Use of Near-Infrared Molecular Imaging For Localizing Visually Occult Parathyroid Glands in Ectopic Locations

xlomafota13 shared this article with you from Inoreader Use of Near-Infrared Molecular Imaging For Localizing Visually Occult Parathyroid Glands in Ectopic Locations Via JAMA Otolaryngology–Head & Neck Surgery Online First This proof-of-principle clinical trial examines use of intraoperative molecular imaging for localizing visually occult parathyroid glands in both anatomic and ectopic locations. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prognostic Role of Tumor‐Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma

xlomafota13 shared this article with you from Inoreader Prognostic Role of Tumor‐Infiltrating Lymphocytes and Tumor Budding in Early Oral Tongue Carcinoma Via The Laryngoscope Objectives/Hypothesis Occult lymph metastasis is an important prognosticator for the treatment of early oral tongue squamous cell carcinoma (SCC). The objective of this study was to evaluate the prognostic significance of tumor‐infiltrating lymphocytes (TILs) in early oral tongue SCC. The combination of the TIL subtype and intermediate‐ or high‐grade budding scores was investigated as a prognostic marker for occult neck metastases. Study Design Retrospective study. Methods Specimens from 62 patients with early oral tongue SCC treated with only primary surgery were analyzed by immunohistochemistry for CD4+, CD8+, FoxP3+, and CD45RO+ T cells and CD163+ macrophages. The highest number of each TIL subtype was counted in two areas of parenchyma and stroma in the tumor (Tumor) and peripheral stroma of the invasion margin. Results Based on multivariate analysis, a high density of Tumor CD163+ macrophages served as the poorest prognostic factor for regional control (RC) and disease‐free survival (DFS). Patients with both a high density of Tumor CD163+ macrophages and an intermediate‐ or a high‐grade budding score had a poor prognosis for RC according to the log‐rank test. Conclusions In summary, each TIL subtype may use different mechanisms during early and advanced stages of oral tongue SCC. A high density of Tumor CD163+ macrophages was determined to be a risk factor for RC and DFS as well as an additional stratification factor for RC in patients with intermediate‐ or high‐grade budding scores. Therefore, identifying TIL subtypes in daily clinical practice can help determine a more successful and individualized therapeutic approach for early oral tongue SCC. Level of Evidence Step 4 (Level 4) Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea

xlomafota13 shared this article with you from Inoreader Intratympanic Lipopolysaccharide Elevates Systemic Fluorescent Gentamicin Uptake in the Cochlea Via The Laryngoscope Objectives/Hypothesis Lipopolysaccharide (LPS), a key component of bacterial endotoxins, activates macrophages and triggers the release of inflammatory cytokines in mammalian tissues. Recent studies have shown that intratympanic injection of LPS simulates acute otitis media (AOM) and results in morphological and functional changes in the inner ear. Here we established an AOM mouse model with LPS to investigate the uptake of ototoxic gentamicin in the inner ear, and elucidated the underlying mechanism by focusing on cochlear inflammation as a result of AOM. Study Design Preclinical rodent animal model. Methods Fluorescently tagged gentamicin (GTTR) was systemically administered to mice with AOM. Iba1‐positive macrophage morphology and inner ear cytokine profile were evaluated by immunofluorescence technique and a mouse cytokine array kit, respectively. Results We observed characteristic symptoms of AOM in the LPS‐treated ears with elevated hearing thresholds indicating a conductive hearing loss. More importantly, the LPS‐induced AOM activated cochlear inflammatory responses, manifested by macrophage infiltration, particularly in the organ of Corti and the spiral ligament, in addition to the up‐regulation of proinflammatory cytokines. Meanwhile, GTTR uptake in the stria vascularis and sensory hair cells from all the LPS‐treated ears was significantly enhanced at 24, 48, and 72‐hour post‐treatment, as the most prominent enhancement was observed in the 48‐hour group. Conclusion In summary, this study suggests that the pathological cochlea is more susceptible to ototoxic drugs, including aminoglycosides, and justified the clinical concern of aminoglycoside ototoxicity in the AOM treatment. Laryngoscope, 2021 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Comprehensive analysis of multi-omics data of recurrent gliomas identifies a recurrence-related signature as a novel prognostic marker

