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J Gutterman

Publications and source records attributed to J Gutterman.

At least 55 records · Page 3Linked to original sources
PubMed1986

Changes in granulocyte-monocyte colony-forming cells among leukocyte-interferon-treated chronic myelogenous leukemia patients.

Myeloid cytoreduction leading to hematologic remissions is frequently seen among patients with chronic phase Philadelphia-positive chronic myelogenous leukemia (CML Ph') treated with leukocyte interferon (IFN-alpha). In order extend our understanding of the events associated with interferon-induced myeloid cytoreductions, we have examined the changes in granulocyte-monocyte colony-forming cells (GM-CFC) in such CML Ph' patients. A total of 28 CML Ph' patients in hematologic remissions following IFN-alpha treatment had a median GM-CFC of 12 (range, 0-182)/1 X 10(5) bone marrow cells. This was significantly lower than the median GM-CFC of 104 (range, 44-815; p less than 0.01) in 22 untreated or minimally treated CML Ph' patients and the median of 72 (range, 30-204; p less than 0.05) in 18 normal controls. A gradual decline in the GM-CFC numbers from a median of 105 to a median of 1.8 was seen in six responding patients who were studied serially over a median period of 7.5 months. In these patients, we also observed a profound decline in the number of aspirated bone marrow nucleated cells and a decline in the bone marrow cellularity. The effect of treatment interruption for a median of 13 days was studied in five patients. In three of the patients who had received IFN-alpha for less than or equal to 6 months, treatment interruption resulted in rapid increase in the GM-CFC, while the GM-CFC did not change in the remaining two patients, who received IFN-alpha for one and two years. We conclude that treatment of CML patients with IFN-alpha resulted in a progressive decline of the bone marrow GM-CFC. The initially expanded pool of committed myeloid stem cells declines gradually, and at the time of hematologic remission the number of GM-CFC/10(5) nucleated bone marrow cells is lower than that of normal controls. In the early phases of IFN-alpha treatment, this inhibitory effect is rapidly reversible, but it seems to persist when the treatment is extended over more than one year.

Bone Marrow↗
PubMed1985

The human cellular abl gene product in the chronic myelogenous leukemia cell line K562 has an associated tyrosine protein kinase activity.

Three antisera against the mouse v-abl gene product were used to identify two potential human c-abl gene products in the chronic myelogenous leukemia cell line K562. Two antipeptide sera were generated in rabbits using the predicted amino acid sequence of the mouse v-abl gene product. One antiserum was made against a polypeptide overlapping the in vivo tyrosine phosphorylation site of murine P120gag-abl and what is believed to be a homologous tyrosine phosphorylation site of the predicted normal human c-abl gene product (v-abl 263-280). The second antipeptide serum, abl 389-403, was generated against a predicted hydrophilic peptide of the v-abl gene product. Immunoprecipitation from K562 cells metabolically labeled with [32P]orthophosphate by a mouse tumor regressor and abl 389-403 antipeptide sera detected two proteins of 190,000 and 240,000 Da. Both proteins were labeled primarily at serine and, to a much lesser extent, at tyrosine residues. Immune complex kinase assays using conditions that allow the tyrosine phosphorylation of P120gag-abl showed that in vitro phosphorylation of P190 and P240 occurs primarily at tyrosine residues. The detection of these enzymatically active human c-abl gene products is a rare observation which may be in part attributed to the c-abl gene translocation from chromosomes 9 to 22 occurring in the vast majority of chronic myelogenous leukemia patients.

Abelson murine leukemia virus↗
PubMed1985

Efficient activation of human blood monocytes to a tumoricidal state by liposomes containing human recombinant gamma interferon.

Human recombinant gamma interferon (INF-gamma) activated human peripheral blood monocytes to a cytotoxic state capable of lysing adherent tumorigenic cells without harming normal cells. The efficiency of INF-gamma activation of monocytes is enhanced by encapsulating INF-gamma within liposomes: The minimum effective dose (MED) of free INF-gamma for monocyte activation was found to be 1-10 U/ml, per 10(5) monocytes, whereas the minimum dose for IFN-gamma encapsulated in liposomes was less than 0.0025 U. Monocytes treated with liposome-encapsulated INF-gamma retained their cytotoxic phenotype for much longer than do monocytes treated with free INF-gamma. Since liposomes can be passively targeted to cells of the reticuloendothelial system following IV administration, these findings suggest that liposome-encapsulated INF-gamma may have therapeutic potential that should be evaluated in vivo.

