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(1/1499) Influence of pharmacogenetic variability on the pharmacokinetics and toxicity of the aurora kinase inhibitor danusertib.

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(2/1499) Correlation analysis between loss of heterozygosity at chromosome 18q and prognosis in the stage-II colon cancer patients.

BACKGROUND AND OBJECTIVE: Colorectal cancer is one of the most common malignant cancers in the world. Although the clinicopathologic staging is the golden criterion for the prognosis at present, the optimum prognostic criteria for colorectal cancer should be a combination of the clinicopathologic staging and the molecular markers. However, there are currently no molecular markers available for the prognosis of colorectal cancer. Several tumor-suppressor genes associated with colorectal cancer have been mapped at the 18q21-23 region. In this study we detected the frequency of loss of heterozygosity (LOH) at chromosome 18q and investigated the relationship between LOH and clinicopathologic features and its prognostic value for patients with stage II colon cancer. METHODS: A total of 106 samples of tumor tissues and corresponding normal mucosa from patients with sporadic stage-II colon cancer were included in this study. All the samples were formalin-fixed and paraffin-embedded. DNA was extracted from tumor tissues and LOH of D18S474, D18S55, D18S58, D18S61 and D18S64 at chromosome 18q was analyzed using polymerase chain reaction (PCR), polyacrylamide gel-electrophoresis, and DNA sequencing method. Multivariate analysis for association between LOH and prognosis in colon cancer patients was performed with Cox proportional hazards regression model. RESULTS: The median follow-up time was 68 months. For 106 patients, 5-year survival rate was 83.6%, which was associated with age and gross tumor type (P = 0.011 and 0.034, respectively). Among 102 patients who were eligible for LOH information, the overall frequency of LOH is 49.0% (50/102), and that of LOH at 5 microsatellite loci of D18S474, D18S55, D18S58, D18S61, and D18S64 was 30.2% (26/86), 23.4% (18/77), 28.6% (20/70), 35.0% (28/80), and 20.8%(15/72), respectively. The occurrence of LOH was significantly associated with tumor location and histopathologic grade (P = 0.023, 0.016 and 0.005, respectively). LOH was more frequent on the left-side, poorly-differentiated adenocarcinoma, and nonmucinous colon cancers. The occurrence of 18q-LOH was significantly associated with 5-year overall survival rate and disease free survival rate (P = 0.008 and 0.006, respectively). The occurrence of 18q-LOH at the loci of D18S474 and D18S61 was significantly associated with 5-year overall survival rate (P = 0.010 and 0.005, respectively). The multivariate analysis showed that only the occurrence of 18q-LOH was significantly associated with prognosis (P = 0.021). CONCLUSIONS: There is a high occurrence of LOH at the loci of 18q. The expression of LOH is significantly associated with tumor location and histopathologic grade. The occurrence of 18q-LOH is an independent poor prognostic factor for the patients with stage-II colon cancer.  (+info)

(3/1499) DNA methylation epigenotypes in breast cancer molecular subtypes.

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(4/1499) Phase II study of cilengitide (EMD 121974, NSC 707544) in patients with non-metastatic castration resistant prostate cancer, NCI-6735. A study by the DOD/PCF prostate cancer clinical trials consortium.

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(5/1499) Bcl-2 promotes malignant progression in a PDGF-B-dependent murine model of oligodendroglioma.

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(6/1499) Expression and unique functions of four nuclear factor of activated T cells isoforms in non-small cell lung cancer.

