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Immune Colon Cancer

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https://www.readbyqxmd.com/read/28938609/pegylated-arginine-deiminase-can-modulate-tumor-immune-microenvironment-by-affecting-immune-checkpoint-expression-decreasing-regulatory-t-cell-accumulation-and-inducing-tumor-t-cell-infiltration
#1
Elena Brin, Katherine Wu, Hsin-Tze Lu, Yudou He, Zhaoming Dai, Wei He
PEGylated arginine deiminase (ADI-PEG 20) is being investigated in clinical studies in arginine auxotrophic cancers and is well-tolerated. The anti-tumor properties of ADI-PEG 20 have been extensively investigated - ADI-PEG 20 inhibits the growth of auxotrophic cancers in vitro and in vivo - however, its impact on immune cells is largely unknown. Here we report the potential impact of ADI-PEG 20 on the tumor immune microenvironment. ADI-PEG 20 induced immunosuppressive programmed death-ligand 1 expression on some cancer cells in vitro, but the magnitude of the increase was cell line dependent and in most relatively small...
August 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28938458/corticotroph-pituitary-carcinoma-in-a-patient-with-lynch-syndrome-ls-and-pituitary-tumors-in-a-nationwide-ls-cohort
#2
Daniel Bengtsson, Patrick Joost, Christos Aravidis, Marie Askmalm Stenmark, Ann-Sofie Backman, Beatrice Melin, Jenny von Salomé, Theofanis Zagoras, Samuel Gebre-Medhin, Pia Burman
Context: Lynch syndrome is a cancer predisposing syndrome caused by germline mutations in genes involved in DNA mismatch repair (MMR). Patients are at high risk for several types of cancer, but pituitary tumors have not previously been reported. Case: A 51-year old man with LS (MSH2 mutation) and a history of colon carcinoma presented with severe Cushing's disease and a locally aggressive pituitary tumor. The tumor harbored a mutation consistent with the patient's germline mutation, and displayed defect MMR function...
August 18, 2017: Journal of Clinical Endocrinology and Metabolism
https://www.readbyqxmd.com/read/28938014/intestinal-helminth-infection-drives-carcinogenesis-in-colitis-associated-colon-cancer
#3
Eva Pastille, Annika Frede, Henry J McSorley, Jessica Gräb, Alexandra Adamczyk, Sebastian Kollenda, Wiebke Hansen, Matthias Epple, Jan Buer, Rick M Maizels, Robert Klopfleisch, Astrid M Westendorf
Inflammatory bowel diseases (IBD) are chronic inflammatory disorders of the gastrointestinal tract, strongly associated with an increased risk of colorectal cancer development. Parasitic infections caused by helminths have been shown to modulate the host's immune response by releasing immunomodulatory molecules and inducing regulatory T cells (Tregs). This immunosuppressive state provoked in the host has been considered as a novel and promising approach to treat IBD patients and alleviate acute intestinal inflammation...
September 22, 2017: PLoS Pathogens
https://www.readbyqxmd.com/read/28932075/role-of-tissue-microenvironment-resident-adipocytes-in-colon-cancer
#4
EDITORIAL
Maria Tabuso, Shervanthi Homer-Vanniasinkam, Raghu Adya, Ramesh P Arasaradnam
Colorectal cancer (CRC) is a multifactorial disease characterized by several genetic and epigenetic alterations occurring in epithelial cells. It is increasingly recognized that tumour progression is also regulated by tumour microenvironment (TME). The bidirectional cross-talk between tumour resident adipocytes and cancer cells within TME has been proposed as active contributor to carcinogenesis. Tumour resident adipocytes exhibit an activated phenotype characterized by increased secretion of pro-tumorigenic factors (angiogenic/inflammatory/immune) which contribute to cancer cell proliferation, invasion, neoangiogenesis, evasion of immune surveillance and therapy resistance...
