Cancers, Vol. 12, Pages 3379: Osteopontin: A Key Regulator of Tumor Progression and Immunomodulation

Alexandros G.Sfakianakis shared this article with you from Inoreader Cancers, Vol. 12, Pages 3379: Osteopontin: A Key Regulator of Tumor Progression and Immunomodulation Μέσω Cancers Cancers, Vol. 12, Pages 3379: Osteopontin: A Key Regulator of Tumor Progression and Immunomodulation Cancers doi: 10.3390/cancers12113379 Authors: Hannah R. Moorman Dakota Poschel John D. Klement Chunwan Lu Priscilla S. Redd Kebin Liu OPN is a multifunctional phosphoglycoprotein expressed in a wide range of cells, including osteoclasts, osteoblasts, neurons, epithelial cells, T, B, NK, NK T, myeloid, and innate lymphoid cells. OPN plays an important role in diverse biological processes and is implicated in multiple diseases such as cardiovascular, diabetes, kidney, proinflammatory, fibrosis, nephrolithiasis, wound healing, and cancer. In cancer patients, overexpressed OPN is often detected in the tumor microenvironment and elevated serum OPN level is correlated with poor prognosis. Initially identified in activated T cells and termed as early T cell activation gene, OPN links innate cells to adaptive cells in immune response to infection and cancer. Recent single cell RNA sequencing revealed that OPN is primarily expressed in tumor cells and tumor-infiltrating myeloid cells in human cancer patients. Emerging experimental data reveal a key role of OPN is tumor immune evasion through regulating macrophage polari zation, recruitment, and inhibition of T cell activation in the tumor microenvironment. Therefore, in addition to its well-established direct tumor cell promotion function, OPN also acts as an immune checkpoint to negatively regulate T cell activation. The OPN protein level is highly elevated in peripheral blood of human cancer patients. OPN blockade immunotherapy with OPN neutralization monoclonal antibodies (mAbs) thus represents an attractive approach in human cancer immunotherapy. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cancers, Vol. 12, Pages 3381: Outcome of Targeted Therapy Recommendations for Metastatic and Recurrent Head and Neck Cancers

Alexandros G.Sfakianakis shared this article with you from Inoreader Cancers, Vol. 12, Pages 3381: Outcome of Targeted Therapy Recommendations for Metastatic and Recurrent Head and Neck Cancers Μέσω Cancers Cancers, Vol. 12, Pages 3381: Outcome of Targeted Therapy Recommendations for Metastatic and Recurrent Head and Neck Cancers Cancers doi: 10.3390/cancers12113381 Authors: Hossein Taghizadeh Robert M. Mader Leonhard Müllauer Thorsten Fuereder Alexandra Kautzky-Willer Gerald W. Prager Recurrent/metastatic (R/M) head and neck cancers bear a poor prognosis. In this analysis, we examined the efficacy and the outcome of targeted therapy recommendations based on the patients’ molecular tumor portrait after failure of all standard therapy options. In this single-center, real-world retrospective analysis of our platform for precision medicine, we analyzed the molecular profile of 50 patients diagnosed with R/M head and neck cancer. Tumor samples of the patients were examined using next-generation sequencing panels of mutation hotspots, microsatellite instability (MSI) testing, and immunohistochemistry (IHC). In 31 cases (62.0% of all patients), a molecular-driven targeted therapy approach was recommended. Eventually, 14 patients (28%) received the suggested targeted therapy. Six of fourteen patients (43%) achieved stable disease conditions and four patients (29%) experienced a progressive disease. The median time to treatment failure was 2.8 months. Therapy recommendations were significantly more often issued for men (p = 0.037) than for women. This analysis demonstrated that precision medicine provided the basis for molecular-driven therapy recommendations in over half of the patients with advanced therapy refractory head and neck cancers, with significantly more therapy recommendations for men. Our analysis showed that although precision medicine approaches are implementable and feasible for the management of recurrent/metastatic head and neck cancers in daily clinical routine, there are major limitations and challenges that have to be overcome. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cancers, Vol. 12, Pages 3380: Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling

