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https://www.readbyqxmd.com/read/28822617/microbiota-dysbiosis-in-select-human-cancers-evidence-of-association-and-causality
#1
REVIEW
Jie Chen, Jada C Domingue, Cynthia L Sears
The human microbiota is a complex ecosystem of diverse microorganisms consisting of bacteria, viruses, and fungi residing predominantly in epidermal and mucosal habitats across the body, such as skin, oral cavity, lung, intestine and vagina. These symbiotic communities in health, or dysbiotic communities in disease, display tremendous interaction with the local environment and systemic responses, playing a critical role in the host's nutrition, immunity, metabolism and diseases including cancers. While the profiling of normal microbiota in healthy populations is useful and necessary, more recent studies have focused on the microbiota associated with disease, particularly cancers...
August 16, 2017: Seminars in Immunology
https://www.readbyqxmd.com/read/28821192/could-the-pd-1-pathway-be-a-potential-target-for-treating-small-intestinal-adenocarcinoma
#2
Ramya Thota, Raul S Gonzalez, Jordan Berlin, Dana B Cardin, Chanjuan Shi
Objectives: The programmed death 1 (PD-1) pathway is upregulated in the immune microenvironment of many cancers. In this study, we examined the PD-1 pathway and the immune microenvironment of small intestinal adenocarcinomas by immunohistochemistry. Methods: From our department pathology archives we identified 42 small intestinal adenocarcinomas from between 2000 and 2015, with blocks available for IHC studies. Tumors were immunohistochemically stained for CD3, CD4, CD8, CD20, PD-1, and programmed death ligand 1 (PD-L1) expression...
September 1, 2017: American Journal of Clinical Pathology
https://www.readbyqxmd.com/read/28819951/metformin-a-new-old-drug
#3
Marta Patrycja Wróbel, Bogdan Marek, Dariusz Kajdaniuk, Dominika Rokicka, Aleksandra Szymborska-Kajanek, Krzysztof Strojek
For many years metformin has been the gold standard in the treatment of type 2 diabetes. According to recommendations of the most important diabetes associations, this is the first-choice drug for use as monotherapy in patients with newly diagnosed type 2 diabetes. Metformin is also recommended in combined treatment when monotherapy is no longer effective. It is then combined with a sulfony-lurea, an incretin, flozin, or insulin, irrespective of the number of insulin injections per day. Besides its properties used in the treatment of diabetes, metformin has been treated for some time as a drug of a so-called pleiotropic activity, as each year brings new reports about its favourable effect in different conditions...
2017: Endokrynologia Polska
https://www.readbyqxmd.com/read/28819421/simultaneous-quantification-of-serum-multi-phospholipids-as-potential-biomarkers-for-differentiating-different-pathophysiological-states-of-lung-stomach-intestine-and-pancreas
#4
Yumei Guo, Junling Ren, Xiaoou Li, Xiaofeng Liu, Ning Liu, Yanmin Wang, Zhili Li
Background: Aberrant lipid metabolism is closely associated with cancer. Materials & Methods: Serum levels of sphingomyelins (SM) (34:1), phosphatidylcholine (PC) (34:2), PC(34:1), PC(36:4), PC(36:3), and PC(36:2) in 1449 serum samples (including 599 normal controls, 69 patients with benign lung diseases (BLDs), 61 with benign colorectal diseases, 54 with benign gastric diseases, 67 with benign pancreatic diseases, and 246 with lung cancer (LC), 144 with colorectal cancer, 94 with gastric cancer, 115 with pancreatic cancer) were quantified simultaneously based on their respective calibration equations with correlation coefficient of >0...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819418/cenph-inhibits-rapamycin-sensitivity-by-regulating-golph3-dependent-mtor-signaling-pathway-in-colorectal-cancer
#5
Wei Wu, Fan Wu, Zaozao Wang, Jiabo Di, Jie Yang, Pin Gao, Beihai Jiang, Xiangqian Su
Background: Centromere protein H (CENPH) is known as a fundamental component of the active centromere complex, and its overexpression is correlated with poor prognosis in various solid tumors. mTOR inhibitor rapamycin has been shown to possess antitumor activity, as well as prevent intestinal tumorigenesis. However, the prognostic value of CENPH in colorectal cancer (CRC) and the role of CENPH in rapamycin sensitivity remain unknown. Materials and methods: The effect of CENPH on the cell proliferation, clonogenicity, and cell response to rapamycin in CRC were evaluated by MTT and/or colony formation assays...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819373/increased-transgenerational-intestinal-tumorigenesis-in-offspring-of-ionizing-radiation-exposed-parent-apc-1638n-mice
#6
Shubhankar Suman, Santosh Kumar, Bo-Hyun Moon, Albert J Fornace, Bhaskar V S Kallakury, Kamal Datta
