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Intratumoral functional heterogeneity and chemotherapy

World Journal of Gastroenterology 2014年第10期20卷 2429-2432页

作者： Ferenc sipos miklós constantinovits Gyrgyi Müzes 2nd Department of Internal Medicine Semmelweis University 1088 Budapest Hungary

Intratumoral heterogeneity including genetic and nongenetic mechanisms refers to biological differences amongst malignant cells originated within the same ***,cell differentiation hierarchy and stochasticity in gene expression and signaling pathways may result in phenotypic differences of cancer *** a tumor consists of cancer cell clones that display distinct behaviours,changes in clonal proliferative behavior may also contribute to the phenotypic variability of tumor *** is a need to reveal molecular actions driving chemotherapeutic resistance in colon cancer *** general,it is widely hypothesized that therapeutic resistance in colorectal cancer is a consequence of the preferential survival of cancer stem ***,recent data regarding colorectal cancer suggest that resistance to anticancer therapy and post-therapeutic tumor reappearence could be related to variations of clonal *** the interaction of genetic and nongenetic determinants influencing the functional diversity and therapy response of tumors should be a future direction for cancer research.

关键词： Colorectal cancer Clonal dynamics Functional heterogeneity Chemotherapy Xenograft Oxaliplatin

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Contribution of TLR signaling to the pathogenesis of colitisassociated cancer in inflammatory bowel disease

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World Journal of Gastroenterology 2014年第36期20卷 12713-12721页

作者： Ferenc sipos István Fri miklós constantinovits Zsolt Tulassay Gyrgyi Mzes 2nd Department of Internal Medicine Semmelweis University 1088 Budapest Hungary Molecular Medicine Research Unit Hungarian Academy of Sciences 1088 Budapest Hungary

In the intestine a balance between proinflammatory and repair signals of the immune system is essential for the maintenance of intestinal homeostasis. The innate immunity ensures a primary host response to microbial invasion, which induces an inflammatory process to localize the infection and prevent systemic dissemination of pathogens. The key elements of this process are the germline encoded pattern recognition receptors including Toll-like receptors (TLRs). If pathogens cannot be eliminated, they may elicit chronic inflammation, which may be partly mediated via TLRs. Additionally, chronic inflammation has long been suggested to trigger tissue tumorous transformation. Inflammation, the seventh hallmark of cancer, may affect all phases of tumor development, and evade the immune system. Inflammation acts as a cellular stressor and may trigger DNA damage or genetic instability. Furthermore, chronic inflammation can provoke genetic mutations and epigenetic mechanisms that promote malignant cell transformation. Colorectal cancers in inflammatory bowel disease patients are considered typical examples of inflammation-related cancers. Although data regarding the role of TLRs in the pathomechanism of cancer-associated colitis are rather conflicting, functionally these molecules can be classified as ”largely antitumorigenic” and ”largely pro-tumorigenic” with the caveat that the underlying signaling pathways are mainly context (i.e., organ-, tissue-, cell-) and ligand-dependent.

关键词： Inflammation Tissue repair Immunoregulation Colitis-associated cancer Toll-like receptor Inflammatory bowel disease Carcinogenesis

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Association of hepatocyte-derived growth factor receptor/caudal type homeobox 2 co-expression with mucosal regeneration in active ulcerative colitis

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World Journal of Gastroenterology 2015年第28期21卷 8569-8579页

作者： Ferenc sipos miklós constantinovits Gábor Valcz Zsolt Tulassay Gy?rgyi M?zes 2nd Department of Internal Medicine Semmelweis University Molecular Medicine Research Group Hungarian Academy of Sciences

AIM:To characterize the regeneration-associated stem cell-related phenotype of hepatocyte-derived growth factor receptor(HGFR)-expressing cells in active ulcerative colitis(UC).METHODs:On the whole 38 peripheral blood samples and 38 colonic biopsy samples from 18 patients with histologically proven active UC and 20 healthy control subjects were *** preparing tissue microarrays and blood smears HGFR,caudal type homeobox 2(CDX2),prominin-1(CD133) and Musashi-1conventional and double fluorescent immunolabelings were *** samples were digitalized using high-resolution Mirax Desk instrument,and analyzed with the Mirax TMA Module *** semiquantitative counting of immunopositive lamina propria(LP) cells 5 fields of view were counted at magnification x 200 in each sample core,then mean ± sD were *** case of peripheral blood smears,30 fields of view with 100 μm diameter were evaluated in every sample and the number of immunopositive cells(mean ± sD) was *** 337 nm UVA Laser MicroDissection system at least 5000 subepithelial cells from the lamina propria were *** expression analysis of HGFR,CDX2,CD133,leucine-rich repeat-containing G-protein coupled receptor 5(Lgr5),Musashi-1 and cytokeratin20(CK20) were performed in both laser-microdisscted samples and blood samples by using real time reverse transcription polymerase chain reaction(RT-PCR).REsULTs:By performing conventional and double fluorescent immunolabelings confirmed by RT-PCR,higher number of HGFR(blood:6.7 ± 1.22 vs 38.5 ±3.18;LP:2.25 ± 0.85 vs 9.22 ± 0.65;P s 0.94 ± 0.64;LP:0.75 ± 0.55 vs 2.11± 0.75;P s 8.3± 1.08;LP:11.1 ± 0.85 vs 26.28 ± 1.71;P sashi-1(blood and LP:0 vs scattered) positive cells were detected in blood and lamina propria of UC samples as compared to ***/CDX2(blood:0 vs 1± 0.59;LP:0.8 ± 0.69 vs 2.06 ± 0.72,P sashi-1/CDX2(blood and LP:0 vs sc

关键词： Hepatocyte-derived growth factor receptor Caudal type homeobox 2 CD133 Musashi-1 Leucinerichrepeat-containing G-protein coupled receptor 5 Ulcerative colitis Regeneration

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