Alexandros G.Sfakianakis shared this article with you from Inoreader Cancers, Vol. 12, Pages 3380: Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling Μέσω Cancers Cancers, Vol. 12, Pages 3380: Cancer-Associated Angiogenesis: The Endothelial Cell as a Checkpoint for Immunological Patrolling Cancers doi: 10.3390/cancers12113380 Authors: Antonio Giovanni Solimando Simona De Summa Angelo Vacca Domenico Ribatti Cancer-associated neo vessels’ formation acts as a gatekeeper that orchestrates the entrance and egress of patrolling immune cells within the tumor milieu. This is achieved, in part, via the directed chemokines’ expression and cell adhesion molecules on the endothelial cell surface that attract and retain circulating leukocytes. The crosstalk between adaptive immune cells and the cancer endothelium is thus essential for tumor immune surveillance and the success of immune-based therapies that harness immune cells to kill tumor cells. This review will focus on the biology of the endothelium and will explore the vascular-specific molecular mediators that control the recruitment, retention, and trafficking of immune cells that are essential for effective antitumor immunity. The literature revision will also explore how abnormalities in the tumor endothelium impair crosstalk with adaptive immune cells and how targeting these abnormalities can improve the success of immune-based therapies for different malignancies, with a particular focus on the paradigmatic example represented by multiple myeloma. We also generated and provide two original bio-informatic analyses, in order to sketch the physiopathology underlying the endothelial–neoplastic interactions in an easier manner, feeding into a vicious cycle propagating disease progression and highlighting novel pathways that might be exploited therapeutically. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Clinical Challenges in the Management of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Literature Review

Alexandros G.Sfakianakis shared this article with you from Inoreader Clinical Challenges in the Management of Hormone Receptor-Positive, Human Epidermal Growth Factor Receptor 2-Negative Metastatic Breast Cancer: A Literature Review Μέσω Advances in Therapy Abstract Endocrine therapy (ET) is integral to the treatment of hormone receptor-positive (HR+), human epidermal growth factor receptor 2-negative (HER2−) metastatic breast cancer (MBC). Aromatase inhibitors (AIs; e.g., anastrozole, letrozole, exemestane), selective estrogen receptor modulators (e.g., tamoxifen), and the selective estrogen receptor degrader, fulvestrant, inhibit tumor cell proliferation by targeting ER signaling. However, the efficacy of ET could be limited by intrinsic and acquired resistance mechanisms, which has prompted the development of targeted agents and combination strategies. In recent years, the treatment landscape for HR+, HER2− MBC has evolved rapidly. AIs, historically the first-line treatment for postmenopausal patients with HR+, HER2− MBC, have been challenged by more effective ET, such as fulvestrant alone or in combination with an AI, and the cyclin-dependent kinase (CDK)4/6 inhibitors, which have increasingly become the new standa rd of care. For endocrine-resistant disease (≥ second-line), clinical trials demonstrated that the mammalian target of rapamycin inhibitor, everolimus, enhanced the efficacy of exemestane or fulvestrant after progression on an AI. CDK4/6 inhibitors in combination with fulvestrant have demonstrated superior progression-free survival and overall survival versus fulvestrant alone. Recently, the combination of fulvestrant with alpelisib in phosphatidylinositol-4,5-bisphosphate 3-kinase (PIK3CA) mutated HR+, HER2− MBC following progression on or after ET was approved, based on the SOLAR-1 study. However, the optimal sequencing of treatments is unknown, especially following disease progression on a CDK4/6 inhibitor. This review aims to provide practical guidance for the management of HR+, HER2− MBC based on available data and the utility of genomic biomarkers, including germline breast cancer genes 1 and 2 (BRCA1/2) mutations, and somatic estrogen receptor alpha gene (ESR1), HER2, and PIK3CA mutations. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Ethosuximide Induced Macroglossia and Oropharyngeal Edema

Alexandros G.Sfakianakis shared this article with you from Inoreader Ethosuximide Induced Macroglossia and Oropharyngeal Edema Μέσω ScienceDirect Publication: International Journal of Pediatric Otorhinolaryngology Publication date: Available online 15 November 2020 Source: International Journal of Pediatric Otorhinolaryngology Author(s): Hanqing Shang, Mica Glaun, Julina Ongkasuwan View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

JPM, Vol. 10, Pages 231: Ocular Vascular Changes in Mild Alzheimer’s Disease Patients: Foveal Avascular Zone, Choroidal Thickness, and ONH Hemoglobin Analysis

