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Biomedical subjects

J U Gutterman

Publications and source records attributed to J U Gutterman.

At least 271 records · Page 15Linked to original sources
PubMed1976

Prolongation of postoperative disease-free interval and survival in human colorectal cancer by B.C.G. or B.C.G. plus 5-fluorouracil.

83 patients with colorectal carcinoma of the Dukes' C class were randomised to receive postoperative adjuvant therapy with B.C.G. alone or in combination with oral doses of 5-fluorouracil (5-F.U.), and have been followed for up to thirty months. Results were compared with carefully selected historical controls who were treated by surgery alone. A statistically significant prolongation of both disease-free interval and overall survival was observed in 50 patients receiving the combination of B.C.G. and 5-F.U. (P=0.03, P=0.01 respectively) as well as in 33 patients receiving B.C.G. alone (P=0.03, P=0.05 respectively). The efficacy of B.C.G.+5-F.U. was independent of the number of tumour-involved lymph-nodes in the surgical specimen. In contrast, B.C.G. given alone appears to be highly effective among 10 patients with 6 or more positive lymph-nodes (P less than 0.04) and ineffective (as yet) among 23 patients with 5 or less positive lymph-nodes. These results suggest that adjuvant immunotherapy, with or without chemotherapy, can improve the prognosis of surgically treated patients with colorectal carcinoma of the Dukes' C class.

Administration, Oral↗
PubMed1976

Mononuclear cell content of human solid tumors.

The mononuclear cell content and mononuclear cell function of human solid tumors were determined. Twenty-eight primary, and 17 metastatic solid tumors, including 6 lymph node metastases, were obtained from 45 patients. Cells were released from the tumors by mincing, scraping, and sieving. Analysis of the cellular content was determined by light microscopy, and tumor lymphocyte function was determined by stimulation of blastogenesis with PHA, PWM, Con-A, MLC, and SLO. A median of 3.3 X 10(7) tumor cells with 12.5% viability was obtained per gram of tumor, and a median of 7.8 X 10(6) lymphocytes with a viability of 96% and 0.35 X 10(6) macrophages with a viability of 85% was also obtained per gram of tumor. Significant lymphocyte responses to various mitogens and antigens were obtained in 31-40% of the tumor lymphocyte preparations. From 9.4% to 23% had vigorous responses with a stimulation index greater than 10. Primary tumors contained significantly more lymphocytes than metastatic tumors; thus, the percent lymphocytes in primary tumors was 13.5% compared to 5% for metastatic tumors. In contrast, some of the lymphocyte responses were significantly greater for metastatic tumors than primary tumors. These data suggest that the direct study of lymphocytes infiltrating primary and metastatic tumors may be a useful approach to understanding tumor immunity in man.

Antigens, Neoplasm↗
PubMed1976

Immunotherapy of leukemia.

The data reviewed in this paper indicate that immunotherapy is effective in prolonging remission and survival in acute and chronic leukemia. The acute lymphocytic leukemias may or may not respond to immunotherapy and further work is needed in this area. No studies of immunotherapy in chronic lymphocytic leukemia have been done, but this will be an important area for investigation, since there is often profound immunodeficiency in this disease. The malignant lymphomas are another fertile area for this type of research, since they have a high response rate, tumor-associated immunodeficiency, and at least differentiation antigens if not tumor-specific antigens. The scientific basis for the use of immunotherapy in leukemia includes the demonstration of a relationship of rate and duration of remission and survival to immunocompetence, the demonstration of unique tumor-associated antigens on leukemia cells, and the demonstration of immune responses to these antigens which can be boosted by immunization. At the present time, active nonspecific immunotherapy with BCG and MER and active specific immunotherapy have been proved effective in acute myelogenous leukemia. Careful attention should be given to dose, schedule, route, and so forth. Other types of immunotherapy remain to be explored.

Acute Disease↗
PubMed1976

Complement activation in vivo in cancer patients receiving C. parvum immunotherapy.

Serum complement levels were assayed in 26 patients with disseminated cancer, who received immunotherapy with infusion of C. parvum. Complement activation, indicated by the consumption of C3 or C4 or both, was found in 46% of the patients. Serum samples showed direct correlation between decreased C3 and conversion of C3 proactivator, whereas such conversion did not occur when C4 alone was decreased. It is concluded that the bypass (properdin) pathway was activated in patients in whom C3 consumption was detected, while the classical (C1) pathway was activated in the patients with C4 consumption unaccompanied by C3 decrease. Direct correlation was observed between delayed cutaneous hypersensitivity reactions to recall antigens and the incidence of C. parvum-associated complement activation.

Complement C3↗
PubMed1976

Evaluation of BCG administered by scarification for immunotherapy of metastatic hepatocarcinoma in the guinea pig.

