Barretts Esophagus and Esophageal Adenocarcinoma Biomarkers.

gnorimies20.15 shared this article with you from Inoreader Barretts Esophagus and Esophageal Adenocarcinoma Biomarkers. Via pubmed: esophageal cancer Barretts Esophagus and Esophageal Adenocarcinoma Biomarkers. Cancer Epidemiol Biomarkers Prev. 2020 Oct 22;: Authors: Grady WM, Yu M, Markowitz SD, Chak A Abstract Esophageal adenocarcinoma (EAC) is a major cause of cancer related morbidity and mortality in Western countries. The incidences of EAC and its precursor Barrett's esophagus (BE) have increased substantially in the last four decades. Current care guidelines recommend that endoscopy be used for the early detection and monitoring of patients with BE, however, the efficacy of this approach is unclear. In order to prevent the increasing morbidity and mortality from EAC, there is a need for early detection and surveillance biomarker assays that are accurate, low-cost, and clinically feasible to implement. The last decade has seen remarkable advances in the development of minimally invasive molecular biomarkers, an effort led in large part by the Early Detection Research Network (EDRN). Advances in multi-omics analysis, the development of swallowable cytology collection devices, and emerging technology have led to promising assays that are likely to be implemented into clinical care in the next decade, with the most promising markers to date being methylated VIM and CCNA1. In this review, an updated overview of the molecular pathology of BE and EAC and emerging molecular biomarker assays, as well as the role of EDRN in biomarker discovery and validation, will be discussed. PMID: 33093162 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Association of Sleep Disorders, Obesity and Sleep-Related Hypoxia with Cancer.

gnorimies20.15 shared this article with you from Inoreader The Association of Sleep Disorders, Obesity and Sleep-Related Hypoxia with Cancer. Via pubmed: esophageal cancer The Association of Sleep Disorders, Obesity and Sleep-Related Hypoxia with Cancer. Curr Genomics. 2020 Sep;21(6):444-453 Authors: Brzecka A, Sarul K, Dyła T, Avila-Rodriguez M, Cabezas-Perez R, Chubarev VN, Minyaeva NN, Klochkov SG, Neganova ME, Mikhaleva LM, Somasundaram SG, Kirkland CE, Tarasov VV, Aliev G Abstract Background: Sleep disorders have emerged as potential cancer risk factors. Objective: This review discusses the relationships between sleep, obesity, and breathing disorders with concomitant risks of developing cancer. Results: Sleep disorders result in abnormal expression of clock genes, decreased immunity, and melatonin release disruption. Therefore, these disorders may contribute to cancer development. Moreover, in sleep breathing disorder, which is frequently experienced by obese persons, the sufferer experiences intermittent hypoxia that may stimulate cancer cell proliferation. Discussion: During short- or long- duration sleep, sleep-wake rhythm disruption may occur. Insomnia and obstructive sleep apnea increase cancer risks. In short sleepers, an increased risk of stomach cancer, esophageal squamous cell cancer, and breast cancer was observed. Among long sleepers (>9 hours), the risk of some hematologic malignancies is elevated. Conclusion: Several factors including insomnia, circadian disruption, obesity, and intermittent hypoxia in obstructive sleep apnea are contributing risk factors for increased risk of several types of cancers. However, further studies are needed to determine the more significant of these risk factors and their interactions. PMID: 33093806 [PubMed] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Primary Esophageal Angiosarcoma.

gnorimies20.15 shared this article with you from Inoreader Primary Esophageal Angiosarcoma. Via pubmed: esophageal cancer Primary Esophageal Angiosarcoma. Ann Thorac Surg. 2020 Oct 20;: Authors: Gutnik L, Goold E, Madsen J, Clayton F, Varghese T, Glasgow R Abstract Primary esophageal angiosarcoma is an extremely rare cancer. Thus, evidence-based guidance on diagnosis and treatment is lacking. The current work up and management is extrapolated from other esophageal and angiosarcoma pathology. We describe a case report which depicts unique diagnostic and therapeutic challenges. PMID: 33096067 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

HPV infection, E6, and p16 expression in men with penile cancer.

