New screening and diagnostic tests for prostate cancer and immunologic assessment.
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Biomedical subjects
Publications and source records attributed to M Menon.
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The action of danazol on 125I-human chorionic gonadotropin (hCG) binding, gonadotropin-stimulated adenosine 3',5' cyclic monophosphate (cAMP) accumulation and progesterone production has been investigated in luteinized rat ovaries. Preincubation of luteal cells for short periods of time with increasing concentrations of danazol caused a significant inhibition of gonadotropin-stimulated steroidogenesis. The inhibitory effect of danazol was both concentration and time dependent. Danazol also reduced progesterone production in response to cholera enterotoxin and 8 bromo-adenosine-cAMP, but it had no effect on hCG, luteinizing hormone, and cholera enterotoxin stimulated cAMP formation. Similarly danazol did not affect 125I-hCG binding as assessed by the equilibrium dissociation constant (Kd) and number of hormone-binding sites on the luteal cell surface. These results suggest that in intact luteal cells danazol inhibits steroidogenesis at a point distal to hormone-receptor interaction and cAMP formation.
Sera of patients with prostatic malignancy were assayed for human chorionic gonadotropin-beta (HCG-beta). The levels of HCB-beta are negligible in the patients and in a control group with benign prostatic hypertrophy. Slight increases in HCG-beta found in a small percentage of patients with advanced malignancy are attributed to cross-reacting gonadotropins.
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Radiographic findings of the 2 new cases of oxyphilic renal adenoma, so-called renal oncocytoma, are reported and compared to previous descriptions. Ultrasonography shows no typical findings, but the vascular capsule of this tumor may show enhancement on computed tomography. Angiography contributes the most specific findings, because of the vascularity of these tumors: In the larger lesions a typical 'spoke wheel pattern' can be expected which may not be as prominent in smaller tumors. Notable is the absence of abrupt arterial caliber changes, AV shunting and contrast puddling which sets this tumor apart from the great majority of vascular renal cell carcinomas. The incidence of renal oncocytomas appears to be rising.
Cytosol receptors for progesterone were assayed in human endometrial tissue during the proliferative and secretory phases of the menstrual cycle and in the hyperplastic and carcinomatous endometrium. The assays were performed utilizing a technique involving prior treatment of the cytosol extract with dextran-coated charcoal to remove endogenous progesterone. The results showed that the progesterone receptor activity was higher during the later proliferative and early secretory phases of the menstrual cycle. Hyperplastic and carcinomatous endometrium also contained specific cytosol receptor for progesterone, and the binding activity of the hyperplastic endometria and endometrial polyps was comparable to that found during the later proliferative phase of the menstrual cycle. No apparent correlation between the progesterone receptor level and the morphologic degree of differentiation in Grades 1 and 2 adenocarcinomas of the endometrium was observed.
Sera from patients with carcinoma of the prostate were screened for the presence of blocking factors by measuring the inhibition of phytohemagglutinin-induced blastogenesis of normal lymphocytes. The blastogenic index obtained in cancer sera is not significantly different from that obtained in sera of patients with benign prostatic hypertrophy (control group). Determination of alpha-2-globulins in the cancer sera by cellulose acetate electrophoresis revealed slightly elevated levels in patients with metastatic disease but it did not correlate with the inhibitory blocking activity of the serum.
Sucrose density gradient analysis of the R3327H tumor cytosol demonstrated the presence of both androgen and estrogen binding proteins. Competitive binding analysis with 17 beta-estradiol, 5 alpha-dihydrotestosterone, R1881, cyproterone acetate, and cortisol was consistent with the presence of 2 different binding sites for androgens and estrogens. Scatchard binding analysis was performed in the dorsal-lateral prostate as well as the R3327H tumor from normal Copenhagen rats. High affinity receptors for androgen and estrogen but not progesterone were found. However, in R3327H tumors relapsing following castration, the presence of high affinity receptors for progesterone were readily detectable.
