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)

We previously reported isolation of human T-cell leukemia virus II (HTLV-II) from a second patient (N.R.A.) with atypical hairy cell leukemia. Follow-up analysis of the characteristics of the patient's HTLV-II infection over a 2-year period has revealed that the patient had two coexistant lymphoproliferative disorders. Oligoclonally integrated HTLV-II was detected in DNA extracted from the patient's peripheral blood mononuclear cells on separate occasions greater than 1 year apart, similar to integration of HTLV-I seen in adult T cell leukemia/lymphoma. Although integrated provirus was readily detected, no HTLV-II viral RNA expression was seen in fresh peripheral blood lymphoid cells. Although the patient's peripheral blood consistently contained a majority of atypical lymphoid cells with a T cell antigenic phenotype, he ultimately developed extensive pleural, hepatic and soft tissue infiltration with malignant Tac+, tartrate-resistant, acid phosphatase-positive (TRAP+) B cells of clonal origin. To further characterize the role of HTLV-II, the patient's peripheral blood mononuclear cells were fractionated into four enriched subpopulations at autopsy. Oligoclonally integrated HTLV-II was detected in DNA from a T cell-enriched fraction and a CD8+ T cell-enriched fraction, but not in a CD4+ T cell-enriched fraction, a non-T cell fraction, or in B cells obtained from the malignant pleural effusion. We conclude that the patient harbored two distinct lymphoproliferative disorders, a TRAP+, Tac+ B cell malignancy consistent with hairy cell leukemia that did not contain HTLV-II and a Tac-, CD8+ lymphoproliferative syndrome with oligoclonally integrated HTLV-II.
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PMID:Integrated human T-cell leukemia virus II genome in CD8 + T cells from a patient with "atypical" hairy cell leukemia: evidence for distinct T and B cell lymphoproliferative disorders. 282 11

Epipodophyllotoxin VP 16213 (4-demethyl-epipodophyllotoxin-beta-D-ethylidene glucoside), given to 250 patients with various types of malignant disease, induced apparently complete remissions in four out of eight cases of acute monocytoid and acute myelomonocytoid leukaemia but only one complete regression and six incomplete remissions in 21 cases of reticulosarcoma. Incomplete regressions occurred in patients with Hodgkin's disease, lymphosarcoma, melanoma, and carcinoma of the breast, ovary, testis, bladder, kidney, and thyroid. Seemingly complete regressions of malignant pleural effusion occurred when the drug was given systemically. Toxic side effects interfered with treatment in 40 patients but stopped it in only nine. No signs of toxicity were seen in 114 patients and in 85 the side effects were negligible. VP 16213 represents an advance in the treatment of acute monocytoid leukaemia, which has been up till now insensitive to any drug.
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PMID:Epipodophyllotoxin VP 16213 in treatment of acute leukaemias, haematosarcomas, and solid tumours. 457 34

Gene therapy may be an important adjuvant for treating cancer in the pleural space. The initial results of retroviral gene transfer to cancer cells in malignant pleural effusions revealed that transduction was markedly inhibited, and studies to characterize the inhibitory factor(s) were performed. The inhibition was contained within the soluble, rather than cellular, components of the effusions and was demonstrated with amphotropic, gibbon ape leukemia virus, and vesicular stomatitis virus-glycoprotein pseudotyped retroviral vectors. After excluding complement proteins, a series of studies identified chondroitin sulfates (CSs) as the inhibitory substances. First, treatment of the effusions with mammalian hyaluronidase or chondroitinases, but not Streptomyces hyaluronidase, abolished the inhibitory activity. Second, addition of exogenous CS glycosaminoglycans mimicked the inhibition observed with pleural effusions. Third, immunoassays and biochemical analyses of malignant pleural effusion specimens revealed CS in relevant concentrations within pleural fluid. Fourth, proteoglycans/glycosaminoglycans isolated from the effusions inhibited retroviral gene transfer. Analyses of the mechanism of inhibition indicate that the chondroitin sulfates interact with vector in solution rather than at the target cell surface. These results suggest that drainage of the malignant pleural effusion, and perhaps enzymatic pretreatment of the pleural cavity, will be necessary for efficient retroviral vector mediated gene delivery to pleural metastases.
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PMID:Retroviral gene transfer is inhibited by chondroitin sulfate proteoglycans/glycosaminoglycans in malignant pleural effusions. 911 27

