Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The influence of interferon-alpha 2 (IFN-alpha 2) on the mRNA levels of cellular proto-oncogenes was studied in malignant cells from patients with chronic lymphocytic leukemia (CLL). These cells can be induced to blast transform, differentiate and, in some cases, proliferate upon exposure to IFN. Treatment with IFN-alpha enhanced the levels of c-myc mRNA in malignant cells from the patients, whereas the levels of c-myb mRNA decreased, as measured by slot blot hybridizations. In cells from some patients, an enhanced expression of c-fos and k-ras was observed following exposure to IFN-alpha. No major effect on the expression of c-raf or of enolase was observed in any of the patients following exposure to IFN-alpha, whereas the levels of beta 2-microglobulin mRNA increased. In contrast to the observed effects on oncogene expression in CLL cells, IFN had no major effect on the expression of any of the tested oncogenes in lymphocytes from healthy donors or in B-cells from three neoplastic cell lines (380, FL18, RS). We conclude that IFN-alpha can enhance or repress the expression of several oncogenes in nondividing primary malignant cells from patients with leukemia. We also show that the response of malignant cells from patients to IFN-alpha is different than that seen with neoplastic cell lines which represent a similar stage of B-cell differentiation.
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PMID:Influence of interferon-alpha on the expression of cellular oncogenes in primary chronic lymphocytic leukemia cells. 306 Jul 97

Mice inoculated IP with L1210 murine leukemia vaccine and subsequently with pyran copolymer-induced macrophages (pyran-M phi) lived for a prolonged time after live L1210 inoculation IP. Pyran-M phi as tentatively identified by anti-AcM.1 monoclonal antibody expressed I-Ad antigen in tumor vaccine-primed recipient mice and contributed to maintaining I-Ad antigen positive (I-Ad+) macrophages at high cell density in the peritoneal cavity of recipient mice. The relevance of these I-Ad+ cells to the host antitumor response was examined by experiments in which I-Ad+ cell density in the peritoneal cavity and host antitumor response behaved in a parallel fashion. Human interferon-alpha A/D, an agent selectively inhibiting Ia antigen expression, and silica, a general antimacrophage agent, strongly suppressed I-Ad antigen expression of peritoneal macrophages of tumor vaccine-primed and pyran-M phi-inoculated mice and, consistently with this, the antitumor response was nullified in these mice. Tumor vaccine-primed mice inoculated with sodium caseinate or thioglycollate-induced peritoneal cells did not survive L1210 inoculation and, in these mice, I-Ad+ peritoneal macrophages were suppressed in number as compared with those of tumor vaccine-primed and pyran-M phi-inoculated mice. These results warrant further study on the contribution of I-Ad+ macrophages to pyran copolymer-induced augmentation of the antitumor response in tumor vaccine-primed mice.
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PMID:I-Ad antigen expression of pyran copolymer-induced peritoneal cells in tumor vaccine-primed mice and its association with the host antitumor response. 310 63

Twelve children ages 3-15 years with relapsed acute lymphocyte leukemia (ALL) were treated over 25 days by intravenous or intramuscular administration of interferon-alpha n1 (IFN-alpha n1). Single doses ranged from 2.5 to 15 MU/m2, total doses from 60 to 200 MU/m2. Serum pharmacokinetics were determined following administration of two different doses. Calculation of area under serum concentration curve (AUC) values showed increased AUC with increased dose. Mean AUC (h x U/ml) ranged from 735 to 3986 at doses of 2.5 and 15 MU/m2, respectively, when given intramuscularly. AUC for i.v. and i.m. administration were similar. Side effects reported most commonly were fever and chills in 11 of 12 patients, nausea/vomiting in 7, mild lethargy in 3, and injection site pain in 4 of 9 treated i.m. Reversible hepatotoxicity occurred in the 3 patients receiving the highest doses, 10 then 15 MU/m2. Three patients had clinically significant bleeding associated with mildly increased coagulation studies and an additional three patients had increased coagulation parameters without bleeding. Four patients were considered to have stable disease; one treated at the highest dose level had clearance of peripheral blasts but remained in bone marrow relapse. IFN-alpha n1 as used in this study produced detectable blood levels with associated side effects. A Phase II intramuscular trial is recommended.
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PMID:Interferon-alpha n1 in children with recurrent acute lymphocytic leukemia: a phase I study of pharmacokinetics and tolerance. 316 26

