic cancer cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3841-3856. eCollection 2021. ABSTRACT Chemoresistance is a major cause of treatment failure in pancreatic cancer (PC). It has been demonstrated that epithelial-to-mesenchymal transition (EMT) is closely related to drug resistance in PC; however, the underlying mechanisms are not yet fully understood. Recently found evidence has suggested that nuclear-enriched abundant transcript 1 (NEAT1) is involved in the development of chemoresistance. However, the role and mechanism of NEAT1 in PC gemcitabine resistance remain unknown. In the present study, we first established two independent gemcitabine-resistant (GR) PC cell lines, PANC-1/GR and SW1990/GR. We found that GR cells displayed markedly enhanced migration and invasion abilities, decreased expression of E-cadherin, and upregulation of N-cadherin, Vimentin, Snail, ZEB1, and ZEB2. Our findings suggested that downregulation of NEAT1 enhanced the sensitiv ity of GR cells to gemcitabine by reversing the EMT process. Mechanistically, NEAT1 mediates ZEB2 mRNA expression through sponging miR-506-3p. Downregulation of NEAT1 can reverse the EMT process of GR PC cells by reducing the expression of ZEB2, thus enhancing the sensitivity of GR PC cells to gemcitabine. These findings were further confirmed in a nude mouse xenograft model. Taken together, downregulation of NEAT1 sensitized the GR PC cells to gemcitabine through modulation of the miR-506-3p/ZEB2/EMT axis. These results provide the novel evidence for understanding the function and molecular mechanism of NEAT1, and a new direction for improving the chemotherapeutic effects in PC. PMID:34522453 | PMC:PMC8414385 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Diagnosis of 'cribriform' prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations

xlomafota13 shared this article with you from Inoreader Diagnosis of "cribriform" prostatic adenocarcinoma: an interobserver reproducibility study among urologic pathologists with recommendations Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3990-4001. eCollection 2021. ABSTRACT Accurate diagnosis of cribriform Gleason pattern 4 (CrP4) prostate adenocarcinoma (PCa) is important due to its independent association with adverse clinical outcomes and as a growing body of evidence suggests that it impacts clinical decision making in PCa management. To identify reproducible features for diagnosis of CrP4, we assessed interobserver agreement among 27 experienced urologic pathologists of 60 digital images from 44 radical prostatectomies (RP) that represented a broad spectrum of potential CrP4. The following morphologic features were correlated with the consensus diagnosis (defined as 75% agreement) for each image: partial vs. transluminal glandular bridging, intraglandular stroma, <12 vs. ≥12 lumina, well vs. poorly formed lumina, mucin (mucinous fibroplasia, extravasation, or extracellular pool), size (compared to benign glands and number o f lumina), number of attachments with gland border by tumor cells forming a "glomeruloid-like" pattern, a clear luminal space along the periphery of gland occupying <50% of glandular circumference, central nerve, dense (cell mass occupying >50% of luminal space) vs. loose, and regular vs. irregular contour. Interobserver reproducibility for the overall diagnostic agreement was fair (k=0.40). Large CrP4 had better agreement (k=0.49) compared to small CrP4 (k=0.40). Transluminal bridging, dense cellular proliferation, a clear luminal space along the periphery of gland occupying <50% of gland circumference, lack of intraglandular mucin, and lack of contact between the majority of intraglandular cells with stroma were significantly associated with consensus for CrP4. In contrast, partial bridging, majority of intraglandular cells in contact with stroma, mucinous fibroplasia, only one attachment to the gland border by tumor cells forming a "glomeruloid-like" pattern, and a clear luminal space along the periphery of gland accounting for >50% of the glandular circumference were associated with consensus against CrP4. In summary, we identified reproducible morphological features for and against CrP4 diagnosis, which could be used to refine and standardize the diagnostic criteria for CrP4. PMID:34522463 | PMC:PMC8414383 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A review of the endocrine resistance in hormone-positive breast cancer

