AI总结:根据提供的论文名称,以下是这些医学研究的整体概要:这些论文主要聚焦于胰腺导管腺癌(PDAC)的分子机制、基因表达调控及其临床意义。具体而言,研究内容涵盖了以下几个关键方面:1. 生物钟基因与肿瘤进展:多篇论文探讨了生物钟基因(如Bmal1)在胰腺癌中的作用。研究表明,这些基因的异常表达可能与肿瘤的进展和不良预后有关。特别是Bmal1基因的下调被发现能够预测肿瘤的发展,并且与较差的预后相关。2. 基因表达与调控:研究还涉及多种基因(如Klotho、Ferritin、Sirt1等)在胰腺癌中的表达模式及其对细胞行为的影响。例如,某些基因的异常表达可能导致细胞增殖失控或凋亡抵抗,进而促进肿瘤的发生和发展。3. 表观遗传学改变:部分研究关注了DNA甲基化状态与胰腺癌之间的关联。结果显示,特定基因的高甲基化状态与胰腺癌细胞的恶性特征密切相关,提示表观遗传学变化可能是胰腺癌发生的重要机制之一。4. 信号通路与分子靶点:TGFB/SMAD4通路的功能失调以及其对细胞命运决定的影响也是研究热点之一。此外,还有关于circadian clock基因如何通过调控p53抑癌途径来影响肿瘤抑制的研究。5. 临床应用前景:一些研究不仅限于基础机制探索,还进一步讨论了潜在的治疗策略。例如,通过调节特定基因或信号通路,可以为开发新型抗癌药物提供理论依据;同时,识别出的生物标志物也有助于改善患者的早期诊断和个性化治疗方案。综上所述,这批论文围绕胰腺导管腺癌这一严重威胁健康的疾病,从不同角度深入剖析了其背后的生物学机制,并初步探讨了一些具有转化潜力的应用方向。这些成果将有助于加深我们对该类癌症的理解,并为未来更有效的防治措施奠定坚实的基础。
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共6篇 平均IF=15.7 (12.5-48.8)更多分析
  • 1区Q1影响因子: 14.8
    1. Expression of a cut-related homeobox gene in developing and polycystic mouse kidney.
    作者:Vanden Heuvel G B , Bodmer R , McConnell K R , Nagami G T , Igarashi P
    期刊:Kidney international
    日期:1996-08-01
    DOI :10.1038/ki.1996.336
    Cut is a diverged homeobox gene that is essential for normal development of the Malpighian tubules in Drosophila melanogaster. Homologues of Drosophila cut that encode transcriptional repressors have been identified in several mammalian species and cell lineages. We examined the expression of a murine cut homologue (named Cux-1) in the developing mouse using Northern blot analysis and in situ hybridization. At 12.5 d.p.c. and 13.5 d.p.c., Cux-1 was highly expressed in a subset of embryonic tissues, including the developing metanephros. Within the metanephros, Cux-1 was expressed in the nephrogenic zone including both mesenchymal cells (uninduced and condensed mesenchyme) and epithelial cells (ureteric buds, renal vesicles, S-shaped bodies). During later stages of nephrogenesis, Cux-1 was down-regulated such that there was minimal expression in mature glomeruli and tubules. In addition, Cux-1 was detected in the mesonephros, mesonephric duct, and bladder. Expression of Cux-1 was also examined in polycystic kidneys from C57BL/6J-cpk/ cpk mice. At 21 days of age, Cux-1 was highly expressed in cyst epithelium of polycystic kidneys but was minimally expressed in kidneys from phenotypically normal littermates. These results demonstrate that a cut-related homeobox gene is expressed in the developing kidney and urinary tract of the mouse. Expression of Cux-1 in the kidney is inversely related to degree of cellular differentiation. Cux-1 may encode a transcriptional repressor that inhibits terminally differentiated gene expression during early stages of nephrogenesis.
