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Biomedical subjects

M Rubenstein

Publications and source records attributed to M Rubenstein.

At least 55 records · Page 3Linked to original sources
PubMed1989

Application of immunohistologic staining to develop a malignant index to aid in distinguishing benign from malignant prostatic tissue.

The development of antisera with reactivities against intermediate filaments, differentiation antigens, and secretory products has aided in identification and characterization of tissue specimens. Such evaluations may assist pathologists in distinguishing between benign (BPH) and malignant (CAP) tissue of prostatic origin. However, attempts to employ this technique are thwarted by 1) the use of frequently incompletely characterized antisera, 2) the use of both paraffin- and frozen-sectioned materials, and 3) a lack of quantitation in the degree of antisera immunoreactivity. To overcome these shortcomings, a mathematical approach was evaluated using eight BPH and 23 CAP specimens. These were sectioned and stained using commercially prepared antisera against cytokeratin (Cyto P, Cyto M), epithelial membrane antigen (EMA), NK cells (Leu-7), prostatic acid phosphatase (PAP), and prostate specific antigen (PSA). Reactivity was quantitated on a scale of 0-5. Mean values for markers elevated in CAP (relative to BPH) were placed in the numerator; those elevated in BPH (relative to CAP) were placed in the denominator: Malignant index = PSA + EMA + Leu-7 + Cyto M/PAP + Cyto P. This malignant index was significantly greater (P less than .001) in CAP tissues than in BPH regardless of Gleason grade (3.2 +/- 0.9 vs 1.6 +/- 0.9). It was also significantly elevated (3.0 +/- 0.8; P less than .01) in nine specimens representing prostatic atypical hyperplasia. These data suggest that immunohistologic staining may be applied as an aid in distinguishing between BPH and CAP.

Diagnosis, Differential↗
PubMed1989

BCG in the management of superficial bladder cancer.

An overall comparison of different types of therapy for any disease is difficult. A definition of the disease, which included carcinoma in situ was not agreed upon in 1961 when thiotepa was first described. Most importantly, many series are not prospective and randomized. Response criteria have varied and have not always included cytologies. With these shortcomings in mind we have attempted to compare the various therapeutic agents. The response rate for BCG appears superior to chemotherapy for the treatment of superficial bladder cancer (59% vs 45%), for prophylaxis (77% vs 53%) and the management of carcinoma in situ (74% vs 52%). Moreover BCG also appears superior to chemotherapy for the management of prior treatment failures, particularly carcinoma in situ. In summary, this review of the literature suggests that BCG is superior, in terms of response rate, to available chemotherapy in the management of superficial bladder cancer.

Administration, Intravesical↗
PubMed1988

Prostatic ultrasound in follow-up of prostatic disease.

Longitudinal and radial transrectal prostatic ultrasound techniques were compared for their consistency and reproducibility in recording prostatic size. While the longitudinal image at the 12:00 position was consistent, radial scanning was variable depending on whether the apex, mid, or base aspects of the prostate were scanned. It is recommended that protocols requiring serial measurements of prostate size utilize a longitudinal ultrasonic transducer and scan at the 12:00 position.

Aged↗
PubMed1988

Effect of BCG upon functional and phenotypic immune markers in rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Rats bearing (or not bearing) the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were treated with Bacillus Calmette-Guérin (BCG) and evaluated for immune competence using functional and phenotypic markers. Tumor presence significantly depressed total T and helper T cell representation along with the helper/suppressor T cell ratio. Functional immunity, measured by phytohemmagglutinin (PHA) induced blastogenesis, was also significantly depressed. When BCG was administered to non-tumor bearing animals, it had no effect upon T cell subset distributions but significantly reduced PHA induced blastogenesis. BCG similarly administered to tumor bearing animals did not alter the depressed helper/suppressor T cell ratio found in tumor bearing rats, but did significantly elevate PHA induced blastogenesis. However, these elevated levels of functional immunity in BCG treated tumor-bearing rats remained significantly below normal. These data demonstrate a poor correlation between functional and phenotypic assessments of immune capability.