xlomafota13 shared this article with you from Inoreader A review of the endocrine resistance in hormone-positive breast cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Aug 15;11(8):3813-3831. eCollection 2021. ABSTRACT Hormone-positive breast cancer (BC) is a unique heterogeneous disease with a favorable prognosis compared to other types of breast cancer. As tumor biology influences the prognosis and clinical treatment, a deep understanding of how the molecular mechanisms regulate hormone sensitivity or resistance is critical in improving the efficacy and overcoming the endocrine resistance. This article comprehensively reviews the endocrine resistance in hormone-positive BC from a molecular and genetic perspective, encompassing the updated treatment and developing direction. This review includes the mechanisms of hormone resistance, which vary from epigenetic changes, crosstalk between signaling networks, cell cycle aberrance, and even change in the tumor microenvironment (TME) or stem cell. These mechanisms may contribute to treatment resistance. Current targeted therapy for h ormone-resistant tumors includes PI3K/AKT/mTOR and cdk4/6 inhibitors. Several relevant pathways, biomarkers, and predictor genes have also been identified. Immunotherapy so far has a relatively less crucial role in hormone-positive than in triple-negative BC. Furthermore, the methodology to identify the PDL1 is not standardized. In a molecule and gene study, next-generation sequencing with circulating tumor DNA (ctDNA) has recently appeared as a sensitive and minimally invasive tool worth investigating. PMID:34522451 | PMC:PMC8414389 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Phonosurgery Training in Human Larynx Preserved with Thiel’s Embalming Method

xlomafota13 shared this article with you from Inoreader Phonosurgery Training in Human Larynx Preserved with Thiel's Embalming Method Via O.R.L. Journal for oto-rhino-laryngology and its borderlands Background: To describe the suitability of larynges preserved with Thiel's embalming method for phonosurgery training. Methods: A training model for phonosurgery techniques simulating vocal pathology and glottal insufficiency is developed to compare and evaluate the perception of embalmed vocal cords through a voluntary and anonymous survey rated on a scale of 1–5. A total of 10 residents and young otolaryngologists participated in the surgical training in phon osurgery. Results: Ten larynges preserved in formalin and 10 Thiel's embalmed larynges were used for the investigation. Phonosurgery procedures were performed following microflap and injection laryngoplasty techniques. The larynges preserved with Thiel's method demonstrated vocal cords that maintain their pliability and good tissue quality allowing a sensation of realism compared to the living body and providing suitable conditions for realistic laryngeal training. Participants held a positive experience, believed them to be useful and that these models of embalmed larynges were similar to the clinical setting and improved skills and confidence in performing phonosurgery. Conclusions: The human larynges embalmed with Thiel's method maintain the pliability of the vocal cords, thus representing a unique model to practice and reproduce training for endolaryngeal procedures without the risks of contamination, anatomical variation, or rigidity of other m odels. ORL View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Post-dural puncture pseudomeningocele ('arachnoid bleb'): An underrecognized etiology of spontaneous intracranial hypotension symptomatology

xlomafota13 shared this article with you from Inoreader Post-dural puncture pseudomeningocele ("arachnoid bleb"): An underrecognized etiology of spontaneous intracranial hypotension symptomatology Via leak of cerebrospinal fluid Clin Imaging. 2021 Sep 7;80:377-381. doi: 10.1016/j.clinimag.2021.08.023. Online ahead of print. ABSTRACT Spontaneous intracranial hypotension (SIH) is an important secondary cause of a persistent headache syndrome, classically presenting as sudden onset debilitating positional headaches related to reduced intracranial cerebrospinal fluid (CSF) volume. Current understanding of SIH pathogenesis recognizes three underlying etiologies: dural tear, meningeal diverticulum, and CSF-venous fistula, with a fourth broad category of indeterminate/unknown etiologies. Post-dural puncture headache (PDPH) is a well-known and common complication of dural puncture, typically remitting spontaneously within two weeks of onset or with autologous epidural blood patch, though with some patients developing complex and difficult to manage chronic PDPH. Herein, we present a case of chronic PDPH resulting in SIH symptomatology secondary to a post-dural puncture pseud omeningocele, or "arachnoid bleb," successfully treated with curative surgical intervention. Increasing awareness of additional potential etiologies of SIH symptomatology will allow for improved detection for targeted definitive therapy, ultimately improving patient outcomes including quality of life in this debilitating and difficult to manage secondary headache syndrome. PMID:34517304 | DOI:10.1016/j.clinimag.2021.08.023 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comparing the efficacy of peritonsillar injection of bupivacaine and intravenous acetaminophen on post-tonsillectomy pain in children