The purpose of the study was to assess transgenerational intestinal tumorigenic effects of low dose ionizing radiation employing a well-characterized mouse model of human colorectal cancer. Mice (6 to 8 weeks old APC(1638N/+) mice; n=20 per study group) were exposed to whole-body 25 cGy x-rays and mated 2 days post-irradiation. Intestinal tumorigenesis in male and female F1 mice from No Parents Irradiated (NPI), Both Parents Irradiated (BPI), and Male Parent Irradiated (MPI) groups were compared 210 days after birth...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819369/in-vitro-cytotoxic-activities-of-the-oral-platinum-iv-prodrug-oxoplatin-and-hsp90-inhibitor-ganetespib-against-a-panel-of-gastric-cancer-cell-lines
#7
Lukas Klameth, Barbara Rath, Gerhard Hamilton
Gastric cancer exhibits a poor prognosis and is the third most common cause of cancer death worldwide. Chemotherapy of metastatic gastric cancer is based on combinations of platinum drugs and fluoropyrimidines, with added agents. Oxoplatin is a stable oral platinum(IV) prodrug which is converted to a highly active tetrachlorido(IV) complex under acidic conditions. In the present work, we studied the cytotoxic effects of oxoplatin against a panel of four gastric cancer cell lines in vitro. Furthermore, the role of HSP90 in chemoresistance of these lines was investigated using the specific inhibitor ganetespib...
2017: Journal of Cancer
https://www.readbyqxmd.com/read/28819089/follow-up-practices-of-surgeons-and-medical-oncologists-in-australia-and-new-zealand-following-resection-of-esophagogastric-cancers
#8
Tim Chew, Tim Bright, Timothy J Price, David I Watson, Peter G Devitt
PURPOSE: Follow-up practices for patients who have undergone surgical resection of esophagogastric malignancies are variable and poorly documented. To better understand practice, a questionnaire was used to survey surgeons and medical oncologists to determine whether any consensus exists. METHODS: An opt-in online questionnaire was sent to esophagogastric surgeons and medical oncologists via the membership lists for the Australian and New Zealand Gastric and Oesophageal Surgery Association (ANZGOSA), the Australian Gastro-Intestinal Trials Groups (AGITG), and the Medical Oncology Group of Australia (MOGA)...
August 15, 2017: Annals of Thoracic and Cardiovascular Surgery
https://www.readbyqxmd.com/read/28818625/the-therapeutic-potential-of-crth2-dp2-beyond-allergy-and-asthma
#9
REVIEW
Katharina Jandl, Akos Heinemann
Prostaglandin (PG) D2 has been in the focus of research for quite a long time, but its biological effects and its roles in human disease are still not fully characterized. When in 2001 a second major PGD2 receptor termed chemoattractant receptor homologue expressed on Th2 cells (CRTH2; alternative name DP2) was discovered, diverse investigations started to shed more light on the complex and often controversial actions of the prostaglandin. With various immunomodulating effects, such as induction of migration, activation, and cytokine release of leukocytes observed both in vivo and in vitro, CRTH2 has emerged as a promising target for the treatment of allergic diseases...
August 14, 2017: Prostaglandins & Other Lipid Mediators
https://www.readbyqxmd.com/read/28817727/pilot-study-of-lithium-to-restore-intestinal-barrier-function-in-severe-graft-versus-host-disease
#10
Gideon Steinbach, David M Hockenbery, Gerwin Huls, Terry Furlong, David Myerson, Keith R Loeb, Jesse R Fann, Christina Castilla-Llorente, George B McDonald, Paul J Martin
Severe intestinal graft-vs-host disease (GVHD) after allogeneic hematopoietic cell transplantation (HCT) causes mucosal ulceration and induces innate and adaptive immune responses that amplify and perpetuate GVHD and the associated barrier dysfunction. Pharmacological agents to target mucosal barrier dysfunction in GVHD are needed. We hypothesized that induction of Wnt signaling by lithium, an inhibitor of glycogen synthase kinase (GSK3), would potentiate intestinal crypt proliferation and mucosal repair and that inhibition of GSK3 in inflammatory cells would attenuate the deregulated inflammatory response to mucosal injury...
2017: PloS One
https://www.readbyqxmd.com/read/28815134/interrogating-patient-level-genomics-and-mouse-phenomics-towards-understanding-cytokines-in-colorectal-cancer-metastasis
#11
Xiaoshu Cai, Yang Chen, Chunlei Zheng, Rong Xu
Background: Colorectal cancer is the second leading cancer-related death worldwide and a majority of patients die from metastasis. Chronic intestinal inflammation plays an important role in tumor progression of colorectal cancer. However, few study works on systematically predicting colorectal cancer metastasis using inflammatory cytokine genes. Results: We developed a supervised machine learning approach to predict colorectal cancer tumor progression using patient level genomic features. To better understand the role of cytokines, we integrated the metastatic-related genes from mouse phenotypic data...