xlomafota13 shared this article with you from Inoreader Comprehensive analysis of multi-omics data of recurrent gliomas identifies a recurrence-related signature as a novel prognostic marker Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1226-1246. eCollection 2021. ABSTRACT Tumor recurrence is a common clinical dilemma in diffuse gliomas. We aimed to identify a recurrence-related signature to predict the prognosis for glioma patients. In the public Chinese Glioma Genome Atlas dataset, we enrolled multi-omics data including genome, epigenome and transcriptome across primary and recurrent gliomas. We included RNA sequencing data from the batch 1 patients (325 patients) as the training set, while RNA sequencing data from the batch 2 patients (693 patients) were selected as the validation set. The R language was used for subsequent analysis. Compared with primary gliomas, more somatic mutations and copy number alterations were revealed in recurrent gliomas. In recurrent gliomas, we identified 113 genes whose methylation levels were significantly different from those of the primary glioma. Through differential expression analysis between primary and recurrent gliomas, we screened 121 recurrence-related genes. Based on these 121 gene expression profiles, consensus clustering of 325 patients yielded two robust groups with different molecular and prognostic features. We developed a recurrence-related risk signature with the lasso regression algorithm. High-risk group had shorter survival and earlier tumor recurrence than the low-risk group. Compared with traditional indicators, the signature showed better prognostic value. In addition, we constructed a nomogram model to predict glioma survival. Functional characteristics analysis found that the signature was associated with cell division and cell cycle. Immune analysis suggested that immunosuppressive status and macrophages might promote glioma recurrence. We demonstrated a novel 18-gene signature that could effectively predict recurrence and prognosis for glioma patients. PMID:33948355 | PMC:PMC8085869 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

CAN017, a novel anti-HER3 antibody, exerted great potency in mouse avatars of esophageal squamous cell carcinoma with NRG1 as a biomarker

xlomafota13 shared this article with you from Inoreader CAN017, a novel anti-HER3 antibody, exerted great potency in mouse avatars of esophageal squamous cell carcinoma with NRG1 as a biomarker Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1697-1708. eCollection 2021. ABSTRACT CAN017 (AV-203), a novel anti-HER3 antibody, exerts very promising anti-tumor activities in several human tumor models. The aim of this study was to further investigated the efficacy and possible responsive biomarkers of CAN017 in esophageal squamous cell carcinoma (ESCC) with Chinese characteristics. Two separate cohorts of ESCC patient-derived xenograft (PDX) models including 24 (cohort 1 as training models, from Crown Bioscience Inc.) and 22 (cohort 2 as validating models, from Peking University Cancer Hospital) models, respectively, were used to study the efficacy and safety of CAN017, as well as the correlation of NRG1 expression to the response of CAN017. In cohort 1, all PDX models showed good tolerance to CAN017 and 8 out of 24 (33.3%) PDX models responded to CAN017 with tumor growth inhibition (TGI) ≥70% compared to controls. Furthermore, the efficacy o f CAN017 was positively correlated with NRG1 expression and the response rates in cohort 1 were 73% (8/11) versus 0% (0/13) in NRG1 high and low expression models, respectively. These results were also validated in PDX models of cohort 2 indicated as the powerful anti-tumor activity of CAN017 in PDX models with NRG1 high expression. In our study, HER3-targeting therapy was first demonstrated to have potency in inhibiting ESCC tumor growth, and NRG1 served as a predictive biomarker to screen patients in future clinical trials. PMID:33948383 | PMC:PMC8085865 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Decursin inhibits cell growth and autophagic flux in gastric cancer via suppression of cathepsin C

xlomafota13 shared this article with you from Inoreader Decursin inhibits cell growth and autophagic flux in gastric cancer via suppression of cathepsin C Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1304-1320. eCollection 2021. ABSTRACT Autophagy plays an important role in the survival of cancer cells under stressful conditions, such as nutrient or oxygen deficiency. Therefore, autophagy inhibition is being considered as a novel therapeutic strategy for cancer. Decursin is a natural compound derived from Angelica gigas; it has been used in the treatment of various diseases, including cancer. However, the mechanism by which decursin regulates autophagy in gastric cancer and other carcinomas remains unclear. Here, we demonstrated that decursin reduced the growth and induced cell cycle arrest in gastric cancer cells in vitro. Decursin blocked autophagic flux by reducing the expression of lysosomal protein cathepsin C (CTSC) and attenuating its activity, thereby causing autophagic dysregulation (i.e., accumulation of LC3 and SQSTM1). Decursin also inhibited cell proliferation and cell c ycle progression by inhibiting CTSC and E2F3, both of which were linked to gastric cancer aggressiveness. The antitumor effects of decursin were confirmed in vivo. We established spheroid and patient-derived organoid models and found that decursin decreased the growth of spheroids and patient-derived gastric organoids, as well as modulated the expression of CTSC and autophagy-related proteins. Hence, our findings uncovered a previously unknown mechanism by which decursin regulates cell growth and autophagy and suggests that decursin may act as a potential therapeutic agent that simultaneously inhibits cell growth and autophagy. PMID:33948359 | PMC:PMC8085838 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Serial assessment of circulating T lymphocyte phenotype and receptor repertoire during treatment of non-muscle invasive bladder cancer with adoptive T cell immunotherapy

