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Biomedical subjects

J U Gutterman

Publications and source records attributed to J U Gutterman.

At least 199 records · Page 11Linked to original sources
PubMed1983

Renal cell carcinoma: antitumor effects of leukocyte interferon.

Partially purified human leukocyte (alpha) interferon was administered i.m. at a dose of 3 x 10(6) units/day to 19 patients with metastatic renal cell carcinoma. Five patients (26%) showed partial responses; two patients (10.5%), objective minor responses; three patients (16%), mixed effects (evidence of biological effect with regression of some lesions but concomitant progression); two patients (10.5%), disease stabilization; and seven patients (37%), progressive disease. All tumor responses were seen in lung or mediastinal metastases. Tumor response significantly correlated with interferon-induced leukopenia and granulocytopenia and with pretreatment performance status. Antibodies to interferon were found in one patient prior to treatment. We concluded that interferon is a potential active antitumor agent in patients with renal cell carcinoma.

Adenocarcinoma↗
PubMed1983

Analysis of natural killer cell cytotoxicity of cancer patients treated with recombinant interferon.

Peripheral blood natural killer (NK) cell cytotoxicity of 24 cancer patients was studied prior to and after single and multiple injections of various doses of human leukocyte recombinant interferon-alpha clone A (IFN-alpha rA). The NK cell cytotoxicity of all cancer patients declined consistently 4 and 8 hours after a single injection of IFN-alpha rA. Twenty-four hours after the injection of IFN-alpha rA, NK cell cytotoxicity of patients with low NK cell phenotype (NK-LR) was significantly augmented, whereas that of patients with medium (NK-MR) or high (NK-HR) NK phenotype was depressed. After multiple injections of IFN-alpha rA, depression of NK cell cytotoxicity was observed in a number of NK-MR and NK-HR patients, but in some patients with NK-LR phenotype, further potentiation was observed. No direct correlation between the NK cell augmentation and serum IFN levels was detected. In in vitro studies, IFN-alpha rA, when added to cultures of target and effector cells of normal individuals in a dose of 10(3) U/ml, was efficient in augmenting NK cell cytotoxicity. NK cell cytotoxicity of cancer patients could also be augmented by the IFN-alpha rA preparation; however, this augmentation occurred only prior to in vivo IFN-alpha rA therapy. After IFN-alpha rA in vivo therapy, their NK cells became refractory to further in vitro IFN-alpha rA treatment.

Adult↗
PubMed1983

Leukocyte interferon (IFN alpha) in patients with epithelial ovarian carcinoma.

Human leukocyte interferon (IFN alpha) was administered to 15 patients with epithelial ovarian carcinoma after previous chemotherapy or therapeutic irradiation. One objective response was observed. Three patients had possible stable disease for up to 6 months, including two patients who were re-explored 6 months after commencing IFN alpha and one patient who was observed to have a less than 50% reduction in her tumor diameters. Three of seven patients demonstrated clinical responses to subsequent chemotherapy, indicating an absence of resistance to subsequent chemotherapy. Toxicity included the relatively mild symptoms of anorexia, lassitude, and diarrhea. Malabsorption was observed in one patient. Platelet depression and abnormal enzyme liver functions were also observed more frequently following IFN alpha. No life-threatening toxicity was observed.

Adult↗
PubMed1983

Regulation of human natural killer cell cytotoxicity by recombinant leukocyte interferon clone A.

