Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023473 (chronic myeloid leukemia)
 18,916 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Polyriboinosinic-polyribocytidylic acid (poly I - poly C), an interferon inducer, was administered in multiple doses of 0.3-75 mg/m2 to 26 patients with a variety of solid tumors, 9 with acute leukemia, and 2 with chronic myelogenous leukemia in blast crisis. Forty-four separate drug trials were comprised of various schedules and routes of administration. Toxic reactions included fever (in 66% of the trials), transient elevation of serum glutamic-oxaloacetic transaminase and serum glutamic-pyruvic transaminase (25%), minimal laboratory evidence of coagulation abnormalities (59%), and hypersensitivity (5%). These toxic manifestations did not relate to dose level or magnitude of interferon induction. Poly I - poly C administered iv induced low serum concentrations of interferon in 24/38 trials (63%), but the correlation between drug dose and peak interferon titer was not linear. Poly I - poly C administered iv or im was not effective as an inducer of interferon in the cerebrospinal fluid. Similarly, poly I - poly C administered im or by inhalation did not produce detectable serum levels of interferon. No patients experienced an objective tumor response to the administration of poly I - poly C, and most (76%) had progression of their disease while receiving the drug.
 ...
PMID:A phase I-II trial of multiple-dose polyriboinosic-polyribocytidylic acid in patieonts with leukemia or solid tumors. 97 71

Interferons produced by recombinant DNA technology began phase I trials little more than a decade ago. Today interferon alfa-2 is a mainstay in the treatment of hairy cell leukemia, and has demonstrated benefit in the more common chronic myelogenous leukemia. Interferon alfa-2 also has activity in other hematologic malignancies, including indolent non-Hodgkin's lymphomas, cutaneous T-cell lymphomas, T-cell lymphoma, and multiple myeloma, and in solid tumors such as disseminated melanoma, renal cell carcinoma, Kaposi's sarcoma, endocrine pancreatic tumors, and malignant carcinoid tumors. Interferon alfa, beta, and gamma remain under investigation to define potential roles in ovarian, breast, bladder, and cervical carcinomas and gliomas. The greatest value of the interferons will be in prolonging the disease-free interval when used in combination with other treatment modalities, including surgery, radiation, chemotherapy, and other biologic agents.
 ...
PMID:Current status of interferons in the treatment of cancer. 128 Jan 53

The examination of the presence of Ph chromosome and of the fused gene BCR-ABL in patients with chronic myeloid leukemia (CML) is significant for the precise diagnosis and in some cases for the prognosis of the disease. We examined peripheral blood for the presence of BCR-ABL fused gene by polymerase chain reaction (PCR) in eight patients with CML consecutively cytogenetically studied before and after the bone marrow transplantation and in two patients treated with interferon. Southern blot analysis was performed before BMT in two patients and the molecular rearrangement of Ph chromosome was found. In all cases our results have proved that cytogenetic and recombinant DNA evaluations confirm each other. Due to the high sensitivity of PCR technique the minimal residual leukemia can be detected.
 ...
PMID:[Use of cytogenetic and molecular biology in the detection of chronic myeloid leukemia]. 128 73