xlomafota13 shared this article with you from Inoreader Serial assessment of circulating T lymphocyte phenotype and receptor repertoire during treatment of non-muscle invasive bladder cancer with adoptive T cell immunotherapy Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1709-1718. eCollection 2021. ABSTRACT Recurrence and progression of non-muscle-invasive bladder cancer (NMIBC), frequent despite the availability of multiple treatment modalities, may be partly explained by the presence of immunosuppressive cell populations. We hypothesized that progression of disease could be prevented by the administration of an activated T cell immunotherapy (ACT) at time points when immunosuppressive populations increased in peripheral blood. In an N-of-1 study, a patient with multiple primary bladder high grade urothelial carcinomas, previously treated with standard local resection and chemotherapy but with evidence of progression, received ACT consisting of dendritic cells mixed with cytokine induced killer cells (DC/CIK), intravenously 18 times over a 6 year period at indicated time of observed increases in peripheral blood immunosuppressive CD8+/CD28- cel ls. Peripheral blood was analyzed for T cell phenotype by flow cytometry, T cell receptor (TCR) repertoire, and circulating tumor DNA (ctDNA) by next generation sequencing (NGS) at the time of each infusion. Cystoscopy and pelvic CT scans were performed at routine intervals to assess clinical status of disease. There has been no recurrence or metastasis of urothelial carcinoma. Peripheral blood cytotoxic T cells and unique TCR clones increased and suppressive T cell populations decreased after DC/CIK infusions evidenced by the two more proof-of concept cases. ctDNA analysis detected mutations in six genes (ARID1B, MYCN, CDH23, SETD2, NOTCH4 and FAT1) which appeared at different times, but all of them disappeared after the DC-CIK infusions. These data suggest that DC/CIK infusions may be associated with beneficial changes in T cell phenotype, TCR repertoire, decreases in circulating tumor DNA and sustained recurrence-free survival. PMID:33948384 | PMC:PMC8085852 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

LHPP impedes energy metabolism by inducing ubiquitin-mediated degradation of PKM2 in glioblastoma

xlomafota13 shared this article with you from Inoreader LHPP impedes energy metabolism by inducing ubiquitin-mediated degradation of PKM2 in glioblastoma Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1369-1390. eCollection 2021. ABSTRACT Phospholysine phosphohistidine inorganic pyrophosphate phosphatase (LHPP) is a new-found tumor suppressor in a variety of tumors. While, it is still unknown about its role in glioma. In this study, we found that LHPP is abnormally decreasing or absent in glioblastoma, and the low expression of LHPP is associated with poor median survival in glioma patients. Functional assay revealed that LHPP-overexpression significantly inhibited U87MG and U118MG growth in vitro and in vivo. As to the mechanism, mass-spectrometric analysis indicated that the LHPP interacting proteins were mainly enriched in regulation of energy metabolism, including Carbon metabolism, Oxidative phosphorylation, and Glycolysis. Seahorse assay and metabolites detection confirmed that LHPP-overexpression obviously impeded glycolysis and respiration in U87MG and U118MG cells. For the further study, w estern blot assay showed that the protein level of PKM2 at dimeric, tetrameric, and total protein, were all decreased significantly, and its enzymatic activity was decreased as well. ChIP and RNAseq integrated analysis indicated that the decreased protein level of PKM2 was independent of PKM2 transcription, and LHPP did not reprogram transcription level of metabolic genome. Co-IP and immunofluorescence assay manifested that LHPP interacted with PKM2, and this interaction interfered the protein stability, then induced ubiquitin-mediated degradation of PKM2. Rescue assay confirmed that restoring the expression of PKM2 effectively reversed the restrained energy metabolism and the inhibited cancer cell growth caused by LHPP-overexpression in U87MG and U118MG cells. Taking together, we demonstrated that LHPP impedes the glycolysis and respiration during energy metabolic process via inducing ubiquitin-mediated degradation of PKM2, thus inhibits the growth of glioblastoma. PMID:33948363 | PMC:PMC8085851 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Contemporary external beam radiotherapy boost or high dose-rate brachytherapy boost for cervical cancer: a propensity-score-matched, nationwide, population-based cohort study

