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https://www.readbyqxmd.com/read/28633898/2-chlorophenyl-substituted-benzofuro-3-2-b-pyridines-with-enhanced-topoisomerase-inhibitory-activity-the-role-of-the-chlorine-substituent
#1
Til Bahadur Thapa Magar, Tara Man Kadayat, Hwa-Jong Lee, Seojeong Park, Ganesh Bist, Aarajana Shrestha, Youngjoo Kwon, Eung-Seok Lee
A new series of 2-chloropheny-substituted benzofuro[3,2-b]pyridines were designed, synthesized, and evaluated for topoisomerase I and II inhibition and antiproliferative activity. Compounds 17-19, 23, 24, 26, and 27 exhibited excellent topo II inhibitory activity. A systematic structure-activity relationship study revealed the important role of chlorine substitution in the strong topoisomerase inhibitory activity.
June 9, 2017: Bioorganic & Medicinal Chemistry Letters
https://www.readbyqxmd.com/read/28632936/peritumoral-cuffing-by-t-cell-tumor-infiltrating-lymphocytes-distinguishes-hpv-related-oropharyngeal-squamous-cell-carcinoma-from-oral-cavity-squamous-cell-carcinoma
#2
Kate Poropatich, David Hernandez, Joel Fontanarosa, Koshonna Brown, Gayle Woloschak, Ajit Paintal, Kirtee Raparia, Sandeep Samant
BACKGROUND: It is unclear why human papillomavirus (HPV)-related head and neck squamous cell carcinoma (HNSCC) has improved clinical behavior compared to HPV-negative HNSCC. We sought to better characterize the immune microenvironment of tongue cancers by examining the CD3 and CD8 TIL pattern in HPV-positive and -negative tumors. METHODS: Histologic sections from 40 oral tongue and oropharyngeal cases were analyzed (n= 21 HPV DNA-positive, n= 19 HPV DNA-negative)...
June 20, 2017: Journal of Oral Pathology & Medicine
https://www.readbyqxmd.com/read/28632718/epigenetic-changes-in-tils
#3
Laurie A Dempsey
No abstract text is available yet for this article.
June 20, 2017: Nature Immunology
https://www.readbyqxmd.com/read/28628234/tumor-targeting-salmonella-typhimurium-a1-r-promotes-tumoricidal-cd8-t-cell-tumor-infiltration-and-arrests-growth-in-a-syngeneic-pancreatic-cancer-orthotopic-mouse-model
#4
Takashi Murakami, Yukihiko Hiroshima, Yong Zhang, Ming Zhao, Tasuku Kiyuna, Ho Kyoung Hwang, Kentaro Miyake, Yuki Homma, Ryutaro Mori, Ryusei Matsuyama, Takashi Chishima, Yasushi Ichikawa, Kuniya Tanaka, Michael Bouvet, Itaru Endo, Robert M Hoffman
The present study determined the effect of tumor-targeting Salmonella typhimurium (S. typhimurium) A1-R on CD8(+) tumor-infiltrating lymphocytes (TILs) in a syngeneic pancreatic cancer orthotopic mouse model. The effect of tumor-targeting Salmonella typhimurium A1-R on CD8(+) TILs was determined on Pan02 murine pancreatic adenocarcinoma cells implanted orthotopically on the pancreatic tail of C57BL/6 mice. Three weeks after orthotopic implantation, mice were randomized into G1: untreated control group (n = 8); and G2: Salmonella typhimurium A1-R treatment group (n = 8, 1 × 10(7) CFU/body, iv, weekly, 3 weeks)...