2017: AMIA Summits on Translational Science Proceedings
https://www.readbyqxmd.com/read/28814670/mtg16-is-a-tumor-suppressor-in-colitis-associated-carcinoma
#12
Elizabeth M McDonough, Caitlyn W Barrett, Bobak Parang, Mukul K Mittal, J Joshua Smith, Amber M Bradley, Yash A Choksi, Lori A Coburn, Sarah P Short, Joshua J Thompson, Baolin Zhang, Shenika V Poindexter, Melissa A Fischer, Xi Chen, Jiang Li, Frank L Revetta, Rishi Naik, M Kay Washington, Michael J Rosen, Scott W Hiebert, Keith T Wilson, Christopher S Williams
MTG16 is a member of the myeloid translocation gene (MTG) family of transcriptional corepressors. While MTGs were originally identified in chromosomal translocations in acute myeloid leukemia, recent studies have uncovered a role in intestinal biology. For example, Mtg16-/- mice have increased intestinal proliferation and are more sensitive to intestinal injury in colitis models. MTG16 is also underexpressed in patients with moderate/severe ulcerative colitis. Based on these findings, we postulated that MTG16 might protect against colitis-associated carcinogenesis...
August 17, 2017: JCI Insight
https://www.readbyqxmd.com/read/28813164/pembrolizumab-in-patients-with-extensive-stage-small-cell-lung-cancer-results-from-the-phase-ib-keynote-028-study
#13
Patrick A Ott, Elena Elez, Sandrine Hiret, Dong-Wan Kim, Anne Morosky, Sanatan Saraf, Bilal Piperdi, Janice M Mehnert
Purpose The safety and efficacy of pembrolizumab, a humanized monoclonal antibody against programmed death 1 (PD-1), were assessed in patients with programmed death ligand 1 (PD-L1)-expressing extensive-stage small-cell lung cancer (SCLC) in the multicohort, phase Ib open-label KEYNOTE-028 study ( ClinicalTrials.gov identifier: NCT02054806). Methods Patients with SCLC received pembrolizumab 10 mg/kg every 2 weeks for 24 months or until disease progression or intolerable toxicity occurred. PD-L1 expression was assessed by immunohistochemistry...
August 16, 2017: Journal of Clinical Oncology: Official Journal of the American Society of Clinical Oncology
https://www.readbyqxmd.com/read/28812582/control-of-intestinal-stem-cell-function-and-proliferation-by-mitochondrial-pyruvate-metabolism
#14
John C Schell, Dona R Wisidagama, Claire Bensard, Helong Zhao, Peng Wei, Jason Tanner, Aimee Flores, Jeffrey Mohlman, Lise K Sorensen, Christian S Earl, Kristofor A Olson, Ren Miao, T Cameron Waller, Don Delker, Priyanka Kanth, Lei Jiang, Ralph J DeBerardinis, Mary P Bronner, Dean Y Li, James E Cox, Heather R Christofk, William E Lowry, Carl S Thummel, Jared Rutter
Most differentiated cells convert glucose to pyruvate in the cytosol through glycolysis, followed by pyruvate oxidation in the mitochondria. These processes are linked by the mitochondrial pyruvate carrier (MPC), which is required for efficient mitochondrial pyruvate uptake. In contrast, proliferative cells, including many cancer and stem cells, perform glycolysis robustly but limit fractional mitochondrial pyruvate oxidation. We sought to understand the role this transition from glycolysis to pyruvate oxidation plays in stem cell maintenance and differentiation...
August 14, 2017: Nature Cell Biology
https://www.readbyqxmd.com/read/28811707/myo-inositol-reduces-%C3%AE-catenin-activation-in-colitis
#15
Emily M Bradford, Corey A Thompson, Tatiana Goretsky, Guang-Yu Yang, Luz M Rodriguez, Linheng Li, Terrence A Barrett
AIM: To assess dietary myo-inositol in reducing stem cell activation in colitis, and validate pβ-catenin(S552) as a biomarker of recurrent dysplasia. METHODS: We examined the effects of dietary myo-inositol treatment on inflammation, pβ-catenin(S552) and pAkt levels by histology and western blot in IL-10(-/-) and dextran sodium sulfate-treated colitic mice. Additionally, we assessed nuclear pβ-catenin(S552) in patients treated with myo-inositol in a clinical trial, and in patients with and without a history of colitis-induced dysplasia...
