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https://www.readbyqxmd.com/read/28439842/controversies-in-the-multimodality-management-of-locally-advanced-rectal-cancer
#1
REVIEW
Robert Díaz Beveridge, Dilara Akhoundova, Gema Bruixola, Jorge Aparicio
Neoadjuvant radiotherapy previous to radical surgery, both as short-course radiotherapy and as long-course radiotherapy combined with 5-FU-based chemotherapy (LCRCT), is routinely used in the management of locally advanced rectal cancer, with consistent benefits in the reduction in the local relapse risk. Unfortunately, survival benefits have been elusive to demonstrate with this approach, especially in the setting of radical surgery in the form of total mesorectal excision (TME). Concerns about over-treating early-stage patients and about the possible long-term side effects have also cast more doubts in a blanket approach of treating all patients with neoadjuvant radiotherapy, especially with LCRCT...
June 2017: Medical Oncology
https://www.readbyqxmd.com/read/28436951/hypoxic-lung-cancer-secreted-exosomal-mir-23a-increased-angiogenesis-and-vascular-permeability-by-targeting-prolyl-hydroxylase-and-tight-junction-protein-zo-1
#2
Y-L Hsu, J-Y Hung, W-A Chang, Y-S Lin, Y-C Pan, P-H Tsai, C-Y Wu, P-L Kuo
Hypoxia plays a critical role during the evolution of malignant cells and tumour microenvironment (TME).Tumour-derived exosomes contain informative microRNAs involved in the interaction of cancer and stromal cells, thus contributing to tissue remodelling of tumour microenvironment. This study aims to clarify how hypoxia affects tumour angiogenesis through exosomes shed from lung cancer cells. Lung cancer cells produce more exosomes under hypoxic conditions than do parental cells under normoxic conditions. miR-23a was significantly upregulated in exosomes from lung cancer under hypoxic conditions...
April 24, 2017: Oncogene
https://www.readbyqxmd.com/read/28433044/-laparoscopic-diverting-ileostomy-in-rectal-cancer-surgery
#3
P Ihnát, P Vávra, P Guňková, A Zatloukal, S Czudek, P Zonča
INTRODUCTION: Low anterior resection (LAR) with total mesorectal excision (TME) represents the gold standard for patients with low rectal carcinoma. Protective ileostomy (PI) is commonly performed during LAR in an effort to protect low rectal anastomosis. The aim of this study is to analyse outcomes in our own patient population, focusing on morbidity associated with PI. METHOD: A retrospective clinical study of patients operated on between 2013 and 2015 was conducted in University Hospital Ostrava...
2017: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/28429950/-can-robotic-rectal-cancer-surgery-improve-quality-of-total-mesorectal-excision
#4
D Langer, I Tučková, J Kalvach, M Ryska
INTRODUCTION: The introduction of total mesorectal excision (TME) in the 1980s was pivotal in the surgical treatment for rectal carcinoma (RC). Routinely applied TME led to a significant reduction in the incidence of local recurrences. The purpose of our paper is to present the results of our non-randomized study comparing prospectively acquired data from radical resection / rectal extirpation using classic open access, laparoscopy and da Vinci robotic system. METHOD: The study group included 116 patients with RC who underwent radical surgical treatment between 1/2014-12/2016, after which the collected resection specimens were assessed in pathology laboratories of the referring hospital using the Quirkes protocol...
2017: Rozhledy V Chirurgii: Měsíčník Československé Chirurgické Společnosti
https://www.readbyqxmd.com/read/28423676/tumor-associated-macrophages-promote-ezrin-phosphorylation-mediated-epithelial-mesenchymal-transition-in-lung-adenocarcinoma-through-fut4-ley-up-regulation
#5
Aman Wang, Chang Lu, Zhen Ning, Wei Gao, Yunpeng Xie, Ningning Zhang, Jinxiao Liang, Faisal S Abbasi, Qiu Yan, Jiwei Liu
Tumor-associated macrophages (TAMs) are key components of tumor microenvironment (TME) during tumorigenesis and progression. However, the role of TAMs in lung adenocarcinoma is still unclear. In this study, we aimed to clarify the mechanism underlying the crosstalk between TAMs and epithelial-mesenchymal transition (EMT) of lung adenocarcinoma. Fucosyltransferase IV (FUT4) and its synthetic cancer sugar antigen Lewis Y (LeY) was aberrantly elevated in various solid tumors, it plays critical role in the invasion and metastasis...
