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.

Restoration of miR-193a expression is tumor-suppressive in MYC amplified Group 3 medulloblastoma.

Abstract: Medulloblastoma, a highly malignant pediatric brain tumor, consists of four molecular subgroups, namely WNT, SHH, Group 3, and Group 4. The expression of miR-193a, a WNT subgroup-specific microRNA, was found to be induced by MYC, an oncogenic target of the canonical WNT signaling. MiR-193a is not expressed in Group 3 medulloblastomas, despite MYC expression, as a result of promoter hypermethylation. Restoration of miR-193a expression in the MYC amplified Group 3 medulloblastoma cells resulted in inhibition of growth, tumorigenicity, and an increase in radiation sensitivity. MAX, STMN1, and DCAF7 were identified as novel targets of miR-193a. MiR-193a mediated downregulation of MAX could suppress MYC activity since it is an obligate hetero-dimerization partner of MYC. MYC induced expression of miR-193a, therefore, seems to act as a feedback inhibitor of MYC signaling. The expression of miR-193a resulted in widespread repression of gene expression that included not only several cell cycle regulators, WNT, NOTCH signaling genes, and those encoding DNA replication machinery, but also several chromatin modifiers like SWI/SNF family genes and histone-encoding genes. MiR-193a expression brought about a reduction in the global levels of H3K4me3, H3K27ac, the histone marks of active chromatin, and an increase in the levels of H3K27me3, a repressive chromatin mark. In cancer cells having high MYC expression, MYC brings about transcriptional amplification of all active genes apart from the induction of its target genes. MiR-193a, on the other hand, brought about global repression of gene expression. Therefore, miR-193a has therapeutic potential in the treatment of not only Group 3 medulloblastomas but possibly other MYC overexpressing aggressive cancers as well.

Structural basis to stabilize the domain motion of BARD1-ARD BRCT by CstF50.

Abstract: BRCA1 associated ring domain protein 1(BARD1) is a tumor suppressor protein having a wide role in cellular processes like cell-cycle checkpoint, DNA damage repair and maintenance of genomic integrity. Germ-line mutation Gln 564 His discovered in linker region of BARD1 leads to loss of binding to Cleavage stimulating factor (CstF50), which in turn instigates the premature mRNA transcript formation and apoptosis. We have studied the dynamics of ARD domain present in the BARD1 wild-type and mutant protein in association with CstF50 using biophysical, biochemical and molecular dynamics simulations. It has been observed that the ARD domain is relatively more flexible than the BRCT domain of BARD1. Further relative orientations of both the ARD and BRCT domains varies due to the highly flexible nature of the connecting linker region present between the domains. It has been observed that mutant ARD domain is more dynamic in nature compared to wild-type protein. Molecular docking studies between BARD1 Gln 564 His mutant and CstF50 shows the loss of interactions. Furthermore, domain motion of ARD present in BARD1 was stabilized when complexed with CstF50.

Impact of smoking amount on clinicopathological features and survival in non-small cell lung cancer.

Abstract: Screening for early detection of lung cancer has been performed in high-risk individuals with smoking history. However, researches on the distribution, clinical characteristics, and prognosis of these high-risk individuals in an actual cohort are lacking. Thus, the objective of this study was to retrospectively review characteristics and prognosis of patients with smoking history in an actual lung cancer cohort. The present study used the lung cancer cohort of the Catholic Medical Centers at the Catholic University of Korea from 2014 to 2017. Patients with non-small cell lung cancer were enrolled. They were categorized into high and low-risk groups based on their smoking history using the national lung screening trial guideline. Distribution, clinical characteristics, and survival data of each group were estimated. Of 439 patients, 223 (50.8%) patients were in the high-risk group. Patients in the high-risk group had unfavorable clinical characteristics and tumor biologic features. Overall survival of the high-risk group was significantly shorter than that of the low-risk group with both early (I, II) and advanced stages (III, IV). In multivariate analysis, heavy smoking remained one of the most important poor clinical prognostic factors in patients with lung cancer. It showed a dose-dependent relationship with patients’ survival. High-risk individuals had poor clinical outcomes. Patients’ prognosis seemed to be deteriorated as smoking amount increased. Therefore, active screening and clinical attention are needed for high-risk individuals.

Pentoxifylline inhibits integrin-mediated adherence of 12(S)-HETE and TNFalpha-activated B16F10 cells to fibronectin and endothelial cells.

Abstract: Background: Pentoxifylline (PTX), a phosphodiesterase inhibitor, inhibits homing of metastatic B16F10 melanoma cells to the lung. Studies on the mechanism of action of PTX showed inhibition of adhesion of cultured melanoma cells to various extracellular matrix substrates and inhibition of cell surface integrin expression. The aim of this study was to determine the effect of PTX on surface expression of integrin and integrin-mediated adhesion induced by biological mediators, tumour necrosis factor (TNF) α and 12(S)-hydroxyeicosatetraenoic acid (HETE), in B16F10 cells. Materials and Methods: B16F10 cells were treated with 12(S)-HETE (1 µM, 1 h), TNFα (5 ng/ml, 2 h) and phorbol 12-myristate 13-acetate (400 nM, 20 min), and the effect of PTX on these treatments was studied by flow cytometry, adhesion assay and confocal microscopy. Results: 12(S)-HETE and TNFα brought about an increase in the surface expression of β1 integrins and F10 cell adhesion to fibronectin and endothelial cells; this increased adhesion was mediated at least in part by alterations in the localization of β1 integrins. Pretreatment with PTX was able to completely abrogate this induction in integrin expression. Conclusion: PTX can inhibit surface expression of integrin and integrin-mediated adhesion induced by several biological mediators, and this might be a possible mechanism for its antimetastatic action, in vivo.