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)

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.
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PMID:Current status of interferons in the treatment of cancer. 128 Jan 53

In the past decade, interferon, the first of a new class of biologic response modifiers, has undergone extensive Phase I and II clinical evaluation in a broad spectrum of cancers, including hematologic malignancies, lymphomas, and solid tumors. Interferon has been found to have important clinical activity in hairy-cell leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T cell lymphoma, chronic myelogenous leukemia, previously untreated multiple myeloma, acquired immunodeficiency syndrome-related Kaposi's sarcoma, malignant carcinoid tumors, intravesically treated superficial bladder cancer, intraperitoneally treated ovarian carcinoma, renal cell carcinoma, and malignant melanoma. Recombinant DNA technology has produced molecules such as the interferons, which are antigenic and can induce antibody formation as part of a generalized immune response. The frequency of antibody occurrence, the magnitude of the antibody response, and the type of antibody induced by the interferons is thought to be related to several factors. These include the specific type of neoplasm for which interferon was administered; the specie of interferon administered; the dose, route, schedule, and duration of interferon administered; and the assay method and sampling time used to determine the antibody titer. Opinions and clinical observations about how these antibodies affect the clinical course of a disease vary among investigators. Some studies have demonstrated that antibody formation is associated with an abrogation of the clinical response, while others have not found any effects on the clinical course of a disease due to antibody presence.
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PMID:Biotherapy with interferon--1988. 246 49

The interferons are the first of a new class of biologic response modifiers that include, among others, the interleukins, colony-stimulating factors, erythropoietin, additional growth factors, and monoclonal antibodies. Interferons have exhibited important clinical activity in hematologic malignancies, lymphomas, and solid tumors. Specific diseases responding to interferons include hairy-cell leukemia (HCL), chronic myelogenous leukemia (CML), low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, multiple myeloma, superficial bladder carcinoma, malignant carcinoid, acquired immunodeficiency syndrome (AIDS)-related Kaposi's sarcoma, ovarian carcinoma, renal cell carcinoma, and malignant melanoma. The potentially antigenic nature of the recombinant interferons can result in the formation of antibodies. These antibodies have been associated with the abrogation of some of the clinical responsiveness of some patients treated with interferons. It is hoped that the controversy existing over the role of antibody formation in treatment efficacy can be resolved by prospective trials using standardized methodology in such areas as assay type, sampling time, route of drug administration, treatment schedule, cumulative dose, and duration of treatment.
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PMID:Biotherapy in clinical practice. 247 4

Many cancers have been cured by chemotherapeutic agents. However, other cancers are intrinsically drug resistant, and some acquire resistance following chemotherapy. Cloning of the cDNA for the human MDR1 gene (also known as PGY1), which encodes the multidrug efflux protein P-glycoprotein, has made it possible to measure levels of MDR1 RNA in human cancers. We report the levels of MDR1 RNA in greater than 400 human cancers. MDR1 RNA levels were usually elevated in untreated, intrinsically drug-resistant tumors, including those derived from the colon, kidney, adrenal gland, liver, and pancreas, as well as in carcinoid tumors, chronic myelogenous leukemia in blast crisis, and cell lines of non-small cell carcinoma of the lung (NSCLC) with neuroendocrine properties. MDR1 RNA levels were occasionally elevated in other untreated cancers, including neuroblastoma, acute lymphocytic leukemia (ALL) in adults, acute nonlymphocytic leukemia (ANLL) in adults, and indolent non-Hodgkin's lymphoma. MDR1 RNA levels were also increased in some cancers at relapse after chemotherapy, including ALL, ANLL, breast cancer, neuroblastoma, pheochromocytoma, and nodular, poorly differentiated lymphoma. Many types of drug-sensitive and drug-resistant tumors, including NSCLC and melanoma, contained undetectable or low levels of MDR1 RNA. The consistent association of MDR1 expression with several intrinsically resistant cancers and the increased expression of the MDR1 gene in certain cancers with acquired drug resistance indicate that the MDR1 gene contributes to multidrug resistance in many human cancers. Thus, evaluation of MDR1 gene expression may prove to be a valuable tool in the identification of individuals whose cancers are resistant to specific agents. The information may be useful in designing or altering chemotherapeutic protocols in these patients.
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PMID:Expression of a multidrug resistance gene in human cancers. 256 56

Alpha interferons have shown significant antitumor activity against B-cell malignancies (especially hairy cell leukemia), and chronic myelogenous leukemia. They are also useful against malignant carcinoid tumors, renal cell carcinoma, and Kaposi's sarcoma. Alpha interferons are less effective against lung, liver, ovary, breast, and colon carcinoma. Side effects vary in severity according to type of interferon, route of administration, schedule, and dose. In general, tolerance and compliance are excellent with doses of one to nine million units per day.
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PMID:Update on the antitumor activity of alpha interferon. 307 24