We have studied the peripheral blood natural killer (NK) cell cytotoxicity of 32 cancer patients prior to and after single and multiple injections of various doses of human recombinant leukocyte interferon clone A (IFN-alpha rA). Consistent decline in NK-cell cytotoxicity of all cancer patients was observed 4 and 8 h after a single injection of IFN-alpha rA. Twenty-four hours after the injection, NK-cell cytotoxicity of patients with low NK cell phenotype (NK-LR) was significantly augmented, whereas that of most patients with medium (NK-MR) or high (NK-HR) NK phenotype was depressed. After multiple IFN-alpha rA injections, depression of NK-cell cytotoxicity was observed in a number of NK-MR and NK-HR patients, whereas in some patients with NK-LR phenotype, elevated NK-cell levels were observed. No direct correlation between NK-cell augmentation and serum IFN levels was detected. In vitro studies demonstrated that NK-cell cytotoxicity of normal donors was augmented by IFN-alpha rA (10(3) U/ml). Augmentation of NK cells was also observed in cancer patients after in vitro addition of IFN-alpha rA, but only prior to and not after in vivo IFN-alpha rA therapy.

Blood Cell Count↗
PubMed1983

Human pharmacokinetics of a new acridine derivative, 4'-(9-acridinylamino)methanesulfon-m-anisidide (NSC 249992).

The clinical pharmacology of 4'-(9-acridinylamino)methanesulfon-m-anisidide (amsacrine) was studied, utilizing [9-14C]amsacrine i.v. in 19 patients with disseminated neoplasms. The mean terminal plasma half-life for total 14C ranged from 34 hr in patients with normal organ function to 46 hr in patients with severe liver disease. For unchanged amsacrine, the mean values of plasma half-life were 7.4 and 17.2 hr for patients with normal and abnormal liver function, respectively. The plasma half-lives of 14C were prolonged, while those for unchanged amsacrine appeared to be normal in patients with renal dysfunction. The mean 72-hr cumulative urinary excretion of total 14C varied from 35% in normal patients to 49% in patients with severe liver disease, while patients with renal disease excreted only 2 to 16%. In comparison, the urinary excretion of unchanged amsacrine was 12, 20 and 2% of the administered dose, respectively, in these same patients. Amsacrine biliary excretion studied in two patients showed about 8 and 36% of the administered radioactivity excreted in the bile in 72 hr, with less than 2% as unchanged amsacrine. Cerebrospinal fluid concentrations of amsacrine were below 2% of the simultaneous plasma levels in three patients. Impaired amsacrine drug clearance was frequently associated with liver dysfunction. Patients with impaired amsacrine drug clearance experienced the most severe clinical toxicity. Hepatic metabolism and biliary excretion appear the most important routes for amsacrine elimination. Renal elimination, although less important, is significant in patients with severe kidney dysfunction. To avoid excessive clinical toxicity, initial dose reductions of 30 to 40% are recommended for patients with severe liver or renal disease or for those who have pharmacologically documented impaired drug clearance.

Aminoacridines↗
PubMed1982

Actinomycin-D plus 5-(3,3-dimethyl-1-triazeno)-imidazole-4-carboxamine (DTIC) with or without intravenous Corynebacterium parvum in metastatic malignant melanoma.

Chemotherapy and chemoimmunotherapy of Stage IV B malignant melanoma were compared in 88 patients. Chemotherapy consisted of DTIC 250 mg/M2 of the body surface area daily x five days and actinomycin-D 2 mg/M2 on day 1 repeated every 3--4 weeks. Chemoimmunotherapy consisted of the same regimen plus C. parvum 2 mg/M2 I.V. daily for 14 days before every third cycle of chemotherapy, plus 2 mg/M2 I.V. daily on days 7 and 14 of each 21--28 day chemotherapy cycle. There was 32 evaluable chemotherapy and 33 evaluable chemoimmunotherapy patients and the groups were well balanced for clinical and pathologic as well as prognostic variables. The complete and partial remission rates, remission and survival durations, and hematologic and gastrointestinal toxicities were different in the two randomized groups being 6 and 3%, 9 and 9%, 7.6 and 12 months, 8.8 and 6.0 months, 20 and 16%, and 62 and 70%, respectively for these parameters. This difference was not statistically significant. Therefore, it can be concluded that the results of chemotherapy with actinomycin-D plus DTIC were not substantially different from those reported using DTIC alone, and that we cannot recommend the addition of actinomycin-D to DTIC for palliative management in these patients. Furthermore, C. parvum immunotherapy did not add to chemotherapy in terms of remission rate, remission duration, or survival for patients with Stage IV B malignant melanoma.