Nuclear factor of activated T cells (NFAT) is an important family of transcription factors that can be activated by calmodulin and calcineurin in human cells. To investigate the expression and clinical significance of NFAT isoforms and calcineurin in non-small cell lung cancer (NSCLC), we collected tumor and adjacent normal tissues from 159 NSCLC patients and assembled them in a tissue microarray. Protein levels of NFAT1, NFAT2, NFAT3, NFAT4, and calcineurin were determined using immunohistochemistry. Correlations between NFAT and calcineurin expression and clinicopathologic characteristics were analyzed. We found that the positive rates of NFAT1 (52.8%, 84/159), NFAT2 (11.3%, 18/159), NFAT3 (28.3%, 45/159), NFAT4 (47.2%, 75/159), and calcineurin (47.8%, 76/159) expression were significantly higher in tumor tissues than in adjacent normal lung tissues (P<0.001), respectively. The positive rate of NFAT1 expression was significantly higher in patients with adenocarcinoma (63.5%, 47/74) than in those with squamous cell carcinoma (43.5%, 37/85) (chi2=6.340, P=0.012); with lymph node metastasis (61.6%, 53/86) than without lymph node metastasis (42.5%, 31/73) (chi2=5.818, P=0.016); and with stage-II and -III diseases (61.8%, 55/89) than with stage-I disease (41.4%, 29/70) (chi2=6.524, P=0.011). Moreover, the overexpression of NFAT1 was associated with poor survival of NSCLC patients (chi2=5.006, P=0.025). The positive rate of NFAT4 was significantly higher in patients with squamous carcinoma (57.6%, 49/85) than in those with adenocarcinoma (35.1%, 26/74) (chi2=8.045, P=0.005) and with high and moderate differentiation (54.9%, 61/111) than with low differentiation (29.2%, 14/48) (chi2=8.943, P=0.003). Calcineurin overexpression was significantly associated with histologic type (higher in squamous carcinoma than in adenocarcinoma, chi2=8.897, P=0.003), differentiation grade (higher in high-moderation grade than in low grade, chi2=9.566, P=0.002) and gender (higher in male than in female, chi2=5.766, P=0.016). Furthermore, calcineurin expression was significantly correlated with NFAT4 level (r=0.429, P<0.001). These results suggest that NFAT1 expression is associated with lung adenocarcinoma progression, and NFAT4 expression, which was higher in squamous lung cancer, is associated with calcineurin expression and differentiation grade.  (+info)

(7/1499) Expressions of the gamma2 chain of laminin-5 and secreted protein acidic and rich in cysteine in esophageal squamous cell carcinoma and their relation to prognosis.

Previous studies have shown that the expressions of the gamma2 chain of laminin-5 and secreted protein acidic and rich in cysteine (SPARC) play important roles in oncogenesis and the development of carcinoma. To assess the expressions of laminin-5 gamma2 chain and SPARC in esophageal squamous cell carcinoma (SCC), and to clarify the prognostic significance of the expressions of laminin-5 gamma2 chain and SPARC in esophageal SCC, we detected the expressions of laminin-5 gamma2 chain and SPARC in cancer tissue and corresponding normal mucosa from 116 patients with advanced (stages II-IV) esophageal SCC using the tissue microarray-based immunohistochemistry and analyzed the correlation of the expressions with clinicopathologic characteristics and survival. We found that in normal esophageal tissues, laminin-5 gamma2 chain was expressed in the basement membrane, whereas in esophageal SCC tissues, laminin-5 gamma2 chain was expressed in the cytoplasm of carcinoma cells, with a positive rate of 72.4%. SPARC was not detected in normal esophageal mucosa, but was expressed in stromal fibroblasts in 84.6% of esophageal SCC cases and in cancer cells in 7.8% of esophageal SCC cases. There was a significant correlation between laminin-5 gamma2 chain and stromal SPARC expression in esophageal SCC (Spearman's rho=0.423, P<0.001). The expressions of both laminin-5 gamma2 chain and stromal SPARC were correlated with survival (P=0.032 and P=0.034, respectively). In stage-II esophageal SCC, the expression of laminin-5 gamma2 chain was significantly correlated with survival (P=0.023), while the expression of SPARC was not significantly correlated with survival (P=0.154). Patients with elevated levels of laminin-5 gamma2 chain and SPARC expressions had a poorer prognosis than did those lacking elevated levels of laminin-5 gamma2 chain expression and/or elevated levels of SPARC expression (P=0.001). In stage-II esophageal SCC, patients with elevated levels of laminin-5 gamma2 chain and SPARC expressions had a poorer prognosis (P<0.001). These results suggest that laminin-5 gamma2 chain and SPARC may play roles in the progression of esophageal SCC and their simultaneous expression is correlated with poorer prognosis, especially in patients with stage-II SCC.  (+info)

(8/1499) Prognostic relevance of number and bilaterality of positive surgical margins after radical prostatectomy.

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