gnorimies20.15 shared this article with you from Inoreader Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer. Via pubmed: hpv infection Italian observational study on HPV infection, E6, and p16 expression in men with penile cancer. Virol J. 2020 Oct 22;17(1):161 Authors: Muresu N, Sotgiu G, Saderi L, Sechi I, Cossu A, Marras V, Meloni M, Martinelli M, Cocuzza C, Tanda F, Piana A Abstract BACKGROUND: Human Papillomavirus (HPV) infection is one of the most important causes of cancer. It can play a role in cervical and extra-cervical cancers. Penile cancer is rare, even if an increasing trend was recently reported. Aim of the present study was to assess the prevalence and distribution of HPV genotypes in cases of penile cancer diagnosed in Sardinia, Italy. Surrogate markers of HPV infection (i.e., E6 and p16 genes) were also evaluated in all cases. METHODS: An observational, retrospective study which recruited all cases of penile cancer diagnosed between 2002 and 2019 at a tertiary care hospital in Sardinia, Italy, was carried out. HPV-DNA detection and genotyping were performed by Real-time PCR. Specimens were tested for oncogene E6 mRNA and for p16(INK4a) expression. RESULTS: HPV prevalence was 28.1% (9/32); HPV-16 was the most prevalent genotype (7/9, 77.8%). p16INK4a positivity was found in 66.7% of the samples with a statistically significant difference between HPV-positive and -negative groups. E6-transcript was detected in 71% of the HPV-16 positive samples. The overall survival was not statistically different between HPV-positives and -negatives. DISCUSSION: The present study confirms the etiologic role of HPV in penile cancer and supports the adoption of vaccination strategies in men and women. Further studies should clarify the diagnostic and prognostic role of E6 and p16 proteins. CONCLUSION: HPV infection can favor the occurrence of penile cancer, whose diagnosis and prognosis could be improved with the implementation of validated molecular techniques. PMID: 33092608 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

FOXM1 drives HPV+ HNSCC sensitivity to WEE1 inhibition.

gnorimies20.15 shared this article with you from Inoreader FOXM1 drives HPV+ HNSCC sensitivity to WEE1 inhibition. Via pubmed: hpv infection FOXM1 drives HPV+ HNSCC sensitivity to WEE1 inhibition. Proc Natl Acad Sci U S A. 2020 Oct 22;: Authors: Diab A, Gem H, Swanger J, Kim HY, Smith K, Zou G, Raju S, Kao M, Fitzgibbon M, Loeb KR, Rodriguez CP, Méndez E, Galloway DA, Sidorova JM, Clurman BE Abstract Head and neck squamous cell carcinoma (HNSCC) associated with high-risk human papilloma virus (HPV) infection is a growing clinical problem. The WEE1 kinase inhibitor AZD1775 (WEE1i) overrides cell cycle checkpoints and is being studied in HNSCC regimens. We show that the HPV16 E6/E7 oncoproteins sensitize HNSCC cells to single-agent WEE1i treatment through activation of a FOXM1-CDK1 circuit that drives mitotic gene expression and DNA damage. An isogenic cell system indicated that E6 largely accounts for these phenotypes in ways that extend beyond p53 inactivation. A targeted genomic analysis implicated FOXM1 signaling downstream of E6/E7 expression and analyses of primary tumors and The Cancer Genome Atlas (TCGA) data revealed an activated FOXM1-directed promitotic transcriptional signature in HPV+ versus HPV- HNSCCs. Finally, we demonstrate the causality of FOXM1 in driving WEE1i sensitivity. These data suggest that elevated basal FOXM1 activity predisposes HPV+ HNSCC to WE E1i-induced toxicity and provide mechanistic insights into WEE1i and HPV+ HNSCC therapies. PMID: 33093209 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Use of Cap Analysis Gene Expression to detect human papillomavirus promoter activity patterns at different disease stages.