June 19, 2017: Journal of Cellular Biochemistry
https://www.readbyqxmd.com/read/28627792/%C3%AE-catenin-in-desmoid-type-fibromatosis-deep-insights-on-the-role-of-t41a-and-s45f-mutations-on-protein-structure-and-gene-expression
#5
C Colombo, A Belfiore, N Paielli, L De Cecco, S Canevari, E Laurini, M Fermeglia, S Pricl, P Verderio, S Bottelli, M Fiore, S Stacchiotti, E Palassini, A Gronchi, S Pilotti, F Perrone
Desmoid- type fibromatosis (DF) is a rare mesenchymal lesion with high risk of local recurrence. Specific β-catenin mutations (S45F) appeared to be related to this higher risk compared to T41A mutated or wild type (WT). We explored the influence of both mutations and WT on structure stability and affinity of β-catenin for α-catenin and the pattern of gene expression that may influence DF behavior. Using 33 surgically resected primary DFs harboring T41A (n=14), S45F (n=10) or WT (n=9), we performed a comparative molecular analysis by protein/protein interaction modeling, gene expression by DASL microarrays, human inflammation gene panel and assessment of immune system-based biomarkers by immunohistochemistry...
June 19, 2017: Molecular Oncology
https://www.readbyqxmd.com/read/28626618/cytoplasmic-expression-of-c-myc-protein-is-associated-with-risk-stratification-of-mantle-cell-lymphoma
#6
Yi Gong, Xi Zhang, Rui Chen, Yan Wei, Zhongmin Zou, Xinghua Chen
AIM: To investigate the association of C-MYC protein expression and risk stratification in mantle cell lymphoma (MCL), and to evaluate the utility of C-MYC protein as a prognostic biomarker in clinical practice. METHODS: We conducted immunohistochemical staining of C-MYC, Programmed cell death ligand 1 (PD-L1), CD8, Ki-67, p53 and SRY (sex determining region Y) -11 (SOX11) to investigate their expression in 64 patients with MCL. The staining results and other clinical data were evaluated for their roles in risk stratification of MCL cases using ANOVA, Chi-square, and Spearman's Rank correlation coefficient analysis...
2017: PeerJ
https://www.readbyqxmd.com/read/28626343/anti-osm-antibody-inhibits-tubulointerstitial-lesion-in-a-murine-model-of-lupus-nephritis
#7
Qingjuan Liu, Yunxia Du, Kejun Li, Wei Zhang, Xiaojuan Feng, Jun Hao, Hongbo Li, Shuxia Liu
The purpose of this study was to investigate the role of oncostatin M (OSM) in tubulointerstitial lesion (TIL) in lupus nephritis (LN). We found that OSM was highly expressed in the renal tissue of LN mice. OSM is one of the interleukin-6 cytokine family members. In order to clarify the role and mechanism of OSM in LN, mice with LN were treated with anti-OSM antibody or isotype antibody. We evaluated the tubular epithelial-mesenchymal transdifferentiation (EMT) by detecting the E-cadherin, α-smooth muscle actin (α-SMA), and fibronectin (FN) expression...
2017: Mediators of Inflammation
https://www.readbyqxmd.com/read/28624814/pd-l1-and-intratumoral-immune-response-in-breast-cancer
#8
Zhi-Qiang Wang, Katy Milne, Heather Derocher, John R Webb, Brad H Nelson, Peter H Watson
PURPOSE: PD-L1 is thought to play an important role in the antitumor immune response. In this study, we investigated the expression of PD-L1 within breast tumor subsets to better define its prognostic significance. METHODS: Immunohistochemistry was performed to determine PD-L1 tumor cell expression and to enumerate CD8, CD4 and CD68 tumor-infiltrating leucocytes (TIL) in a cohort of 443 breast cancers categorized by molecular subtype. RESULTS: Across the entire cohort, PD-L1 tumor cell expression was observed in 73/443 (16...
May 30, 2017: Oncotarget
https://www.readbyqxmd.com/read/28621322/reliability-of-tumor-infiltrating-lymphocyte-and-tertiary-lymphoid-structure-assessment-in-human-breast-cancer
#9
Laurence Buisseret, Christine Desmedt, Soizic Garaud, Marco Fornili, Xiaoxiao Wang, Gert Van den Eyden, Alexandre de Wind, Sebastien Duquenne, Anais Boisson, Celine Naveaux, Francoise Rothé, Sandrine Rorive, Christine Decaestecker, Denis Larsimont, Martine Piccart-Gebhart, Elia Biganzoli, Christos Sotiriou, Karen Willard-Gallo
The presence of tumor-infiltrating lymphocytes (TIL), reflecting host immune activity, is frequently correlated with better clinical outcomes, particularly in HER2-positive and triple-negative breast cancer. Recent findings suggest that organization of immune infiltrates in tertiary lymphoid structures also has a beneficial effect on survival. This study investigated inter- and intra-observer variation in TIL assessment using conventional hematoxylin-eosin versus immunohistochemical staining to identify immune cells...
