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Biomedical subjects

B R Rao

Publications and source records attributed to B R Rao.

At least 55 records · Page 3Linked to original sources

Correlation between nuclear DNA content and steroid receptor status in ovarian cancer.

The nuclear DNA content of 47 malignant epithelial ovarian tumours and five ovarian tumours of borderline malignancy was correlated with estrogen (ER), progesterone (PR) and androgen receptor (AR) status. Aneuploidy was observed in 60% of the malignant tumours. The DNA index of poorly differentiated tumours was higher than that of well differentiated tumours (P less than 0.05). Ploidy did not correlate with histological type, stage of disease and ER content. Of the diploid tumours, 74% was PR-positive, in contrast to 36% of the aneuploid tumours (P less than 0.05). In addition, 89% of the diploid tumours had high AR levels (greater than or equal to 30 fmol/mg cytosol protein), in contrast to only 54% of the aneuploid tumours (P less than 0.05). These observations strengthen our previous findings on the prognostic importance of PR and also suggest that androgens may have a role in ovarian cancer.

Adenocarcinoma↗

Literature statistics do not support a growth stimulating role for female sex steroid hormones in haemangiomas and meningiomas.

A literature review of pregnancy-related vertebral haemangiomas, pregnancy-related haemangiomas outside the nervous system and its coverings, and pregnancy-related meningiomas was performed. All three conditions tended to occur during the first pregnancy, the second or third trimester, to ameliorate postpartum, and to recur during a subsequent pregnancy. These results suggested a hormonal influence on the clinical expression of haemangiomas and meningiomas. To test whether a hormonal factor is also operative in the (not pregnancy related) symptomatic and asymptomatic counterparts of these conditions we also reviewed the literature concerning the symptomatic and asymptomatic haemangiomas and meningiomas for the following: frequency, sex and age distribution. No arguments were found to suggest that steroid hormones are strong factors in the development of asymptomatic and symptomatic lesions. The pregnancy-related counterparts have to be considered as subsets with their own behaviour.

Adolescent↗

Radiation sensitivity of Copenhagen rat prostatic carcinoma (R3327-AT and R3327-MATLyLu).

The radiosensitivity of two variants of the Dunning Copenhagen rat prostatic tumor R3327 was investigated. The R3327-AT variant, which is a poorly differentiated anaplastic, fast-growing tumor, was irradiated both in vivo and in vitro. Following irradiation, monodispersed cells were plated in vitro and colonies were counted after 7 days. The survival curve of R3327-AT cells irradiated in vivo showed an initial shoulder (Dq-value 0.97 Gy), followed by two exponential parts. The D0-value for the first part of the curve (0-10 Gy) was 2.76 Gy and for the second part of the curve (greater than 10 gy) 9.05 Gy. Extrapolation of the second part of the curve to the Y-axis indicated that the proportion of more radioresistant cells was about 10%. The survival curve for R3327-AT cells irradiated in vitro also suggested the presence of a radioresistant subpopulation, although the proportion was lower (about 3%). This difference might be due to the presence of an hypoxic fraction in the tumors irradiated in vivo, but not in vitro. Tumor cells from the R3327 tumor variant metastatic to lymph nodes and lungs (R3327-MATLyLu), were irradiated in vitro. The radiation effect was evaluated by in vitro colony formation in agar and by in vivo lung colony assay. The colony formation in agar yielded a D0-value of 1.09 Gy. No radioresistant subpopulation was identified in this variant. A similar radiosensitivity was observed by the in vivo lung colony assay (D0 1.39 Gy). The mean inactivation dose calculated for R3327-AT cells (3.45 Gy) was significantly higher than for the metastatic variant (2.00 Gy).

Animals↗

Survival of patients with ovarian cancer. Apart from stage and grade, tumor progesterone receptor content is a prognostic indicator.

