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Biomedical subjects

V L Kumar

Publications and source records attributed to V L Kumar.

18 recordsLinked to original sources
PubMed1998

Comparative analysis of epidermal growth factor receptor mRNA levels in normal, benign hyperplastic and carcinomatous prostate.

Epidermal growth factor receptor (EGFR), a mediator of mitogenic activity of epidermal growth factor and transforming growth factor-alpha, has been shown to be associated with tumour progression. We have detected a level of EGFR transcript in normal, hyperplastic (BPH) and carcinomatous (CaP) prostate tissues by cytoplasmic dot hybridization. Our results show that the majority of CaP cases (62% of untreated cases and 71% of treated cases) were positive for EGFR mRNA while about 50% of normal and BPH cases were positive for EGFR mRNA. The level of EGFR transcript was significantly higher in the untreated CaP group as compared to the normal group (P < 0.05), while the difference in the normal and BPH groups was not statistically significant.

Adult↗
PubMed1998

Detection of receptor transcripts for androgen, epidermal growth factor and basic fibroblast growth factor in human prostate postmortem.

RNA isolated from frozen human postmortem prostate tissue was evaluated for its utility in molecular biological studies based on RNA analysis. Our results on slot-blot analysis show the presence of receptor transcripts for androgen, epidermal growth factor and basic fibroblast growth factor in postmortem prostate tissue obtained 20-120 hrs after death. However, the RNA in these samples was found to be degraded as revealed by the absence of ribosomal bands on gel electrophoresis. AR mRNA was found to be present in one of the five samples when analysed by northern blotting.

Adult↗
PubMed1997

Androgen receptor mRNA detection in the human foetal prostate.

In order to get an insight into androgen-mediated differentiation and development of the prostate, we detected the androgen receptor (AR) mRNA in the urogenital sinus of human foetuses at 12 and 16 weeks of gestation. Cytoplasmic dot hybridization using radiolabelled cDNA probe for human androgen receptor (AR) was performed. The AR mRNA could be detected at 12 weeks of gestation and its level was higher at 16 weeks of gestation.

Autoradiography↗
PubMed1997

Androgen deprivation causes up-regulation of androgen receptor transcript in the rat prostate.

We have studied the effect of androgenic deprivation on the level of androgen receptor transcript in the rat ventral prostate. The rats were treated with estradiol benzoate, flutamide and [D Trp6, des Gly10]gonadotropin releasing hormone (GnRH) for different time periods. These treatments produced a significant decrease in the weight of prostate. Total RNA isolated from the ventral prostates was hybridized with the cDNA probe for androgen receptor. Densitometric analysis of the autoradiographic signal revealed a rise in the level of androgen receptor RNA following treatment of rats with estradiol benzoate and flutamide. Treatment of rats with [D Trp6, des Gly10] GnRH brought about a transient rise in the level of androgen receptor RNA. Thus, our results indicate that androgenic deprivation up-regulates the level of androgen receptor transcript.

Androgens↗
PubMed1997

Androgen receptor transcript level in benign hypertrophy and carcinoma of the human prostate.

OBJECTIVE: Current reports suggest the presence of androgen receptor (AR) defects in prostate cancer. We have detected the AR mRNA in normal, benign hypertrophied (BPH) and carcinomatous (CaP) prostate tissues and evaluated the difference in the level of AR transcript in these groups. MATERIALS AND METHODS: Cytoplasmic dot hybridization assay was used to measure the levels of AR mRNA in 21 normal, 45 BPH and 30 CaP specimens. Tissue samples of 14 CaP patients receiving endocrine treatment were also analyzed. Blots were autoradiographed and the intensity of the signal was measured by densitometry. RESULTS AND CONCLUSIONS: The majority of cases in all the 3 groups were positive for the AR mRNA. All the patients who had received endocrine treatment were also positive for the AR mRNA. The level of the AR mRNA was significantly higher in BPH and treated CaP cases as compared to normal cases (p < 0.05). Among the CaP cases the level of AR transcript was significantly higher in the treated group as compared to the untreated group.

