Biomedical subjects

Rajesh Shinghal

Publications and source records attributed to Rajesh Shinghal.

5 recordsLinked to original sources

PubMed2004

Analysis of vitamin D-regulated gene expression in LNCaP human prostate cancer cells using cDNA microarrays.

BACKGROUND: 1,25-dihydroxyvitamin D(3) [1,25(OH)2D3] exerts growth inhibitory, pro-differentiating, and pro-apoptotic effects on prostate cells. To better understand the molecular mechanisms underlying these actions, we employed cDNA microarrays to study 1,25(OH)2D3-regulated gene expression in the LNCaP human prostate cancer cells. METHODS: mRNA isolated from LNCaP cells treated with vehicle or 50 nM 1,25(OH)2D3 for various lengths of time were hybridized to microarrays carrying approximately 23,000 genes. Some of the putative target genes revealed by the microarray analysis were verified by real-time PCR assays. RESULTS: 1,25(OH)2D3 most substantially increased the expression of the insulin-like growth factor binding protein-3 (IGFBP-3) gene. Our analysis also revealed several novel 1,25(OH)2D3-responsive genes. Interestingly, some of the key genes regulated by 1,25(OH)2D3 are also androgen-responsive genes. 1,25(OH)2D3 also down-regulated genes that mediate androgen catabolism. CONCLUSIONS: The putative 1,25(OH)2D3 target genes appear to be involved in a variety of cellular functions including growth regulation, differentiation, membrane transport, cell-cell and cell-matrix interactions, DNA repair, and inhibition of metastasis. The up-regulation of IGFBP-3 gene has been shown to be crucial in 1,25(OH)2D3-mediated inhibition of LNCaP cell growth. 1,25(OH)2D3 regulation of androgen-responsive genes as well as genes involved in androgen catabolism suggests that there are interactions between 1,25(OH)2D3 and androgen signaling pathways in LNCaP cells. Further studies on the role of these genes and others in mediating the anti-cancer effects of 1,25(OH)2D3 may lead to better approaches to the prevention and treatment of prostate cancer.

Biological Transport↗

PubMed2004

Molecular activity of 1,25-dihydroxyvitamin D3 in primary cultures of human prostatic epithelial cells revealed by cDNA microarray analysis.

1,25-Dihydroxyvitamin D(3) [1,25(OH)(2)D(3)] exerts anti-proliferative, differentiating and apoptotic effects on prostatic cells. These activities, in addition to epidemiologic findings that link Vitamin D to prostate cancer risk, support the use of 1,25(OH)(2)D(3) for prevention or therapy of prostate cancer. The molecular mechanisms by which 1,25(OH)(2)D(3) exerts antitumor effects on prostatic cells are not well-defined. In addition, there is heterogeneity among the responses of various prostate cell lines and primary cultures to 1,25(OH)(2)D(3) with regard to growth inhibition, differentiation and apoptosis. To understand the basis of these differential responses and to develop a better model of Vitamin D action in the prostate, we performed cDNA microarray analyses of primary cultures of normal and malignant human prostatic epithelial cells, treated with 50 nM of 1,25(OH)(2)D(3) for 6 and 24 h. CYP24 (25-hydroxyvitamin D(3)-24-hydroxylase) was the most highly upregulated gene. Significant and early upregulation of dual specificity phosphatase 10 (DUSP10), validated in five additional primary cultures, points to inhibition of members of the mitogen-activated protein kinase (MAPK) superfamily as a key event mediating activity of 1,25(OH)(2)D(3) in prostatic epithelial cells. The functions of other regulated genes suggest protection by 1,25(OH)(2)D(3) from oxidative stress. Overall, these results provide new insights into the molecular basis of antitumor activities of Vitamin D in prostate cells.

Calcitriol↗

PubMed2003

Gene expression patterns in renal cell carcinoma assessed by complementary DNA microarray.

Renal cell carcinoma comprises several histological types with different clinical behavior. Accurate pathological characterization is important in the clinical management of these tumors. We describe gene expression profiles in 41 renal tumors determined by using DNA microarrays containing 22,648 unique cDNAs representing 17,083 different UniGene Clusters, including 7230 characterized human genes. Differences in the patterns of gene expression among the different tumor types were readily apparent; hierarchical cluster analysis of the tumor samples segregated histologically distinct tumor types solely based on their gene expression patterns. Conventional renal cell carcinomas with clear cells showed a highly distinctive pattern of gene expression. Papillary carcinomas formed a tightly clustered group, as did tumors arising from the distal nephron and the normal kidney samples. Surprisingly, conventional renal cell carcinomas with granular cytoplasm were heterogeneous, and did not resemble any of the conventional carcinomas with clear cytoplasm in their pattern of gene expression. Characterization of renal cell carcinomas based on gene expression patterns provides a revised classification of these tumors and has the potential to supply significant biological and clinical insights.

Adenocarcinoma, Clear Cell↗

PubMed2003

Biochemical recurrence without PSA progression characterizes a subset of patients after radical prostatectomy. Prostate-specific antigen.

OBJECTIVES: To characterize a subset of patients with biochemical recurrence after radical prostatectomy but with little, if any, subsequent rise in serum prostate-specific antigen (PSA) and no clinical progression during long-term follow-up. METHODS: Of a series of 600 patients, 158 with biochemical recurrence after radical prostatectomy were examined. We identified a subset with measurable serum PSA levels during long-term follow-up, but with very low PSA velocity and no clinical recurrence. Serum PSA was measured with the ultrasensitive TOSOH assay with a PSA recurrence defined as a serum PSA of 0.07 ng/mL or greater. RESULTS: We identified 14 patients (8.8% of biochemical recurrences) with a detectable serum PSA level after radical prostatectomy yet without clinical or PSA progression at a mean follow-up after radical prostatectomy of 10.3 years. The mean time to PSA recurrence was 5.8 years, and the mean PSA velocity after recurrence was 0.028 ng/mL/yr. No clinical or pathologic features were found that could be used to identify this subset of patients. CONCLUSIONS: A subset of patients with biochemical recurrence after radical prostatectomy will not exhibit a progressive rise in serum PSA or clinical progression at 10 years follow-up. This suggests that serum PSA kinetics should be observed after biochemical recurrence before adjuvant hormonal therapy or radiotherapy.

Aged↗

PubMed2003

Cavoatrial tumor thrombus excision without circulatory arrest.

INTRODUCTION: Traditional methods of cavoatrial thrombus excision use deep hypothermic circulatory arrest with significant associated morbidity and mortality. We describe a novel technique that avoids circulatory arrest, yet provides a bloodless field for tumor excision. TECHNICAL CONSIDERATIONS: A 59-year-old woman presented with a left renal mass and tumor thrombus with extension into the right atrium. After left radical nephrectomy, an aortic occlusion balloon was placed in the abdominal aorta at the level of the diaphragm, limiting flow in the inferior vena cava for tumor excision and maintaining both cerebral and spinal cord perfusion during cardiopulmonary bypass. Tumor excision was successfully performed using this technique with minimal postoperative morbidity in the patient described. She remained free of recurrence at 9 months of follow-up. CONCLUSIONS: Cavoatrial tumor thrombus excision can be successfully performed without deep hypothermic circulatory arrest.

Aorta, Abdominal↗