Estrogen (ER), progesterone (PR), and androgen receptors (AR) were determined by saturation analysis in 100 cases of primary ovarian cancer and correlated with patient survival. The mean follow-up period was 5.4 years (range, 4 to 6.5 years). Positivity for PR was associated with a significantly better survival rate (P less than 0.05). A similar observation was made for AR (P less than 0.05). Tumor ER content did not correlate with survival. Ten patients with tumors that had negative results for both PR and AR all died of the disease. In 91 cases of serous, endometrioid, and mucinous carcinomas, grade, stage, and tumor PR content, but not AR content, were identified as independent prognostic factors with the use of the Cox proportional hazards model. The relative risk of patients with PR-negative tumors was 2.3 times higher than that of patients with tumors containing high (greater than or equal to 30 fmol/mg) PR levels.

Adolescent↗

Prostatic tumor (R3327) skeletal metastasis.

Male Copenhagen rats were inoculated with monodispersed R3327-MatLyLu prostate tumor cells via the tail vein under concomitant temporal occlusion of the inferior vena cava to develop an animal model for skeletal metastasis of prostate cancer. This procedure reproducibly resulted in metastatic tumor growth in the lumbar region of the vertebral column. Microscopically, tumor growth became visible in the fifth and sixth lumbar vertebrae within 4 days after inoculation. Clinical signs of nerve function disablement (hind leg paresis and paralysis) followed within 14 days of such a procedure. Cell culture technique confirmed the presence of a viable, proliferating tumor cell population within the spinal canal of the fifth and sixth lumbar vertebrae. Histologically, a clear response of osteoclastic and concomitant osteoblastic activities was observed in the lumbar spinal column. In the serum, a transient phase of hypercalcemia could be demonstrated. The development of skeletal metastases in these animals was not reflected by significant alteration in serum levels of acid phosphatase, prostatic-specific antigen, or osteocalcin. These observations support the concept of the vertebral venous plexus being involved in the dissemination of prostate tumor cells. The surgical procedures described permit experimental investigations of bone metastasis of prostatic cancer.

Animals↗

Life expectancy for a class of life distributions having the "setting the clock back to zero" property.

It is demonstrated that the expression for the life expectancy of an individual in biomedical investigations can be greatly simplified if the class of life distributions possesses what has been called the "setting the clock back to zero" property, studied previously by Raja Rao and Talwalker. It is shown that the Gompertzian growth process, Krane's family of life distributions, and the linear hazard exponential distribution have this property. To illustrate the use of this property, an individual's life expectancy is tabulated for several choices of the parameter values when the individual's life distribution belongs to a Gompertzian growth process. In addition, it is shown that a new survival model considered by Chiang and Conforti for the estimation of time to tumor has the "setting the clock back to zero" property. Its life expectancy is evaluated at any given time chi 0 using this property.

Humans↗

Ovarian cancer: radiation sensitivity in vitro.

The radiosensitivity of four human ovarian cancer cell lines was investigated in vitro by a clonogenic assay and analyzed using the linear-quadratic model. Two cell lines were found to be highly radiosensitive (mean inactivation dose (D) 0.82-0.92 Gy; surviving fraction 2 Gy (SF2) less than or equal to 0.13). Two other cell lines were less sensitive to radiation (D 1.31-1.94 Gy; SF2 0.22-0.38). Although the use of external radiotherapy in ovarian cancer has been limited due to the pattern of metastatic spread of this cancer, the present data support the view that ovarian carcinomas are radiosensitive tumors. Investigations on the effects of new approaches, such as delivering radiation more specifically to intraperitoneal ovarian cancer cells, are warranted.

Cell Count↗

Correlation between tumor histology, steroid receptor status, and adenosine deaminase complexing protein immunoreactivity in ovarian cancer.

Adenosine deaminase complexing protein (ADCP) immunoreactivity was investigated in 40 ovarian tumors and correlated with clinicopathologic parameters, including tumor steroid receptor content. Ten (29%) of 34 common epithelial ovarian carcinomas showed ADCP reactivity. Reactivity for ADCP was seen more frequently in mucinous (100%; p less than 0.001), well-differentiated (73%; p less than 0.001) and Stage I (56%; p less than 0.05) ovarian carcinomas. Furthermore, tumors that contained high levels of androgen receptors and tumors that did not contain estrogen receptors were more frequently ADCP positive (p less than 0.05). However, after stratifying for histologic grade, no correlation between ADCP reactivity and receptor status was found. Determination of ADCP reactivity appears to be of limited value in ovarian cancer.

