Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0178874 (tumor progression)
 40,807 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Deregulation of apoptosis plays an important role in carcinogenesis, tumor progression, and resistance to chemotherapy. XIAP is considered to be the most potent caspase inhibitor of all known IAP (inhibitor of apoptosis) family members. To explore the relevance of XIAP for progression and prognosis in renal cell carcinomas (RCCs) of the clear-cell type, we analyzed XIAP protein expression in formalin-fixed tissue from 145 clear-cell RCCs by immunohistochemistry. XIAP protein expression was found in 95% of clear-cell RCCs. A significant increase of XIAP expression became evident from well (G1) to poorly (G3) differentiated clear-cell RCCs (P < 0.0001) and from low (pT1) to advanced (pT3) tumor stages (P = 0.0016). Log-rank test showed a significant inverse correlation (P = 0.0174) between XIAP expression and tumor aggressiveness as indicated by patients' survival. Most important, multivariate Cox regression analysis revealed that XIAP expression is an independent prognostic parameter (P = 0.018) in clear-cell RCCs. Our results suggest an important role for XIAP-mediated inhibition of apoptosis during progression of clear-cell RCCs and introduce XIAP expression as a new independent prognostic marker in this tumor type.
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PMID:XIAP expression is an independent prognostic marker in clear-cell renal carcinomas. 1529 70

Cell surface carbohydrates expressed on epithelial cells are thought to play an important role in tumor progression. Previously, we have shown that expression of core 2-branched O-glycans is closely correlated with vessel invasion and depth of invasion in colon and lung carcinomas. In this study, we found that expression of core 2 beta1,6-N-acetylglucosaminyltransferase-1, Core2GnT, is positively correlated with the progression of prostate cancer in human patients. Statistical analysis demonstrated that Core2GnT is an independent predictor for progressed pathological stage (pT3) and for prostate-specific antigen (PSA) relapse. To determine directly the roles of Core2GnT in prostate cancer progression, we set up an experimental tumor model using the LNCaP prostate cancer cell line. Because this line does not express Core2GnT, we established an LNCaP line stably expressing Core2GnT, LNCap-Core2GnT, by transfecting cDNA encoding Core2GnT. When mock-transfected LNCaP cells and LNCaP-Core2GnT were inoculated in the prostate of nude mice, LNCaP-Core2GnT cells produced three times heavier prostate tumors than mock-transfected LNCaP cells. Furthermore, we found that LNCaP-Core2GnT cells adhered more strongly to prostate stromal cells, type IV collagen and laminin than did LNCaP-mock cells, but LNCaP and LNCaP-Core2GnT cells grew almost at the same rate on plates coated with type IV collagen or laminin. These results indicate that Core2GnT is an extremely useful prognostic marker for prostate cancer progression. The results also suggest that acquiring Core2GnT in prostate carcinoma cells facilitates adhesion to type IV collagen and laminin, and this increased adhesion may be a cause for aggressive tumor formation by prostate cancer cells expressing Core2GnT.
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PMID:Expression of core 2 beta1,6-N-acetylglucosaminyltransferase facilitates prostate cancer progression. 1593 19

Carbonyl reductase (CBR) is a cytosolic NADPH-dependent oxidoreductase metabolizing prostaglandins, steroids, quinines, and anthracycline antibiotics. Many experimental studies have shown that CBR plays important roles in the regulation of tumor progression, but clinical significance of CBR status remains unclear. Thus, we conducted a retrospective study on CBR mRNA expression in lung cancer. Tumor tissues obtained from 59 non-small-cell lung cancer patients were analyzed by quantitative real-time reverse transcription-PCR assay to reveal clinical significance of CBR expression. Angiogenesis was measured immunohistochemically as intratumoral microvessel density (IMVD) using anti-CD34 monoclonal antibody CD34-IMVD) and anti-CD105 monoclonal antibody (CD105-IMVD). CBR mRNA expression was significantly reduced along with progression of primary tumors (the mean CBR mRNA/GAPDH mRNA, 3.288x10(-2) for pT1, 1.628x10(-2) for pT2, and 1.175x10(-2) for pT3-4 disease, respectively; P=0.02). Moreover, CBR mRNA expression in tumor with nodal involvement seemed to be reduced as compared with that in tumor without nodal involvement (the mean CBR mRNA/GAPDH mRNA, 1.446x10(-2) and 2.531x10(-2), respectively), whereas the difference did not reach a statistical significance (P=0.09). The mean CD105-IMVD for CBR-high tumor was 59.2, which was significantly lower than that for CBR-low tumor (130.6, P=0.02), whereas no significant difference between the mean CD34-IMVDs for CBR-high tumor and CBR-low tumor was found. The 5-year survival rate of CBR-high patients was 68.3%, significantly higher than that of CBR-low patients (36.5%; P=0.03). A multivariate analysis confirmed that CBR-high expression was a significant factor to predict a favorable prognosis (P=0.04; relative risk, 0.39; 95% confidence interval, 0.16-0.98). Expression of CBR mRNA was a significant prognostic factor in non-small-cell lung cancer and was inversely associated with tumor progression and angiogenesis.
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PMID:Carbonyl reductase expression and its clinical significance in non-small-cell lung cancer. 1610 46