August 28, 2017: World Journal of Gastroenterology: WJG
https://www.readbyqxmd.com/read/28928840/a-cytokine-signal-inhibitor-for-rheumatoid-arthritis-enhances-cancer-metastasis-via-depletion-of-nk-cells-in-an-experimental-lung-metastasis-mouse-model-of-colon-cancer
#5
Hideki Shimaoka, Shinsuke Takeno, Kenji Maki, Takahide Sasaki, Suguru Hasegawa, Yuichi Yamashita
Current therapy for rheumatoid arthritis (RA) relies on global suppression of the immune response or specific blockade of inflammatory cytokines. However, it is unclear how immunosuppressants affect patients with cancer. Therefore, in the present study, the effect of three biological agents, tofacitinib, anti-mouse IL-6 receptor antibody (MR16-1) and etanercept, which are used for the treatment of RA diseases, on a tumor-bearing mouse model was investigated. The effect of the three agents was examined using a mouse lung-metastasis model with the murine colon 26 cancer cell line...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28928833/disrupted-fibroblastic-reticular-cells-and-interleukin-7-expression-in-tumor-draining-lymph-nodes
#6
Jianbao Gao, Lintao Zhao, Lina Liu, Yang Yang, Bo Guo, Bo Zhu
The immune system of patients with cancer is usually in an inhibitory state. Lymph node (LN) draining of pathological sites provides a suitable microenvironment where adaptive immune responses mainly occur. However, the microenvironment in the tumor draining lymph nodes (TDLNs) of patients with cancer appears to be in favor of tolerance. The effects of tumor cells on TDLNs have not been elaborated clearly. The present results have indicated that tumor cells may directly affect TDLNs by decreasing the fibroblastic reticular cell population that led to less interleukin-7 secretion...
September 2017: Oncology Letters
https://www.readbyqxmd.com/read/28923859/upregulation-of-cystathionine-%C3%AE-synthase-in-colonic-epithelia-reprograms-metabolism-and-promotes-carcinogenesis
#7
Ches'Nique M Phillips, John Zatarain, Michael E Nicholls, Craig Porter, Steve G Widen, Ketan Thanki, Paul Johnson, Muhammad U Jawad, Mary Pat Moyer, James W Randall, Judith L Hellmich, Manjit Maskey, Suimin Qiu, Thomas Wood, Nadiya Druzhyna, Bartosz Szczesny, Katalin Modis, Csaba Szabo, Celia Chao, Mark R Hellmich
The transsulfuration enzyme cystathionine-β-synthase (CBS) and its product hydrogen sulfide (H2S) are aberrantly upregulated in colorectal cancers, where they contribute to tumor growth and progression by both autocrine and paracrine mechanisms. However, it is unknown whether the CBS/H2S axis plays a role in colorectal carcinogenesis. Here, we report upregulation of CBS in human biopsies of precancerous adenomatous polyps and show that forced upregulation of CBS in an adenoma-like colonic epithelial cell line is sufficient to induce metabolic and gene expression profiles characteristic of colorectal cancer cells...
September 18, 2017: Cancer Research
https://www.readbyqxmd.com/read/28923497/cholera-vaccine-use-is-associated-with-a-reduced-risk-of-death-in-patients-with-colorectal-cancer-a-population-based-study
#8
Jianguang Ji, Jan Sundquist, Kristina Sundquist
BACKGROUND & AIMS: Cholera toxin can act as a modulator of the immune response with anti-inflammatory effects; it reduces development of colon polyps in mouse models of colorectal cancer (CRC). We performed a population-based study to determine whether, in patients with a diagnosis of CRC, subsequent administration of the cholera vaccine (killed Vibrio cholerae O1 whole cells and recombinant cholera toxin B subunit) affects mortality. METHODS: We identified patients from the Swedish Cancer Register who were diagnosed with CRC from July 2005 through December 2012...