June 16, 2017: Modern Pathology: An Official Journal of the United States and Canadian Academy of Pathology, Inc
https://www.readbyqxmd.com/read/28614802/mitochondrial-dysregulation-and-glycolytic-insufficiency-functionally-impair-cd8-t-cells-infiltrating-human-renal-cell-carcinoma
#10
Peter J Siska, Kathryn E Beckermann, Frank M Mason, Gabriela Andrejeva, Allison R Greenplate, Adam B Sendor, Yun-Chen J Chiang, Armando L Corona, Lelisa F Gemta, Benjamin G Vincent, Richard C Wang, Bumki Kim, Jiyong Hong, Chiu-Lan Chen, Timothy N Bullock, Jonathan M Irish, W Kimryn Rathmell, Jeffrey C Rathmell
Cancer cells can inhibit effector T cells (Teff) through both immunomodulatory receptors and the impact of cancer metabolism on the tumor microenvironment. Indeed, Teff require high rates of glucose metabolism, and consumption of essential nutrients or generation of waste products by tumor cells may impede essential T cell metabolic pathways. Clear cell renal cell carcinoma (ccRCC) is characterized by loss of the tumor suppressor von Hippel-Lindau (VHL) and altered cancer cell metabolism. Here, we assessed how ccRCC influences the metabolism and activation of primary patient ccRCC tumor infiltrating lymphocytes (TIL)...
June 15, 2017: JCI Insight
https://www.readbyqxmd.com/read/28612127/expression-and-clinical-significance-of-herpes-virus-entry-mediator-hvem-in-breast-cancer
#11
Julia Y S Tsang, Kit-Wing Chan, Yun-Bi Ni, Thazin Hlaing, Jintao Hu, Siu-Ki Chan, Sai-Yin Cheung, Gary M Tse
BACKGROUND: Immune checkpoint blockades are currently actively investigated in invasive breast cancers. Given the complexity of immune regulation, multiple inhibitory molecules within the immune checkpoint framework would be involved in tumor immune escape. Evaluation of the components within the framework is a prerequisite for not only identification of additional treatment targets and optimization of immunotherapeutic strategies but also understanding the prognostic value of these molecules...
June 13, 2017: Annals of Surgical Oncology
https://www.readbyqxmd.com/read/28611201/relationship-of-the-breast-ductal-carcinoma-in-situ-immune-microenvironment-with-clinico-pathological-and-genetic-features
#12
Shona Hendry, Jia-Min B Pang, David Byrne, Sunil R Lakhani, Margaret C Cummings, Ian G Campbell, G Bruce Mann, Kylie L Gorringe, Stephen B Fox
The immune microenvironment of breast ductal carcinoma in situ (DCIS) has yet to be fully explored, and the relationship of immune cells to genetic features of DCIS is unknown. <br /><br />Experimental Design: We quantified tumour associated lymphocytes (TILs) and evaluated PD-L1 protein levels by immunohistochemistry in a cohort of pure DCIS (138 and 79 cases respectively), some of which had copy number (n=55) and mutation data (n=20). <br /><br />Results: TILs were identified in the stroma surrounding DCIS (119/138, 86%) and present at a median TIL score of 5% (range 0-90%)...