Use of DEAE-dextran (a polycation) increases and stabilizes the rosettes formed between sheep red cells and human peripheral blood lymphocytes. Under its influence, reproducible stable rosettes are formed after one hour of incubation in an ice bath instead of the usually required 18 to 24 hours. We have shown that rosettes are specific for T-cells and not due to "co-rosetting" of nonrosette forming cells into the T-cell rosette clusters. Only the cells from normal controls consistently show an increase in rosette formation hence routine use of this 'stabilizer' in clinical immunology is not recommended.
This review is an attempt to simplify the myriad descriptions of tumor antigens, by considering such antigens in the perspective of their mechanisms of formation. We believe that most and possibly all tumor antigens previously described and currently under study will ultimately fit into one of the categories discussed in this article, since there are only a finite number of biochemical mechanisms for producing new antigens in any cell--cancerous or otherwise. Pragmatically, we view the vagaries of expression of tumor antigens as among their most important properties, and the search for tumor antigens has in fact opened a Pandora's box of molecular variability. Large tumor masses consisting of multiple subclones with different karyotypes, chromosomal anomalies and mutations would appear to be capable of expressing a motley group of tumor antigens. To the best of our knowledge, no tumor antigen has been shown to be necessary and causal in transformation, except in virally-induced tumors. The presence of tumor antigens appears to be coincidental and reflects dedifferentiation and karyotypic, metabolic and nutritional variations occurring in tumors. Undoubtedly, some antigens may give a tumor a selective advantage of growth, metabolism or metastatic potential, but many antigens may simply reflect the vagaries of the tumor cell. The intratumor and intertumor variations of tumor antigens, their mechanisms of origin and their rather uncanny capabilities to change their phenotype--antigen expression--secondary to environmental selection during tumor expansion or following therapy should be kept in mind when tumor antigens and immunotherapy are considered.
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The immune competence of 65 patients with prostatic cancer was evaluated by 2 in vivo and 2 in vitro tests to study the contribution of host factors to the progress of the disease. Patients with benign prostatic hypertrophy served as controls. Our results indicate that the delayed skin hypersensitivity response to common microbial recall antigens (streptokinase/streptodornase, purified protein derivative, dermatophytin 0 and dermatophytin) is unaltered in advanced stages of malignancy. The ability to be sensitized by dinitrochlorobenzene declines significantly in patients with metastatic disease. Blastogenic response of peripheral blood lymphocytes to phytohemagglutinin stimulation is not depressed in late stages of malignancy, although in the circulating T cells per cent and absolute values are somewhat lower in patients with metastases. Herein we show that immune competence (measured by the 4 tests) of patients with prostatic carcinoma does not decrease markedly even in the late stages of the disease. Primary sensitization to dinitrochlorobenzene is the only test showing a decline in responsiveness related to the tumor stage.
Mature males of Nauphoeta cinerea produce a sex pheromone 'seducin' which has short-range effects in attracting mature females of the same species. Exposure of newly-emerged adult males to 3.5, 7, 14 or 21 krad of gamma-radiation decreased their life expectancy and affected their mating behaviour. Bioassay of dichloromethane extracts of males showed that radiation doses (14 krad) sufficient to induce sterility did not affect the ability to produce pheromone but significantly reduced the release of pheromone by inhibiting wing-raising. The sterile-male technique using males sterilized by ionizing radiation in air may not be the method of choice for control of Nauphoeta cinerea.
Peripheral blood lymphoid cells from normal donors, patients with non-malignant diseases, and patients with malignant diseases were evaluated for cytotoxicity against a cultured carcinoma cell line, using a chromium release assay. The natural spontaneous lymphocyte-mediated cytotoxicity was significantly higher in tumor-free groups. The observed decreased response in patients with malignancies correlated with depressed responsiveness to phytohemagglutinin stimulation. Removal of cell subpopulations bearing Fc receptors significantly decreased the cytotoxicity, while depletion of phagocytic mononuclear cells did not. We suggest that natural cytotoxicity is a measure of cell membrane integrity of lymphocytes and should be included as a routine test for evaluation of general immune competence.