March 8, 2017: Oncotarget
https://www.readbyqxmd.com/read/28421069/engineering-chimeric-antigen-receptor-t-cells-for-racing-in-solid-tumors-don-t-forget-the-fuel
#6
REVIEW
Melita Irving, Romain Vuillefroy de Silly, Kirsten Scholten, Nahzli Dilek, George Coukos
T-cells play a critical role in tumor immunity. Indeed, the presence of tumor-infiltrating lymphocytes is a predictor of favorable patient prognosis for many indications and is a requirement for responsiveness to immune checkpoint blockade therapy targeting programmed cell death 1. For tumors lacking immune infiltrate, or for which antigen processing and/or presentation has been downregulated, a promising immunotherapeutic approach is chimeric antigen receptor (CAR) T-cell therapy. CARs are hybrid receptors that link the tumor antigen specificity and affinity of an antibody-derived single-chain variable fragment with signaling endodomains associated with T-cell activation...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28419513/genetic-recombination-between-stromal-and-cancer-cells-results-in-highly-malignant-cells-identified-by-color-coded-imaging-in-a-mouse-lymphoma-model
#7
Miki Nakamura, Atsushi Suetsugu, Kousuke Hasegawa, Takuro Matsumoto, Hitomi Aoki, Takahiro Kunisada, Masahito Shimizu, Shigetoyo Saji, Hisataka Moriwaki, Robert M Hoffman
The tumor microenvironment (TME) promotes tumor growth and metastasis. We previously established the color-coded EL4 lymphoma model with red fluorescent protein expressing EL4 implanted in transgenic C57BL/6 green fluorescent protein (GFP) mice. Color-coded imaging of the lymphoma tumor suggested an important role of stromal cells in lymphoma progression and metastasis. In the present study, we used color-coded imaging of RFP-lymphoma cells and GFP stromal cells to identify yellow-fluorescent recombinant cells appearing only during metastasis...
April 17, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28416797/unification-of-de-novo-and-acquired-ibrutinib-resistance-in-mantle-cell-lymphoma
#8
Xiaohong Zhao, Tint Lwin, Ariosto Silva, Bijal Shah, Jiangchuan Tao, Bin Fang, Liang Zhang, Kai Fu, Chengfeng Bi, Jiannong Li, Huijuan Jiang, Mark B Meads, Timothy Jacobson, Maria Silva, Allison Distler, Lancia Darville, Ling Zhang, Ying Han, Dmitri Rebatchouk, Maurizio Di Liberto, Lynn C Moscinski, John M Koomen, William S Dalton, Kenneth H Shain, Michael Wang, Eduardo Sotomayor, Jianguo Tao
The novel Bruton's tyrosine kinase inhibitor ibrutinib has demonstrated high response rates in B-cell lymphomas; however, a growing number of ibrutinib-treated patients relapse with resistance and fulminant progression. Using chemical proteomics and an organotypic cell-based drug screening assay, we determine the functional role of the tumour microenvironment (TME) in ibrutinib activity and acquired ibrutinib resistance. We demonstrate that MCL cells develop ibrutinib resistance through evolutionary processes driven by dynamic feedback between MCL cells and TME, leading to kinome adaptive reprogramming, bypassing the effect of ibrutinib and reciprocal activation of PI3K-AKT-mTOR and integrin-β1 signalling...