Adenocarcinoma↗

High energy shock waves do not affect either primary tumor growth or metastasis of prostate carcinoma, R3327-MatLyLu.

We investigated the possibility that extracorporeal high energy shock wave (HESW) treatment of solid tumors increased metastatic tumor cell spread using a rapidly metastasising rat prostate tumor variant (R3327-MatLyLu). Volume of HESW treated primary tumor, the volume of metastatic lymph nodes and the number of lung tumor nodules formed were compared with values in untreated control rats. HESW treatment resulted in marked hemorrhage and readily visible hematoma at the focal point of treatment. Tumor histology directly after treatment showed extravascular blood cells due to breakage of blood vessels. Contrary to previous reports we could not observe a delay in tumor growth rate in either small or medium sized tumors. More importantly the extent of metastatic spread was not influenced by HESW treatment.

Animals↗

The presence of a hitherto undefined high-capacity androgen binding macromolecule in human ovarian cancer tissue.

Sex hormone binding globulin (SHBG) is known to interfere in the quantitation of androgen receptors (AR) if dihydrotestosterone (DHT) is used. We used a monoclonal antibody to remove SHBG from cytosol. In cytosol of benign prostatic hyperplastic (BPH) tissue low capacity binding for DHT, but not for R1881, was found after removal of SHBG. AR were detected in 18 of 20 ovarian cancer cytosols. In the two AR-negative cases, non-saturable binding for DHT, testosterone and R1881 was observed. Incubation with anti-SHBG did not change this. An hitherto undefined androgen binding macromolecule(s), with high-capacity binding for natural and synthetic androgens, but not for estrogen and progesterone, seems to be present in these ovarian cancer tissues. The functionality of these androgen binding macromolecules in ovarian cancer is yet to be demonstrated.

Androgen-Binding Protein↗

Bounds on life expectancy for the Rayleigh and Weibull distributions.

Bounds are presented for the life expectancy or the mean residual life of an individual whose lifetime is a random variable X following a Rayleigh distribution or more generally a Weibull distribution. Simple transformations of the variables give inequalities on the Mills' ratio and the incomplete gamma functions. Some numerical computations are also reported to compare the lower and upper bounds with the exact value of the life expectancy function for several values of the parameter. When the lifetime follows a Gompertz distribution, the problem becomes complicated, and it has not been possible to construct bounds on the life expectancy function. The importance of the Gompertz distribution in the dynamics of normal and tumor growth and in the embryonic and postnatal growth of birds and mammals is demonstrated, and life expectancy is evaluated by numerical methods for a number of parameter values.

Animals↗

Premature ovarian failure. I: The association with autoimmunity.

Twenty-four patients were investigated for non-organ-specific and organ-specific autoantibodies (Aab) in order to establish a relationship between premature ovarian failure (POF) and autosensitization. Regarding the non-organ-specific Aab, prevalences of clearly raised ANA (42%), nDNA Ab (25%), rheumatoid factors (41%) and smooth muscle Aab (53%) were found in the POF patients. Less outspoken higher prevalences of organ-specific Aab in these patients were also found: parietal cell Aab (23%), islet of Langerhans Aab (20%). Fifteen percent of the patients showed Aab to the adrenal gland, and a single patient had Aab towards the steroid-producing cells (Stpc) of the ovary. Although no single immune parameter could be clearly identified to correlate with POF, autoimmune (AI) phenomena were detected in the majority of the patients (92%). Since AI disease could be present for a considerable time without any clinical symptoms, a further immunological screening and follow up of POF patients may enable us to better understand and manage these patients.

Adolescent↗

Premature ovarian failure. II: Considerations of cellular immunity defects.

