Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0598934 (tumor growth)
 58,965 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostate cancer is the most frequently diagnosed cancer in men and the second leading cause of male cancer death in the United States. Early detection and improved procedures for surgical intervention and radiation therapy have reduced the fatalities; however, there is no effective cure for men with advanced disease and additional therapy is urgently needed. We have previously shown that MBP-1 acts as a general transcriptional repressor and exerts an antiproliferative effect on several human cancer cells. MBP-1 possesses two repressor domains, located at the amino and carboxyl termini. In this study, we have examined the potential of the repressor domains of MBP-1 as a gene therapeutic candidate in regression of prostate tumor growth. Our results suggested that replication-deficient adenovirus-mediated delivery of amino-terminal (MBP-AR) or carboxyl-terminal (MBP-CR) repressor domain of MBP-1 exerted an antiproliferative effect, like the full-length MBP-1, and induced caspase-independent apoptosis in prostate cancer cells. Next, we investigated the therapeutic effectiveness of MBP-1 repressor domain on prostate tumors. When tested in human tumor xenografts in nude mice, MBP-CR suppressed prostate tumor growth more effectively than full-length MBP-1, whereas MBP-AR delayed prostate tumor growth. Together, these results suggested that MBP-CR expression has an antiproliferative effect in human prostate cancer cells, being more effective than the full-length MBP-1 in preventing tumor growth.
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PMID:Carboxyl-terminal repressor domain of MBP-1 is sufficient for regression of prostate tumor growth in nude mice. 1570 66

Lung cancer is the leading cause of cancer death among both men and women. Only approximately 15% of people diagnosed with non-small cell lung cancer (NSCLC) survive this disease beyond 5 years. Thus, novel therapeutic strategies are urgently needed to improve the clinical management of this devastating disease. We have previously shown the antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of non-small cell lung tumor growth. We have observed that exogenous expression of MBP-1 in NSCLC cells (H1299) induces massive cell death. To determine the gene therapeutic potential of MBP-1, replication-deficient recombinant adenovirus expressing MBP-1 was given intratumorally in human lung cancer xenografts in nude mice. Our results showed a significant regression of lung tumor growth and prolonged survival on treatment with MBP-1 compared with the control groups (saline or dl312). Subsequently, the mechanism of MBP-1-mediated H1299 cell death was investigated. Our results suggested that MBP-1 induced poly(ADP-ribose) polymerase cleavage in H1299 cells; however, treatment with pan-caspase inhibitor did not protect against MBP-1-induced cell death. Cells transduced with MBP-1 displayed early plasma membrane permeability, mitochondrial damage without cytochrome c release, and extensive cytoplasmic vacuolation, yielding a morphotype that is typical of necrosis. Taken together, this study suggests that MBP-1 expression induces a novel form of necrosis-like cell death and MBP-1 could be a potential gene therapeutic candidate against non-small cell lung tumor growth.
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PMID:Tumor-suppressive effects of MBP-1 in non-small cell lung cancer cells. 1717 88

MBP-1 acts as a general transcriptional repressor. Overexpression of MBP-1 induces cell death in a number of cancer cells and regresses tumor growth. However, the function of endogenous MBP-1 in normal cell growth regulation remains unknown. To unravel the role of endogenous MBP-1, we knocked down MBP-1 expression in primary human foreskin fibroblasts (HFF) by RNA interference. Knockdown of MBP-1 in HFF (HFF-MBPsi-4) resulted in an induction of premature senescence, displayed flattened cell morphology, and increased senescence-associated beta-galactosidase activity. FACS analysis of HFF-MBPsi-4 revealed accumulation of a high number of cells in the G1-phase. A significant upregulation of cyclin D1 and reduction of cyclin A was detected in HFF-MBPsi-4 as compared to control HFF. Senescent fibroblasts exhibited enhanced expression of phosphorylated and acetylated p53, and cyclin-dependent kinase inhibitor, p21. Further analysis suggested that promyolocytic leukemia protein (PML) bodies are dramatically increased in HFF-MBPsi-4. Together, these results demonstrated that knockdown of endogenous MBP-1 is involved in cellular senescence of HFF through p53-p21 pathway.
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PMID:Knockdown of MBP-1 in human foreskin fibroblasts induces p53-p21 dependent senescence. 1885 84

Breast cancer is the leading cause of cancer death among women. We have shown previously an antiproliferative effect of MBP-1 on several human cancer cells. In this study, we have examined the potential of MBP-1 as a gene therapeutic candidate in regression of breast cancer growth and metastasis in an immunocompetent mouse model. For this, we have used a mouse breast cancer cell line (EO771) and syngeneic C57BL/6 mice. EO771 cells were implanted into the mammary fat pad of C57BL/6 mice. Replication-deficient recombinant adenovirus expressing MBP-1 was administered intratumorally to determine gene therapeutic potential. The results showed a significant regression of primary and distant (lung) tumor growth. Animals exhibited prolonged survival on treatment with MBP-1 compared with the control group (dl312). Subsequent studies suggested that MBP-1 inhibits matrix metalloproteinase expression in human breast cancer cells. Cells transduced with MBP-1 displayed inhibition of migration in a wound-healing assay. The conditioned medium from MBP-1-transduced cells blocked in vitro tube formation assay and inhibited expression of several angiogenic molecules. Taken together, our study shows that MBP-1 acts as a double-edged sword by inhibiting primary and metastatic tumor growth and modulating matrix metalloproteinase expression with a therapeutic potential against breast cancer progression.
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PMID:MBP-1 inhibits breast cancer growth and metastasis in immunocompetent mice. 1993 12

c-myc promoter binding protein (MBP-1) is a multi-functional protein known to regulate expression of targets involved in the malignant phenotype. We have previously demonstrated that exogenous expression of MBP-1 inhibits prostate tumor growth, although the mechanism of growth inhibition is not well understood. We hypothesized that MBP-1 may modulate microRNA (miRNA) expression for regulation of prostate cancer cell growth. In this study, we demonstrated that exogenous MBP-1 upregulates miR-29b by 5-9 fold in prostate cancer cells as measured by real-time quantitative reverse transcription-PCR. Subsequent studies indicated that exogenous expression of miR-29b inhibited Mcl-1, COL1A1, and COL4A1. Further, a novel target with potential implications for invasion and metastasis, matrix metallopeptidase-2 (MMP-2), was identified and confirmed to be a miR-29b target in prostate cancer cells. Together our results demonstrated that exogenous expression of miR-29b regulates prostate cancer cell growth by modulating anti-apoptotic and pro-metastatic matrix molecules, implicating therapeutic potential of miR-29b for prostate cancer inhibition.
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PMID:MBP-1 upregulates miR-29b that represses Mcl-1, collagens, and matrix-metalloproteinase-2 in prostate cancer cells. 2065 50