Cells, Cultured↗
PubMed1984

Antibodies to chromosome 21 coded cell surface components block binding of human alpha interferon but not gamma interferon to human cells.

Antisera raised against a human X mouse hybrid cell line containing human chromosome 21 as its only human chromosome, block induction of an antiviral state by human alpha interferon (IFN-alpha), block induction of (2'-5')oligoisoadenylate synthetase [2'-5')A synthetase), and block binding of 125I-labeled and 35S-labeled recombinant, human IFN-alpha A, but not 125I-labeled IFN-gamma, to cell surface receptors. The data presented clearly demonstrate that the cell surface receptors for IFN-alpha and IFN-gamma are different, and provide independent evidence of the role of a chromosome 21 coded cell surface molecule in the pathway to the generation of the antiviral state.

2',5'-Oligoadenylate Synthetase↗
PubMed1984

Oncogene expression in human leukemia.

The transforming genes of retroviruses (v-onc) are derived from normal cellular genes referred to as proto-oncogenes. These cellular genes have the capacity for conversion to oncogenes (c-onc) that are capable of inducing or maintaining the transformed state when they are overly expressed or altered by mutation or rearrangement. To study the possible involvement of these genes in human leukemia, we have analyzed their expression in a variety of fresh samples. We found that a number of oncogenes are expressed in different leukemic types and that although the transcript size did not vary for each gene, the copy number did. The myc gene (2.4 kb transcript) and the rasHa gene (1.5 kb transcript) were universally expressed. But in contrast to rasHa, the myc signal intensity varied. Myb (4.5 kb transcript) was expressed in all samples except B cell diseases. We detected low levels of abl expression (multiple mRNA species) in all leukemic types analyzed. Sis gene (4.2 kb transcript) expression was restricted to one patient sample with chronic myelogenous leukemia in blast transformation.

Acute Disease↗
PubMed1982

The natural history of resectable metastatic melanoma (Stage IVA melanoma).

One-hundred-two patients with malignant melanoma who had distant metastases surgically resected and were judged to be clinically free of disease (M. D. Anderson Stage IVA melanoma) were studied. The median survival for all the patients from time of diagnosis of stage IVA disease was 18 months. The site of the resected metastases did not appear to influence survival, being approximately the same for the brain (15 months), lung (16 months), intraabdominal (18 months), and skin and/or lymph nodes (23 months). The site of the resected metastases also did not influence the median disease-free interval. Patients who had metastases resected from several organs at the same time had a median survival of 15 months, which was similar to that of patients with one resected site. Patients who were rendered Stage IVA on several occasions by surgical excisions had a median survival of 36 months. Thirty-five patients received surgery only and 67 patients received adjuvant chemotherapy, immunotherapy, or combined chemoimmunotherapy after surgery. For the group treated with surgery only, the median disease-free interval and survival from diagnosis of stage IVA disease were 6 months and 16 months, respectively, and for the adjuvant group 6 months and 21 months, respectively. Specifically, by the type of adjuvant therapy, the median disease-free interval and survival from stage IVA for 23 patients receiving Corynebacterium parvum were 6.9 and 19 months; for 39 patients receiving BCG, eight months and 26 months; for 24 patients receiving BCG + DTIC, eight and 17.4 months; and for all 51 DTIC treated patients 6.3 and 17.8 months, respectively. Patients receiving BCG had a median survival superior to the surgery only group (P = 0.02). An increase in survival was seen predominantly in patients who achieved IVA status more than once and received BCG. Patients with recurrent soft-tissue metastases appeared to benefit most from BCG in prolonging the disease-free interval. Only 1/10 treated by surgery alone had a disease-free interval longer than 1 year, compared with 9/16 who received BCG (P = 0.01). Stage IVA melanoma appears to be distinctly different in prognosis from Stage IVB melanoma and should be classified separately. Patients with recurrent soft-tissue disease may benefit significantly from treatment with BCG.

Adolescent↗
PubMed1982

Activity of human leukocyte interferon in a human tumor cloning system.