September 15, 2017: Gastroenterology
https://www.readbyqxmd.com/read/28922790/the-balance-between-cytotoxic-t-cell-lymphocytes-and-immune-checkpoint-expression-in-the-prognosis-of-colon-tumors
#9
Laetitia Marisa, Magali Svrcek, Ada Collura, Etienne Becht, Pascale Cervera, Kristell Wanherdrick, Olivier Buhard, Anastasia Goloudina, Vincent Jonchère, Janick Selves, Gerard Milano, Dominique Guenot, Romain Cohen, Chrystelle Colas, Pierre Laurent-Puig, Sylviane Olschwang, Jérémie H Lefèvre, Yann Parc, Valérie Boige, Côme Lepage, Thierry André, Jean-François Fléjou, Valentin Dérangère, François Ghiringhelli, Aurélien de Reynies, Alex Duval
Background: Immune checkpoint (ICK) expression might represent a surrogate measure of tumor-infiltrating T cell (CTL) exhaustion and therefore be a more accurate prognostic biomarker for colorectal cancer (CRC) patients than CTL enumeration as measured by the Immunoscore. Methods: The expression of ICKs, Th1, CTLs, cytotoxicity-related genes, and metagenes, including Immunoscore-like metagenes, were evaluated in three independent cohorts of CRC samples (260 microsatellite instable [MSI], 971 non-MSI)...
January 1, 2018: Journal of the National Cancer Institute
https://www.readbyqxmd.com/read/28916526/monoclonal-antibodies-directed-against-cadherin-rgd-exhibit-therapeutic-activity-against-melanoma-and-colorectal-cancer-metastasis
#10
Ruben A Bartolomé, Carmen Aizpurua, Marta Jaén, Sofia Torres, Eva Calviño, Juan I Imbaud, J Ignacio Casal
PURPOSE: New targets are required for the control of advanced metastatic disease. We investigated the use of cadherin RGD motifs, which activate the α2β1integrin pathway, as targets for the development of therapeutic monoclonal antibodies (mAbs). EXPERIMENTAL DESIGN: CDH17 fragments and peptides were prepared and used for immunization and antibody development. Antibodies were tested for inhibition of β1 integrin and cell adhesion, proliferation and invasion assays using cell lines from different cancer types: colorectal, pancreatic, melanoma and breast cancer...
September 15, 2017: Clinical Cancer Research: An Official Journal of the American Association for Cancer Research
https://www.readbyqxmd.com/read/28915590/combination-of-desi2-and-ip10-gene-therapy-significantly-improves-therapeutic-efficacy-against-murine-carcinoma
#11
Chao Lin, HuaYing Yan, Jun Yang, Lei Li, Mei Tang, Xinyu Zhao, Chunlai Nie, Na Luo, Yuquan Wei, Zhu Yuan
DESI2 (also known as PNAS-4) is a novel pro-apoptotic gene activated during the early response to DNA damage. We previously reported that overexpression of DESI2 induces S phase arrest and apoptosis by activating checkpoint kinases. The present study was designed to test whether combination of DESI2 and IP10 could improve the therapy efficacy in vitro and in vivo. The recombinant plasmid co-expressing DESI2 and IP10 was encapsulated with DOTAP/Cholesterol nanoparticle. Immunocompetent mice bearing CT26 colon carcinoma and LL2 lung cancer were treated with the complex...
August 22, 2017: Oncotarget
https://www.readbyqxmd.com/read/28910211/establishment-of-cmab-43-a-sensitive-and-specific-anti-cd133-monoclonal-antibody-for-immunohistochemistry
#12
Shunsuke Itai, Yuki Fujii, Takuro Nakamura, Yao-Wen Chang, Miyuki Yanaka, Noriko Saidoh, Saori Handa, Hiroyoshi Suzuki, Hiroyuki Harada, Shinji Yamada, Mika K Kaneko, Yukinari Kato
CD133, also known as prominin-1, was first described as a cell surface marker on early progenitor and hematopoietic stem cells. It is a five-domain transmembrane protein composed of an N-terminal extracellular tail, two small cytoplasmic loops, two large extracellular loops containing seven potential glycosylation sites, and a short C-terminal intracellular tail. CD133 has been used as a marker to identify cancer stem cells derived from primary solid tumors and as a prognostic marker of gliomas. Herein, we developed novel anti-CD133 monoclonal antibodies (mAbs) and characterized their efficacy in flow cytometry, Western blot, and immunohistochemical analyses...
