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)

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

Of 2,143 biopsy proven cancer patients seen at our hospital over a six year period, 4 (0.19%) patients developed active tuberculosis (TB) during anticancer therapy or shortly after its completion. The cancer diagnoses of those patients were non-Hodgkin's lymphoma, breast cancer, chronic myelogenous leukemia, and astrocytoma. Institution of antituberculous therapy was successful in three patients, however, the TB course was rapidly fatal in the fourth patient with non-Hodgkin's lymphoma despite therapy. The association between TB and neoplasia is emphasized. TB complicating malignant disorders represents complex problem regarding its early recognition and its managements.
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PMID:Tuberculosis in patients with malignant disease. 259 98

Circulating immune complexes (CIC) were measured by C1q-solid phase method in ninety-five patients with various hematologic diseases. The results showed significantly higher CIC levels in patients with acute myelocytic leukemia, chronic myelocytic leukemia, aplastic anemia and idiopathic thrombocytopenic purpura (ITP) than CIC levels in normal controls. However, there was no significant difference in such levels in patients with acute lymphocytic leukemia, non-Hodgkin's lymphoma and multiple myeloma when compared to normal controls. In this study, the level of CIC did not relate to prognosis for patients with non-Hodgkin's lymphoma. The findings demonstrated that a high level of CIC in patients with ITP usually responded poorly to steroid treatment. Other immunosuppressive agents were indicated in these cases. Therefore, the CIC level may serve as a therapeutic guide for the treatment of patients with ITP.
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PMID:Circulating immune complexes in patients with hematologic diseases. 260 74

108 patient over 75 years of age, treated in an internal diseases ward during a five-year period, were studied. 62 of them were with benign blood diseases, the women prevailing. The malignant hemopathies were found more frequently in men than in women, the ratio being 2.83:1. 35 of the patients (76%) were with non-Hodgkin's lymphoma and 10.8% of the patients were with Hodgkin's lymphoma. Only single patients suffered from chronic myeloid leukemia, myelofibrosis and blastic leukemia. The survival of the patients with benign hemopathies was shortened considerably because of the polymorbidity in elderly people. The survival of the elderly patients with malignant hemopathies did not differ from that of the patients from the other age groups.
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PMID:[Benign and malignant hemopathies in elderly patients]. 263 81

Bone marrow purging with cyclophosphamide derivatives (Mafosfamide) requires the establishment of a defined experimental procedure for reliable leukemic cell destruction while sparing normal hematopoietic stem cells to ensure engraftment. We previously defined the granulocyte-macrophage colony-forming unit (CFU-GM) LD95 as being the maximum tolerable dose of drug to use. We now report, in 20 patients with acute non-lymphoblastic leukemia (n = 5), acute lymphoblastic leukemia (n = 5), chronic myelogenous leukemia (n = 5), and non-Hodgkin's lymphoma (n = 5), that the nature of the cells treated (i.e., buffy coat cells or mononuclear cells) significantly influences the accuracy of the LD95 determination, whereas other parameters such as hematocrit or nucleated cell concentration do not. We subsequently define the most reliable experimental procedure for in vitro purging with Mafosfamide: incubation of 2 x 10(7) buffy coat cells/ml with a hematocrit of 5%. We show that the wide individual susceptibility to the drug is not related to any incubation procedure. In a series of 163 patients with hematological malignancies, we confirm the large variation of sensitivity to the drug according to patient susceptibility and diagnosis. These data favor the adjustment of the dose of Mafosfamide on an individual basis, prior to bone marrow purging for autologous bone marrow transplantation.
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PMID:Establishment of a reliable experimental procedure for bone marrow purging with mafosfamide (ASTA Z 7557). 265 56

Knowing the good penetration of systemic HDara-C into the CNS, we treated with this approach overt meningeal leukemia, either isolated or with bone marrow (BM) disease, in 31 adults: 18 ALL, 4 ANLL, 1 lymphoid blast crisis of CGL (LBC-CGL), and 8 non-Hodgkin's lymphoma (NHL). Treatment consisted of Ara-C, 3 g/m2 i.v. q 12 h, by 3 h infusion for 8 doses, followed by 4 doses at day 21. Complete remitters received consolidation with four monthly 4-dose courses of HDara-C. Additional multidrug consolidation and direct CNS therapy with intrathecal (i.t.) methotrexate (MTX) or Ara-C +/- cranial RT was administered to the 11 remitters last treated. Twenty of 31 patients (64%) achieved CR: 10/10 with isolated meningeal leukemia and 10/21 with concurrent CNS and BM disease. Of the remaining 11 patients, 8 had cerebrospinal fluid (CSF) clearing with persistent BM disease. In all cases but one CNS symptoms resolved promptly. CR median duration was 6 months (range 2 to 20). The main toxicity was myelosuppression requiring intensive support. There was no neurologic toxicity. These results show that systemic HDara-C is highly effective in acute leukemias and NHL with CNS involvement, and suggest the utility of this regimen for sanctuary chemoprophylaxis in patients at high risk for CNS disease.
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PMID:Central nervous system (CNS) leukemia: the role of high dose cytarabine (HDAra-C). 271 52