gnorimies20.15 shared this article with you from Inoreader Use of Cap Analysis Gene Expression to detect human papillomavirus promoter activity patterns at different disease stages. Via pubmed: hpv infection Use of Cap Analysis Gene Expression to detect human papillomavirus promoter activity patterns at different disease stages. Sci Rep. 2020 Oct 22;10(1):17991 Authors: Taguchi A, Nagasaka K, Plessy C, Nakamura H, Kawata Y, Kato S, Hashimoto K, Nagamatsu T, Oda K, Kukimoto I, Kawana K, Carninci P, Osuga Y, Fujii T Abstract Transcription of human papillomavirus (HPV) genes proceeds unidirectionally from multiple promoters. Direct profiling of transcription start sites (TSSs) by Cap Analysis Gene Expression (CAGE) is a powerful strategy for examining individual HPV promoter activity. The objective of this study was to evaluate alterations of viral promoter activity during infection using CAGE technology. We used CAGE-based sequencing of 46 primary cervical samples, and quantitatively evaluated TSS patterns in the HPV transcriptome at a single-nucleotide resolution. TSS patterns were classified into two types: early promoter-dominant type (Type A) and late promoter-dominant type (Type B). The Type B pattern was more frequently found in CIN1 and CIN2 lesions than in CIN3 and cancer samples. We detected transcriptomes from multiple HPV types in five samples. Interestingly, in each sample, the TSS patterns of both HPV types were the same. The viral gene expression pattern was determined by the differ entiation status of the epithelial cells, regardless of HPV type. We performed unbiased analyses of TSSs across the HPV genome in clinical samples. Visualising TSS pattern dynamics, including TSS shifts, provides new insights into how HPV infection status relates to disease state. PMID: 33093512 [PubMed - in process] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Genomic characterization of human papillomavirus type 13, associated to multifocal epithelial hyperplasia, in a Mayan community.

gnorimies20.15 shared this article with you from Inoreader Genomic characterization of human papillomavirus type 13, associated to multifocal epithelial hyperplasia, in a Mayan community. Via pubmed: hpv infection Genomic characterization of human papillomavirus type 13, associated to multifocal epithelial hyperplasia, in a Mayan community. Infect Genet Evol. 2020 Oct 20;:104595 Authors: Conde-Ferraéz L, Ek-Hernández GE, Canché-Pech JR, Gómez-Carballo JG, Kantún-Moreno NE, Del Refugio González-Losa M Abstract Human papillomavirus type 13 (HPV13) is a low-risk HPV type associated with Multifocal Epithelial Hyperplasia (MEH). It is considered a rare pathology of oral mucosa, more prevalent in certain ethnical groups, such as the Maya from Yucatan in Mexico. As for 2020 only two complete genomes of HPV13 are publicly available in Genbank database (one from Turkey one from the Amazonian). We aimed to obtain the complete genome sequence of HPV13 associated to MEH, obtained from a community in the Mayan area from Mexico. A bank of oral swabs from children with MEH were used. To enrich the sample, a Rolling Cycle Amplification (RCA) method was performed followed by overlapping end-point PCR of 500 bp fragments, Sanger sequencing and assembly. Eight open reading frames (ORFs) were annotated (E1, E2, E4, E5, E6, E7, L1 and L2 genes). When compared with the other two previously reported genomes the identity at nucleotide level is high 98.9% and 99.6%, respectively. The phylogenetic tree s hows that Yucatan HPV13 is more closely related to HPV13 obtained from the Amazonian. Most changes identified at amino acid level are substitutions derived from nucleotide variations or SNPs in coding regions. Amino-acid changes were observed in E2 and E1 proteins (n ≥ 8), and in L1, L2, E6 and E5 proteins (n ≤ 5). E7 protein from Yucatan has 100% identity with the reported from Amazonian and differs (94.1% identity) with the one from Turkey due to 3 substitutions and three missing amino acids. In conclusion, the genome from HPV13 (7831 bp, 49 nt missing) associated to MEH in the Mayan area from Yucatan was obtained from stored swabs; this is the first effort in Mexico, the second in Latin America, and the third of the world. More research that contributes to the knowledge of the determinants underlying this neglected pathology are urged. PMID: 33096300 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cumulative suppressive index as a predictor of relapse free survival and overall survival in Human Papilloma Virus-negative oral squamous cell carcinomas with negative resection margins.