Adenocarcinoma↗
PubMed1988

Definition of the pulmonary antibody response to ovalbumin following local challenge in systemically immunized rats.

The in vivo pulmonary immune response of rats to local stimulation with antigen was assessed by measuring antigen-specific antibody and antibody-secreting cells utilizing enzyme-immunoassay technology. Sprague-Dawley rats were immunized subcutaneously with ovalbumin (OA) emulsified in Freund's incomplete adjuvant, challenged with OA intratracheally on Day 19 and sacrificed 1, 2, 3, or 4 days later. Specific antibody-secreting cells in the lung-associated lymph nodes were enumerated with the ELISA-SPOT assay and antibody concentration in the pulmonary lavage fluids and sera was assessed with the ELISA. The greatest response for each parameter was on Day 2. Cellular infiltration of the lung was minimal. Cellular infiltrates consisted mainly of polymorphonuclear leukocytes and were most numerous in the lavage fluid on Days 1 and 2 and in the lung parenchyma on Day 2 after challenge. Local production versus serum transudation of antibody was evaluated by comparing the levels of OA-specific antibody to albumin in the lavage fluid and serum. The data showed that antibody in the lungs was primarily produced locally.

Animals↗
PubMed1988

Review of acid phosphatase in the diagnosis and prognosis of prostatic cancers.

Acid phosphatase is a secretory product frequently utilized as a tumor marker for disseminated, late stage (D2) prostatic cancer. In the 40 years since this association has been recognized, this enzyme has been subjected to extensive biochemical and immunological characterizations. These techniques have also been adapted for rapid and specific determinations of the prostatic isoenzyme levels using a variety of techniques. Since acid phosphatase levels do not become significantly elevated until late stage cancer, newer markers such as prostate-specific antigen have been sought which appear earlier and may be more useful for the screening and monitoring of high risk populations. At this time it is appropriate to review the current and future status of acid phosphatase as a diagnostic aid.

Acid Phosphatase↗
PubMed1987

Methods of early diagnosis in genitourinary cancer.

The commonly employed methods for the early detection of urologic cancers remain the traditional techniques of a carefully performed history and physical examination. Newer developments include, among others, prostate-specific antigen and monoclonal antibodies in prostate cancer, flow cytometry in bladder cancer, computerized axial tomography (CAT) scanning in renal cancer, and ultrasound in testicular cancer. These and other new diagnostic techniques, with further testing and wider use, will hopefully permit the earlier diagnosis of genitourinary cancer.

Humans↗
PubMed1987

Immunoregulatory markers in rats carrying Dunning R3327 H, G, or MAT-LyLu prostatic adenocarcinoma variants.

The Dunning R3327 tumor represents a system for studying prostate cancer in Copenhagen X Fischer rats. Animals bearing variant sublines (H, G, and MAT-LyLu) differing in growth rate, differentiation, hormone responsiveness, and metastatic ability were assayed for three immunological markers. Spleens were passed through a tissue sieve, and mononuclear cells were obtained by Ficoll-Hypaque centrifugation. These were assayed for leukocytic subsets using monoclonal antibodies. An adherent population was isolated and evaluated using thin-layer chromatography for conversion of radiolabeled arachidonic acid to E series prostaglandins. Finally, sera from these animals were assayed for levels of circulating immune complexes using polyethylene glycol precipitation. Data from 52 rats bearing the various tumors were obtained, correlated with subline aggressiveness, and compared to 15 controls. Each tumor group demonstrated significantly lower helper/suppressor T-cell ratios than controls, probably due to general tumor presence. In addition, the most aggressive R3327 MAT-LyLu variant had significantly increased prostaglandin E synthesis by adherent spleen cells compared to the H or G sublines and significantly increased levels of circulating immune complexes relative to the H subline. G subline values for both prostaglandin E and circulating immune complexes levels were intermediate, suggesting that these markers correlate better with tumor aggressiveness than helper/suppressor T-cell ratios.

