Biomedical subjects

B R Rao

Publications and source records attributed to B R Rao.

137 records · Page 8Linked to original sources

PubMedDate not supplied

Factors in prostate cancer metastasis.

Death related to prostate cancer is invariably due to the tumor metastasis (to lungs, skeleton and lymph nodes). Tumor cell metastatic behaviour is still poorly understood. The R3327 prostate tumor model in the male Copenhagen rat offers an opportunity to investigate the different aspects of metastatic processes in vivo and to evaluate effects of current and new treatment approaches. Lymphatic spread of cancer cells can be measured by determining volume of local load in successive draining lymph node stations. Surgical removal of primary tumor and inguinal lymph node shows that lymphatic metastasis in the R3327-MATLyLu tumor variant is a continuous progressive phenomenon, which starts already in early stages of tumor growth after subcutaneous transplantation. Spread to the lungs can be quantified by enumeration of macroscopically visible pleural lung colonies. Metastatic spread to the lungs can be mimicked by intravenous injection of monodispersed tumor cell suspension. Within 10 days pleural tumor colonies become visible. Effects of different agents and treatments like chemotherapeutic drugs, heparin, surgery and high energy shock wave (HESW) treatment have been described using these methods. Recently, metastasis to the vertebral column was induced by temporal occlusion of venous blood flow through the caval veins while injecting tumor cells in the lateral tail vein. The resulting osteoblastic metastatic lesions in the lumbar vertebrae and the concomitant spinal cord compression led in time to the loss of motoric and sensory function of the hind legs. These observations permit investigation of the mechanisms of bone metastasis based on biological functions, i.e. sensory and motoric function of the hind legs. Finally, it can be said that the various variants of the R3327 rat prostate tumor offer an appropriate model to study various aspects of prostate cancer and metastasis.

Animals↗

PubMedDate not supplied

Metastasis of prostate tumor cells to bronchus associated lymphoid tissue.

We investigated the metastatic process to the lungs from subcutaneous transplants of R3327-MatLyLu tumor, a rat model for anaplastic prostatic carcinoma. Considerable metastasis of tumor cells to bronchus associated lymphoid tissue (BALT) was observed with time. Immunocytochemistry clearly showed the presence of the epithelial type of intermediate filaments (cytokeratin) in these cells, confirming their carcinomatous origin. No positive staining for cytokeratin could be observed in the BALT in controls. Localization of tumor cells within the BALT was mainly confined to the region near the adjacent artery. After intravenous injection of monodispersed tumor cells, an influx of tumor cells was observed within minutes in this same region of the BALT. These observations suggest that BALT is involved in the metastatic process of tumor cells to the lungs. Its role in controlling metastasis and in tumor cell kill, if any, remains to be elucidated.

Animals↗

PubMedDate not supplied

A direct LHRH-agonist action on cancer cells is unlikely to be the cause of response to LHRH-agonist treatment.

LHRH-Agonist therapy has been shown to have some effect in cancer treatment. Chronic administration of LHRH-agonists may lead to a decreased gonadal steroidogenesis. A direct anti-tumor action of LHRH-agonists has also been reported. We observed only a small direct inhibitory effect of the LHRH-agonist Buserelin at high concentrations on the proliferation of three human ovarian cancer cell lines, and on estrogen-stimulated proliferation of human breast cancer cells in vitro. Proliferation of rat prostate cancer cells was not inhibited by Buserelin. It is unlikely that a direct anti-tumor effect is the major mechanism of action of LHRH-agonists in cancer treatment.

Animals↗

PubMedDate not supplied

Correlation of aromatase activity and steroid receptors in human ovarian carcinoma.