Adolescent↗
PubMed1982

Antibody-dependent cell-mediated cytotoxicity in human cancer: characterization of patient leukocyte activity and treatment effects.

Antibody-dependent cell-mediated cytotoxicity (ADCC), medicated by peripheral blood Hypaque-Ficoll separated mononuclear cells, was studied in humans using chicken erythrocytes (CRBC) incubated in a 1:1200 dilution of rabbit anti-CRBC and human B erythrocytes (HRBC) incubation in a 1:20 dilution of isoantibody. At the optimal target effector ratio of 3:1, ADCC to both CRBC and HRBC was significantly higher than normal in 27 lung cancer, 18 malignant melanoma, and seven colon cancer patients, but not in 20 breast cancer patients. Chemotherapy (single-agent or combination) in 12 patients did not effect ADCC in vitro but significantly suppressed ADCC to both targets after only four or five days of therapy in vivo (ADCC to CRBC, 47.4 to 24.1% lysis: ADCC to HRBC, 48.1 to 16.3% lysis). Immunotherapy with intravenous (IV) corynebacterium parvum or IV methanol extraction residue of BCG (MER) boosted ADCC to both targets within four to seven days of the first dose. It was found that ADCC to HRBC but not to CRBC was completely absent in three cases of active hairy cell leukemia but was present in two cases in remission. The ADCC to HRBC showed an age-dependent increase in both the 51 normal subject and the cancer patients. This was not observed for ADCC to CRBC. The ADCC to CRBC was mediated mainly by an Fc-receptor-positive, nonadherent, small lymphocyte, and ADCC to HRBC was mediated entirely by an adherent monocyte. The ADCC did not correlate significantly with the H3 thymidine incorporation of peripheral blood mononuclear cells, cultured without stimulation for either one or seven days. It also did not correlate with the number of residual granulocytes in the mononuclear cell suspensions. Measurement of ADCC is a useful method of characterizing host defense in malignant disease and its modification by therapy.

Age Factors↗
PubMed1982

Human leukocyte interferon-mediated granulopoietic differentiation arrest and its abrogation by lithium carbonate.

Interferon has been shown to inhibit erythropoietic and granulopoietic differentiation. Since lithium carbonate (Li) elevates granulocyte levels in a variety of neutropenic disorders, we investigated the effect of Li on human leukocyte interferon (HLIF)-mediated inhibition of granulopoietic differentiation. Using an agar culture technique for cloning granulocyte-macrophage progenitor cells (GM-CFC), we demonstrated that Li blocks HLIF-induced granulopoietic differentiation arrest in a dose-dependent manner. Results of removal of T lymphocytes from marrow cells suggest that this Li effect is not mediated through marrow T lymphocytes.

Cell Differentiation↗
PubMed1982

Clinical and immunological study of beta interferon by intramuscular route in patients with metastatic breast cancer.

Partially purified human beta interferon (HuIFN-beta) was administered to six patients with metastatic breast carcinoma by the intramuscular route at doses of 3 X 10(6) and 6 X 10(6) units on a daily schedule. Objective antitumor effects were observed in three patients (one partial remission, two minor responses) in soft tissue and lymph node metastases. Systemic side effects (fatigue, fever, pruritus, nausea, etc.) attributable to the treatment occurred in all patients. Augmenting effects by IFN-beta on cell-mediated immunity in vivo (delayed-type hypersensitivity) and in vitro natural killer cell and antibody-dependent cell-mediated cytotoxicity were observed in several patients. The clinical and immunological effects were considered evidence of systemic biological activity despite very low or undetectable serum antiviral activity following administration of this agent.

