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.

Binding of RNA m6A by IGF2BP3 triggers chemoresistance of HCT8 cells via upregulation of ABCB1

xlomafota13 shared this article with you from Inoreader Binding of RNA m6A by IGF2BP3 triggers chemoresistance of HCT8 cells via upregulation of ABCB1 Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1428-1445. eCollection 2021. ABSTRACT The overexpression of ATP-binding cassette transporters subfamily B member 1 (ABCB1) is known to be the primary trigger of multidrug resistance (MDR) in colorectal cancer (CRC), leading to chemotherapy failure. However, factors that regulate chemoresistance in CRC cells are largely unknown. To identify proteins involved in MDR in CRC, we used proteomics and transcriptomics approaches to analyze HCT8/T cells and parental HCT8 cells. Results showed that the expression of insulin-like growth factor-2 mRNA-binding protein 3 (IGF2BP3) was upregulated in HCT8/T cells, and siIGF2BP3 remarkably elevated the sensitivity of HCT8/T cells to DOX. Overexpression of IGF2BP3 promoted ABCB1 expression, and reduced the sensitivity to ABCB1 substrates. Conversely, knockdown of IGF2BP3 reduced ABCB1 expression, and increased the sensitivity to ABCB1 substrates in vitro and in vivo. This phenomeon was further confirmed by the strong association of IGF2BP3 and ABCB1 expression with DOX sensitivity. Mechanistically, IGF2BP3, as a N6-methyladenosine (m6A) reader, directly bound to the m6A-modified region of ABCB1 mRNA, thereby promoting the stability and expression of ABCB1 mRNA. Overall, the results showed that IGF2BP3 bound to the m6A modification region of ABCB1 mRNA, and conferred chemoresistance in CRC cells via upregulation of ABCB1. These findings suggest that IGF2BP3 might be a potential biomarker for predicting the development of MDR in CRC. Targeting IGF2BP3 might be an important chemotherapeutic strategy for preventing MDR development in CRC. PMID:33948366 | PMC:PMC8085870 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinicopathological and molecular features between synchronous and metachronous metastases in colorectal cancer

xlomafota13 shared this article with you from Inoreader Clinicopathological and molecular features between synchronous and metachronous metastases in colorectal cancer Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1646-1658. eCollection 2021. ABSTRACT The molecular difference between synchronous and metachronous metastases in colorectal cancer (CRC) remains unclear. Between 2000 and 2010, a total of 492 CRC patients were enrolled, including 280 with synchronous metastasis and 212 with metachronous metastasis. Clinicopathological and molecular features were compared between the two groups. Patients with synchronous metastasis were more likely to have right-sided CRC, poorly differentiated tumors, lymphovascular invasion, advanced pathological tumor (T) and node (N) categories, and liver metastases than those with metachronous metastasis. For right-sided CRC, patients with synchronous metastasis had more lymphovascular invasion and liver metastases than those with metachronous metastasis. For left-sided CRC, patients with synchronous metastasis were more likely to have poorly differentiated tumors, lymphovascular invasion, advanced pathological T and N categories, and liver metastases than those with metachronous metastasis. Regarding the genetic mutations, patients with metachronous metastasis had more mutations in TP53, NRAS, and HRAS and fewer mutations in APC than those with synchronous metastasis; for right-sided CRC, synchronous metastasis was associated with more APC mutations than metachronous metastasis, while for left-sided CRC, metachronous metastasis was associated with more TP53 and NRAS mutations than synchronous metastasis. The 5-year overall survival (OS) rates were significantly higher in metachronous metastasis patients than in synchronous metastasis patients, especially those with left-sided CRC. Multivariate analysis showed that age, sex, lymphovascular invasion, pathological N category, metachronous metastasis, and BRAF and NRAS mutations were independent prognostic factors affecting OS. CRC patients with synchrono us metastasis had a worse OS than those with metachronous metastasis and exhibited distinct genetic mutations. PMID:33948379 | PMC:PMC8085873 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Prostate cancer racial, socioeconomic, geographic disparities: targeting the genomic landscape and splicing events in search for diagnostic, prognostic and therapeutic targets

xlomafota13 shared this article with you from Inoreader Prostate cancer racial, socioeconomic, geographic disparities: targeting the genomic landscape and splicing events in search for diagnostic, prognostic and therapeutic targets Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1012-1030. eCollection 2021. ABSTRACT Prostate cancer (PCa) is one of the leading causes of deaths in men globally. This is a heterogeneous and complex disease that urgently warrants further insight into its pathology. Developed countries have thus far the highest PCa incidence rates, with comparatively low mortality rates. Even though PCa in the Asian population seems to have high incidence and mortality rates, the African countries are emerging as the focal center for this disease. It has also been reported that the Sub-Saharan (SSA) countries have both the highest incidence and mortality rates. To date, few studies have reported the link between PCa and African populations. Adequate evidence is still missing to fully comprehend this relationship. While it has been brought to attention that racial, geographical and socioeconomic status are contributing factors, men of African descent across the glob e, irrespective of their geographical position have higher PCa incidence and mortality rates compared to their white counterparts. To date, hormone therapy is the mainstay treatment of PCa, while the dysregulation of androgen receptor (AR) signaling is a hallmark of PCa. One of the emerging problems with this therapeutic approach is resistance to antiandrogens, and that AR splice isoforms implicated in the progression of PCa lack the therapeutic ligand-binding domain (LBD) target. AR splice variants targeted therapy is emerging and in clinical trials. Leveraging PCa transcriptomics is key towards PCa precision medicine. The aim of this review is to outline the PCa epidemiology globally and in Africa, PCa associated risk factors, discuss AR signaling and PCa mechanisms, the role of dysregulated splicing in PCa as novel prognostic indicators and therapeutic targets. PMID:33948343 | PMC:PMC8085879 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Angiogenesis is associated with an attenuated tumor microenvironment, aggressive biology, and worse survival in gastric cancer patients

xlomafota13 shared this article with you from Inoreader Angiogenesis is associated with an attenuated tumor microenvironment, aggressive biology, and worse survival in gastric cancer patients Via American Journal of Cancer Research Am J Cancer Res. 2021 Apr 15;11(4):1659-1671. eCollection 2021. ABSTRACT Angiogenesis is a cornerstone of cancer as it allows tumors to receive oxygen and nutrients. A high level of angiogenesis within a tumor may therefore be indicative of its aggressiveness. In this study, we examined this hypothesis in gastric cancer. Gene set variation analysis was used to measure the level of angiogenesis in tumors in 1,348 gastric cancer patients using the Hallmark_angiogenesis gene set to score tumor transcriptomes. As we predicted, there was a significant correlation between angiogenesis score and expression of angiogenesis-related genes. The score moderately correlated with abundance of vessel-related stromal cells, fibroblasts and chondrocytes in the tumor microenvironment (TME). Tumors with high score had low infiltration of T helper type 1 and 2 cells but a greater infiltration of M1 macrophages and dendritic cells. They also had enriched e xpression of gene sets for coagulation, hypoxia, epithelial mesenchymal transition (EMT), and TGF-β signaling. High angiogenesis score was significantly associated with advanced AJCC stage and higher T- but not N-parameters in the TNM staging system. Patients with a high score also had shorter survival. In conclusion, bulk tumor transcriptome-based quantification of tumor angiogenesis using a computational algorithm may serve to identify patients with worse survival in gastric cancer. PMID:33948380 | PMC:PMC8085878 View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.