Androgen receptors (AR) predominated (98%) in the cytosols of human ovarian carcinomas (n = 40), compared to estrogen (ER)-45%, and progestin (PgR)-53% receptors. The average age of the patients was 58 years. Serum levels of estradiol-17 beta (E2), testosterone (T), follicle stimulating hormone (FSH) and luteinizing hormone (LH) were within the normal range. One third of the cases showed a measurable aromatase activity, while in the majority of the cases this activity was undetectable. The distribution of PgR in the 40 tumors studied appeared to correlate with aromatase activity. The distribution of ER and AR did not differ significantly in aromatase positive and aromatase negative tumors. Interestingly the majority of aromatase positive cases were the endometrioid type of carcinomas. Patients with this type of ovarian carcinoma may probably benefit from anti-estrogen, progestin or aromatase inhibitor treatment. All tumors which were negative for aromatase activity contained AR. In these aromatase negative tumors androgens may not be further metabolized into estrogens and the tumor cells may be influenced by the androgens through the AR present in them. Anti androgen treatment could possibly benefit the patients with such tumors.

Aromatase↗

PubMedDate not supplied

Doxorubicin treatment increases metastasis of prostate tumor (R3327-MatLyLu).

Doxorubicin (Dx) effects on metastatic spreading of prostate cancer were investigated using a rat metastatic tumor (R3327-MatLyLu). Intravenous injection of monodispersed tumor cells resulted in tumor nodule formation in the lungs. A simultaneous bolus injection of Dx (3.2 mg/Kg) caused a significant decrease in lung colony formation and growth. However, Dx administered during the course of spontaneous metastasis, or as adjuvant chemotherapy 24 hours before surgical removal of primary tumor, caused a significant increase in metastasis to the lungs. It is concluded that an intravenous doxorubicin bolus injection does not provide an antimetastatic effect, but increases metastatic spreading of prostate tumor.

Animals↗

PubMedDate not supplied

Ovarian cancer (review). Etiology, diagnosis, prognosis, surgery, radiotherapy, chemotherapy and endocrine therapy.

The increased incidence of ovarian cancer in women whose ovulations were not suppressed by pregnancy or oral contraceptives and the increase in the incidence of the disease with the onset of climacterium support the hypothesis that ovarian cancer is an endocrine-related disease. Animal experimental results further support this contention. However, identification of a population at risk, prevention, and early detection is difficult. At present, tumor markers are useful in monitoring the disease, though cannot be used for screening. Most of the diagnosed cases are of advanced stages. Besides staging, tumor histology, and residual tumor load are of prognostic importance. The need for accurate initial surgical staging with optimal tumor cytoreduction and the importance of second-look surgery to confirm the response to therapy are emphasized. The precise role for radiotherapy in the treatment of ovarian cancer is still to be established. Presently, response rates of 80% are achieved using cisplatin based combination chemotherapy. In spite of this, long term survival has not improved. Endocrine therapy has hitherto been used empirically and mainly as a last resort in the treatment of advanced ovarian cancer. Response rates of about 10% have been reported. Information on tumor predisposition related to hormonal control should be a key parameter in selecting the appropriate therapy. Tumor analysis has shown that androgen receptors predominate in ovarian cancer, compared to estrogen and progestin receptors. A clinical trial based on endocrine parameters is warranted.

Antineoplastic Combined Chemotherapy Protocols↗

PubMedDate not supplied

Multiple parameter analyses of human ovarian cancer: morphology, immunohistochemistry, steroid hormone receptors and aromatase.

All human ovarian tumors (n = 32) analysed were positive for cytokeratin except for a single case. OV-TL 3 stained 96% (26/27) and 1 out of 4 controls, while OC-125 stained 86% (24/27) and 3 out of 4 non-ovarian carcinomas. Androgen receptors predominated (AR-96%) compared to estrogen (ER-32%) or progestin (PgR-50%) receptors in the ovarian carcinomas. Aromatase activity was detected in 6 ovarian carcinomas and in 3 non-ovarian carcinomas. No definite relationship was observed between the parameters measured. Ovarian carcinomas stained brightly with OV-TL 3 and OC-125 had high AR levels, while focal or absent reaction was related to low AR levels. A role for androgens in ovarian cancer is suggested.

Adult↗

PubMedDate not supplied

Implementation of tests for monitoring drug compliance of leprosy out-patients under multi-drug therapy.