Cell cycle and apoptosis regulatory proteins are markers of tumor progression in colorectal cancer. In a series of 1,274 mismatch repair-proficient colorectal cancers, immunohistochemical analysis of p21, p27, p53, and bcl-2 expression was performed using the tissue microarray technique. In univariate analysis, p21 expression was associated with tumor location and pN0; p27 expression with tumor location, lower tumor grade, early pT, and pN; p53 expression with tumor location; and bcl-2 with early pT and pN. Expression of p27 identified subgroups with worse prognosis in pT3 N0 and pT3 N+ patients. None of the 4 tumor markers were independent prognostic indicators of survival. The multimarker phenotypes p21/p27/p53 and p21/p27/bcl-2 were associated with survival. In mismatch repair-proficient colorectal cancer, p27 expression is associated with a better prognosis, and pT, pN, and vascular invasion are independent prognostic factors. In addition, multimarker phenotypes are useful to identify colorectal cancer subgroups with different prognoses.
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PMID:Prognostic value of cell cycle and apoptosis regulatory proteins in mismatch repair-proficient colorectal cancer: a tissue microarray-based approach. 1714 38

Transcriptional downregulation of the putative tumor suppressor gene XIAP-associated Factor 1 (XAF1) by promoter methylation has been shown to relate to tumor progression of gastric and bladder cancer. This study determined the mRNA expression levels and the methylation status of XAF1 by real-time RT-PCR and quantitative methylation specific PCR in tumor tissue obtained from 91 renal cell carcinoma (RCC) patients (median follow-up 50.5 months) following surgical treatment. Expression data was correlated to histopathological variables and outcome. XAF1 expression levels were not related to standard pathological parameters for outcome prediction but results from crude and explorative multivariable-adjusted analyses revealed low XAF1 levels to significantly increase the relative risk (RR) for tumor recurrence (RR 4.6; CI 95%: 1.4-14.6) and tumor-related death (RR 3.6; CI 95%: 1.4-9.7). The association of low XAF1 expression with an abbreviated recurrence-free (p=0.009) and disease-specific survival (p=0.005) was most pronounced in patients with locally advanced (pT3) tumors. XAF1 promoter methylation was rarely detected (10%) but, if present, XAF1 mRNA expression levels correlated inversely to the normalized index of methylation (p=0.01). Our findings suggest that low XAF1 mRNA expression levels relate to an unfavorable clinical course in RCC patients. Promoter methylation may be one, but probably not the essential mechanism for transcriptional downregulation of the XAF1 gene in RCC.
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PMID:Gene expression and promoter methylation of the XIAP-associated Factor 1 in renal cell carcinomas: correlations with pathology and outcome. 1744 73

Heat shock proteins (HSPs) play an important role in the cellular response to environmental stress and exert a cytoprotective effect. Especially HSP70 is an effective inhibitor of apoptosis, suggesting a role of HSP70 in carcinogenesis and tumor progression. To explore the relevance of HSP70 in renal cell carcinomas (RCCs), we analyzed nuclear and cytoplasmic HSP70 protein expression in formalin-fixed tissue from 145 clear cell RCCs by immunohistochemistry as well as Western blot analysis. Nuclear HSP70 expression was found in all RCCs and 75% of the tumors also exhibited a cytoplasmic HSP70 staining. Importantly, RCCs showed significantly reduced cytoplasmic (p=0.001) and combined nuclear/cytoplasmic (p=0.0022) HSP70 expression when compared with their cells of origin. A significant (p=0.0176) decrease of nuclear HSP70 expression became evident from well to poorly differentiated clear cell RCCs. Quite similarly, a trend (p=0.0558) for reduced combined nuclear/cytoplasmic HSP70 expression was shown from early (pT1) to advanced (pT3) tumor stages. Nevertheless, no correlation between HSP70 expression and patients survival became evident. In conclusion, our investigation demonstrates a significant decrease of antiapoptotic HSP70 protein expression during carcinogenesis and during progression from well (G1) to poorly (G3) differentiated clear cell RCCs. Our results suggest that HSP70-mediated inhibition of apoptosis seems to be of minor importance for carcinogenesis and tumor progression in RCCs.
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PMID:Expression of heat shock protein 70 in renal cell carcinoma and its relation to tumor progression and prognosis. 1761 37