Adenocarcinoma↗
PubMed1987

Combination therapy using polyamine synthesis inhibitor alpha-difluoromethylornithine and adriamycin in treatment of rats carrying the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Prostate cells of human and rat origin produce polyamines in high content, whose apparent functions relate to cellular proliferation and secretory activities. Formation is dependent on the enzyme ornithine decarboxylase (ODC) which is irreversibly inhibited by alpha-difluoromethylornithine (DFMO). It has been postulated that pretreatment with DFMO may render cells more susceptible to subsequent chemotherapy. Copenhagen X Fischer F1 rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma were given DFMO or adriamycin (ADR), alone or in combination. Those receiving DFMO were continuously provided the drug ad libitum, in water (2.5%), for the duration of the experiment, beginning 2 days prior to ADR administration. At intervals, tumor sizes were measured, animal survivals noted and comparisons made to nontreated, tumor-bearing controls. The results indicate that ADR alone or in combination with DFMO significantly reduced tumor progression, but that only combination therapy significantly prolonged survivals. Decreased tumor progression produced by DFMO alone was not statistically significant. Differences produced with combined use were additive and suggest that DFMO may augment ADR chemotherapy.

Adenocarcinoma↗
PubMed1987

Effect of cyclophosphamide on leukocytic subset distributions in rats carrying the Dunning R3327-MAT-LyLu prostatic adenocarcinoma.

The Dunning R3327 adenocarcinoma represents a model for studying prostate cancer in rats; early studies have indicated its utility for studying relationships between tumor growth, immunologic markers, and chemotherapy. Normal animals and those bearing the metastatic Dunning R3327 MAT-LyLu tumor were treated with 10, 30, and 100 mg/kg doses of cyclophosphamide (CTX) and their spleens assayed for leukocytic subset distributions using monoclonal antibodies. Tumor-bearing animals had significant reductions in helper T cell content as well as reduced helper/suppressor T cell ratios, compared to controls. These effects occurred rapidly following implantation and were not reversed by chemotherapy. When administered to both tumor- and non-tumor-bearing animals, CTX also depleted T cell populations. Despite reductions produced in all subsets, two administrations of CTX (30 mg/kg) were capable of retaining (in non-tumor-bearing animals) or restoring (in tumor-bearing) normal helper/suppressor T cell ratios. Such studies aid in identifying therapeutically effective dosages of cytotoxic drugs that minimize their deleterious effects on the immune system.

Adenocarcinoma↗
PubMed1987

Lymphocyte subsets in urologic cancer patients.

Peripheral blood T lymphocyte subsets were quantitated by monoclonal antibodies in 91 patients with urologic malignancies as well as eight age-matched controls. In general, the presence of cancer and increasing stage were associated with a relative decrease in helper and an increase in suppressor T-cell activity as well as a decreased T4/T8 cell ratio. Therapy in the form of androgen depletion reversed these trends and restored helper and suppressor levels as well as the T4/T8 ratio to control values. In a small subset of sixteen patients surgery had only modest immediate (prostate) and long term (kidney) effects on these parameters.

Androgens↗
PubMed1987

BCG in management of superficial bladder cancer.

Superficial bladder cancer and particularly carcinoma in situ has the potential for invasiveness for which the treatment is cystectomy with a resultant disappointing 50 per cent five-year survival and urinary diversion with a certain diminished quality of life. BCG therapy is a new method of treating aggressive superficial bladder cancer with better response rates than conventional chemotherapy. It may be immunologically mediated and, if so, may be the first major success of a therapeutic modality that offers less morbidity than the currently standard options of surgery, radiotherapy, or chemotherapy.

Administration, Intravesical↗
PubMed1987

An evaluation of five tests to diagnose prostate cancer.