gnorimies20.15 shared this article with you from Inoreader Cumulative suppressive index as a predictor of relapse free survival and overall survival in Human Papilloma Virus-negative oral squamous cell carcinomas with negative resection margins. Via pubmed: "head neck"[jour] Cumulative suppressive index as a predictor of relapse free survival and overall survival in Human Papilloma Virus-negative oral squamous cell carcinomas with negative resection margins. Head Neck. 2020 Oct 23;: Authors: Hum L, Bethmann D, Feng Z, Chang SC, Eckert A, Ballesteros-Merino C, Keschke C, Kappler M, Bifulco CB, Wickenhauser C, Seliger B, Fox BA, Bryan Bell R Abstract BACKGROUND: This study aimed to analyze margin status and the impact of the immune elements on recurrence in patients with oral squamous cell carcinoma (OSCC), employing a prognostic biomarker, cumulative suppressive index (CSI), which reflects FoxP3+, PD-L1+, and CD8+ cell spatial relationships in the tumor microenvironment. METHODS: Cox proportional hazards regression was used to evaluate the interactive effect of the margin by CSI discrepancy (high, 3-4 vs low, 0-2) on recurrence free survival (RFS) and overall survival (OS) in 119 patients with stage I to IVA OSCC. RESULTS: In cases with negative margins, multivariable analysis showed high CSI was significantly associated with worse RFS (HR = 2.59, 95% CI [1.03, 6.49], P = .04) and OS (HR = 5.49, 95% CI [1.48, 20.35], P = .01) compared to low CSI. However, high CSI was not significantly associated with recurrence in cases with positive margins. CONCLUSIONS: Immune architecture analysis can augment our current histopathological risk assessment of margin status. PMID: 33094869 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Hypomagnesemia and incidence of osteoradionecrosis in patients with head and neck cancers.

gnorimies20.15 shared this article with you from Inoreader Hypomagnesemia and incidence of osteoradionecrosis in patients with head and neck cancers. Via pubmed: "head neck"[jour] Hypomagnesemia and incidence of osteoradionecrosis in patients with head and neck cancers. Head Neck. 2020 Oct 23;: Authors: Liu W, Qdaisat A, Zhou S, Fuller CD, Ferrarotto R, Guo M, Lai SY, Cardoso R, Mohamed ASR, Lopez G, Narayanan S, van Dijk LV, Cohen L, Bruera E, Yeung SJ, Hanna EY Abstract BACKGROUND: We aimed to determine whether hypomagnesemia predicts osteoradionecrosis development in patients with squamous cell carcinoma of the oropharynx and oral cavity who received platinum-based concurrent chemoradiation with or without induction therapy. METHODS: We reviewed data from patients with head and neck cancers who had undergone chemoradiation with weekly cisplatin/carboplatin between January 1, 2010 and December 31, 2014 at our institution. Pathologic features, laboratory test results, disease stage, and social histories were recorded. The association between hypomagnesemia and osteoradionecrosis was analyzed controlling for known confounding factors. RESULTS: Hypomagnesemia during cancer treatment was associated with osteoradionecrosis development (HR = 2.72, P = .037) independent of total radiation dose (HR = 1.07, P = .260) and smoking history (HR = 2.05, P = .056) among the patients who received platinum-based induction chemotherapy followed by concurrent chemoradiation. CONCLUSIONS: Hypomagnesemia was predictive of the development of osteoradionecrosis in patients with cancers of the oropharynx and oral cavity receiving platinum-based induction followed by concurrent chemoradiation. PMID: 33094893 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Unc-13 homologue D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a.

gnorimies20.15 shared this article with you from Inoreader Unc-13 homologue D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a. Via Oral Mucositis Unc-13 homologue D mediates an antiviral effect of the chromosome 19 microRNA cluster miR-517a. J Cell Sci. 2020 Oct 22;: Authors: Krawczynski K, Ouyang Y, Mouillet JF, Chu T, Coyne CB, Sadovsky Y Abstract The function of microRNAs (miRNAs) can be cell autonomous or communicated to other cell types, and has been implicated in diverse biological processes. We previously demonstrated that miR-517a-3p (miR-517a), the highly expressed member of the chromosome 19 miRNA cluster (C19MC) that are transcribed almost exclusively in human trophoblasts, attenuates viral replication via induction of autophagy in non-trophoblastic, recipient cells. However, the molecular mechanisms underlying these effects remain unknown. Here we identified Unc-13 homologue D (UNC13D) as a direct, autophagy-related gene target of miR-517a, leading to repression of UNC13D. In line with the antiviral activity of miR-517a, silencing UNC13D suppressed replication of vesicular stomatitis virus (VSV), whereas overexpression of UNC13D increased VSV levels, suggesting a role for UNC13D silencing in the antiviral activity of miR-517a. We also found that miR-517a activated NFκB signaling in HEK-293XL cells expressing TLR8, but the effect was not-specific to C19MC miRNA. Together, we define mechanistic pathways that link C19MC miRNA with inhibition of viral replication. PMID: 33093239 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Audiovestibular neuropathy in an immunocompetent man with cryptococcal meningitis.