xlomafota13 shared this article with you from Inoreader Comparing the efficacy of peritonsillar injection of bupivacaine and intravenous acetaminophen on post-tonsillectomy pain in children 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 Sep 14. doi: 10.1007/s00405-021-07049-0. Online ahead of print. ABSTRACT INTRODUCTION: In this study we aimed to compare the efficacy of peritonsillar injection of bupivacaine and intravenous acetaminophen on post-tonsillectomy pain in children. MATERIALS AND METHODS: In this randomized double-blind clinical trial study 60 children with ASA = I-II aged 5-12 years undergoing tonsillectomy were involved. The first group received bupivacaine at a dose of 0.1 mg/kg that was injected into the bed and the anterior crease of each tonsil. The second group was given intravenous acetaminophen at a dose of 12.5 mg/kg. The patient's pain score at 10, 30, 60 min after his/her admission to recovery room and 120, 240 and 360 min after the surgery was recorded using CHEOPS. Patient's sedation score, nausea or vomiting, the time of the first request for analgesia and the time of starting oral feeding were recorded and analyzed too. RESULTS: There was no significant differences in mean age (p value = 0.44), gender (p value = 0.79), weight (p value = 0.36), height (p value = 0.17), anesthesia duration (p.value = 0.85) and surgery duration (p.value = 0.73) between two groups. Postoperative pain was significantly less in the bupivacaine group at 240 and 360 min after the surgery. The mean sedation score was higher in the bupivacaine group but not significantly. There was no significant difference between groups regarding the nausea and vomiting, the first analgesics request time and the start time of oral feeding. CONCLUSION: According to the results of the present study, since administration of peritonsillar bupivacaine compared to acetaminophen had a better effect on managing postoperative pain and improving sedation and also since no complications were reported; therefore, peritonsillar infiltration with bupivacaine is suggested for pediatric tonsillectomy. PMID:34518906 | DOI:10.1007/s00405-021-07049-0 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The impact of comorbid allergic airway disease on the severity and mortality of COVID-19: a systematic review and meta-analysis

xlomafota13 shared this article with you from Inoreader The impact of comorbid allergic airway disease on the severity and mortality of COVID-19: a systematic review and meta-analysis 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 Sep 14. doi: 10.1007/s00405-021-07072-1. Online ahead of print. ABSTRACT PURPOSE: To analyze the impact of AAD on the severity and mortality of COVID-19 patients and compare clinical outcomes between patients with and without AAD. METHODS: In the systematic review and meta-analysis, we searched PubMed, Embase, Web of Science for studies reporting allergic rhinitis, asthma prevalence in COVID-19 patients and compared clinical outcomes, and excluded duplicate publications, reviews, comments, single or few cases reports (< 100 cases). We determined the pooled effect estimates using random effect model. RESULTS: Thirty-four studies (345,091) were finally included for the meta-analysis. On the basis of 32 studies (337,821) involving with the severity of COVID-19, we did not find significant association between AAD and the severity of COVID-19 (p = 0.35, OR 1.10, 95% CI 0.90-1.35). Subgroup anal ysis indicated there was no the variability in the prevalence of AAD among COVID-19 patients in different study designs, disease categories, countries, the definition of severity, and population size of AAD. Based on 21 studies (306,331) involving with the mortality of COVID-19, AAD was significantly associated with the decreased mortality of COVID-19 (p < 0.05, OR 0.83, 95% CI 0.70-0.99). The subgroup analysis showed AAD was not associated with the mortality of COVID-19 in different countries or regions. Based on the population size of AAD, we found AAD within 100 cases was not associated with the mortality of COVID-19 (p = 0.63, OR 1.15, 95% CI 0.65-2.03). Moreover, study design was possible heterogeneity source as the heterogeneity I2 was reduced to 0 in prospective studies. CONCLUSION: The preexisting AAD was not inclined to deteriorate the course of COVID-19. The prevalence of AAD was not associated with the severity of COVD-19 patients and inclined to be si gnificantly associated with the decreased mortality risk of COVID-19. PMID:34519838 | DOI:10.1007/s00405-021-07072-1 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The prognostic value of before treatment neutrophil-to-lymphocyte ratio in nasopharyngeal carcinoma