A 49-year-old white woman who presented with multiple lytic bone lesions was found to have Gaucher-like storage cells in multiple bone marrow aspirates and a percutaneous bone marrow biopsy several months before the development of overt disseminated lymphoma. Open bone biopsies of three different sites at initial presentation revealed only necrotic debris and a nondiagnostic polymorphic infiltrate. Elevated leukocyte beta-glucocerebrosidase levels ruled out the diagnosis of classic Gaucher's disease. The ultrastructural characteristics of these storage cells were found to be identical to those of pseudo-Gaucher cells found in patients with chronic myelogenous leukemia and distinctly different from those previously reported in other non-Hodgkin's lymphoma or plasma cell dyscrasias. A possible pathogenetic mechanism is suggested.
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PMID:Pseudo-Gaucher cells preceding the appearance of immunoblastic lymphoma. 297 94

Autologous bone marrow reinfusion rapidly repopulates severely damaged bone marrow thus shortening the period of myelosuppression following high-dose chemotherapy programs. This strategy has been successfully employed in several hematologic malignancies such as acute leukemia, Hodgkin's disease, non-Hodgkin's lymphoma, and chronic myelogenous leukemia. More recently a number of clinical trials have investigated the role of high-dose chemotherapy with autologous bone marrow transplant in solid tumors. This strategy, when used in patients with advanced refractory metastatic breast cancer, results in a high objective response rate (30-70%) but most of these remissions are of short duration (3-4 months). When using high-dose single agents complete remissions are rare; with combination chemotherapy they are more frequent (20-50%). The utilization of high-dose chemotherapy with autologous marrow transplant as a consolidation after achieving a partial or complete remission with standard chemotherapy has shown more promising results with complete remissions approaching 70% in some series. The impact of any of these strategies on overall survival of patients with metastatic breast cancer remains to be demonstrated. The optimal patient selection criteria and strategies for additional development of this field are discussed.
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PMID:The role of high-dose chemotherapy with autologous bone marrow transplantation in the treatment of breast cancer. 306 20

A monoclonal antibody (anti-BL4) recognizing a previously characterized Mr 54,000 glycoprotein (gp54) was developed by immunizing BALB/c mice with cells from a precursor B-cell line (Josh-7). In normal individuals, this antigenic molecule was present on tonsillar B-cells (60-80%) and on a fraction of peripheral blood B-cells (5-25%). BL4 (gp54) expression was investigated in 186 patients with a variety of hematological malignancies using indirect immunofluorescence and flow cytometric analysis. Twenty-six of 37 cases of B-cell chronic lymphocytic leukemia (CLL) and 18 of 33 cases of B-cell non-Hodgkin's lymphoma were BL4 positive. Surface expression of BL4 on reactive cases of CLL and non-Hodgkin's lymphoma was brighter than those of B1, B2, and B4, BL4 positive CLL cases expressed a higher proportion of mouse rosette forming cells and Leu-1 positive cells than the BL4 negative subgroup and were not associated with elevated serum immunoglobulin levels. Four of 7 BL4 negative CLL cases were associated with increased serum levels of immunoglobulin M. Lymphoblasts from 14 of 14 cases of non-T acute lymphoblastic leukemia and 3 of 3 pre-B lymphoid blast crisis of chronic myeloid leukemia were BL4 negative. Neoplastic cells from 2 of 3 cases of Waldenstrom's macroglobulinemia and 4 of 7 cases of hairy cell leukemia were BL4 reactive. None of 7 cases of multiple myeloma and plasma cell leukemia were BL4 positive. All 11 T acute lymphoblastic leukemia cases, 6 other T-cell malignancies, 5 cases of Hodgkin's disease, 51 cases of acute nonlymphocytic leukemia, and 9 cases of chronic myeloid leukemia in chronic phase thus far studied were BL4 negative. An in vitro induction experiment using phorbol ester on a case of B-CLL demonstrated disappearance of BL4 accompanied with further B-cell differentiation. Our study further substantiates the previous finding that gp54 is a differentiation antigen restricted to the B-cell lineage and expressed during the intermediate stage of B-cell ontogeny.
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PMID:Cellular distribution of a B-cell specific surface antigen (gp54) detected by a monoclonal antibody (anti-BL4). 309 65

The alpha-interferons have been explored in a wide variety of clinical applications in cancer. Significant activity has been demonstrated in AIDS-related Kaposi's sarcoma, ovarian carcinoma, bladder carcinoma, malignant glioma, non-Hodgkin's lymphoma, chronic granulocytic leukemia, the carcinoid syndrome and hairy cell leukemia. Although these leads are promising, the research has only just begun.
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PMID:Alpha interferon: a look to the future. 329 35


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