September 14, 2017: Monoclonal Antibodies in Immunodiagnosis and Immunotherapy
https://www.readbyqxmd.com/read/28903381/tumor-location-impacts-immune-response-in-mouse-models-of-colon-cancer
#13
Xianda Zhao, Lihua Li, Timothy K Starr, Subbaya Subramanian
Existing preclinical models of human colorectal cancer (CRC) that rely on syngeneic subcutaneous grafts are problematic, because of increasing evidence that the immune microenvironment in subcutaneous tissue is significantly different from the gastrointestinal tract. Similarly, existing orthotopic models that use a laparotomy for establishing grafts are also problematic, because the surgical procedure results in extensive inflammation, thereby creating a nonphysiologic tumor microenvironment. To facilitate the bench-to-bedside translation of CRC immunotherapy strategies, we developed a novel orthotopic model in mice that uses endoscopy-guided microinjection of syngeneic cancer cells...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28903332/myeloid-derived-suppressor-cell-and-macrophage-exert-distinct-angiogenic-and-immunosuppressive-effects-in-breast-cancer
#14
Zhaoxu Fang, Chengwen Wen, Xiaolan Chen, Rongping Yin, Chenglin Zhang, Xiaohua Wang, Yuhui Huang
The immunosuppressive tumor microenvironment is a key obstacle to hinder a cancer immunotherapy. Myeloid-derived suppressor cells (MDSCs) have been considered as a major player in immunosuppression. In this study, we find that tumor-infiltrating MDSCs (tiMDSCs) are less immunosuppressive than tumor-associated macrophages (TAMs) in multiple murine orthotopic breast tumor models. Compared to TAMs, tiMDSCs produce higher levels of pro-inflammatory factors and lower levels of anti-inflammatory factors. Furthermore, tiMDSCs are preferentially located in hypoxic areas and are more pro-angiogenic than TAMs...
August 15, 2017: Oncotarget
https://www.readbyqxmd.com/read/28891130/pathogenesis-of-helicobacter-pylori-infection
#15
REVIEW
Vania Camilo, Toshiro Sugiyama, Eliette Touati
Helicobacter pylori is responsible for the most commonly found infection in the world's population. It is the major risk factor for gastric cancer development. Numerous studies published over the last year provide new insights into the strategies employed by H. pylori to adapt to the extreme acidic conditions of the gastric environment, to establish persistent infection and to deregulate host functions, leading to gastric pathogenesis and cancer. In this review, we report recent data on the mechanisms involved in chemotaxis, on the essential role of nickel in acid resistance and gastric colonization, on the importance of adhesins and Hop proteins and on the role of CagPAI-components and CagA...
September 2017: Helicobacter
https://www.readbyqxmd.com/read/28889950/exploring-metabolic-configurations-of-single-cells-within-complex-tissue-microenvironments
#16
Anne Miller, Csörsz Nagy, Bernhard Knapp, Johannes Laengle, Elisabeth Ponweiser, Marion Groeger, Philipp Starkl, Michael Bergmann, Oswald Wagner, Arvand Haschemi
Over the past years, plenty of evidence has emerged illustrating how metabolism supports many aspects of cellular function and how metabolic reprogramming can drive cell differentiation and fate. Here, we present a method to assess the metabolic configuration of single cells within their native tissue microenvironment via the visualization and quantification of multiple enzymatic activities measured at saturating substrate conditions combined with subsequent cell type identification. After careful validation of the approach and to demonstrate its potential, we assessed the intracellular metabolic configuration of different human immune cell populations in healthy and tumor colon tissue...