gnorimies20.15 shared this article with you from Inoreader Audiovestibular neuropathy in an immunocompetent man with cryptococcal meningitis. Via pubmed: hearing and balance Audiovestibular neuropathy in an immunocompetent man with cryptococcal meningitis. Eur Ann Otorhinolaryngol Head Neck Dis. 2020 Oct 19;: Authors: Reynard P, Bascoul A, Biotti D, Karsenty J, Ionescu E, Thai-Van H Abstract INTRODUCTION: Cryptococcus spp. is a fungus responsible for 600,000 deaths per year worldwide, mainly in immunosuppressed subjects. However, 20% of cases occur in immunocompetent subjects. Neuropathic disorders involving the auditory nerve have been reported, but vestibular disorders have never been described in detail. We report the case of an immunocompetent man, who presented audiovestibular disorders leading to a diagnosis of cryptococcal meningitis. CASE REPORT: A 39-year-old man was referred for balance disorders and right sensorineural hearing loss. He presented right vestibulo-saccular impairment and bilateral absence of auditory brainstem responses. Brain MRI was suggestive of cryptococcal meningitis. A cystic lesion in the right flocculus compressed the vestibulocochlear nerve. During monthly follow-up, pure tone audiometry gradually improved and speech audiometry in silence returned to normal. Partial resynchronization of the auditory afferent pathways was observed only on the contralateral side to vestibulocochlear nerve compression, while complete recovery of saccular function was observed. DISCUSSION: Cryptococcal meningitis in immunocompetent subjects may be accompanied by lesions of the auditory and vestibular afferent pathways. Recovery of hearing and balance was observed in response to medical treatment and early vestibular rehabilitation. PMID: 33092984 [PubMed - as supplied by publisher] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Gas6 is a reciprocal regulator of mitophagy during mammalian oocyte maturation.

gnorimies20.15 shared this article with you from Inoreader Gas6 is a reciprocal regulator of mitophagy during mammalian oocyte maturation. Via pubmed: quinazolinones Related Articles Gas6 is a reciprocal regulator of mitophagy during mammalian oocyte maturation. Sci Rep. 2019 07 17;9(1):10343 Authors: Kim KH, Kim EY, Ko JJ, Lee KA Abstract Previously, we found that the silencing of growth arrest-specific gene 6 (Gas6) expression in oocytes impairs cytoplasmic maturation through mitochondrial overactivation with concurrent failure of pronuclear formation after fertilization. In this study, we report that Gas6 regulates mitophagy and safeguards mitochondrial activity by regulating mitophagy-related genes essential to the complete competency of oocytes. Based on RNA-Seq and RT-PCR analysis, in Gas6-silenced MII oocytes, expressions of mitophagy-related genes were decreased in Gas6-silenced MII oocytes, while mitochondrial proteins and Ptpn11, the downstream target of Gas6, was increased. Interestingly, GAS6 depletion induced remarkable MTOR activation. Gas6-depleted MII oocytes exhibited mitochondrial accumulation and aggregation caused by mitophagy inhibition. Gas6-depleted MII oocytes had a markedly lower mtDNA copy number. Rapamycin treatment rescued mitophagy, blocked the increase in MTOR and phosphorylated-MT OR, and increased the mitophagy-related gene expression in Gas6-depleted MII oocytes. After treatment with Mdivi-1, a mitochondrial division/mitophagy inhibitor, all oocytes matured and these MII oocytes showed mitochondrial accumulation but reduced Gas6 expression and failure of fertilization, showing phenomena very similar to the direct targeting of Gas6 by RNAi. Taken together, we conclude that the Gas6 signaling plays a crucial role in control of oocytes cytoplasmic maturation by modulating the dynamics and activity of oocyte mitochondria. PMID: 31316104 [PubMed - indexed for MEDLINE] View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.