Michael W. Shaw

Condyloma Acuminatum in A 2½-Year-Old Girl

Abstract Condyloma acuminatum is a viral growth, usually transmitted venereally, and is rare in the pediatric age group. We report on a 2 ½ -year-old girl with condyloma acuminatum.

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.

Tumor Infiltrating Lymphocytes: The Effect of Bacillus Calmette Guerin on Helper/Suppressor-T Cell Ratios of Treated and Untreated Tumors

Copenhagen X Fischer rats bearing single and bilateral Dunning R3327 AT-3 tumors were either treated or not treated at a single site with bacillus Calmette Guerin (BCG). One week later tumors were removed, tumor infiltrating lymphocytes (TILs) isolated, and then characterized for total-T, helper-T and suppressor-T cell subsets utilizing monoclonal antibodies. The purpose was to determine the effect of BCG on TILs in treated as well as untreated tumors. In summary: 1) BCG treatment significantly alters TIL distributions at both injected and noninjected sites; 2) a noninjected contralateral tumor compromises the effectiveness of BCG therapy at the suppressor T cell level; 3) contralateral tumors, whether inoculated or not, have similar TIL distributions.

Evaluation of gleason classification system in prostate cancer

To compare the relative prognostic accuracy of the Gleason classification, the Whitmore staging, and the Broder grading systems, 111 patients with prostate cancer undergoing radical surgery were assessed utilizing these systems. The assessments were correlated with the presence or absence of disease six months to eight years after surgery. Of the three systems the Gleason classification system was the least accurate.

Suramin as adjuvant therapy with radical prostatectomy.

Suramin is a newer agent employed in the management of prostate cancer. One suggested method of action is growth factor inhibition. While suramin has been employed to treat advanced disease its adjuvant role remains unexplored. To address this question we have employed a new model: the orthotopic placement of the Dunning AT‐3 tumor. The purpose of this research was to assess the efficacy of adjuvant therapy in controlling residual disease.

Efficacy of immunopriming prior to isolation of tumor infiltrating lymphocytes for use in adoptive immunotherapy.

Adoptive immunotherapy is dependent upon the leukocytic subsets isolated as tumor infiltrating lymphocytes (TIL) prior to in vitro expansion with interleukin-2. To favorably influence T-cell subset representation in TIL the efficacy of bacillus Calmette Guerin (BCG) and cyclophosphamide (CTX) priming was evaluated in rats bearing Dunning R3327-AT prostatic tumors. When assessed by immunohistochemistry, both agents significantly (p less than 0.001) increased helper-T representation and decreased that by suppressor-T cells. As a result helper/suppressor (H/S) T cell ratios of TIL from untreated tumors (0.73 +/- 0.11) were significantly (p less than 0.001) elevated by both BCG (1.93 +/- 0.39) and CTX (1.40 +/- 0.25). Immunopriming might enhance adoptive immunotherapy by increasing the H/S ratio of TIL prior to their culture.

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.

Pelvic lymph node dissection prostate cancer

The results of pelvic lymph node dissections in 105 prostate cancer patients were analyzed to compare the clinical with the pathologic stages. Twenty-four per cent of patients clinically believed to be node-negative had positive nodal involvement with cancer.

Inhibition of sensitized leukocyte's in vitro reactivity by circulating immune complexes in prostate cancer.

Circulating immune complexes in the sera of patients with confirmed histological diagnosis of carcinoma of the prostate, were found to interfere in the sensitized leukocytes in vitro reactivity to prostate cancer associated antigen as evaluated by tube leukocyte adherence inhibition assay, thereby suggesting an inhibitory role of such serum factors in hosts anti tumor cell mediated immune responses.

Adherent Spleen Cell Production of E Series Prostaglandins in Rats Bearing Variants of the R3327 Dunning Prostatic Adenocarcinoma: Effect of Cyclophosphamide

Prostaglandins of the E series (PGE) have been implicated in many facets of immunoregulation, as well as having a possible role in metastatic dissemination. Variant sublines of the Dunning R3327 rat prostatic adenocarcinoma, differing in growth rate, hormonal responsiveness and in propensity for metastasis, were carried in Fisher X Copenhagen F1 animals. Adherent spleen cells were assayed in vitro for their ability to convert arachidonic acid to prostaglandins of the E series. These glass adherent cells presumably include the monocytic and T cell populations which have been implicated as being immunoregulatory. The results indicated that those spleen cells obtained from animals carrying the metastatic R3327-MAT-LyLu subline tumor converted more arachidonic acid to PGEs than cells derived from animals bearing non-metastatic sublines. Cyclophosphamide therapy did not alter such conversion. Multiple regulatory mechanisms for prostaglandin metabolism are suggested.