  • 1区Q1影响因子: 12.5
    2. Characterization of a tissue-specific CDP/Cux isoform, p75, activated in breast tumor cells.
    作者:Goulet Brigitte , Watson Peter , Poirier Madeleine , Leduy Lam , Bérubé Ginette , Meterissian Sarkis , Jolicoeur Paul , Nepveu Alain
    期刊:Cancer research
    日期:2002-11-15
    Two isoforms of the CCAAT-displacement protein/cut homeobox (CDP/Cux) transcription factor have been characterized thus far. The full length protein, p200, which contains four DNA binding domains, transiently binds to DNA and carries the CCAAT-displacement activity. The p110 isoform is generated by proteolytic processing at the G1-S transition and is capable of stable interaction with DNA. Here we demonstrate the existence of a shorter CDP/Cux isoform, p75, which contains only two DNA binding domains, Cut repeat 3 and the Cut homeodomain, and binds more stably to DNA. CDP/Cux p75 was able to repress a reporter carrying the promoter for the cyclin-dependent kinase inhibitor p21 gene and to activate a DNA polymerase alpha gene reporter. Expression of CDP/Cux p75 involved a novel mechanism: transcription initiation within intron 20. The intron 20-initiated mRNA (I20-mRNA) was expressed at higher level in the thymus and in CD4+/CD8+ and CD4+ T cells. I20-mRNA was expressed only weakly or not at all in normal human mammary epithelial cells and normal breast tissues but was detected in many breast tumor cells lines and breast tumors. In invasive tumors a significant association was established between higher I20-mRNA expression and a diffuse infiltrative growth pattern (n = 41, P = 0.0137). In agreement with these findings, T47D breast cancer cells stably expressing p75 could not form tubule structures in collagen but rather developed as solid undifferentiated aggregates of cells. Taken together, these results suggest that aberrant expression of the CDP/Cux p75 isoform in mammary epithelial cells may be associated with the process of tumorigenesis in breast cancer.
  • 1区Q1影响因子: 14.8
    3. Cux-1 transgenic mice develop glomerulosclerosis and interstitial fibrosis.
    作者:Brantley Jennifer G , Sharma Madhulika , Alcalay Neal I , Heuvel Gregory B Vanden
    期刊:Kidney international
    日期:2003-04-01
    DOI :10.1046/j.1523-1755.2003.00889.x
    BACKGROUND:Cux-1 is a murine homeobox gene that is highly expressed in the nephrogenic zone of the developing kidney. Transgenic mice ectopically expressing Cux-1 develop renal hyperplasia associated with down-regulation of the cyclin kinase inhibitor p27. Because the reduction of p27 has been associated with mesangial cell proliferation and glomerular disease, we evaluated glomerular changes in Cux-1 transgenic mice. METHODS:Adult kidneys from Cux-1 transgenic mice were analyzed morphologically for changes in glomerular cell number and for changes in mesangial and interstitial extracellular matrix deposition. Mesangial matrix expansion was identified by light microscopy. Glomerular cell number was performed following immunohistochemistry. Type IV collagen deposition was analyzed by immunofluoresence and Western blotting. Renal function was evaluated by serum protein, blood urea nitrogen (BUN), creatinine, and electrolyte analysis, and by urine protein and creatinine analysis. RESULTS:In adult transgenic glomeruli, Cux-1 was ectopically expressed in mesangial cells, and this was associated with an increase in mesangial cell number, resulting from an increase in proliferation. There was a marked increase in mesangial matrix area in transgenic mice compared to non-transgenic littermates, related to an increase in type IV collagen. Podocyte foot process effacement was observed in transgenic mice, and this was related to an increase in urinary albumin. Interstitial fibrosis was also observed in transgenic kidneys. CONCLUSION:These observations indicate that increased expression of Cux-1 in mesangial cells results in cell proliferation and mesangial expansion. In addition, these changes are potentially related to disruption of podocyte architecture leading to loss of filtration. These results suggest that expression of Cux-1 is sufficient to induce the early events of mesangioproliferative glomerulonephritis.
  • 1区Q1影响因子: 48.8
    4. CUTL1 is a target of TGF(beta) signaling that enhances cancer cell motility and invasiveness.
    作者:Michl Patrick , Ramjaun Antoine R , Pardo Olivier E , Warne Patricia H , Wagner Martin , Poulsom Richard , D'Arrigo Corrado , Ryder Kenneth , Menke Andre , Gress Thomas , Downward Julian
    期刊:Cancer cell
    日期:2005-06-01
    DOI :10.1016/j.ccr.2005.05.018
    CUTL1, also known as CDP, Cut, or Cux-1, is a homeodomain transcriptional regulator known to be involved in development and cell cycle progression. Here we report that CUTL1 activity is associated with increased migration and invasiveness in numerous tumor cell lines, both in vitro and in vivo. Furthermore, we identify CUTL1 as a transcriptional target of transforming growth factor beta and a mediator of its promigratory effects. CUTL1 activates a transcriptional program regulating genes involved in cell motility, invasion, and extracellular matrix composition. CUTL1 expression is significantly increased in high-grade carcinomas and is inversely correlated with survival in breast cancer. This suggests that CUTL1 plays a central role in coordinating a gene expression program associated with cell motility and tumor progression.