September 5, 2017: Cell Metabolism
https://www.readbyqxmd.com/read/28883292/reactive-swelling-of-the-regional-lymph-nodes-in-patients-with-stage-ii-colorectal-cancer-as-a-prognostic-factor
#17
Daiki Sato, Masahiro Shimoyamada, Yuka Ito, Shigemasa Yoshida, Hiroyasu Ishida, Takashi Yamaguchi, Haruo Ohtani
The aim of this study was to examine the relationship between reactive swelling of regional lymph node (LN) and survival in colorectal carcinoma. We retrospectively studied 170 patients with surgically resected colorectal carcinoma histopathologically diagnosed as stage II (pStage II). These patients were classified into two groups:a) a "reactive LN swelling" group (clinically diagnosed as positive for LN metastasis, but pathologically negative) and b) a "no LN swelling" group. Survival analyses of the two groups showed that overall survival (OS) and disease-specific survival (DSS) were longer in the reactive LN swelling group than in the no LN swelling group in patients with total colorectal and right-sided colon cancer...
2017: Nihon Shokakibyo Gakkai Zasshi, the Japanese Journal of Gastro-enterology
https://www.readbyqxmd.com/read/28882699/neutrophil-infiltration-is-a-favorable-prognostic-factor-in-early-stages-of-colon-cancer
#18
Maria L Wikberg, Agnes Ling, Xingru Li, Åke Öberg, Sofia Edin, Richard Palmqvist
The tumor immune response has been proven critical to prognosis in colorectal cancer (CRC), but studies on the prognostic role of neutrophil infiltration have shown contradictory results. The aim of this study was to elucidate the prognostic role of infiltrating neutrophils at different intratumoral subsites and in different molecular subgroups of CRC. The relations between neutrophil infiltration and infiltration of other immune cells (T-cell and macrophage subsets) were also addressed. Expression of the neutrophil marker CD66b was assessed by immunohistochemistry in 448 archival human tumor tissue samples from patients surgically resected for CRC...
September 4, 2017: Human Pathology
https://www.readbyqxmd.com/read/28881611/inhibition-and-deficiency-of-the-immunoproteasome-subunit-lmp7-suppress-the-development-and-progression-of-colorectal-carcinoma-in-mice
#19
Julia Koerner, Thomas Brunner, Marcus Groettrup
New treatment options and drug targets for colorectal carcinoma are a pressing medical need. Inflammation and pro-inflammatory cytokines produced by Th1 and Th17 cells like IL-6, TNF, IL-17 and IL-23 promote the development and growth of colorectal cancer (CRC). The immunoproteasome is a proteasome subtype highly expressed in immune cells but also in the intestine. Since the immunoproteasome promotes Th1 and Th17 differentiation and pro-inflammatory cytokine production, we investigated here whether deficiency or inhibition of the immunoproteasome subunit LMP7 would interfere with CRC development and exacerbation in preventive and therapeutic mouse models...
August 1, 2017: Oncotarget
https://www.readbyqxmd.com/read/28879546/the-btk-dependent-pip5k1%C3%AE-lipid-kinase-activation-by-fas-counteracts-fasl-induced-cell-death
#20
Aurélie Rossin, Nadia Lounnas, Jérôme Durivault, Giorgia Miloro, Laurent Gagnoux-Palacios, Anne-Odile Hueber
The Fas/FasL system plays a critical role in death by apoptosis and immune escape of cancer cells. The Fas receptor being ubiquitously expressed in tissues, its apoptotic-inducing function, initiated upon FasL binding, is tightly regulated by several negative regulatory mechanisms to prevent inappropriate cell death. One of them, involving the non-receptor tyrosine kinase Btk, was reported mainly in B cells and only poorly described. We report here that Btk negatively regulates, through its tyrosine kinase activity, the FasL-mediated cell death in epithelial cell lines from colon cancer origin...
September 6, 2017: Apoptosis: An International Journal on Programmed Cell Death
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