Adult↗
PubMed1982

Recombinant leukocyte A interferon: pharmacokinetics, single-dose tolerance, and biologic effects in cancer patients.

Sixteen patients with advanced cancer were treated with recombinant-DNA-produced pure leukocyte A interferon (IFLrA) intramuscularly in doses ranging from 3 to 198 X 10(6) units. with interval periods of 72 to 96 hours between doses. At the two lowest doses of 3 and 9 million units, there was a cross-over evaluation between IFLrA and partially pure leukocyte interferon (IFN-C) produced from human cells. THe maximum observed serum concentration of IFLrA measured by enzyme immunoassay and bioassay increased with increasing doses. The mean serum concentrations of IFLrA and IFN-C were similar. Clinical effects produced by IFLrA and IFN-C were similar, including fever, chills, myalgias, headache fatigue, and reversible leukopenia and granulocytopenia. Eight patients had transient and mild numbness of the hands or feet, or both. Three patients developed low titers of antibody to IFLrA, Seven of 16 patients showed objective evidence of tumor regression during the study.

Adult↗
PubMed1982

Leukocyte-derived interferon (alpha) in human breast carcinoma. The American Cancer Society phase II trial.

A multi-institutional trials program was initiated to define the effects of interferons in disseminated human breast carcinoma. Interferon alpha, prepared from buffy coats, was administered intramuscularly at 3 x 10(6) U daily for an initial period of 28 days. Of 23 patients who entered the program, five had an objective partial response of 92 days mean duration at diverse sites of involvement. Patients who responded were significantly older (p = 0.05) than nonresponders. Dose escalation in eight patients did not result in any clear evidence of additional responses. Major toxicities were fatigue, anorexia with weight loss, and reversible leukopenia (less than 3.5 x 10(9) leukocytes/L in 16 patients). Natural killer cell and antibody-dependent cell-mediated cytotoxicity were significantly (p less than 0.05) enhanced 48 hours after interferon administration began but subsequently declined despite continued therapy. Serum beta 2-microglobulin concentration increased on day 15 (p less than 0.05) and remained significantly elevated on day 22 (p less than 0.005). Peak interferon titers (mean, 62 U) occurred 6 hours after interferon was started, varied widely between patients, and were higher and more persistent with dose escalation. Once an optimal dose is defined, prospectively randomized trials will define what role interferons may have in systemic therapy of breast carcinoma.

Adult↗
PubMed1981

A four-year experience with anthracycline, cytosine arabinoside, vincristine and prednisone combination chemotherapy in 325 adults with acute leukemia.

Combination chemotherapy with an anthracycline, Adriamycin or rubidazone, cytosine arabinoside, vincristine and prednisone resulted in a complete remission rate of 62% in 325 consecutive unselected adults with acute leukemia. The results by morphologic categories were 58% for acute myelogenous leukemia (AML), 70% for acute undifferentiated leukemia (AUL), and 77% for acute lymphoblastic leukemia (ALL). The median survival was 43 weeks. Ten percent of all patients are projected to be alive and in remission at five years. The median remission duration for the whole group was 51 weeks, durations being significantly longer for AML (60 wks) than ALL (30 wks) and AUL (21 wks). Central nervous system involvement was uncommon in AML (4%), but much more common in patients with AUL (37%) and ALL (32%). One in five complete responders with AML is projected to be in their first remission at five years off all chemotherapy. Age, sex, morphology, cytogenetic pattern, temperature of presentation, and presence of a documented preceding hematologic abnormality are found to be significant variables for response and survival.

Adolescent↗
PubMed1981

Prolonged remissions in adults with acute leukemia following late intensification chemotherapy and immunotherapy.