Serial in vitro immune function studies of peripheral blood mononuclear cells (PBMC) were carried out during the long-term treatment with recombinant interferon-alpha 2 (IFN-alpha 2) in a patient with hairy-cell leukemia (HCL). Parameters of B- and T-cell functions as well as NK-cell activity were determined. Treatment with IFN-alpha 2 is associated with temporary and long-term depression of some immune functions, but can also normalize immune responses: in vitro-induced immunoglobulin synthesis, which was normal at diagnosis, was inhibited during the first weeks of IFN therapy but subsequently rose to normal levels. Lymphocyte proliferative responses to mitogens and antigens that were markedly reduced pretherapeutically were further depressed by IFN treatment but, with the exception of pokeweed mitogen (PWM)-induced responses, normalized completely by the 15th to 17th week of treatment. Cocultivation of PBMC with monocytes from normal individuals enhanced depressed lymphocyte proliferative responses. NK-cell activity, which was low at diagnosis, did not rise to the normal range during IFN treatment, but rapidly normalized when IFN therapy was stopped. A discussion is presented on the implications of the alteration of immune functions by treatment with IFN.
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PMID:Modulation of immune functions by long-term treatment with recombinant interferon-alpha 2 in a patient with hairy-cell leukemia. 325 51

Twelve patients with documented, progressive hairy-cell leukaemia were treated with human lymphoblastoid interferon-alpha. All patients initially received a three-month course of interferon-alpha (3 x 10(6) U each day) which resulted in two complete remissions and 10 partial remissions. All eight patients who were dependent upon packed red-cell transfusions became independent of them and the three patients with the most severe, pretreatment pancytopenia also became independent of platelet transfusions. The histological appearance of the bone marrow improved in all patients; in three patients, a complete resolution of the leukaemic infiltrate was recorded. Adverse reactions occurred in 10 patients, but these were mild and did not interrupt treatment in seven patients. Moderate reactions that required a temporary reduction in the dose of interferon-alpha were seen in three patients. Ten patients subsequently received maintenance therapy with interferon-alpha (3 x 10(6) U, three times a week). A haematological improvement continued to be seen in all patients, and the results, with a minimum of one year of follow-up, are presented.
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PMID:Clinical response of hairy-cell leukaemia to interferon-alpha: results of an Australian study. 341 74

Twelve evaluable patients with progressive hairy cell leukemia were treated with deoxycoformycin at a dose of 4 mg/m2 every 2 weeks. Five patients had not been splenectomized, and one had failed to respond to interferon-alpha. Complete remission, as defined by absence of hairy cells in the bone marrow and normalization of the peripheral blood and regression of splenomegaly, was obtained in 11 of 12 patients (92%). These patients have remained in unmaintained remission for 1+ to 13 months with an average of 7.5 months. Two of these patients had a bone marrow relapse at 8 and 12 months, respectively. During treatment the monocytopenia corrected, and, after complete remission was obtained, marrow was aspirable. Toxicity was mild and reversible. There were no significant infections associated with this treatment. It was of interest that we could treat two patients with creatinine clearance of 50 and 60 ml/min using lower doses (and 2-3 mg/m2) than our conventional therapy of 4 mg/m2 every 2 weeks. They obtained a complete remission after 6 and 10 treatments, respectively. Low-dose deoxycoformycin has proven to be an excellent treatment for hairy cell leukemia.
Leukemia 1987 Apr
PMID:Treatment of hairy cell leukemia: the Ohio State University experience with deoxycoformycin. 349 42