xlomafota13 shared this article with you from Inoreader Contemporary external beam radiotherapy boost or high dose-rate brachytherapy boost for cervical cancer: a propensity-score-matched, nationwide, population-based cohort study Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1719-1732. eCollection 2021. ABSTRACT To estimate the survival effects of contemporary external beam radiotherapy (EBRT) boost modalities (intensity-modulated radiation therapy or volumetric modulated arc therapy) and high dose-rate brachytherapy (HDR-BT) boost in patients with cervical cancer (CC). Patients who had been diagnosed as having CC were recruited from the Taiwan Cancer Registry Database. Propensity score matching was performed, and Cox proportional-hazards model curves were used to analyze the all-cause mortality of patients who received standard whole-pelvis irradiation with different boost modalities. The matching process yielded a final cohort of 1,630 patients (815 in the EBRT boost and HDR-BT boost groups, respectively) eligible for further analysis. The multivariate Cox regression analyses indicated that the adjusted hazard ratio (95% confidence intervals) for EBRT boost compared wit h HDR-BT boost was 1.62 (1.43-1.84). Multivariable analysis revealed that the independent poor prognostic factors of all-cause mortality among patients with CC were adenocarcinoma, no chemotherapy, Charlson comorbidity index score ≥ 1, age ≥ 60 years, and advanced International Federation of Gynecology and Obstetrics stage. HDR-BT boost may be more beneficial than contemporary EBRT boost in selected patients with CC. PMID:33948385 | PMC:PMC8085 872 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Genetically determined elevated C-reactive protein associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions

xlomafota13 shared this article with you from Inoreader Genetically determined elevated C-reactive protein associated with primary colorectal cancer risk: Mendelian randomization with lifestyle interactions Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1733-1753. eCollection 2021. ABSTRACT Systemic inflammation-related etiologic pathways via inflammatory cytokines in the development of colorectal cancer (CRC) have not been convincingly determined and may be confounded by lifestyle factors or reverse causality. We investigated the genetically predicted C-reactive protein (CRP) phenotype in the potential causal pathway of primary CRC risk in postmenopausal women in a Mendelian randomization (MR) framework. We employed individual-level data of the Women's Health Initiative Database for Genotypes and Phenotypes Study, which consists of 5 genome-wide association (GWA) studies, including 10,142 women, 737 of whom developed primary CRC. We examined 61 GWA single-nucleotide polymorphisms (SNPs) associated with CRP by using weighted/penalized MR weighted-medians and MR gene-environment interactions that allow some relaxation of the strict variable requiremen ts and attenuate the heterogeneous estimates of outlying SNPs. In lifestyle-stratification analyses, genetically determined CRP exhibited its effects on the decreased CRC risk in non-viscerally obese and high-fat diet subgroups. In contrast, genetically driven CRP was associated with an increased risk for CRC in women who smoked ≥ 15 cigarettes/day, with significant interaction of the gene-smoking relationship. Further, a substantially increased risk of CRC induced by CRP was observed in relatively short-term users (< 5 years) of estrogen (E)-only and also longer-term users (5 to > 10 years) of E plus progestin. Our findings may provide novel evidence on immune-related etiologic pathways connected to CRC risk and suggest the possible use of CRP as a CRC-predictive biomarker in women with particular behaviors and CRP marker-informed interventions to reduce CRC risk. PMID:33948386 | PMC:PMC8085861 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical endpoints in oncology - a primer

xlomafota13 shared this article with you from Inoreader Clinical endpoints in oncology - a primer Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1121-1131. eCollection 2021. ABSTRACT Clinical endpoints are essential for assessing the safety and efficacy of new cancer therapies. They are used by oncologists to help guide clinical decision making. While overall survival (OS) has frequently been regarded as the "gold standard" primary clinical endpoint, it's utility is constrained by several disadvantages. The time-consuming nature of trials using OS has led to a recent push to explore surrogate clinical endpoints and their potential to serve as primary clinical endpoints in lieu of OS. Additionally, it is becoming evident that other endpoints add valuable information about quality of life and treatment failure as their use is becoming increasingly prevalent in oncology clinical trials. Without a doubt, the use of clinical endpoints will continue to expand and evolve as new cancer therapies are developed and novel treatments, including immunother apy, draw interest. This review explores the roles of primary and surrogate clinical endpoints as well as the benefits and drawbacks of each specific endpoint. In addition, it directly compares the unique features of each suggesting some of the specific uses each one fulfills. PMID:33948349 | PMC:PMC8085844 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.