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Biomedical subjects

C M Pinsky

Publications and source records attributed to C M Pinsky.

At least 37 records · Page 2Linked to original sources
PubMed1985

Intravesical administration of bacillus Calmette-Guérin in patients with recurrent superficial carcinoma of the urinary bladder: report of a prospective, randomized trial.

In an attempt to prevent, delay, or reduce further tumor occurrence, 88 patients with recurrent, superficial carcinoma of the urinary bladder were randomly assigned to receive either standard therapy (cystoscopy with fulguration) or standard therapy and bacillus Calmette-Guérin (BCG). BCG was administered intravesically and percutaneously once weekly for 6 weeks. No serious toxicity was seen. There were 43 evaluable patients in each of the two groups. Results in the BCG group versus the control group were as follows: reduction in the number of recurrent tumors (43 vs 27 patients [P less than 0.001] ); conversion to negative cytology (11 of 33 vs three of 34 patients [P less than 0.05] ); and tumor progression requiring cystectomy (three vs 15 patients [P less than 0.001] ). Disease-free interval (P less than 0.001), time with negative cytology (P less than 0.001), and time to progression of disease (P less than 0.003) were longer in patients treated with BCG. These results indicate that the combination of standard therapy and BCG is more effective than standard therapy alone in patients with recurrent superficial bladder tumors.

Adult↗
PubMed1985

Effect of intravesical Bacillus Calmette-Guérin on detection of a urothelial differentiation antigen in exfoliated cells of carcinoma in situ of the human urinary bladder.

Flow cytometry was used to detect and quantify expression of a urothelial differentiation antigen (Om5) and nuclear DNA in exfoliated epithelial cells of the urinary bladder from 15 patients with nonpapillary carcinoma in situ during and after intravesical therapy with Bacillus Calmette-Guérin (BCG). Before BCG treatment exfoliated cells reacting with the mouse monoclonal antibody Om5 were found in 13 cases. Following treatment Om5 positive cells were still present in 9 cases but 4 patients who had had Om5 positive cells prior to BCG therapy no longer had detectable antigen-positive cells after therapy. Thus intravesical BCG therapy can alter detection of a urothelial differentiation antigen in exfoliated bladder epithelial cells. It is not certain whether this antigen or other differentiation antigens measured by flow cytometry will advance our present techniques for assessing effects of therapy on carcinoma in situ and other bladder tumors. However, five of nine patients showing persistence of Om5 positive cells after therapy were found to have recurrent tumor by biopsy and two others had positive cytology (median follow-up, 13 months). None of the four without detectable antigen-positive cells after therapy had clinical evidence of tumor by cystoscopy, biopsy, or cytology (median follow-up, 12 months). It now appears feasible and desirable to initiate clinical investigations of this and other differentiation antigens in combination with DNA by flow cytometry of bladder irrigation specimens.

Antigens, Neoplasm↗
PubMed1984

Corynebacterium parvum toxicity in patients with limited and advanced malignancy.

The toxicity of intravenously administered Corynebacterium parvum was observed in 14 patients with stage II melanoma and in 14 patients with advanced ovarian carcinoma. Those with melanoma were rendered disease-free by surgery prior to treatment. The ovarian cancer patients had failed chemotherapy with alkylating agents and were receiving C. parvum prior to chemotherapy as part of an immunochemotherapy trial. Both clinical and laboratory parameters were observed. The mean daily C. parvum dose for melanoma patients was 2.03 mg/m2 and for ovarian carcinoma patients 2.02 mg/m2. The most important clinical toxic effects noted were fever, chills, blood pressure changes, headache, nausea, vomiting and diaphoresis. Laboratory toxicity was mild, with small decreases in hemoglobin levels, white blood cell counts and uric acid and albumin concentrations occurring in some patients. Serum bilirubin and SGOT levels tended to rise. In addition to determining the frequency of clinical toxic effects by treatment course, consideration was also given to frequency per treatment day, correlation of the occurrence of different toxicities in the same patient, time of onset of each toxicity and, for vital signs, to intensity of change and duration. In this analysis no major differences in toxicity were observed when C. parvum was given to the two patient groups.

Adjuvants, Immunologic↗
PubMed1983

Serological responses of melanoma patients to vaccines derived from allogeneic cultured melanoma cells.

Twenty melanoma patients were immunized with a whole-cell vaccine prepared from irradiated cells of the melanoma cell line SK-MEL-13. This line, derived from the melanoma of patient AH, expresses a differentiation antigen (initially defined by autologous antibody) which is restricted to melanomas and other cells of neural crest origin. The patients' sera were tested in rosetting assays before and after vaccination for antibodies against cell surface antigens of autologous cultured melanoma cells and SK-MEL-13, and the specificity of observed reactions was defined by absorption tests. Nine patients developed antibodies against autologous cultured melanoma cells. In only one case, patient DM, were these antibodies directed against the AH antigen. In the remaining patients, the antibodies were related to fetal bovine serum in the vaccine growth medium. All patients developed antibodies against cell surface HLA alloantigens of the immunizing cell, SK-MEL-13, as demonstrated by absorption analysis with B cells from the donor of SK-MEL-13 and by serological typing with a panel of HLA typed peripheral blood T cells and B-cell CLL cells. No specificity other than the AH antibody found in patient DM was detected after removal of alloantigens with B cells. We conclude that vaccines prepared from irradiated allogeneic melanoma cells expressing AH antigen, a demonstrably immunogenic differentiation antigen of the melanocyte lineage, are not effective in inducing AH antibody.