Alexandros G.Sfakianakis shared this article with you from Inoreader JPM, Vol. 10, Pages 231: Ocular Vascular Changes in Mild Alzheimer's Disease Patients: Foveal Avascular Zone, Choroidal Thickness, and ONH Hemoglobin Analysis Μέσω Journal of Personalized Medicine JPM, Vol. 10, Pages 231: Ocular Vascular Changes in Mild Alzheimer's Disease Patients: Foveal Avascular Zone, Choroidal Thickness, and ONH Hemoglobin Analysis Journal of Personalized Medicine doi: 10.3390/jpm10040231 Authors: Elena Salobrar-Garcia Carmen Méndez-Hernández Rosa de Hoz Ana I. Ramírez Inés López-Cuenca José A. Fernández-Albarral Pilar Rojas Surina Wang Julián García-Feijoo Pedro Gil Juan J. Salazar José M. Ramírez In Alzheimer’s disease (AD), vascular changes could be caused by amyloid beta (Aβ) aggregates replacing the contractile smooth musculature of the arteriole walls. These changes happen in the brain vascular network, but also in the eye, and are related to decreased vascular density and low blood flow. In patients with Alzheimer’s disease, thinning of the choroid and the retina has been shown. The aim of this prospective study was to assess the retinal and choroidal vascular systems, analyzing the choroidal thickness with optical coherence tomography (OCT), the foveal avascular zone (FAZ) with OCT-angiography (OCTA), and the optic nerve head (ONH) hemoglobin with the Laguna ONhE program, to evaluate which of the two ocular vascular systems shows earlier changes in mild AD patients. These patients, compared to controls, showed a significantly thinner choroid at all the analyzed points, with the exception of the temporal macula (at 1000 and 1500 &micr o;m from the fovea). On the other hand, the FAZ and ONH hemoglobin did not show significant differences. In conclusion, a thinner choroid was the main ocular vascular change observed in mild AD patients, while the retinal vessels were not yet affected. Therefore, choroidal thickness could be used an early biomarker in AD. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Contralateral tension pneumothorax during video-assisted thoracic surgery for lung cancer in a patient with obesity and rib fractures: a case report and review of the literature

Alexandros G.Sfakianakis shared this article with you from Inoreader Contralateral tension pneumothorax during video-assisted thoracic surgery for lung cancer in a patient with obesity and rib fractures: a case report and review of the literature Μέσω Journal of Medical Case Reports - Latest Articles Intraoperative contralateral pneumothorax during one-lung ventilation is a rare but life-threatening complication. Although the exact incidence is unknown, only 14 cases with this complication have been report... View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

A Subset of Intrahepatic Cholangiocarcinomas Express Albumin RNA as Detected by In Situ Hybridization

Alexandros G.Sfakianakis shared this article with you from Inoreader A Subset of Intrahepatic Cholangiocarcinomas Express Albumin RNA as Detected by In Situ Hybridization Μέσω Applied Immunohistochemistry & Molecular Morphology - Published Ahead-of-Print Intrahepatic cholangiocarcinomas (ICCs) show morphologic diversity, ranging from tumors composed of nonmucinous small ducts to mucin-producing large duct tumors to tumors with mixed hepatocellular carcinoma features. Diagnosing ICCs can be difficult, especially on biopsy, not only because of the morphologic diversity, but also because metastatic tumors are often in the differential diagnosis. Recently, branched DNA-based albumin RNA in situ hybridization (ISH) has been shown to be a potential sensitive and specific marker for ICC with 99% sensitivity. Using a different RNA ISH technology, we evaluated the expression of albumin RNA ISH in ICC. We performed RNA ISH for albumin using RNAscope on 43 ICCs in a triplicate tissue microarray. Albumin RNA ISH was positive in 18 of 43 (42%) I CCs. Five of the 6 (83%) combined hepatocellular carcinoma-CC were positive in the CC component. None of the tumors with mucin production were positive (0/9). In our cohort, albumin RNA ISH showed a sensitivity of 42% in ICCs, supporting the morphologic diversity of ICCs. Albumin RNA ISH does not appear to be a highly sensitive marker for ICC and hence cannot be used as a stand-alone marker for ICC. The authors declare no conflict of interest. Reprints: Vaidehi Avadhani, MD, Emory University Hospital/Grady Memorial, 80 Jesse Hill Jr. Drive SE, Atlanta, GA 30303 (e-mails: vavadha@emory.edu; vpathology@gmail.com). Received April 22, 2020 Accepted October 7, 2020 Copyright 2020 Wolters Kluwer Health, Inc. All rights reserved. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as HPV hot spot integration site

Alexandros G.Sfakianakis shared this article with you from Inoreader Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of <i>MACROD2</i> gene as HPV hot spot integration site Μέσω British Journal of Cancer - Issue - nature.com science feeds British Journal of Cancer, Published online: 16 November 2020; doi:10.1038/s41416-020-01153-4 Human papilloma virus (HPV) integration signature in Cervical Cancer: identification of MACROD2 gene as H PV hot spot integration site View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