July 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28810912/inhibition-of-trpm7-suppresses-cell-proliferation-of-colon-adenocarcinoma-in-vitro-and-induces-hypomagnesemia-in-vivo-without-affecting-azoxymethane-induced-early-colon-cancer-in-mice
#16
Junhao Huang, Hideki Furuya, Malika Faouzi, Zheng Zhang, Mahealani Monteilh-Zoller, F Kelly Galbraith Kawabata, David Horgen, Toshihiko Kawamori, Reinhold Penner, Andrea Fleig
BACKGROUND: Magnesium (Mg(2+)) is an essential cation implicated in carcinogenesis, solid tumor progression and metastatic potential. The Transient Receptor Potential Melastatin Member 7 (TRPM7) is a divalent ion channel involved in cellular and systemic Mg(2+) homeostasis. Abnormal expression of TRPM7 is found in numerous cancers, including colon, implicating TRPM7 in this process. METHODS: To establish a possible link between systemic magnesium (Mg(2+)) status, the Mg(2+) conducting channel TRPM7 in colon epithelial cells, and colon carcinogenesis, in vitro whole-cell patch clamp electrophysiology, qPCR, and pharmacological tools were used probing human colorectal adenocarcinoma HT-29 as well as normal primary mouse colon epithelial cells...
August 15, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28810875/role-of-iqgap3-in-metastasis-and-epithelial-mesenchymal-transition-in-human-hepatocellular-carcinoma
#17
Yongjie Shi, Nan Qin, Qiang Zhou, Yanqiu Chen, Sicong Huang, Bo Chen, Gang Shen, Hongyun Jia
BACKGROUND: Hepatocellular carcinoma (HCC) is one of the most lethal cancers worldwide owing to its high rates of metastasis and recurrence. The oncogene IQ motif-containing GTPase activating protein 3 (IQGAP3) is ubiquitously overexpressed in several human cancers, including liver, ovary, lung, large intestine, gastric, bone marrow, and breast malignancies and is involved in the invasion and metastasis of cancer cells. Therefore, we aimed to determine the biological role and molecular mechanism of IQGAP3 in HCC...
August 15, 2017: Journal of Translational Medicine
https://www.readbyqxmd.com/read/28810829/blocking-il-10-signalling-at-the-time-of-immunization-does-not-increase-unwanted-side-effects-in-mice
#18
Guoying Ni, Zaowen Liao, Shu Chen, Tianfang Wang, Jianwei Yuan, Xuan Pan, Kate Mounsey, Shelley Cavezza, Xiaosong Liu, Ming Q Wei
BACKGROUND: Cancer therapeutic vaccine induced cytotoxic T cell (CTL) responses are pivotal for the killing of tumour cells. Blocking interleukin 10 (IL-10) signalling at the time of immunization increases vaccine induced CTL responses and improves prevention of tumour growth in animal models compared to immunization without an IL-10 signalling blockade. Therefore, this immunization strategy may have potential to curtail cancer in a clinical setting. However, IL-10 deficiency leads to autoimmune disease in the gut...
August 15, 2017: BMC Immunology
https://www.readbyqxmd.com/read/28808878/role-of-intestinal-microbiome-in-american-ginseng-mediated-colon-cancer-protection-in-high-fat-diet-fed-aom-dss-mice
#19
C-Z Wang, W-H Huang, C-F Zhang, J-Y Wan, Y Wang, C Yu, S Williams, T-C He, W Du, M W Musch, E B Chang, C-S Yuan
OBJECTIVE: Chronic intestinal inflammation is a risk factor for colorectal cancer (CRC) initiation and development. Diets that are rich in Western style fats have been shown to promote CRC. This study was conducted to investigate the role of intestinal microbiome in American ginseng-mediated CRC chemoprevention in a mouse model. The population and diversity of enteric microbiome were evaluated after the ginseng treatment. METHODS: Using an azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced gut inflammation and tumorigenesis mouse model, the effects of oral American ginseng on high fat diet-associated enteric pathology were determined...
August 14, 2017: Clinical & Translational Oncology
https://www.readbyqxmd.com/read/28808491/distribution-patterns-of-the-metastases-of-the-lung-carcinoma-in-relation-to-histological-type-of-the-primary-tumor-an-autopsy-study
#20
Ivana Savic Milovanovic, Mihailo Stjepanovic, Dragan Mitrovic
INTRODUCTION: Lung cancer is among leading causes of death worldwide. Different histological types of the lung carcinoma show significant differences in behavior. OBJECTIVES: The aim of this study is to determine the distribution patterns of metastases of different lung cancer histological types in autopsied individuals. METHODS: Protocols from all autopsies performed at the Institute of Pathology from 2008 till 2014 were reviewed retrospectively, and information on individuals' age, sex, histological type of primary lung cancer, presence and location of metastases, and causes of death were recorded...
July 2017: Annals of Thoracic Medicine
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