The field workers of two MDT districts (Srikakulam in Andhra Pradesh and Ganjam in Orissa) were trained for implementation of 'Paper Spot Test together with Pill/Capsule count methods' of monitoring the treatment compliance of leprosy out-patients receiving MDT. All the workers recognized the importance of implementing these methods and found them operationally feasible, in field. Of the 672 Paucibacillary and 749 multibacillary cases monitored for drug compliance, 85-88% cases showed regular compliance (more than 75% drug intake) to dapsone. The compliance to Clofazimine among Multibacillary cases was better (94% regular) than dapsone compliance. Both these monitoring methods are advocated to be used on larger scale under our National Leprosy Eradication Programme.

Clofazimine↗

PubMedDate not supplied

Direct effects of chemotherapeutic agents on rat prostate tumor clonogenic cells.

A semisolid agar assay to determine the number of colony forming cells in monodispersed cell suspensions of the rat prostate hormone independent tumor variant R3327-Mat Lu was established. Using this technique the effects of several chemotherapeutic agents upon the clonogenic potential of the tumor cells were investigated. Adriamycin and cisplatinum proved to be effective in reducing the number of colonies formed, in a dose dependent manner. The combined, sequential incubation with adriamycin and cisplatinum did not have a synergistic effect. Cyclophosphamide. Hydroxyurea, 5-fluorouracil and methotrexate were not effective in the reduction of the number of colonies in vitro at concentrations as high as 500 micrograms/ml. Interestingly treatment with these agents increased the number of colonies formed, compared to control.

Animals↗

PubMedDate not supplied

Inhibition of 3 beta-hydroxysteroid-dehydrogenase: an approach for prostate cancer treatment?

Over 80% of clinically manifested prostate cancers respond to androgen withdrawal. Several alternatives to castration have been explored. Since a growth promoting role for androstenedione has been suggested, we investigated the effect of inhibition of 3 beta-hydroxy-steroid-dehydrogenase (3 beta-HSD), a key enzyme involved in the biosynthesis of practically all steroids. In a previous study a reduced proliferation rate of androgen responsive R3327-H tumor was demonstrated after in vivo treatment with 17 beta-N,N-diethylcarbamoyl-4-aza-5 alpha-androstan-3-one (4MA) - a putative 5 alpha-reductase inhibitor. In the present investigation 3 beta-HSD enzyme activity derived from human placenta, testis and ovarian cancer cell line and from rat testis was determined using radiolabeled dehydroepiandrosterone (DHEA) or pregnenolone. Among different synthetic compounds known to interfere with steroidogenesis, only 4MA was shown to potently inhibit in vitro 3 beta-HSD activity from all tissue sources. 4MA was administered to male Copenhagen rats bearing R3327-H androgen dependent prostate tumors and levels of different androgens in serum and prostate tumor were measured using reversed phase HPLC and radioimmunoassay. The decreased content of androstenedione in serum and tumor tissue with DHEA accumulation in prostate tumor tissue showed an effective 3 beta-HSD inhibition by 4MA occurring in vivo as well. These observations unequivocally demonstrate a 3 beta-HSD inhibiting effect of 4MA in vitro as well as in vivo and point to a role for androstenedione in the promotion of cell proliferation in androgen sensitive tumors. 3 beta-HSD dependent androstenedione production could thus constitute a proper target -eventually combined with other endocrine treatment - for the treatment of hormone dependent prostate cancer.

3-Hydroxysteroid Dehydrogenases↗

PubMedDate not supplied

Pregnancy associated highly vascularized tumours negatively correlate with the levels of anti-angiogenic 17 alpha-hydroxy-progesterone.

Seventeen alpha hydroxyprogesterone (17-OHP, is an anti-angiogenic steroid. The existence of a significant negative correlation between the levels of 17-OHP and the appearance of highly vascularized brain and spinal tumours seen during pregnancy is described. However, glioma appears to be an exception to this rule. This exception may be due to the blood brain barrier which permits only a small proportion of the synthesized 17-OHP to reach the brain and may be due to gliomas not being highly vascularized. It is proposed that testing the efficacy of 17-OHP as an anti-angiogenic agent in the highly vascularized brain and spinal tumours would be useful since 17-OHP is essentially without any foreseeable side effects even in large doses, inexpensive, widely available, and in some cases may be conveniently administered via a nasal inhaler.

17-alpha-Hydroxyprogesterone↗