Recent developments in biotechnology have resulted in a substantial renewal of cancer immunotherapy. In particular, the availability of murine monoclonal antibodies and recombinant biological response modifiers by genetic manipulation has made it possible to re-test abandoned concepts of adoptive humoral and cellular immunotherapy and to reconsider the biomodulation of the patient's immune system. Thus, the utilization of monoclonal antibodies to purge ex vivo autologous marrow from residual tumor cells has reached an advanced stage of clinical investigation in the field of autologous bone marrow transplantation for leukemia or lymphoma. Numerous promising clinical trials are being performed by the injection of monoclonal antibodies directed at tumor-associated antigens, coupled with cytotoxic agents (isotopes, drugs, toxins). In the area of recombinant technology, interferon-alpha has become the drug of choice for a particular form of chronic leukemia (hairy-cell leukemia). Interleukin-2 administered in conjunction with autologous activated lymphocytes has been shown to mediate significant anti-tumor activity in metastatic cancer patients. This review briefly describes recent clinical results obtained in cancer immunotherapy and discusses the potential of these new approaches.
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PMID:[Current possibilities in immunotherapy of cancer]. 355 Oct 61

Spontaneous mutants with altered HLA-A,B,C response to interferon-alpha (IFN-alpha) were isolated from the human thymus leukemia cell line Molt 4. Using fluorescein isothiocyanate (FITC)-conjugated W6/32 (a monoclonal antibody to HLA-A,B,C) and the fluorescence-activated cell sorter, the cells with highest and lowest fluorescence after 24-48 h of IFN-alpha treatment were selected and expanded. After several cycles of selection, mutant clones with low (greater than 10% of wild-type) and high (three times better) response were obtained. A similar protocol was employed to derive high responder mutants with the monoclonal antibody YT76, which recognises a subset of HLA strongly induced by IFN-alpha. Stable clones were derived for which YT-HLA induction was 7-fold that of Molt 4 cells and for which HLA induction occurred at 100-fold lower concentrations of IFN-alpha. The high response phenotype of the mutants was not accompanied by a significant increase in the constitutive level of expression of HLA-A,B,C (in the absence of IFN). The increase in the level of HLA-A,B,C expression after IFN-alpha treatment is mostly accounted for by the increase in the expression of a subset of HLA molecules, detected by the monoclonal antibody YT76 including HLA-B molecules.
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PMID:Stimulation of HLA-A,B,C by IFN-alpha. The derivation of Molt 4 variants and the differential expression of HLA-A,B,C subsets. 386 39

Twenty-two patients with advanced haemopoietic and other malignancies were treated intramuscularly with recombinant interferon-alpha 2C in a daily escalating dose. The most common side-effects were flu-like symptoms. Two patients showed severe neurotoxicity, which was completely reversible in 1 case. Doses above 30 X 10(6) IU/day were poorly tolerated and could only be achieved in a minority of the patients. Objective tumour responses were documented in malignant lymphomas, hairy cell leukaemia, and renal cell carcinoma.
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PMID:Phase I study of recombinant human interferon alpha-2C in patients with chemotherapy-refractory malignancies. 408 Feb 99

The efficacy of recombinant interferon-alpha 2 in the treatment of advanced hairy cell leukaemia is investigated in 31 patients. Preliminary results show a complete and partial response rate of 69%. An optimal dose study utilizing maximal stimulation of an interferon-dependent pathway was carried out in 5 patients. The optimal dose of the order of 5 X 10(5) IU/day is effective and without side-effects. Interferon treatment did not enhance natural killer cell activity and therefore a direct mode of action upon tumour cells is proposed.
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PMID:Interferon-alpha-2C in the treatment of advanced hairy cell leukaemia. Results of a phase II trial. 408 Mar


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