xlomafota13 shared this article with you from Inoreader The prognostic value of before treatment neutrophil-to-lymphocyte ratio in nasopharyngeal carcinoma 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 Sep 12. doi: 10.1007/s00405-021-07070-3. Online ahead of print. ABSTRACT OBJECTIVE: The aim of this analysis was to evaluate the prognostic significance of inflammatory biomarkers (NLR, dNLR, PLR and LMR) in NPC patients. METHODS: This was a retrospective analysis of 111 NPC patients from January 2013 and December 2016. Receiver-operating characteristic (ROC) curve was plotted to determine the cut-off values of these inflammatory biomarkers. Univariate analysis and multivariate Cox regression model were used to evaluate the association between these parameters and progression-free survival (PFS) and overall survival (OS). RESULTS: The optimal critical value of NLR was 2.02, by which cases were divided into high NLR group (NLR ≥ 2.02) and low NLR group (NLR < 2.02). The elevated NLR was significantly associated with decreased OS (P = 0.009) and remained significant in multivariate analysi s (HR 8.48, 95% CI 1.69-42.46, P = 0.009). CONCLUSIONS: The before treatment NLR may be an independent prognostic biomarker for OS in patients with NPC. NLR, dNLR and PLR might be a useful complement to TNM staging in the prognosis evaluation of NPC patients. PMID:34510259 | DOI:10.1007/s00405-021-07070-3 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Influences of GABAergic Inhibition in the Dorsal Medulla on Contralateral Swallowing Neurons in Rats

xlomafota13 shared this article with you from Inoreader Influences of GABAergic Inhibition in the Dorsal Medulla on Contralateral Swallowing Neurons in Rats Via The Laryngoscope Objectives We aimed to examine the effect of unilateral inhibition of the medullary dorsal swallowing networks on the activities of swallowing-related cranial motor nerves and swallowing interneurons. Methods In 25 juvenile rats, we recorded bilateral vagal nerve activity (VNA) as well as unilateral phrenic and hypoglossal activity (HNA) during fictive swallowing elicited by electrical stimulation of the superior laryngeal nerve during control and following microinjection of the GABA agonist muscimol into the caudal dorsal medulla oblongata in a perfused brainstem preparation. In 20 animals, swallowing interneurons contralateral to the muscimol injection side were simultaneously recorded extracellularly and their firing rates were analyzed during swallowing. Results Integrated VNA and HNA to the injection side decreased to 49.0 ± 16.6% and 32.3 ± 17.9%, respectively. However, the VNA on the uninjected side showed little change after muscimol injection. Following local inhibition, 11 out of 20 contralateral swallowing interneurons showed either increased or decreased of their respective firing discharge during evoked-swallowing, while no significant changes in activity were observed in the remaining nine neurons. Conclusion The neuronal networks underlying the swallowing pattern generation in the dorsal medulla mediate the ipsilateral motor outputs and modulate the contralateral activity of swallowing interneurons, suggesting that the bilateral coordination of the swallowing central pattern generator regulates the spatiotemporal organization of pharyngeal swallowing movements. Level of Evidence NA Laryngoscope, 131:2187–2198, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Case of Parotid Gland Fistula After Microtia Reconstruction Successfully Treated With Botulinum Toxin Type A

xlomafota13 shared this article with you from Inoreader A Case of Parotid Gland Fistula After Microtia Reconstruction Successfully Treated With Botulinum Toxin Type A Via ear nose throat Ear Nose Throat J. 2021 Sep 13:1455613211038325. doi: 10.1177/01455613211038325. Online ahead of print. ABSTRACT Parotid gland fistula after microtia reconstruction is relatively rare, with only 3 cases having been reported in the literature. It may be caused by the presence of an accessory parotid gland or surgical damage to parotid gland tissues. The principal treatment is dressing the wound. Here, we report the first case of parotid fistula after microtia reconstruction u sing a delayed retroauricular flap, which healed following wound dressing and an injection of botulinum toxin type A (CBTXA) into the parotid gland. PMID:34510956 | DOI:10.1177/01455613211038325 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.