April 18, 2017: Nature Communications
https://www.readbyqxmd.com/read/28412591/baseline-%C3%AE-catenin-programmed-death-ligand-1-expression-and-tumour-infiltrating-lymphocytes-predict-response-and-poor-prognosis-in-braf-inhibitor-treated-melanoma-patients
#9
Daniela Massi, Emanuela Romano, Eliana Rulli, Barbara Merelli, Romina Nassini, Francesco De Logu, Ivan Bieche, Gianna Baroni, Laura Cattaneo, Gongda Xue, Mario Mandalà
BACKGROUND: The activation of oncogenic Wnt/β-catenin pathway in melanoma contributes to a lack of T-cell infiltration. Whether baseline β-catenin expression in the context of tumour-infiltrating lymphocytes (TILs) and programmed death ligand-1 (PD-L1) overexpression correlates with prognosis of metastatic melanoma patients (MMPs) treated with mitogen-activated protein kinase, MAPK inhibitor (MAPKi) monotherapy, however, has not been fully clarified. PATIENTS AND METHODS: Sixty-four pre-treatment formalin-fixed and paraffin embedded melanoma samples from MMP treated with a BRAF inhibitor (n = 39) or BRAF and MEK inhibitors (n = 25) were assessed for presence of β-catenin, PD-L1, cluster of differentiation (CD)8, CD103 and forkhead box protein P3 (FOXP3) expression by immunohistochemistry, and results were correlated with clinical outcome...
April 13, 2017: European Journal of Cancer
https://www.readbyqxmd.com/read/28405776/immune-mediated-and-hypoxia-regulated-programs-accomplices-in-resistance-to-anti-angiogenic-therapies
#10
Diego O Croci, Santiago P Mendez-Huergo, Juan P Cerliani, Gabriel A Rabinovich
In contrast to mechanisms taking place during resistance to chemotherapies or other targeted therapies, compensatory adaptation to angiogenesis blockade does not imply a mutational alteration of genes encoding drug targets or multidrug resistance mechanisms but instead involves intrinsic or acquired activation of compensatory angiogenic pathways. In this article we highlight hypoxia-regulated and immune-mediated mechanisms that converge in endothelial cell programs and preserve angiogenesis in settings of vascular endothelial growth factor (VEGF) blockade...
April 13, 2017: Handbook of Experimental Pharmacology
https://www.readbyqxmd.com/read/28405495/biological-and-clinical-significance-of-tryptophan-catabolizing-enzymes-in-cutaneous-t-cell-lymphomas
#11
Pilvi Maliniemi, Kirsi Laukkanen, Liisa Väkevä, Katja Dettmer, Tuomas Lipsanen, Leila Jeskanen, Alban Bessede, Peter J Oefner, Marshall E Kadin, Annamari Ranki
Indoleamine 2,3-deoxygenase 1 (IDO1) induces immune tolerance in the tumor microenvironment (TME) and is recognized as a potential therapeutic target. We studied the expression of both IDO1 and the related tryptophan 2,3-dioxygenase (TDO) in several different subtypes of cutaneous T-cell lymphoma (CTCL), and evaluated the kynurenine (KYN) pathway in the local TME and in patient sera. Specimens from the total of 90 CTCL patients, including mycosis fungoides (MF, n = 37), lymphomatoid papulosis (LyP, n = 36), primary cutaneous anaplastic large cell lymphoma (pcALCL, n = 4), subcutaneous panniculitis-like T-cell lymphoma (SPTCL n = 13), and 10 patients with inflammatory lichen ruber planus (LRP), were analyzed by immunohistochemistry (IHC), immunofluorescence (IF), quantitative PCR, and/or liquid chromatography-tandem mass spectrometry (LC-MS/MS)...
2017: Oncoimmunology
https://www.readbyqxmd.com/read/28391975/evaluation-of-endorectal-ultrasound-erus-and-mri-for-prediction-of-circumferential-resection-margin-crm-for-rectal-cancer
#12
Catherine Tsai, Cameron Hague, Wei Xiong, Manoj Raval, Ahmer Karimuddin, Carl Brown, P Terry Phang
ERUS and MRI are used for preoperative imaging of rectal cancer. Here, we compare ERUS and MRI for accuracy of CRM prediction at mid- and distal rectal locations. In retrospective review, 20 rectal cancer patients having TME surgery had both ERUS and MRI preoperatively: 8 mid rectum and 12 in distal rectum. Predicted CRM by ERUS and MRI were compared to TME pathology. Overall, predicted CRM was 6.5 ± 3.6 mm by ERUS, 7.7 ± 5.0 mm by MRI, and 6.0 ± 4.6 mm by pathology. Overall, correlation coefficients to pathology were 0...