June 13, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28611044/characterization-of-mk-4166-a-clinical-agonistic-antibody-that-targets-human-gitr-and-inhibits-the-generation-and-suppressive-effects-of-t-regulatory-cells
#13
Selvakumar Sukumar, Douglas C Wilson, Ying Yu, Jerelyn Wong, Saraswathi Naravula, Grigori Ermakov, Romina Riener, Bhagyashree Bhagwat, Antoaneta S Necheva, Jeff Grein, Tatyana Churakova, Ruban Mangadu, Peter Georgiev, Denise Manfra, Elaine M Pinheiro, Venkataraman Sriram, Wendy J Bailey, Danuta Herzyk, Terrill K McClanahan, Aarron Willingham, Amy M Beebe, Svetlana Sadekova
GITR is a T cell co-stimulatory receptor that enhances cellular and humoral immunity. The agonist anti-mouse GITR antibody DTA-1 has demonstrated efficacy in murine models of cancer primarily by attenuation of Treg-mediated immune suppression, but the translatability to human GITR biology has not been fully explored. Here we report the potential utility of MK-4166, a humanized GITR monoclonal antibody selected to bind to an epitope analogous to the DTA-1 epitope, which enhances the proliferation of both naïve and tumor-infiltrating T lymphocytes (TILs)...
June 13, 2017: Cancer Research
https://www.readbyqxmd.com/read/28608409/neoadjuvant-chemoradiotherapy-of-pancreatic-cancer-induces-a-favorable-immunogenic-tumor-microenvironment-associated-with-increased-major-histocompatibility-complex-class-i-related-chain-a-b-expression
#14
Takashi Murakami, Yuki Homma, Ryusei Matsuyama, Ryutaro Mori, Kentaro Miyake, Yusaku Tanaka, Kanechika Den, Yoji Nagashima, Masatoshi Nakazawa, Yukihiko Hiroshima, Michio Ueda, Kuniya Tanaka, Robert M Hoffman, Michael Bouvet, Itaru Endo
BACKGROUND: Damage-associated molecular patterns (DAMPs) are related to immune responses in malignant tumors including tumor-infiltrating lymphocytes (TILs). The aim of the present study was to determine the relationship between expression of components of DAMPs and TILs in pancreatic cancer patients who underwent neoadjuvant chemoradiotherapy (NACRT) versus those who did not. METHODS: NACRT was administered to 51 patients with borderline-resectable pancreatic cancer and not to 33 patients with resectable pancreatic cancer...
June 12, 2017: Journal of Surgical Oncology
https://www.readbyqxmd.com/read/28599288/prognostic-role-of-tumor-infiltrating-lymphocytes-in-gastric-cancer-a-meta-analysis
#15
Xiao Zheng, Xing Song, Yingjie Shao, Bin Xu, Lujun Chen, Qi Zhou, Wenwei Hu, Dachuan Zhang, Changping Wu, Min Tao, Yibei Zhu, Jingting Jiang
BACKGROUND: In patients with gastric cancer, the prognostic value of tumor-infiltrating lymphocytes (TILs) is still controversial. A meta-analysis was performed to evaluate the prognostic value of TILs in gastric cancer. MATERIALS AND METHODS: We identify studies from PubMed, Embase and the Cochrane Library to assess the prognostic effect of TILs in patients with gastric cancer. Fixed-effects models or random-effects models were used estimate the pooled hazard ratios (HRs) for overall survival (OS) and disease-free survival (DFS), which depend on the heterogeneity...
May 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28593443/impact-of-diclofenac-sodium-on-tilmicosin-induced-acute-cardiotoxicity-in-rats-tilmicosin-and-diclofenac-cardiotoxicity
#16
Samah S Oda, Amira E Derbalah
To assess the influence of diclofenac sodium (DIC) treatment on tilmicosin (TIL) prompted cardiotoxicity, forty albino rats were randomly divided into four equal groups: control, TIL group (single subcutaneous injection of 75 mg/kg BW tilmicosin phosphate 30%), TIL + DIC group (single subcutaneous injection of tilmicosin phosphate 30% and then injection intramuscularly of 13.5 mg/kg BW/day for 6 days diclofenac sodium) and DIC group (intramuscular injection of 13.5 mg/kg BW/day diclofenac sodium for 6 days)...