In the current study, we analysed the prognostic value of vascular endothelial growth factor receptor-1 (VEGFR-1) in clinically-localized prostate cancer (PCa). Forty patients who had undergone radical prostatectomy (RP) for clinically-localized PCa were included. Two groups were compared: 17 patients who experienced cancer progression following RP (group 1) and 23 patients who remained free of recurrence after intervention (group 2). Paraffin-embedded sections obtained from the RP specimens of the 40 patients were used to build tissue microarrays. The expression of VEGFR-1 was examined in the RP specimens using immunohistochemistry and was compared between the groups of patients. The two groups had similar tumor characteristics in terms of PSA, Gleason score and pathological stage of cancer. The median intensity score of VEGFR-1 expression was significantly higher in pT3 tumors than in pT2 tumors. Nevertheless, the intensity scores of VEGFR-1 expression were similar in the two groups of patients. Our results suggest that VEGFR-1 expression is not associated with the risk of cancer progression following RP. Therefore, VEGFR-1 may not be of prognostic value in clinically-localized PCa.
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PMID:The association of vascular endothelial growth factor receptor-1 with the risk of cancer progression following radical prostatectomy. 1809 92

A 59-year-old man admitted for upper gastrointestinal endoscopy of the health examination in the middle of October 2005 was diagnosed with advanced lower esophageal cancer. After a precise examination, he received a subtotal esophagectomy followed by three-field lymphadenectomy in the beginning of November 2005. The histopathological diagnosis was well differentiated squamous cell carcinoma (pT3, ie (+), ly2, v2, pIM0, pN3, pStage III). After two courses of systemic chemotherapy so called FP therapy, solitary liver metastasis in S8 area was detected in May 2007. He received additional two courses of FP chemotherapy, but the CT scan revealed that the lesion was progress disease (PD) in December 2007. It seemed to be difficult to reduce the tumor progression by systemic chemotherapy, so S8 semi-segmental lobectomy was performed. After the operation, the patient received the combination chemotherapy with docetaxel and nedaplatin once a week on day 1 for 4 weeks in five courses, but the CT scan revealed the appearance of the recurrence of residual liver and abdominal lymphnodes in January 2009. So a right hepatic lobectomy and lymphadenectomy were performed. The patient also received chemoradiotherapy after the operation, no recurrence of the liver and lymphnodes metastases has been shown. Surgical resection was sometimes seemed to be effective for treating liver metastasis of esophageal cancer, thus indication of operation need to be discussed for accumulation of many liver metastasis of esophageal cancer.
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PMID:[A case of postoperative liver metastasis of esophageal cancer remains in progression free after successfully resected]. 2003 56

The major biomarker for rectal cancer is the pathologic development of the tumor. In our study, we identified Dikkopf-1 (DKK1) as a novel biomarker and a therapeutic target for rectal cancer. To emphasize the biological and clinicopathologic significance, we performed tumor tissue and serum analysis of 150 rectal cancer samples with enzyme-linked immunosorbent assay. Serum DKK-1 levels are found significantly higher in controls, in poor differentiation, and depth of invasion (in pT3 and pT4), present lymph node metastasis, and TNM stage (in pT3 and pT4) according to good differentiation, depth of invasion (in pT1 and pT2), absent lymph node metastasis, and TNM stage (in pT1 and pT2; P < 0.001 and P < 0.0001, respectively). Tissue DKK-1 levels are found in patients with rectal cancer than in control tissues (P < 0.0001). Dikkopf-1 correlated significantly with depth of invasion (P = 0.009), lymph node metastasis (P = 0.028), venous involvement (P = 0.019), and advanced pTNM stage (P = 0.001). There was no correlation between DKK-1 and age or sex (P > 0.05). This marker is also a potential candidate for development of rectal cancer cells and cancer progression.
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PMID:Relationship between clinicopathologic variables and serum and tissue levels of dickkopf-1 in patients with rectal cancer. 2171 26

Elevated serum interleukin-6 (IL-6) levels have been associated with tumor progression and poor prognosis in patients with esophageal carcinoma. The purpose of the present study was to clarify such a relationship in patients with esophageal squamous cell carcinoma with a focus on the possible influence of chemoradiotherapy (CRT) on tumor IL-6 expression. Data regarding 41 patients with clinical T3-T4 tumors who underwent induction chemoradiotherapy followed by surgery (CRT group) and 60 patients with clinical T1-T4 tumors who underwent surgery alone (Surgery group) between 2001 and 2010, were retrospectively analyzed. Tumor IL-6 expression in resected specimens was evaluated by immunohistochemistry. Tumor IL-6 expression was detected in patients with advanced tumors in the Surgery group (21.1% in p(stage) III-IV vs. 0.2% in p(stage) I-II; 27.8% in pT3-4 vs. 0% in pT1-2), and also correlated with primary tumor progression and surgical curability in the Surgery group. In addition, patients with IL-6-positive tumors had significantly shorter overall survival than those with IL-6-negative tumors in the CRT group, and tumor IL-6 expression had an independent prognostic value in multivariate analysis, whereas no significant difference in overall survival was observed between patients with IL-6-positive and those with IL-6-negative tumors in the Surgery group. These results indicate that pre-treatment tumor IL-6 expression correlates with primary tumor progression, and CRT-induced tumor IL-6 expression predicts poor prognosis.
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PMID:Prognostic impact of tumor IL-6 expression after preoperative chemoradiotherapy in patients with advanced esophageal squamous cell carcinoma. 2374 29


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