Clinical trials using interferon to treat human malignancies are currently hampered by limited supplies of the compound. We have utilized a human tumor cloning system as an assay for the antitumor effects of human leukocyte interferon. Interferon was tested against 62 patients' tumors growing in this soft agar system. A dose-dependent cytotoxic effect of interferon was noted against only five of the patients' tumors. A greater than or equal to 70% decrease in tumor colony-forming units (TCFUs) was noted with one lymphosarcoma cell leukemia, one small cell lung cancer, one adenocarcinoma of the lung, one breast cancer, and a pancreatic cancer. One patient had his tumor cultured in vitro and had a clinical trial with interferon. This patient whose tumor demonstrated in vitro sensitivity had a clinical antitumor effect with interferon therapy. The in vitro results in this study suggest that the human leukocyte interferon currently available has a low level of activity in a human tumor cloning system. Additional testing is needed to determine whether the cloning system can identify the patient(s) who might have an antitumor effect from the interferon.

Clone Cells↗
PubMed1981

Chemoimmunotherapy for multiple myeloma.

The effect of chemoimmunotherapy consolidation treatment using alternating courses of alkylating agents and BCG was studied in 105 responding patients with multiple myeloma. The survival time of these patients was similar to that of responding patients treated on previous maintenance programs, indicating no apparent value from BCG for myeloma. The duration of unmaintained remission was longest in those with low numbers of residual plasma cells, and relapse usually developed within one year in patients with persistent serum myeloma peaks. Disease recontrol was achieved in 50% of relapsing patients whose median survival from retreatment was 20 months. Patient follow-up without chemotherapy until relapse was justified mainly for those responding patients with disappearance of myeloma proteins.

Adult↗
PubMed1981

Effects of interferon on the cAMP-adenylate cyclase system of human, mouse, and bovine thyroid tissue.

This report studied the action of interferon on the thyroidal adenylate cyclase-cAMP system. It was found that human interferon did not increase cAMP levels in human or bovine thyroid slices during a 60-min incubation. Mouse interferon also had no effect on cAMP levels in mouse thyroidal lobes over the 60-min incubation, nor did it increase adenylate cyclase activity in mouse homogenates.

Adenylyl Cyclases↗
PubMed1980

Factors related to length of complete remission in adult acute leukemia.

Two hundred and two adult patients with acute leukemia were analyzed to determine pretreatment and treatment factors that could predict for duration of bone marrow remission. Several factors had a significant effect on remission duration, including morphologic diagnosis (AML greater than ALL greater than AUL), initial blast cell count, age, serum LDH, fibrinogen level, labeling index, and in vitro agar colony growth. Patients who attained a remission quickly or in whom leukemic cells in blood and bone marrow were rapidly cleared had long remissions. After applying regression model fitting methods, the six major factors, in order of significance, were the initial serum LDH level, pretreatment fibrinogen level, the number of courses of treatment to obtain a remission, morphologic diagnosis, the halving rate of leukemic cells in the blood, and the age of the patient. The model derived from this study was applied to the 202 patients and suggested that patients likely to have short or long bone marrow remission can be identified.

Adolescent↗
PubMed1976

Late intensification therapy for acute leukemia in remission. Chemotherapy and immunotherapy.

Nineteen patients in continous complete remission of acute leukemia for at least one year received late intensification therapy, after which they received no further chemotherapy, but most received BCG immunotherapy. Five patients have relapsed. The 14 patients still in remission have been followed up for at least 60 weeks after late intensification, with a median time of 98 weeks. The length of complete remission subsequent to a comparable time was 44 weeks for a reference control group and 24 weeks for a matched control group. These results support this type of approach for long-term control of acute leukemia in adults.

Acute Disease↗
PubMed1976

Hydroxyldaunomycin (Adriamycin) combination chemotherapy in malignant lymphoma.

Combination chemotherapy with CHOP (cyclophosphamide, Adriamycin, vincristine, and prednisone) and HOP (Adrimycin, vincristine, and prednisone, was used as treatment for patients with pathologically staged, advanced non-Hodgkin's lymphoma. Among 204 evaluable patients treated on CHOP there were 71% complete remissions with 92% overall responses. Among the 216 evaluable patients on HOP there were 61% complete remissions and 88% responses. Complete remission rates among patients with histiocytic lymphoma were comparable to those of patients with lymphocytic disease. Patients with nodular lymphoma had higher rates of complete remission than their counterparts with diffuse lymphoma. This was noted with both CHOP (78% vs. 67%) and HOP (67% vs. 60%) induction therapy. Rapid responses were common, as more than 14% of complete remissions and 66% of overall responses were achieved with the first course of treatment. Patients in complete remission have been maintained with either cyclophosphamide, vincristine, and prednisone (COP) or arabinosyl cytosine, vincristine, and prednisone (OAP). After 1 year, 86% of patients on COP and 80% on OAP are projected to be free of disease.

Cyclophosphamide↗