Cancer Research Institute

About: Cancer Research Institute is a nonprofit organization based out in New York, New York, United States. It is known for research contribution in the topics: Cancer & Population. The organization has 1061 authors who have published 754 publications receiving 26712 citations.

Celecoxib potentiates the anticancer effect of cisplatin on vulvar cancer cells independently of cyclooxygenase.

Abstract: Cyclooxygenase-2 (COX-2) has been found to be associated with the development and progression of various cancers. Our previous study showed a high expression rate of COX-2 in paraffin-embedded tissue specimens from patients with vulvar cancer. In this study, we evaluated the efficacy of celecoxib, a selective COX-2 inhibitor, as a chemosensitizing agent with cisplatin in vulvar cancer cells A431 and SW962. COX-2 was expressed in both A431 and SW962 vulvar cancer cell lines. COX-1 was expressed in A431 but not in SW962. MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazoliumbromide] assay showed that treatment with 30 micromol/L celecoxib had no effect on cell growth in A431 cells for 72 h. However, combined treatment with celecoxib and cisplatin induced a significant reduction in cell growth compared to single treatment with cisplatin. Interestingly, single treatment with celecoxib or cisplatin and combined treatment of 10 micromol/L celecoxib with 10 micromol/L cisplatin increased COX-2 expression. However, the combination of 30 micromol/L celecoxib and 30 micromol/L cisplatin reduced COX-2 expression to the control state. Inhibition of cell growth by celecoxib alone and in combination with cisplatin was independent of the expression level of COX-2 induced by these agents. While treatment with 10 micromol/L celecoxib or 10 micromol/L piroxicam significantly suppressed the activity of COX enzymes, neither agent affected the growth of A431 and SW962 cells at this concentration. Taken together, celecoxib could be used as a chemosensitizing agent in vulva cancer cells; the anticancer activity of celecoxib seemed to be independent of COX.

Methyl-CpG binding domain 1 gene polymorphisms and risk of primary lung cancer.

Abstract: The methyl-CpG binding domain 1 (MBD1) protein plays an important role for transcriptional regulation of gene expression. Polymorphisms and haplotypes of the MBD1 gene may have an influence on MBD1 activity on gene expression profiles, thereby modulating an individual's susceptibility to lung cancer. To test this hypothesis, we investigated the association of MBD1 −634G>A, −501delT (−501 T/T, T/−, −/−), and Pro401Ala genotypes and their haplotypes with the risk of lung cancer in a Korean population. The MBD1 genotype was determined in 432 lung cancer patients and in 432 healthy control subjects who were frequency matched for age and gender. The −634GG genotype was associated with a significantly increased risk of overall lung cancer compared with the −634AA genotype [adjusted odds ratio (OR), 3.10; 95% confidence interval (95% CI), 1.24-7.75; P = 0.016]. When analyses were stratified according to the tumor histology, the −634GG genotype was associated with a significantly increased risk of adenocarcinoma compared with the −634AA genotype (adjusted OR, 4.72; 95% CI, 1.61-13.82; P = 0.005). For the MBD1 −501delT and Pro401Ala polymorphisms, the −501 T/T genotype was associated with a marginal significantly increased risk of adenocarcinoma compared with the −501−/− genotype (adjusted OR, 2.07; 95% CI, 1.02-4.20; P = 0.045), and the Pro/Pro genotype was associated with a significantly increased risk of adenocarcinoma compared with the Ala/Ala genotype (adjusted OR, 3.41; 95% CI, 1.21-9.60; P = 0.02). Consistent with the genotyping analyses, the −634G/−501T/401Pro haplotype was associated with a significantly increased risk of overall lung cancer and adenocarcinoma compared with the −634A/−501−/401Ala haplotype (adjusted OR, 1.44; 95% CI, 1.08-1.91; P = 0.012 and P c = 0.048; adjusted OR, 1.75; 95% CI, 1.20-2.56; P = 0.004 and P c = 0.016, respectively). On a promoter assay, the − 634A allele had significantly higher promoter activity compared with the − 634G allele in the Chinese hamster ovary cells and A549 cells ( P A, −501delT, and Pro401Ala polymorphisms and their haplotypes contribute to the genetic susceptibility for lung cancer and particularly for adenocarcinoma.

MiR-206, a Cerebellum Enriched miRNA Is Downregulated in All Medulloblastoma Subgroups and Its Overexpression Is Necessary for Growth Inhibition of Medulloblastoma Cells

Abstract: Medulloblastoma is the most common and a highly malignant pediatric brain tumor located in the cerebellar region of the brain. Medulloblastomas have recently been shown to consist of four distinct molecular subgroups, viz., WNT, SHH, group 3, and group 4. MiR-206, a miRNA first identified as a myomiR due to its enriched expression in skeletal muscle was found to be expressed specifically in the cerebellum, the site of medulloblastoma occurrence. MiR-206 expression was found to be downregulated in medulloblastomas belonging to all the four molecular subgroups as well as in established medulloblastoma cell lines. Further, the expression of murine homolog of miR-206 was also found to be downregulated in SHH subgroup medulloblastomas from the Smo +/+ transgenic mice and the Ptch1 +/− knockout mice. MiR-206 downregulation in all the four medulloblastoma subgroups suggests tumor-suppressive role for miR-206 in medulloblastoma pathogenesis. The effect of miR-206 expression was analyzed in three established medulloblastoma cell lines, viz., Daoy, D425, and D283 belonging to distinct molecular subgroups. Restoration of miR-206 expression to the levels comparable to those in the normal cerebellum, however, was found to be insufficient to inhibit the growth of established medulloblastoma cell lines. OTX2, an oncogenic miR-206 target, overexpressed in all non-SHH medulloblastomas, is known to inhibit myogenic differentiation of medulloblastoma cells. Overexpression of miR-206 was necessary to downregulate OTX2 expression and inhibit growth of medulloblastoma cell lines.