Interferon alpha (INF-alpha)--In systemic diseases, most indications for INF-alpha result from its effect on haematological or hepatological manifestations. The spectacular effect of INF-alpha in chronic myeloid leukemia has led to its use for the treatment of hypereosinophilia syndrome and systemic mastocytosis. Over the last 6 years, we have treated 7 patients with the hypereosinophilia syndrome who were resistant to corticotherapy and had markers of myeloproliferation. Although both hydroxyurea and INF-alpha can be effective alone, their combination led to a decrease in the eosinophilia count to 1,000/ml, a decrease which was long-lasting in most cases. INF-alpha is also used in histiocytosis X alone or in combination with retinoids or with etoposide and has been found effective in several observations. In carcinoid syndromes whether treated priorly or not with a 5-fluoro-uracil-streptozoticin combination, INF-alpha leads to an objective response in two-thirds of the patients. Several multicentric protocols are currently assessing the efficacity of INF-alpha in mixed cryoglobulinaemias. In most observations these cryoglobulinaemias are seen in patients with markers of hepatitis C (mainly HCV) and the early results are encouraging. Temporary improvement has been reported in discoid or subacute lupus in 8 out of 10 cases. Haemangiomas of the infant, when life-threatening and corticoresistant, may be a good indication for INF-alpha. Thus 20 newborns or infants (including 4 with Kasabach-Merrit syndrome) have been treated with good results in 18. Interferon gamma (INF-gamma).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Interferons. Interferons alpha and gamma: indications in systemic diseases]. 817 44

Carcinoid tumors are relatively rare neuroendocrine malignancies with an indolent clinical behavior. The majority of cases arise within the gastrointestinal tract, but they may also be encountered in other organs such as the bronchial system. While occurrence of carcinoid tumors has been reported in association with the multiple endocrine neoplasia (MEN) type I syndrome, no clear-cut risk factors have been established for the development of these malignancies. We report the case of a 50-year-old woman who was diagnosed with a pulmonary carcinoid in 2001 after having undergone allogeneic stem cell transplantation for chronic myeloid leukemia (CML) in 1997. This is the first case report of a carcinoid tumor following allogeneic bone marrow transplantation. At the moment, however, an association with CML as well as a causative role of transplantation and intake of immunosuppressants remains speculative. Apart from highlighting the occurrence of a carcinoid in this setting, our case again underscores the importance of nuclear medicine methods, i.e., somatostatin receptor scintigraphy, in staging and follow-up of patients with carcinoid tumors.
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PMID:Occurrence of a pulmonary carcinoid following allogeneic stem cell transplantation for chronic myelogenous leukemia: a case report. 1271 84

Imatinib mesylate (IM), a small molecule that is a selective inhibitor of the ABL, platelet derived growth factor receptor (PDGFR-R) and stem cell ligand receptor (c-kit) tyrosine kinases (TK). IM was also found to inhibit the TK activity of BCR/ABL fusion protein produced in chronic myelogenous leukemia, with marked clinical activity against the disease. Since both PDGF-R and c-kit both having a putative role in tumorigenesis, we investigated the efficacy and safety of the use of IM in patients with endocrine tumors unresponsive to conventional therapies that expressed c-kit and/or PDGF-R (within the framework of a comprehensive phase II multi-center study of IM in patients with solid tumors). IM was initiated at a dose of 400 mg/day, with possible dose escalation within 1 week to 600 mg/day and an option to raise the dose to 800 mg/day in the event of progression and in the absence of safety concerns for a period of up to 12 months. Between September 2002 and July 2003, 15 adult patients with disseminated endocrine tumors were recruited as follows: medullary thyroid carcinoma (MTC, n = 6); adrenocortical carcinoma (ACC, n = 4); malignant pheochromocytoma (pheo, n = 2); carcinoid (non-secreting, n = 2), neuroendocrine tumor (NET, n = 1). No objective responses were observed. MTC--disease progression in 4 patients, and treatment discontinuation in 2 patients due to adverse events; ACC--disease progression in 3 patients, and treatment discontinuation in 1 patient due to severe psychiatric adverse event; Pheo--disease progression in 2 patients; Carcinoid--stable disease in 1 patient (6.5 months), and disease progression in 1 patient; NET--disease progression in 1 patient. IM does not appear to be useful for treatment of malignant endocrine tumors, also causing significant toxicity in this patient population.
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PMID:The role of imatinib mesylate (Glivec) for treatment of patients with malignant endocrine tumors positive for c-kit or PDGF-R. 1672 80

Patients diagnosed with ulcerative colitis (UC) are known to be at an increased risk of colorectal and liver cancers and leukemia. UC is an autoimmune disease, which may present a wider spectrum of cancers. We wanted to examine the risk of cancer in a large population of UC patients in order to reach high statistical power. A UC research database was constructed by identifying UC patients from the Swedish Hospital Discharge Register and cancer patients from the Cancer Registry. Follow-up of 27,606 UC patients hospitalized for the first time during the years 1964-2004 identified 2,058 patients with cancer. Standardized incidence ratios were calculated for cancer in UC patients by comparing to subjects without hospitalization for UC. The novel tumor sites in UC patients included small intestinal (carcinoid), pancreatic, breast and prostate cancers, nonthyroid endocrine gland tumors, non-Hodgkin lymphoma and multiple myeloma. A total of 11 sites showed an increased risk, which remained at 6 sites when tumors diagnosed in the year of UC hospitalization were excluded; even chronic myeloid leukemia was in excess. Cancer risks depended on the age at first hospitalization for UC. The SIRs for colon, rectal, liver and pancreatic cancers declined by age at hospitalization for UC, while for endocrine tumors the older patients were at higher risk. Our large study identified novel subsequent cancers in UC patients. However, some of these, including small intestinal carcinoids, prostate cancers and nonthyroid endocrine tumors, may be in excess because of intensified medical surveillance of the patients.
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PMID:Cancer risks in ulcerative colitis patients. 1856 19