March 27, 2017: American Journal of Surgery
https://www.readbyqxmd.com/read/28388539/preferential-accumulation-of-regulatory-t-cells-with-highly-immunosuppressive-characteristics-in-breast-tumor-microenvironment
#13
Azharuddin Sajid Syed Khaja, Salman M Toor, Haytham El Salhat, Issam Faour, Navid Ul Haq, Bassam R Ali, Eyad Elkord
Immunosuppressive cells such as regulatory T cells (Tregs) have an ambiguous role in breast cancer prognosis, with studies reporting both positive and negative correlations between Treg infiltration and prognosis. This discrepancy could be due to the different immunosuppressive molecules present in these cells. In the present study, we phenotypically characterize different Treg subsets infiltrating the tumor microenvironment (TME), compared to adjacent normal tissue and peripheral blood of primary breast cancer (PBC) patients...
March 25, 2017: Oncotarget
https://www.readbyqxmd.com/read/28382138/role-of-tumor-microenvironment-in-tumorigenesis
#14
REVIEW
Maonan Wang, Jingzhou Zhao, Lishen Zhang, Fang Wei, Yu Lian, Yingfeng Wu, Zhaojian Gong, Shanshan Zhang, Jianda Zhou, Ke Cao, Xiayu Li, Wei Xiong, Guiyuan Li, Zhaoyang Zeng, Can Guo
Tumorigenesis is a complex and dynamic process, consisting of three stages: initiation, progression, and metastasis. Tumors are encircled by extracellular matrix (ECM) and stromal cells, and the physiological state of the tumor microenvironment (TME) is closely connected to every step of tumorigenesis. Evidence suggests that the vital components of the TME are fibroblasts and myofibroblasts, neuroendocrine cells, adipose cells, immune and inflammatory cells, the blood and lymphatic vascular networks, and ECM...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28381943/transanal-total-mesorectal-excision-a-novel-approach-to-rectal-surgery
#15
REVIEW
Pasithorn A Suwanabol, Justin A Maykel
Less invasive approaches continue to be explored and refined for diseases of the colon and rectum. The current gold standard for the surgical treatment of rectal cancer, total mesorectal excision (TME), is a technically precise yet demanding procedure with outcomes measured by both oncologic and functional outcomes (including bowel, urinary, and sexual). To date, the minimally invasive approach to rectal cancer has not yet been perfected, leaving ample opportunity for rectal surgeons to innovate. Transanal TME has recently emerged as a safe and effective technique for both benign and malignant diseases of the rectum...
April 2017: Clinics in Colon and Rectal Surgery
https://www.readbyqxmd.com/read/28381673/iron-ii-porphyrin-cyclodextrin-supramolecular-complex-as-a-carbon-monoxide-depleting-agent-in-living-organisms
#16
REVIEW
Hiroaki Kitagishi, Saika Minegishi
The specific intermolecular interaction between an anionic tetraarylporphyrin and per-O-methylated β-cyclodextrin (TMe-β-CD) paved the way to produce a functional supramolecule that works as a strong carbon monoxide (CO)-depleting agent in living organisms. The supramolecular complex, hemoCD, that is composed of meso-tetrakis(4-sulfonatophenyl)porphinatoiron(II) and a TMe-β-CD dimer linked by a pyridine linker, captured internal CO from carboxyhemoglobin during its circulation in the blood of animals. HemoCD thus produced the pseudo-knockdown (loss-of-functional) state of endogenous CO in the animals...
2017: Chemical & Pharmaceutical Bulletin
https://www.readbyqxmd.com/read/28369422/ileal-pouch-anal-anastomosis-for-dysplasia-or-cancer-complicating-inflammatory-bowel-disease-is-total-mesorectal-excision-always-mandatory-an-analysis-of-36-consecutive-patients
#17
Chloé Coton, Léon Maggiori, Diane Mège, Clotilde Naudot, Justine Prost À la Denise, Yves Panis
Background & Aim: The extent of lymph node harvesting during surgery for colorectal neoplasm (dysplasia and/or cancer) complicating inflammatory bowel disease (IBD) is the matter of debate. This study aimed to assess the risk of invasive rectal cancer in patients undergoing ileal pouch-anal anastomosis (IPAA) for colonic neoplasm complicating IBD, and thus to clarify if a systematic total mesorectal excision (TME) should be systematically performed or not in those patients. Methods: From 1998 to 2015, all patients who underwent IPAA for colorectal neoplasm complicating IBD were included...
