Tetraheterocyclic compounds, derived from natural sources and contemporary pharmaceuticals, have shown promise as multitarget therapeutic agents. However, their mechanisms of action remain partially understood. In thi...
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Ovarian cancer remains the third most prevalent and deadliest gynecologic malignancy worldwide, with most patients eventually developing resistance to platinum-based chemotherapy. This highlights a critical unmet need...
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In situ CuI-mediated cyclization methodology helped yield benzimidazoles with different substitution manner, such as 1,2-diarylbenzimidazoles (4 and 5) and 1-arylbenzimidazoles (6-15). The result of structure-activity...
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Adenosine receptors are a family of G-coupled receptors which mediate the anti-inflammatory and immune-suppressive effects of adenosine in a damaged tissue.A large number of evidence indicate that the accumulation of ...
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Adenosine receptors are a family of G-coupled receptors which mediate the anti-inflammatory and immune-suppressive effects of adenosine in a damaged tissue.A large number of evidence indicate that the accumulation of adenosine under hypoxic conditions favors tumor progression,helping cancer cells to evade immune *** cells and/or lymphoid and myeloid cells can express the adenosine-generating enzyme CD73 and/or A2A receptor,which in turn strongly suppresses an effective T-cell-mediated response,while promotes the activity of suppressive cells such as Treg and myeloid-derived suppressor ***73 inhibitors and A2A antagonists,either as single agents,or in combination with immune-checkpoints inhibitors such as anti PD-1 monoclonal antibodies,are currently in Phase I clinical trial in cancer *** studies show that A2B receptor plays an important role in mediating the pro-tumor effects of adenosine,since its selective blockade can inhibit tumor growth in some murine tumor *** A2B receptor reduces immunosuppression induced by myeloid cells and inhibits the stromal cells activity within the tumor microenvironment,limiting tumor angiogenesis and metastatic ***,the authors review the current data on involvement of A2B receptor in regulating tumor progression and discuss the development of A2B receptor inhibitors as potential therapeutic agents in cancer treatment.
ABSTRACTIntroductionEndometrial cancer is a common gynaecological cancer in western countries. Death and prognosis of most patients with cancer are related to tumour metastasis and invasion. In cancer metastasis, epit...
ABSTRACTIntroductionEndometrial cancer is a common gynaecological cancer in western countries. Death and prognosis of most patients with cancer are related to tumour metastasis and invasion. In cancer metastasis, epithelial– mesenchymal transition (EMT) is a key mechanism. EMT can be induced by transforming growth factor beta (TGF-β) signalling pathway, promoting the ability of migration and invasion of cancer cells. Isoliquiritigenin (ISL) is a flavonoid isolated from licorice and bean sprouts. It has been shown that ISL has antitumor activities. However, the effects of ISL on EMT and TGF-β signalling pathway in endometrial cancer remain unclear. Thus, the purpose of this study was to investigate the antimetastatic potential of ISL on endometrial cancer. Material and methodsIn vivo study: Hec-1A implanted into nude mice and treated with isoliquiritigenin by i.p. injection for four weeks. In vitro study: Human endometrial cell lines (HEC-1A, RL95-2 and Ishikawa) were treated with isoliquiritigenin and then subjected to immunoblotting analysis, Immunofluorescence analysis and migration assay. Results and discussionsThe in vitro results showed isoliquiritigenin inhibited migration and invasion through the TGF- β/Smad signalling pathway. Isoliquiritigenin enhanced the expression of E-cadherin but reduced the expression of N-cadherin. In vivo, isoliquiritigenin reduced peritoneal dissemination. decreased the levels of TGFβRI, p-Smad2, N-cadherin, and MMP-9 expression, and increased E-cadherin expression levels. ConclusionThis is the first study, to the best of our knowledge that explores the anti-metastasis effect of ISL on endometrial carcinoma in vitro and in vivo study. Isoliquiritigenin inhibited migration and invasion through the TGF-β/Smad signalling pathway. Thus, ISL shows potential as an anti-metastatic agent for 3 the therapeutic treatment of endometrial *** is the first study, to the best of our knowledge that explores the anti-metastasis effect of IS
The biotechnology revolution started in early 1970s following advances in molecular biology,specifically:(1)sophisticated methodologies for manipulating DNA in mammalian cells;(2)hybridoma technology for the generatio...
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The biotechnology revolution started in early 1970s following advances in molecular biology,specifically:(1)sophisticated methodologies for manipulating DNA in mammalian cells;(2)hybridoma technology for the generation of preselected monoclonal antibodies;(3)genomic and recombinant DNA technology that allowed the production of large quantities of specific proteins;and(4)improved understanding of cancer *** the 1980s,we further witnessed another wave of technological revolution which includes our ability to molecularly clone many growth factors,cytokines and immunogenic molecules,and to discover immune checkpoint molecules such as cytotoxic T-lymphocyte antigen 4,programmed death 1 and programmed death ligand-1 and their inhibitors,to develop various vaccines(dendritic cells,personalized human leukocyte antigen-binding peptides and RNA mutanomes),and to expand and/or genetically modify effector cells for adoptive cell based immunotherapy,such as chimeric antigen receptor T-cell therapy.
Aim:As our understanding of cancer stem cell(CSC)biology improves,search for inhibitory agents of CSCs and metastatic CSCs(mCSCs)positive for CXCR4 is *** A(WA),a withanolide extracted from the medicinal plant Withani...
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Aim:As our understanding of cancer stem cell(CSC)biology improves,search for inhibitory agents of CSCs and metastatic CSCs(mCSCs)positive for CXCR4 is *** A(WA),a withanolide extracted from the medicinal plant Withania somnifera,has been shown to exhibit anti-cancer effects through multiple *** WA could selectively target CSCs,mCSCs,or non CSCs of a gastrointestinal(GI)carcinoma tumor remains ***:Side-population(SP)analysis,flow cytometric phenotyping and sorting,non-invasive imaging in conjunction with xenotransplantation,and immunohistology were used in this ***:Using the lymph node metastatic GI cancer cell line UP-LN1,consisting of CD44^(high)/CD24^(low)floating(F)and CD44^(low)/CD24^(high)adherent(A)cell subsets,this study demonstrated that as compared with parental UP-LN1 cells or A cells,WA preferentially reduced F-cell proliferation,tumor sphere formation,and SP cells in vitro in greater effi ciencies by *** action was mechanistically mediated via the down-regulation of CXCR4/CXCL12 and STAT3/interleukin-6 axes,both of which are instrumental in the acquisition of metastatic *** of interferon-γ-induced CXCR4 expression in F cells by knockdown with siRNA or blocking with an anti-CXCR4 antibody,followed by Western blot analysis,showed signifi cantly reduced metastatic potential in *** extent of in vitro anti-invasive effect of WA on the IFN-γ-treated F cells was signifi cantly greater than on the F cells without WA treatment,or F cells treated with control siRNA or with control IgG *** observed in vitro effects of WA on the CSC and mCSC targeting were validated by data obtained with non-invasive imaging in NOD/SCID mouse ***:WA could effi ciently block the formation of both CSCs and mCSCs in the UP-LN1 cell line,suggesting that WA may be considered an effective therapeutic agent for this type of GI malignancies.
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