June 7, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28593281/simultaneous-antidepressant-and-benzodiazepine-new-use-and-subsequent-long-term-benzodiazepine-use-in-adults-with-depression-united-states-2001-2014
#17
Greta A Bushnell, Til Stürmer, Bradley N Gaynes, Virginia Pate, Matthew Miller
Importance: Benzodiazepines have been prescribed for short periods to patients with depression who are beginning antidepressant therapy to improve depressive symptoms more quickly, mitigate concomitant anxiety, and improve antidepressant treatment continuation. However, benzodiazepine therapy is associated with risks, including dependency, which may take only a few weeks to develop. Objectives: To examine trends in simultaneous benzodiazepine and antidepressant new use among adults with depression initiating an antidepressant, assess antidepressant treatment length by simultaneous new use status, estimate subsequent long-term benzodiazepine use in those with simultaneous antidepressant and benzodiazepine new use, and identify determinants of simultaneous new use and long-term benzodiazepine use...
June 7, 2017: JAMA Psychiatry
https://www.readbyqxmd.com/read/28589910/pd-l1-pd-1-expression-and-tumor-infiltrating-lymphocytes-in-conjunctival-melanoma
#18
Jinfeng Cao, Niels J Brouwer, Kate E Richards, Marina Marinkovic, Sjoerd van Duinen, Daan Hurkmans, Els M E Verdegaal, Ekaterina S Jordanova, Martine J Jager
Conjunctival melanoma (CM) is an infrequent but potentially lethal malignancy, with limited therapeutic options for metastases. Recent inhibitors of the interaction of programmed cell death protein 1 (PD-1) and its ligand PD-L1 are associated with good clinical responses in many malignancies. To investigate the therapeutic potential of targeting the PD-1/PD-L1 axis in CM, we analyzed the expression of PD-1 and PD-L1 and the density of various types of tumor-infiltrating lymphocytes (TILs) in primary CM (n = 27), using immunofluorescence staining...
May 20, 2017: Oncotarget
https://www.readbyqxmd.com/read/28588092/stunning-and-right-ventricular-dysfunction-is-induced-by-coronary-balloon-occlusion-and-rapid-pacing-in-humans-insights-from-right-ventricular-conductance-catheter-studies
#19
Richard G Axell, Joel P Giblett, Paul A White, Andrew Klein, James Hampton-Til, Michael O'Sullivan, Denise Braganza, William R Davies, Nick E J West, Cameron G Densem, Stephen P Hoole
BACKGROUND: We sought to determine whether right ventricular stunning could be detected after supply (during coronary balloon occlusion [BO]) and supply/demand ischemia (induced by rapid pacing [RP] during transcatheter aortic valve replacement) in humans. METHODS AND RESULTS: Ten subjects with single-vessel right coronary artery disease undergoing percutaneous coronary intervention with normal ventricular function were studied in the BO group. Ten subjects undergoing transfemoral transcatheter aortic valve replacement were studied in the RP group...
June 6, 2017: Journal of the American Heart Association
https://www.readbyqxmd.com/read/28577153/tumor-infiltrating-lymphocytes-in-acral-lentiginous-melanoma-a-study-of-a-large-cohort-of-cases-from-latin-america
#20
C A Castaneda, C Torres-Cabala, M Castillo, V Villegas, S Casavilca, L Cano, J Sanchez, J Dunstan, G Calderon, M De La Cruz, J M Cotrina, H L Gomez, R Galvez, J Abugattas
PURPOSE: Acral lentiginous melanoma (ALM) is a poor prognosis subtype and is the most prevalent in non-Caucasian populations. The presence of tumor infiltrating lymphocytes (TILs) has been associated with poor prognosis in melanoma. A large cohort of ALM cases was studied to determine status of TIL and its association with outcome. METHODS: All patients with cutaneous melanoma presenting from 2005 to 2012 at Instituto Nacional de Enfermedades Neoplasicas in Peru were retrospectively identified...
June 2, 2017: Clinical & Translational Oncology
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