The chemistry, biological activity, and pharmacokinetics of gamma-interferon and recombinant interferon gamma are reviewed, and the agent's clinical efficacy, adverse effects, and dosage and administration for the treatment of chronic granulomatous disease (CGD) and other disorders are described. Endogenous gamma-interferon is a 166-amino-acid protein encoded by a single gene on chromosome 12. Recombinant human interferon gamma is purified from Escherichia coli as a monomer containing 139 amino acids. Gamma-interferon has antiviral, immunomodulatory, and antiproliferative activity. Serum concentrations of recombinant interferon gamma increase in proportion to the dose. Clearance after i.m. or s.c. administration fits a two-compartment model. The half-life is 3.5-7.5 hours, and bioavailability is 89%. Evidence that recombinant interferon gamma can enhance phagocytic oxidative metabolism led to its evaluation for use in the treatment of CGD. Clinical studies showed that the agent decreases the frequency of serious infections in patients with CGD. Recombinant interferon gamma has shown only limited success in the treatment of metastatic renal cell carcinoma (RCC), both as a single agent and in combination with recombinant interferon alfa. Similarly, although interferons appear to be able to change cytogenetic abnormalities in some patients with Philadelphia chromosome-positive chronic myelogenous leukemia, therapy with recombinant interferon gamma has led to minimal success. However, the agent has produced some encouraging results in atopic dermatitis. The adverse effects of recombinant interferon gamma in patients with CGD usually consist only of fever, chills, headache, and erythema. The recommended dosage in CGD-afflicted children whose body surface area is greater than 0.5 sq m is 50 micrograms/sq m given by s.c. injection three times a week for life. Recombinant interferon gamma has given new hope to patients with CGD. Although the drug is very expensive, the cost may be offset by fewer hospitalizations to treat infection.
 ...
PMID:Recombinant interferon gamma for treatment of chronic granulomatous disease and other disorders. 134 90

Recent studies have generated data demonstrating significant clinical activity of alpha-interferon therapy in each of six hematological malignancies, chronic myeloid leukaemia, essential thrombocythemia, polycythemia rubra vera, non-Hodgkin's lymphomas, multiple myelomatosis and hairy cell leukaemia.
 ...
PMID:alpha-Interferon in hematological malignancies. 136 59

In four patients with Philadelphia chromosome-positive (Ph1) chronic myelogenous leukemia (CML), bone marrow hypoplasia (three patients) and aplasia (one patient) developed during or after therapy with either alpha-interferon (IFN) or gamma-IFN. The predominant clinical characteristic of this complication was protracted pancytopenia, which required 2 to 5 months recovery time after treatment and did not resolve in one patient. Bone marrow cytogenetic analysis in two of the patients demonstrated 100% Ph1 metaphases despite the profound bone marrow suppression. Overall, this complication was uncommon, occurring in less than 2% of the patients with CML treated with various IFN. The possible underlying causes include previous therapy with alkylating agents, lack of "reservoir" or normal stem cells, or pronounced sensitivity of the malignant cell clone to the suppressive effect of IFN.
 ...
PMID:Bone marrow hypoplasia and aplasia complicating interferon therapy for chronic myelogenous leukemia. 137 Feb 12

Previous in vitro and in vivo studies have shown a synergism between interferon (IFN) and 5-fluorouracil (5-FU) against different tumor cell lines. In the present study we report that the combination of IFN-alpha and 5-FU has a significant effect not only on the inhibition of tumor cell growth but also on the regulation of natural killer cell-mediated cytotoxicity (NK-CMC). The addition of 5-FU to effector cell population neither affects NK cell activity nor activation of NK cells by IFN or by interleukin (IL)-2. However, pretreatment of target cells with 5-FU increased their susceptibility to NK activity and abolished the protective effect induced by IFN against NK-CMC. This dual effect of IFN-alpha and 5-FU was found to be applicable to target cells of different origins including a cervical carcinoma cell line (ME-180), a hairy cell leukemia-like cell line (Eskol), a CML cell line (K-562) and a primary culture of AIDS-related Kaposi's sarcoma cells. Similar results were found with IL-2 treatment of Eskol cells but not other cells. Combination of IL-2 with 5-FU resulted in enhancement of the sensitivity of the cells to NK activity and abolished the protection against NK-CMC. Based on these results we propose that the combination of IFN-alpha and 5-FU not only has a direct growth inhibitory effect on tumor cells but also has a regulatory role on the immunological arm of the NK-CMC. Moreover, since the combination gave the same pattern of response in different tumor cells, both NK-sensitive and NK-resistant, this combination treatment may be a candidate for clinical trials in various types of tumors.
 ...
PMID:A dual anti-tumor effect of a combination of interferon-alpha or interleukin-2 and 5-fluorouracil on natural killer (NK) cell-mediated cytotoxicity. 137 Feb 57