Adult↗
PubMed1982

Serological response of melanoma patients receiving melanoma cell vaccines. I. Autologous cultured melanoma cells.

Our past studies have defined Class 1 (unique), Class 2 (shared) and Class 3 (widely distributed) melanoma cell surface antigens by serological typing with autologous antibody. These definitions provide the basis for determining the immunogenicity of a series of melanoma vaccines in patients with malignant melanoma. The first vaccine we tested in this way was prepared from autologous melanoma cell lines, and the results of our trial are the basis of this report. Thirteen patients with metastatic malignant melanoma were vaccinated with irradiated, cultured autologous melanoma cells mixed with BCG in an attempt to induce a serological response to Class 1 or 2 melanoma antigens. Antibodies were measured by protein A (PA), mixed hemadsorption (MHA), immune adherence (IA), C3-mixed hemadsorption (C3-MHA) and antibody-dependent cell-mediated cytotoxicity (ADCC) assays. The specificity of observed reactions was defined by absorption analysis. Eight patients showed an increase in the titer of antibodies to autologous melanoma cell surface antigens after vaccination. In two of these patients, the antibodies had specificity for shared melanoma antigens. In six patients, the antibodies were directed solely against antigens related to the fetal calf serum (FCS) used in growing cells for serological testing and vaccine preparation. We conclude that unmodified autologous cultured melanoma cells, administered as they were in this trial, induce a serological response to melanoma cell surface antigens only in exceptional cases.

Adult↗
PubMed1981

Multivariate analysis of T-cell functional defects and circulating serum factors in Hodgkin's disease.

A comprehensive immunologic and serologic analysis was performed on 31 untreated patients with Hodgkin's disease. Immune evaluations stressed T-cell functional activity and included traditional parameters (PHA responsiveness and delayed hypersensitivity skin reactivity), as well as newer functional assays (T-cell colony formation, chemotaxis, spontaneous and antibody-dependent cytotoxicity, and concanavalin A-induced suppressor cell activity (CISA). Serum factors included ferritin, prostaglandins, zinc, copper, immune complexes, and thymic hormone activity. Every patient exhibited at least one T-cell or serum abnormality. The greatest percentage of patients exhibited T-cell defects in chemotaxis (85%), colony formation (81%). and PHA reactivity (64%). Immune defects were more common with advanced disease but were not related to absolute T-cell or monocyte count, skin test anergy, or abnormalities of T mu/T gamma cell proportions. Linear relationships were identified among abnormalities in the three assays employing mononuclear cells (PHA, colony formation, CISA) which may have reflected the inhibitory influence of monocytes present in the mononuclear cell preparations. Low serum zinc correlated with marked impairment of T-cell chemotaxis. Elevated prostaglandins were associated with high PHA reactivity and with depressed colony formation. Our results indicate that many complex factors, including intrinsic T-cell defects, contribute to the impaired immunity associated with Hodgkin's disease.

Adolescent↗
PubMed1981

Surgical adjuvant therapy of malignant melanoma with corynebacterium parvum.

The authors' previous surgical adjuvant trial in patients with malignant melanoma at high risk of recurrence has shown no difference in disease-free interval or survival between patients randomized to surgery + BCG or surgery alone. Reported here is a subsequent nonrandomized trial in 30 similar patients who received surgery + Corynebacterium parvum (CP) 4 mg I.V. daily x 5, followed by 4 mg S.C. weekly for up to three years. After I.V. C. parvum, chills, fever, headache, and hypertension were common. After S.C. C. parvum, varying degrees of local induration, erythema, and pain were experienced. Dose reduction was necessary for 14 patients during I.V. treatment and for six patients during S.C. treatment. A marked decrease in absolute lymphocyte count and a decreased proliferative response of lymphocytes to common antigens in vitro was observed after 2-3 days of I.V. C. parvum. Lymphocyte reactivity to mitogens decreased, particularly with Con A. Marked increase in nitroblue tetrazolium reduction by granulocytes was seen in 20 patients. Although changes in delayed cutaneous hypersensitivity reactions to recall antigens followed no consistent pattern, reactivity to DNCB increased in 18 patients. In addition, median time to recurrence was 33 weeks, significantly shorter than in the previous trial, but the survival distribution was no different from before. It can be concluded, therefore, that the administration of C. parvum in this dose and schedule had essentially no effect on the outcome of these patients.

Adolescent↗
PubMed1981

DNCB reactivity and prognosis in 419 patients with malignant melanoma.