Adult↗
PubMed1995

Prostate gland: structure, functions and regulation.

The prostate gland plays an important role in male reproduction. It secretes enzymes, lipids, amines and metal ions essential for the normal function of spermatozoa. Development, differentiation and maintenance of the prostate gland depend on steroid and peptide hormones. Beside hormones growth factors also regulate the prostate gland. This review will focus on the structure, functions and mode of regulation of the prostate gland.

Animals↗
PubMed1995

In vivo functional analysis of the mouse estrogen receptor gene promoter: a transgenic mouse model to study tissue-specific and developmental regulation of estrogen receptor gene transcription.

Understanding the molecular and morphological basis of estrogen responsiveness in the various tissues and organs that make up an adult organism and its onset during ontogenesis requires identification of the genetic controls that determine timed expression of the estrogen receptor (ER) gene in multiple cell types. With this goal in mind, we describe here the results of the functional analysis of the mouse (m) ER gene promoter, carried out in vivo in transgenic mice. The mER gene promoter was cloned and spliced to the coding sequence of the bacterial lacZ gene (fused to the nuclear localization signal of SV40 large T: nls-beta-GAL) and then stably reintegrated into the genome of mice. Analysis of beta-GAL mRNA and protein expression in multiple organs of both female and male transgenic animals was then performed. Results show that the transgenic mER promoter, much like the endogenous one, is active in several organs and tissues of adult female and male mice. The first 0.4 kilobases of 5'-flanking DNA (up to -364) are sufficient to direct widespread expression of the transgene in mouse organs. This indicates that genetic elements functional in various cell types are included in this segment. Furthermore, the first exon and intron of the mER gene are necessary to achieve sexually dimorphic expression of the transgene in neurons located at specific sites within the central nervous system. These mER promoter transgenic mice will be useful in mapping estrogen- responsive cell types under different physiological and pathological conditions in vivo, in defining ontogenesis of estrogen action in the mouse, and in studying the mechanisms that regulate ER gene transcription.

Animals↗
PubMed1995

Inhibitory effects of formaldehyde on the reproductive system of male rats.

Formaldehyde, when administered to rats at a dose of 10 mg/kg body weight/day for a period of 30 days, resulted in a significant fall in sperm motility, viability and count. In addition, the DNA content was significantly lower in testis and prostate while the tissue protein content of prostate and epididymis had decreased in the treated rats. In vitro exposure to formaldehyde also inhibited the sperm motility and viability.

Animals↗
PubMed1994

Anti-inflammatory activity of the latex of Calotropis procera.

The anti-inflammatory property of the latex of Calotropis procera was studied on carrageenin- and formalin-induced rat paw oedema model. A single dose of the aqueous suspension of the dried latex was effective to a significant level against the acute inflammatory response.

Animals↗
PubMed1993

Anaesthetic steroids--a review.

Steroids produce anaesthesia besides producing the well known metabolic and hormonal effects. A number of anaesthetic steroids have been synthesized and tried clinically. Hydroxydione, althesin, minaxolone and pregnanolone are among those studied in detail. They act through GABAergic mechanism and are known to be advantageous over barbiturates.

Alfaxalone Alfadolone Mixture↗
PubMed1990

Androgen, estrogen, and progesterone receptor contents and serum hormone profiles in patients with benign hypertrophy and carcinoma of the prostate.

Cytosolic and nuclear androgen, estrogen and progesterone receptor content was measured in the groups of 11 prostatic carcinoma (PCA) and 32 benign prostatic hypertrophy (BPH) samples. All BPH cases were positive for the cytosolic progesterone (PRc) and estrogen receptor (ERc), whereas only 85% of cases (23/27) contained the androgen receptor (ARc). Only those five patients who received estrogen treatment in the PCA group had detectable ARc. PRc was present in all of the PCA cases, whereas ERc could be detected in only 82% (9/11) of cases. Cytosolic contents of all three steroid receptors, however, were higher in the PCA group. The level of nuclear steroid receptors, although present in fewer cases in both groups, was higher than the cytoplasmic receptors. The serum profile of estradiol, cortisol, and prolactin was normal in both groups, whereas LH, FSH, and progesterone levels were higher than in normal adults. Serum testosterone level was within normal range in the BPH group, but it was significantly below normal (P less than 0.005) in PCA patients.