  • 1区Q1影响因子: 23
    5. CUX1: target of Akt signalling and mediator of resistance to apoptosis in pancreatic cancer.
    作者:Ripka S , Neesse A , Riedel J , Bug E , Aigner A , Poulsom R , Fulda S , Neoptolemos J , Greenhalf W , Barth P , Gress T M , Michl P
    期刊:Gut
    日期:2010-05-04
    DOI :10.1136/gut.2009.189720
    BACKGROUND AND AIMS:The transcription factor CUX1 is known as a regulator of cell differentiation and cell cycle progression. Previously, CUX1 was identified as a modulator of invasiveness in various cancers. Based on expression profiles suggesting a role for CUX1 in mediating chemoresistance, the aim of this study was to characterise the effect of CUX1 on apoptosis as well as its regulation by signalling pathways modulating drug resistance in pancreatic cancer. METHODS:The effect of CUX1 on TRAIL- (tumour necrosis factor-related apoptosis-inducing ligand) and drug-induced apoptosis was analysed using overexpression and knock-down strategies. Regulation of CUX1 by phosphatidylinositol-3-kinase (PI3K)/Akt signalling was examined at the mRNA and protein level. The effect of CUX1 knock-down by nanoparticle-complexed small interfering RNA (siRNA) in vivo was analysed in a murine xenograft model. Furthermore, CUX1 RNA and protein expression was evaluated in human pancreatic cancer and adjacent normal tissues. RESULTS:Knock-down of CUX1 resulted in significantly enhanced TRAIL- and drug-induced apoptosis, associated with increased PARP (poly ADP-ribose polymerase) cleavage and caspase activity. Vice versa, overexpression of CUX1 inhibited apoptosis. CUX1 expression was induced by activation of Akt/protein kinase B signalling, and decreased by PI3K inhibitors. The antiapoptotic effect of CUX1 was associated with upregulation of BCL2 and downregulation of tumour necrosis factor alpha. CUX1 was significantly overexpressed in pancreatic cancers, as analysed by in situ hybridisation and immunohistochemistry. In vivo, silencing of CUX1 by intratumourally administered polyethylenimine-complexed siRNA led to reduced tumour growth and increased apoptosis in pancreatic cancer xenografts. CONCLUSION:CUX1 was identified as an important mediator of tumour cell survival in pancreatic cancer in vitro and in vivo.
  • 2区Q1影响因子: 16.6
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    6. CUX1 transcription factor is required for optimal ATM/ATR-mediated responses to DNA damage.
    作者:Vadnais Charles , Davoudi Sayeh , Afshin Mojdeh , Harada Ryoko , Dudley Rachel , Clermont Pier-Luc , Drobetsky Elliot , Nepveu Alain
    期刊:Nucleic acids research
    日期:2012-02-08
    DOI :10.1093/nar/gks041
    The p110 Cut homeobox 1 (CUX1) transcription factor regulates genes involved in DNA replication and chromosome segregation. Using a genome-wide-approach, we now demonstrate that CUX1 also modulates the constitutive expression of DNA damage response genes, including ones encoding ATM and ATR, as well as proteins involved in DNA damage-induced activation of, and signaling through, these kinases. Consistently, RNAi knockdown or genetic inactivation of CUX1 reduced ATM/ATR expression and negatively impacted hallmark protective responses mediated by ATM and ATR following exposure to ionizing radiation (IR) and UV, respectively. Specifically, abrogation of CUX1 strongly reduced ATM autophosphorylation after IR, in turn causing substantial decreases in (i) levels of phospho-Chk2 and p53, (ii) γ-H2AX and Rad51 DNA damage foci and (iii) the efficiency of DNA strand break repair. Similarly remarkable reductions in ATR-dependent responses, including phosphorylation of Chk1 and H2AX, were observed post-UV. Finally, multiple cell cycle checkpoints and clonogenic survival were compromised in CUX1 knockdown cells. Our results indicate that CUX1 regulates a transcriptional program that is necessary to mount an efficient response to mutagenic insult. Thus, CUX1 ensures not only the proper duplication and segregation of the genetic material, but also the preservation of its integrity.
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