March 22, 2017: Journal of Crohn's & Colitis
https://www.readbyqxmd.com/read/28360267/decoupling-genetics-lineages-and-microenvironment-in-idh-mutant-gliomas-by-single-cell-rna-seq
#18
Andrew S Venteicher, Itay Tirosh, Christine Hebert, Keren Yizhak, Cyril Neftel, Mariella G Filbin, Volker Hovestadt, Leah E Escalante, McKenzie L Shaw, Christopher Rodman, Shawn M Gillespie, Danielle Dionne, Christina C Luo, Hiranmayi Ravichandran, Ravindra Mylvaganam, Christopher Mount, Maristela L Onozato, Brian V Nahed, Hiroaki Wakimoto, William T Curry, A John Iafrate, Miguel N Rivera, Matthew P Frosch, Todd R Golub, Priscilla K Brastianos, Gad Getz, Anoop P Patel, Michelle Monje, Daniel P Cahill, Orit Rozenblatt-Rosen, David N Louis, Bradley E Bernstein, Aviv Regev, Mario L Suvà
Tumor subclasses differ according to the genotypes and phenotypes of malignant cells as well as the composition of the tumor microenvironment (TME). We dissected these influences in isocitrate dehydrogenase (IDH)-mutant gliomas by combining 14,226 single-cell RNA sequencing (RNA-seq) profiles from 16 patient samples with bulk RNA-seq profiles from 165 patient samples. Differences in bulk profiles between IDH-mutant astrocytoma and oligodendroglioma can be primarily explained by distinct TME and signature genetic events, whereas both tumor types share similar developmental hierarchies and lineages of glial differentiation...
March 31, 2017: Science
https://www.readbyqxmd.com/read/28358369/mirna199a-3p-suppresses-tumor-growth-migration-invasion-and-angiogenesis-in-hepatocellular-carcinoma-by-targeting-vegfa-vegfr1-vegfr2-hgf-and-mmp2
#19
Alip Ghosh, Debanjali Dasgupta, Amit Ghosh, Shrabasti Roychoudhury, Dhiraj Kumar, Mahadeo Gorain, Ramesh Butti, Simanti Datta, Shaleen Agarwal, Subash Gupta, Gopal Krishna Dhali, Abhijit Chowdhury, Thomas D Schmittgen, Gopal C Kundu, Soma Banerjee
Increasing significance of tumor-stromal interaction in development and progression of cancer implies that signaling molecules in the tumor microenvironment (TME) might be the effective therapeutic targets for hepatocellular carcinoma (HCC). Here, the role of microRNA miR-199a-3p in the regulation of TME and development of HCC has been investigated by several in vitro and in vivo assays. Expression of miR-199a-3p was observed significantly low in HCC tissues and its overexpression remarkably inhibited in vivo tumor growth and metastasis to lung in NOD-SCID mice...
March 30, 2017: Cell Death & Disease
https://www.readbyqxmd.com/read/28356331/dna-damage-induces-a-secretory-program-in-the-quiescent-tme-that-fosters-adverse-cancer-phenotypes
#20
Luis Gomez-Sarosi, Yu Sun, Ilsa Coleman, Daniella Bianchi-Frias, Peter S Nelson
Carcinomas develop in complex environments that include a diverse spectrum of cell types that influence tumor cell behavior. These microenvironments represent dynamic systems that con-tribute to pathological processes. Damage to DNA is a notable inducer of both transient and permanent alterations in cellular phenotypes. Induction of a DNA-damage secretory program is known to promote adverse tumor cell behaviors such as proliferation, invasion, metastasis, and treatment resistance. However, prior studies designed to identify genotoxic stress-induced fac-tors evaluated actively proliferating in vitro cultures of cells such as fibroblasts as experimental models...
March 29, 2017: Molecular Cancer Research: MCR
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