Granulocyte colony-stimulating factor (G-CSF) is known to act on the neutrophilic granulocytes from chronic myelogenous leukemia (CML) patients to induce neutrophil alkaline phosphatase (NAP) activity. Gamma-interferon (IFN-gamma) and granulocyte-macrophage colony-stimulating factor (GM-CSF) have been reported to suppress NAP induction with G-CSF. We confirmed that this inhibitory effect of GM-CSF is accompanied by the decrease of the NAP mRNA level. Moreover, we found that the simultaneous addition of retinoic acid completely neutralized this inhibitory effect of GM-CSF. Recovery of the NAP activity brought about by the retinoic acid was also accompanied by the increase of NAP mRNA level. These results indicate that retinoic acid neutralizes the inhibitory effect of GM-CSF on the induction of NAP activity through the change of the NAP mRNA level.
 ...
PMID:Retinoic acid acts to neutralize the inhibitory effect of granulocyte-macrophage colony-stimulating factor (GM-CSF) on alkaline phosphatase activity of neutrophils that is induced by granulocyte colony-stimulating factor (G-CSF). 137 89

We investigated the marrows of 19 patients with advanced Philadelphia chromosome positive (Ph+) chronic myeloid leukemia (CML) in long-term marrow culture (LTMC) to determine the frequency of loss of clonogenic leukemic cells in vitro. Sixteen patients were in first chronic phase at a median of 24 months from diagnosis and had received prior therapy with busulphan and/or hydroxyurea. The effect of interferon therapy on loss of Ph+ clonogenic cells in LTMC was also investigated. Of 16 patients who had not previously received interferon, complete loss of Ph+ progenitors was documented by 4-5 weeks in the LTMCs from two (12.5%). Ph+ progenitors persisted at 4-5 weeks in the LTMC derived from 12 patients. Marrows from nine patients treated with interferon were also established in LTMC. Cultures from four patients did not yield colonies with detectable metaphases at 3-5 weeks, while Ph+ clones were present in the cultures initiated with marrows from five patients. Mean hematopoietic colony yields from the adherent layer at 2-4 weeks, and from the supernatant layer at 1-3 weeks, of cultures derived from interferon-treated patients were significantly lower than in LTMCs of patients not treated with interferon (p less than 0.05). The results indicate that in previously treated patients with late chronic phase CML there is a low frequency of conversion of Ph-negative hematopoiesis in long-term culture. Interferon therapy is associated with impaired progenitor yields in LTMC and does not improve selective loss of Ph+ progenitors.
 ...
PMID:Maintenance of Philadelphia-chromosome-positive progenitors in long-term marrow cultures from patients with advanced chronic myeloid leukemia. 137 77

Activity of the interferon-induced enzyme 2'-5' oligoadenylate synthetase (2-5 OAS) was measured in peripheral blood mononuclear cells (PBMCs) and serum of patients with chronic phase Ph'-positive chronic myelogenous leukemia (CML) treated with interferon-alpha (IFN-alpha) (4 x 10(6) IU/m2) alone or in combination with 50 micrograms IFN-gamma. At the beginning of IFN therapy, marked elevation of 2-5 OAS titers was detected in PBMCs (pretreatment 0.03-1.62, median 0.2; during treatment 0.8-13.14, median 4.31; 22 patients studied) and in serum (pretreatment 21-156 pmol/dl, median 62; during treatment 532-1740 pmol/dl, median 800; eight patients studied). However, 2-5 OAS titers were not related to clinical outcome or IFN therapy and also during IFN resistance elevated 2-5 OAS activity in PBMCs (median 3.45; range 1.05-13.14; 11 patients studied) were detected. These data argue against direct involvement of the 2-5 OAS system in the therapeutic effect of IFN in CML. However, 2-5 OAS titers in PBMCs or serum appear to be a reliable control of biologically active IFN therapy.
 ...
PMID:Induction of 2'-5' oligoadenylate synthetase during interferon treatment of chronic myelogenous leukemia. 138 Nov 90


1 2 3 4 5 6 7 8 9 10 Next >>