Sixty-two patients with acute leukemia who remained in continuous complete remission for 8 to 45 months received three courses of intensified therapy with new chemotherapeutic agents, after which they received no further chemotherapy. Immunotherapy with BCG was then administered to 55 of these patients. They have been observed for up to 117 months off all chemotherapy, and 37 patients have relapsed. Thirty-two relapses occurred within 24 months, and 22 occurred within six months after completion of late intensification therapy. Only 1 of 24 patients who remained in unmaintained remission for four years after late intensification therapy has relapsed subsequently. Toxicity from intensification therapy was usually mild, and the most serious side effects were liver function abnormalities. These results suggest that late intensification therapy plus BCG immunotherapy results in prolonged disease-free survival for some patients with acute leukemia.

Adult↗
PubMed1981

Prognostic value of prechemotherapy skin tests in patients with metastatic breast carcinoma.

Two hundred patients with metastatic breast cancer who were treated with combination chemotherapy and nonspecific immunotherapy with BCG or MER were skin tested prior to, and at regular intervals during the administration of chemotherapy with a battery of six antigens (Dermatophytin, Varidase, candida, mumps, PPD, and KLH). Delayed-type hypersensitivity responses to this battery of antigens were analyzed to assess whether they correlated with ability to respond to chemotherapy, length of survival, and a number of other host and tumor characteristics of known prognostic significance. Responsiveness to individual recall antigens or the number of positive skin test responses did not correlate with overall or complete response rates. The correlation did exist with KLH, a primary antigen. A positive response to two or more antigens correlated with a longer survival. Inability to mount a skin test response to any antigen correlated with poor survival. PPD conversions during serial BCG administration did not correlate with a better prognosis. Serial skin testing with a battery of antigens did not correlate with prognosis. Skin test responsiveness to the antigens used in this study did not correlate with the other pretreatment factors of prognostic importance such as tumor burden, absolute lymphocyte count, performance status, prior radiation therapy, menopausal status, and age. Therefore, responsiveness to skin testing with these antigens appears to be an independent prognostic variable and should be incorporated in the planning and analysis of systemic treatment programs in metastatic breast cancer.

Adult↗
PubMed1981

Combination therapy for advanced malignant melanoma with BCNU, pseudomonas vaccine, and heparin.

A study was undertaken to investigate the addition of heparin and pseudomonas vaccine to BCNU in the treatment of patients with progressive malignant melanoma refractory to front-line therapeutic regimens containing DTIC. Out of 27 evaluable patients, there was one partial remission (4%), and an additional ten patients (41%) had at least stable disease with a median survival time of 39 weeks compared to 15 weeks for those with progressive disease. The therapy was well tolerated. A schedule of pseudomonas vaccine that seemed to be tolerated has been established.

Adult↗
PubMed1981

Organ distributions and clearance studies of 99mtechnetium-labeled Corynebacterium parvum in patients with leukemia.

The clearance, metabolism and localization of Corynebacterium parvum (C. parvum) labeled with 99mtechnetium (99mTc) given intravenously was studied in various leukemia patients to develop the method and to evaluate reticuloendothelial systems (RES) function. A computer program was utilized to characterize the clearance. C. parvum 0.05 mg was labeled aseptically with 10 mCi of 99mTc with a reducing agent. It was injected intravenously over 5 s and clearance was characterized over the next 60 min. The low dose of C. parvum did not cause any symptoms. The blood or plasma clearance time (t 1/2) was in the range of 0.65 to 1.96 min, in eight patients. By whole body imaging, the distribution of C. parvum was found mainly in the liver, and to a much lesser extent in the spleen, lungs, and bone marrow. Nonparticulate 99mTc (which was not sedimented by centrifugation of blood samples at 3000 rpm for 30 min) appeared rapidly in the blood after i.v. injection accounting for more than half of the radioactivity in a few minutes. In vitro incubation of 99mTc labeled C. parvum with saline, whole blood, serum or leukocytes revealed that the release of free 99mTc resulted from the combined action of serum and leukocytes. The rapid clearance will limit the utility of this preparation in characterizing RES function in man and its modification by disease or therapy.

Adult↗