Cancers, Vol. 12, Pages 3382: Comprehensive Gene Mutation Profiling of Circulating Tumor DNA in Ovarian Cancer: Its Pathological and Prognostic Impact

Alexandros G.Sfakianakis shared this article with you from Inoreader Cancers, Vol. 12, Pages 3382: Comprehensive Gene Mutation Profiling of Circulating Tumor DNA in Ovarian Cancer: Its Pathological and Prognostic Impact Μέσω Cancers Cancers, Vol. 12, Pages 3382: Comprehensive Gene Mutation Profiling of Circulating Tumor DNA in Ovarian Cancer: Its Pathological and Prognostic Impact Cancers doi: 10.3390/cancers12113382 Authors: Tomoko Noguchi Naoyuki Iwahashi Kazuko Sakai Kaho Matsuda Hitomi Matsukawa Saori Toujima Kazuto Nishio Kazuhiko Ino Liquid biopsies from circulating tumor DNA (ctDNA) have been employed recently as a non-invasive diagnostic tool for detecting cancer-specific gene mutations. Here, we show the comprehensive gene mutation profiles of ctDNA in 51 patients with different histological subtypes of stage I–IV ovarian cancer, and their association with clinical outcomes. The ctDNA extracted from pre-treatment patients’ plasma were analyzed using Cancer Personalized Profiling by Deep Sequencing targeting 197 genes. Of 51 patients, 48 (94%) showed one or more non-synonymous somatic mutations, including TP53 (37.3%), APC (17.6%), KRAS (15.7%), EGFR (13.7%), MET (11.8%), PIK3CA (11.8%), NPAP1 (11.8%), and ALK (9.8%). The most frequently mutated genes were as follows: TP53 in high-grade serous carcinoma (66.7%), APC in clear cell carcinoma (30.8%), PIK3CA in endometrioid carcinoma (40%), and KRAS in mucinous carcinoma (66.7%). Higher cell-free (cf)DNA concentration significantly correlat ed with worse progression-free survival (PFS) in all patients as well as stage III–IV patients (p = 0.01 and 0.005, respectively). Further, patients with any pathogenic mutations showed significantly worse PFS (p = 0.048). Blood tumor mutational burden detected from ctDNA did not significantly correlate with the histological subtypes or survival. Collectively, clinico-genomic profiles of individual ovarian cancer patients could be identified using ctDNA and may serve as a useful prognostic indicator. These findings suggest that ctDNA-based gene profiling might help in establishing personalized therapeutic strategies. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.

The Influence of Weight-Related Self-Esteem and Symptoms of Depression on Shape and Weight Concerns and Weight-Loss 12 Months After Bariatric Surgery

alkiviadis.1961 shared this article with you from Inoreader The Influence of Weight-Related Self-Esteem and Symptoms of Depression on Shape and Weight Concerns and Weight-Loss 12 Months After Bariatric Surgery Via Latest Results for Obesity Surgery Abstract Introduction While body image can improve following bariatric surgery, a portion of patients continue to experience concerns about weight and shape regardless of weight lost. Research is needed to identify risk factors for post-surgical weight and shape concerns given that body dissatisfaction may contribute to poor outcomes. Aims To evaluate whether (1) change in weight-related self-esteem and symptoms of depression from pre- to 12-month post-surgery were associated with change in weight and shape concerns independent of weight-loss; (2) improvement in weight and shape concerns, symptoms of depression, and/or weight-related self-esteem predict greater weight-loss 12 months after bariatric surgery; and (3) improvements in weight-related self-esteem, symptoms of depression, weight concerns, or shape concerns predict weight loss. Methods Fifty adults approved to receive bariatric surgery self-reported body mass index and completed validated measures of weight-related self-esteem, symptoms of depression, and weight and shape concerns pre- and 12-month post-surgery. Results Improvements were observed for weight-related self-esteem, concerns over shape and weight, symptoms of depression, and body mass index from pre- to 12-month post-surgery. Improvement in weight-related self-esteem was associated with concomitant improvements in concerns over shape and weight, independent of weight loss. Improvement in symptoms of depression was associated with improvement in concerns over weight, but not shape. Finally, exploratory analyses indicated that improvements in weight-related self-esteem, and concerns over shape and weight, but not symptoms of depression were associated with improvement in weight-loss. Conclusions Weight-related self-esteem may represent an overlooked and important target throughout the bariatric surgery process that could enhance surgical outcomes. View on the web Inoreader. Take back control of your news feed. Follow us on Twitter and Facebook.