Twenty-three patients with premature ovarian failure (POF), were investigated on the basis of cell-mediated immunity. An increase in T-cells and especially T-helper cells was found in the group of POF patients, while T-suppressor cells and B-cells did not exceed the counts compared to healthy controls matched for age and sex. The macrophage migration inhibition factor (MIF) assay showed a decreased activity towards Haemophiles influenza. Candida albicans and Varidase antigens in the POF group. Levels of immunoglobulins (IgG, IgA, IgE and IgM) did not exceed the normal levels. The relationship between the hormonal status of POF patients and their immunological profile is discussed.

Adolescent↗

Importance of steroid receptors and aromatase activity in the prognosis of ovarian cancer: high tumor progesterone receptor levels correlate with longer survival.

The presence of steroid receptors (82 tumors) and aromatase activity (39 tumors) in ovarian carcinomas was correlated with patient survival. No statistically significant correlation was found between the presence or absence of estrogen receptors (ER, 56.1%), progesterone receptors (PR, 57.3%), androgen receptors (AR, 91.5%), or aromatase activity (33.3%) and survival. However, high levels of PR were associated with better survival (P less than 0.05). Furthermore, there was a tendency for patients with advanced disease and PR-positive tumors to have better survival than those with advanced disease and PR-negative tumors (P = 0.13). Patients with tumors that did not contain any of the receptors and those in which ER and AR were absent, or in which PR and AR were absent, had poor survival. It is concluded that receptor status, especially of PR, may be of prognostic importance and that status of receptors and aromatase activity may become useful in selecting ovarian cancer patients for endocrine therapy.

Adenocarcinoma↗

Response to inhibition of androgen action of human ovarian cancer cells in vitro.

The effect of androgens, anti-androgens and epostane on the proliferation of three established human ovarian cancer cell lines was investigated. In one cell line, containing androgen receptors, a dose-dependent inhibitory effect of anti-androgens and epostane was observed. Adaptation of this cell line to flutamide resulted in decreased sensitivity to anti-androgens and epostane. Following adaptation of the cell lines to androgen, androgen receptors were present in all of them and an increased sensitivity to higher concentrations of anti-androgens and epostane was observed. These results suggest that androgens may play a role in the proliferation of ovarian cancer cells, and that these cells may respond to blockage of androgen action or synthesis.

Androgen Antagonists↗

Termination of early pregnancy by the 3 beta-hydroxysteroid dehydrogenase inhibitor epostane.

Progesterone is essential to sustain pregnancy in the first eight weeks. Its synthesis requires the enzyme 3 beta-hydroxysteroid dehydrogenase (3-HSD). We tested the efficacy of an orally administered 3-HSD inhibitor, epostane, in terminating unwanted early pregnancy. Fifty women in the fifth through eight weeks of pregnancy took epostane (200 mg orally every six hours) for seven days. By day 14, pregnancy had been terminated in 42 of the 50 patients (84 percent). Eight women (16 percent) did not abort and underwent dilation and curettage. Vaginal blood loss occurred on average on the third day of epostane treatment, and abortion on the fifth day. Two patients had incomplete abortions; one required a transfusion because of blood loss. Nausea was frequent (in 86 percent), but 76 percent of the participants concluded that epostane was preferable to dilation and curettage. The mean (+/- SD) pretreatment progesterone level (76 +/- 16 nmol per liter) decreased by day 7 (to 16 +/- 11 nmol per liter) and day 14 (to 10 +/- 9 nmol per liter) in those who aborted; levels of human chorionic gonadotropin also decreased from the mean at base line (73 +/- 72 kIU per liter) to 18 +/- 7 kIU per liter on day 7 and 9 +/- 5 kIU per liter on day 14. In those who did not abort after epostane treatment, progesterone levels decreased only slightly by day 7 (to 52 +/- 21 nmol per liter) and rose again (to 81 +/- 18 nmol per liter) by day 14. Among women who responded to epostane, normal menstrual periods had resumed by day 42 after the beginning of treatment in 72 percent. We conclude that epostane taken orally is an effective and safe method for the noninvasive termination of undesired early pregnancy.

3-Hydroxysteroid Dehydrogenases↗