In an effort to determine which of five tests was the most efficient in the diagnosis of prostate cancer, 280 male patients were screened employing aspiration cytology, transrectal ultrasound, acid phosphatase, prostate specific antigen, and the digital rectal examination. The digital rectal examination was the most efficient (75%) and in order of decreasing accuracy were prostate specific antigen (74%), prostatic ultrasound (71%), acid phosphatase (66%), and finally aspiration cytology (63%). In an era when what are more expensive and more technology are assumed to be better, what is simple and traditional is ignored. From an evaluation of these patients it appears that the digital rectal examination still retains its diagnostic efficiency. Finally, in this age of escalating medical costs and physician accountability for these expenses, you can't beat the cost - benefit ratio for the old fashioned rectal exam.

Acid Phosphatase↗
PubMed1987

Administration of recombinant tumor necrosis factor to rats bearing the Dunning R3327 MAT-LyLu prostatic adenocarcinoma.

Copenhagen X Fischer F1 rats bearing palpable Dunning R3327 MAT-LyLu prostatic adenocarcinomas were treated by intraperitoneal (i.p.) or intratumor (i.t.) injection with either human serum albumin alone or in combination with recombinant tumor necrosis factor (rTNF). At intervals tumors were measured and survivals noted. A maximum tolerable dose and least toxic route of administration was then determined. Those treated i.t. with rTNF survived significantly longer and ultimately developed significantly smaller tumors than untreated controls. Those administered rTNF by the i.p. route had less significant increases in survival with intermediate final tumor sizes.

Animals↗
PubMed1986

In vitro stimulation by prostate extracts of rat ventral prostate stromal and epithelial cell division.

We examined the effect of prostate cell extracts on the replication of highly enriched rat ventral prostate stromal and epithelial cells cultured in RPMI-1640. Extracts from normal rat prostates completely inhibited cell division in both fractions, while a 10% (v/v) extract of Dunning R-3327G adenocarcinoma inhibited replication of stromal cells but permitted that of epithelial cells. The cytotoxic effect of prostate extracts was dialyzable, heat stable, unaffected by proteases, soluble in acid/alcohol, and insoluble in chloroform. These properties are consistent with those of polyamines incubated in the presence of fetal calf serum. Dialyzed extracts from Dunning adenocarcinomas, and from human benign hypertrophic and carcinomatous prostates stimulated rat prostate stromal and epithelial cell division, in keeping with other reports of "growth factors" in prostate tissue. This mitogenic activity was stable to temperature (70 degrees C, 4 hours), and marginally if at all affected by exposure to trypsin or to pronase coupled to Sephadex. Short-term culture of separated prostate cells should provide a useful assay system for detecting putative autocrine or paracrine stromal and/or epithelial cell growth factors and identifying suspected homo- or heterotypic cellular interactions in normal and diseased prostates.

Adenocarcinoma↗
PubMed1986

Leukocytic subset distributions of spleen cells obtained from rats bearing variants of the Dunning prostatic adenocarcinoma.

Employing monoclonal antibodies, the relative frequencies of mononuclear cell types found in spleen cell populations were compared between rats bearing variants of the Dunning prostate adenocarcinoma and a series of non-tumor bearing control animals. The identification and quantitation of such subsets greatly expands our knowledge of immune status and function. The results indicate that the spleen cell populations from animals bearing either the Dunning R3327-H, G or MAT-LyLu sublines have significant decreases in their helper T cell/suppressor T cell ratios when comparisons are made to cells obtained from non-tumor bearing animals. In addition decreases in total T cell content and increases in splenic monocytes were noted. It appears that most of these deviations are the result of general Dunning tumor presence, rather than due to any particular subline characteristic. These changes may be analogous to similar alterations reported in the peripheral blood of humans bearing Stage D prostatic cancer, suggesting that the Dunning tumor may provide an appropriate model for evaluating interactions between the immune response, the tumor and therapy.

Adenocarcinoma↗