Delayed cutaneous hypersensitivity to 2,3-dinitrochlorobenzene (DNCB) was tested in 419 patients with malignant melanoma to determine whether DNCB reactivity was associated with prognosis. At the time of definitive surgery, a positive DNCB test was seen in 82% of the patients in State I (regional lymph node histologically negative) and in 81% of patients in Stage II (regional lymph node positive). A positive DNCB test, obtained at the time of staging in patients with more advanced disease, was seen in 70% of patients in State III (metastases in, at most, on internal organ) and in 68% of patients in Stage IV (metastases in more internal organ). Using the chi 2 test, the trend of a decrease in DNCB reactivity from Stage I to Stage IV is significant (P less than 0.04). In regard to DNCB reactivity and prognosis, the following statistical differences (P less than 0.05) were obtained: In Stage II, the recurrence distribution for DNCB-positive patients is more favorable than for DNCB-negative patients (estimated median time to recurrence 16 vs. 7 months); the survival distribution again in Stage II was more favorable for DNCB-positive patients tha DNCB-negative patients (estimated survival time 31 vs. 18 months). When the group of State II patients was divided into subgroups with different prognoses (state of primary at the time of lymphadenectomy), a survival advantage was seen in all substages but was statistically significant (P less than 0.05) only in Stage II d (regional lymph node involvement diagnosed more than two months after resection of primary melanoma). The results of DNCB tests in patients with malignant melanoma correlate with stage of disease and, in Stage II, with prognosis.

Dinitrochlorobenzene↗
PubMed1980

Effect of short-term levamisole therapy on delayed hypersensitivity.

A randomized trial of short-term Levamisole treatment was undertaken in a cancer population unresponsive to dinitrochlorobenzene (DNCB) to determine whether this agent increased delayed hypersensitivity. Of 100 patients entered, 50 received Levamisole (150 mg daily x 3) during DNCB challenge. The other 50 patients were challenged but not given the drug. The conversion rate to DNCB+ was 20% (10/50) for those treated and 12% (6/50) for controls. The difference is not significant. When all 100 patients were considered there was a statistically significant inverse relationship between extent of disease and the incidence of conversion to a DNCB reactive state. Levamisole as given does not appear to have a major influence on delayed cutaneous hypersensitivity.

Adult↗
PubMed1980

Immunologic function in patients with carcinoma of the pancreas.

The immune fuction of 41 patients with duct cell adenocarcinoma of the pancreas or carcinoma of the periampullary region was studied by skin testing with 2,4-dinitrocholorobenzene and common microbial antigens, in vitro lymphocyte reactivity to mitogens, T-lymphocyte and B-lymphocyte cell counts and measurements of complement levels. Results show that a great proportion of patients had depressed immune function. Depression is particularly severe in lymphocyte reactivity. Positive response to skin tests with a microbial antigen carries a slightly better prognosis. The complement level is usually normal or elevated. Correlation between immune function, prognosis and tumor resectability in individual patients is generally poor.

Adenocarcinoma↗
PubMed1979

Cell-mediated cytotoxicity for cultured autologous melanoma cells.

Peripheral blood lymphocytes from 32 patients with malignant melanoma were tested for cell-mediated cytotoxicity (CMC) against cultured autologous melanoma cells. Effector cells were prepared from venous blood by defibrination, gel sedimentation, nylon column filtration, and lysis of remaining erythrocytes with NH4Cl. Melanoma cells prelabelled with [3H])proline were used as target cells in a 40-h assay and CMC was evaluated against standards obtained with blood lymphocytes from the least reactive normal donor. Reproducible autologous CMC was detected in 18 of 32 patients in a series of 367 total tests. CMC correlated with tumor volume (5-500 cm3) but not with tumor stage or DNCB reactivity. Preliminary results indicated that autologous CMC was not affected by treatment with DTIC, dexamethasone, intralesional BCG, radiation therapy, or partial surgical excision. Lack of consistent CMC in 14 patients could not be attributed to a measurable decrease in general immune capacity or to increased resistance of the patients' melanoma cells to CMC in general. Fibroblasts were more resistant to CMC than melanoma cells, and therefore of questionable value for defining specificity in direct tests.

Adult↗
PubMed1978

Preoperative carcinoembryonic antigen level as a prognostic indicator in colorectal cancer.

We examined the relation of carcinoembryonic antigen levels to time, site and extent of recurrence in 358 patients with colorectal cancer. The recurrence rate was higher in patients with Dukes' B and Dukes' C lesions who had preoperative levels higher than 5 ng per milliliter. There was a linear inverse correlation between preoperative levels and estimated mean time to recurrence in patients with Dukes' B and C lesions, ranging from 30 months for a level of 2 to 9.8 months for a level of 70 ng per milliliter. In patients with Dukes' C lesions the median time to recurrence was 13 months if preoperative levels were higher than 5 ng per milliliter, and 28 months if they were lower. Preoperative carcinoembryonic antigen levels in patients with resectable Dukes' B and C cancer provided an additional criterion for allocating these patients to groups at high or low risk for recurrence.

Carcinoembryonic Antigen↗