In inbred guinea pigs, administration of Mycobacterium bovis strain BCG by scarification at a site distant from an excised skin tumor, but in the regional lymph node drainage, was evaluated for its immunotherapeutic effect on the development of lymph node metastases. Scarification was performed after surgical excision of intradermally transplanted syngeneic (line-10) hepatocarcinoma at a time when microscopic foci of tumor cells were present in regional lymph nodes. Various strains of BCG were evaluated for their immunotherapeutic potential: fresh-frozen Phipps, Pasteur, and Tice; and lyophilized Pasteur, Tice, and Connaught. Scarification commenced 3 days after surgical removal of the tumor and continued once a week for 5 weeks. Only lymph nodes from fresh-frozen Phipps- and Pasteur-scarified animals were significantly smaller than those in the control groups. Differences in lymph node weight correlated histologically with less detectable metastases. This cytostatic effect was short lived; eventually, the metastatic tumor growth was not significantly different from that of control animals. No significant differences were observed in mean survival time: All animals died as a result of metastases 3 months after tumor inoculation. These results demonstrated that limited scarification with BCG of certain strains temporarily inhibits the growth and proliferation of metastases in regional lymph nodes after removal of the primary tumor.

Administration, Topical↗
PubMed1976

Effect of BCG (Tice strain) on primary sensitization to 2,4-dinitrochlorobenzene and on established delayed hypersensitivity in human malignant melanoma.

Studies of primary sensitization and delayed hypersensitivity reactions to 2,4-dintrochlorobenzene (DNCB) and recall antigens were conducted in 71 patients with melanoma who were receiving BCG (Tice strain) immunotherapy by scarification. Similar studies were conducted in 32 control patients with melanoma who did not receive BCG. No significant differences were observed, in the various clinical stages, between patients receiving and those not receiving BCG, in terms of the frequency or intensity of primary sensitization to DNCB. Furthermore, there was no significant difference in delayed hypersensitivity to recall antigens between these groups of patients. The apparent discrepancy between the clinical benefit from BCG immunotherapy and its failure to stimulate certain parameters of cellular immunity in patients with melanoma is discussed.

Antigens↗
PubMed1976

Immunocompetence, immunodeficiency and prognosis in cancer.

Immunocompetence and prognosis are related in solid tumors, malignant lymphomas, and acute leukemia. Among the parameters of immunocompetence vigorous delayed-type hypersensitivity responses to recall antigens or to primary immunization with Keyhole limpet hemocyanin, vigorous in vitro lymphocyte blastogenic responses to mitogens such as PHA, and relatively high B-lymphocyte levels, all correlate with a good prognosis. The spectrum of immune reactivity as measured by established delayed-type hypersensitivity to recall antigens and in vitro blastogenic responses to mitogens and antigens is similar in melanoma patients and their nontumor-bearing spouses. In melanoma, only patients with widespread inoperable metastatic disease show severe immunological deficiency and this is selective for certain antigens. There are highly significant differences in response to specific antigens when patients with melanoma and lung cancer are compared. Immunotherapy with BCG and C. parvum can boost immunocompetence as measured by recall DTH skin testing. However, the relationship between the initial immunocompetence and prognosis still holds in patients receiving BCG immunotherapy to prevent recurrence of melanoma. These data indicate that a broader survey of immunological reactivity in cancer patients is needed, that immunological testing is useful in cancer prognosis clinically, and that the results of immunological testing can be used to evaluate therapy and to indicate new pathways for improved treatment.

B-Lymphocytes↗
PubMed1976

In vitro and in vivo studies with thymosin in cancer patients.

Thymosin, fraction V, prepared by the method of Goldstein et al., was studied in in vitro lymphocyte cultures with cells obtained from normal subjects and patients with disseminated cancer. Thymosin lowered blastogenic activity in some patients, did not affect it in others, and increased counts in still others. There was a statistically significant depression in baseline (prethymosin) counts from both normals and patients when individuals whose counts increased in the presence of thymosin were compared with other subjects. We conclude that thymosin tended to raise depressed blastogenesis into the normal range without causing supranormal activity or without itself acting as a mitogen or antigen. Eighty-two in vivo courses in thymosin were given to 32 patients. Analysis of the first thymosin courses in these 32 patients shows that immunologic reconstitution occurred in patients with originally depressed T-cell function and numbers, whereas little change was apparent in patients with initially intact tests of T-cell activity. Clinical effects were equivocal; however, no systematic clinical trial was conducted. Toxicity was minimal (four of the 32 patients); in each case, it consisted of inflammation at the injection site. The in vitro and in vivo results of this study suggest that thymosin therapy modulates and partially normalizes T-lymphocyte numbers and function.

Humans↗
PubMed1976

Chemotherapy versus chemoimmunotherapy of head and neck cancer: report of a randomized study.

Thirty-four patients with recurrent squamous cell carcinoma of the head and neck were randomized to receive the five-drug chemotherapy regimen BACON (bleomycin, adriamycin, CCNU, vincristine [Oncovin], and mechlorethamine [nitrogen mustard]; 14 patients) or the same regimen plus bacillus Calmette-Gu erin (BCG) by scarification (20 patients). The majority of both patient groups had received prior surgery and radiation. The patients treated with BACON plus BCG experienced a significantly longer survival (P = 0.014) than those treated with BACON alone. There were five drug-related deaths, and eight other patients required hospitalization for treatment of drug-related morbidity.

Adult↗