Aged↗
PubMed1990

Different methylation of oestrogen receptor DNA in human breast carcinomas with and without oestrogen receptor.

The methylation of the human oestrogen receptor (ER) gene was analysed by restriction enzymes in normal and neoplastic human breast tissues and cell lines. CCGG sequences in regions inside the gene, which are methylated both in normal breast and in tissues that are not the target of the oestrogen, are hypomethylated in 30% of tumours, both ER+ and ER- carcinomas. Moreover, 5' sequences of the gene, which are hypomethylated in normal breast and not in tissues not the target of oestrogen, are methylated to a lower degree in ER+ carcinomas, whereas they are methylated to a greater degree in ER- carcinomas. However, the same region is equally hypomethylated in both ER+ and ER- cancer cell lines. Our results indicate that in breast carcinomas ER DNA methylation is deranged, and in cancer cell lines is different from that observed in primary tumours. Furthermore, the abnormal methylation in the 5' end seems to be related to abnormal expression, namely diffuse hypomethylation in carcinomas with high ER content and hypermethylation in carcinomas without ER. These findings support our previous hypothesis that DNA methylation could be involved in the control of ER gene expression and demonstrate that abnormal ER gene methylation is a typical feature of breast cancers.

Adenofibroma↗
PubMed1989

Abnormal methylation of estrogen receptor gene and reduced estrogen receptor RNA levels in human endometrial carcinomas.

Demethylation of specific sites or restricted genomic regions has been reported to correlate with gene activation and also with carcinogenesis. As abnormal expression of Estrogen Receptor (ER) could be involved in the genesis or progression of tumors in estrogen target tissues, the methylation of ER gene has been compared in 8 endometrial carcinomas and 29 normal endometria. In order to look for a correlation between methylation and expression, levels of ER RNA were also measured. While the 5' region of ER gene was found to be demethylated in both normal and carcinomatous tissues, there was demethylation of some specific sites in the internal part of the gene only in the carcinomas examined. In addition, in the carcinomatous tissues the levels of ER RNA were low, indicating that an increase of ER gene hypomethylation does not raise, and even may reduce, the ER expression in endometrium. The abnormal undermethylation observed in ER gene appears to be unrelated to general DNA hypomethylation which is frequently present in neoplastic tissues; nor has it been found in ER DNA isolated from breast carcinomas. These data strongly support the hypothesis that such a methylation is specifically related to endometrial transformation and therefore it can be considered an additional marker of this disease.

Blotting, Southern↗
PubMed1988

Estrogen induced increase of estrogen receptor RNA in human breast cancer cells.

Estrogen Receptor (ER) RNA has been studied in ER positive and ER negative cells, grown in alpha medium and fetal calf serum (FCS), with and without estrogen addition. ER mRNA was detected only in ER positive cells. When cells were grown without estrogen addition, a progressive and transient increase of ER RNA levels was observed. When cells were cultured with estradiol, the ER RNA increase took place early and ER RNA levels remained 2 times higher than in untreated cells. Therefore, a down-regulation of ER RNA is not apparent in neoplastic breast cells. We hypothesize that the increase of ER expression is caused by stabilization of ER transcripts, due to the estrogen induced ER cytoplasmic depletion.

Breast Neoplasms↗
PubMedDate not supplied

Gene therapy.

Gene therapy replaces or supplements the activity of a resident defective or missing gene by a cloned functional one. A functional gene may be delivered to the target tissues ex vivo or in vivo using various physical methods and several chemical and biological vehicles. In this article we present an overview of different experimental models and the progress made in clinical studies on gene therapy and discuss the prospects of the antisense approach and the ethical concerns related to the technique.

Genetic Therapy↗