Primary effusion lymphoma (PEL; also known as body cavity-based lymphoma) is recognized as a new and unique lymphoma entity occurring predominantly, but not exclusively in human immunodeficiency virus (HIV)-seropositive patients with acquired immunodeficiency syndrome (AIDS). PEL grows exclusively in body cavities as serous lymphomatous effusion without evidence of mass disease or dissemination. Their most unique feature is infection with the newly discovered human herpesvirus-8 (HHV-8; also known as Kaposi's sarcoma-associated herpesvirus), often accompanied by co-infection with Epstein-Barr virus (EBV). A number of continuous lymphoma cell lines have been established from the malignant pleural effusion, ascitic fluid and peripheral blood of patients with AIDS- and non-AIDS-associated PEL. While all cell lines are HHV-8+, about half of them also contain EBV sequences. Stimulation of the cell lines causes switch from latent to lytic HHV-8 infection. The cells are generally negative for T and B cell immunomarkers (except for CD138 suggesting a pre- or terminal plasma cell stage) and positive for some activation and adhesion markers; they are genotypically B cells with their immunoglobulin genes rearranged. Complex, hyperdiploid karyotypes with multiple structural abnormalities are seen in the cell lines examined. No alterations of known proto-oncogenes are detected in PEL, with the exception of BCL-6 mutations occurring in a large percentage of cases. Heterotransplantation of the cell lines into immunodeficient mice leads to the development of lymphomatous effusion and marked angiogenesis. As HHV-8 contains DNA sequences of several protein homologues, the cell lines express various cytokines, cytokine receptors, chemokines, cell cycle and anti-apoptosis modulators which are upregulated upon stimulation. Indeed, some cell lines produce high levels of (human) interleukin-6 and interleukin-10. Taken together, these cell lines represent very important model systems for the elucidation of the pathobiology of PEL; furthermore, the cell lines are extremely useful scientific tools providing a resource to pursue studies of HHV-8-mediated pathogenic mechanisms.
Leukemia 1998 Oct
PMID:Lymphoma cell lines: in vitro models for the study of HHV-8+ primary effusion lymphomas (body cavity-based lymphomas). 976 92

Human herpes virus 8 (HHV-8; or KSHV, Kaposi's sarcoma-associated herpes virus) is a gamma herpes virus with sequence homology to Epstein-Barr virus (EBV). It was first isolated from Kaposi's sarcoma tumor cells and subsequently from tumor cells and peripheral blood mononuclear cells from patients with primary effusion lymphomas (PEL; or body cavity-based lymphomas). PEL has been recognized as an individual nosologic entity based on its distinctive biological-pathological features and its consistent infection with HHV-8 (commonly, but not always co-infected with EBV), occurring predominantly in human immunodeficiency virus (HIV)-infected patients but occasionally also in HIV-negative cases. Whether HHV-8 sequences can be found also in non-hematopoietic tumor cells other than Kaposi's sarcoma and in malignant hematopoietic malignancies other than PEL, has been the focus of the present studies. We examined the presence of HHV-8 sequences by polymerase chain reaction (PCR) using (1) a panel of 133 human cell lines established from a large variety of solid tumors; (2) a spectrum of 114 hematopoietic cell lines derived from the different cell lineages including 50 B cell leukemia/lymphoma-derived cell lines and seven cell lines established from patients with PEL. Besides the seven PEL cell lines, 46 cell lines that were derived from malignant pleural effusion or ascitic fluid material (25 non-hematopoietic and 21 hematopoietic cell lines) were examined. Except for the seven PEL cell lines that were strongly HHV-8+ in the PCR, all solid tumor cell lines and all hematopoietic cell lines scored consistently negative for the presence of HHV-8 sequences. These results confirm the absolute specificity of HHV-8 infection (within the hematopoietic malignancies) for PEL. PEL cell lines represent useful tools for the analysis of the biology of this neoplasm and of the pathogenetic role of the virus in the disease development.
Leukemia 1998 Nov
PMID:HHV-8 infection is specific for cell lines derived from primary effusion (body cavity-based) lymphomas. 982 57

We performed retrospectively study on 136 thoracoscopies done in our clinic in the period January 2000 and December 2004. We reviewed 136 thoracoscopies, 71 patients were male and 65 were female (mean age 58.4 years). Straw colored effusions were present in 78 cases (57%) and hemorrhagic in 58 cases (43%). The surgical procedure consist in diagnostic of thoracoscopy with drainage of pleural effusion, multiply pleural biopsy, pleurodesis and continuous pleural drainage. In our study, the talc powder (5g) was successfully as sclerosing agent. The primary tumor was: lung-63 (46%), breast-26 (19%), mesothelioma-21 (15.5%), stomach-3, ovarian-3, prostate-3, colon-2, lymphoma-1, leukemia-2, plasmocytoma-1 and unknown primary tumor in 11 cases (8%). Adverse effects included-chest pain-35 cases (25%), fever-20 cases (15%), empyema-6 cases (4.5%), prolonged air leak-5 cases (4%), pulmonary infection-2 cases, acute respiratory failure-1 case, malignant invasion of scar-1 patient. For statistical analysis, the success of talc pleurodesis was defined as the absence of pleural fluid on the follow-up chest radiographs. Pleurodesis was successful in 125 cases (92%) of the patients after 1 month-follow-up. Thoracoscopic talc pleurodesis is a safe, economical and effective treatment for malignant pleural effusion.
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PMID:[Thoracoscopic pleurodesis in malignant pleural effusions]. 1661 48

Determination of the cause of malignant pleural effusions is important for treatment and management, especially in cases of unknown primaries. There are limited biomarkers available for prediction of the cause of malignant pleural effusion in clinical practice. Hence, we evaluated pleural levels of five tumor biomarkers (CEA, AFP, CA125, CA153 and CA199) in predicting the cause of malignant pleural effusion in a retrospective study. Kruskal-Wallis or Mann-Whitney U tests were carried out to compare levels of tumor markers in pleural effusion among different forms of neoplasia - lung squamous cell carcinoma, adenocarcinoma, or small cell carcinoma, mesothelioma, breast cancer, lymphoma/leukemia and miscellaneous. Receiver operator characteristic analysis was performed to evaluate sensitivity and specificity of biomarkers. The Kruskal-Wallis test showed significant differences in levels of pleural effusion CEA (P<0.01), AFP (P<0.01), CA153 (P<0.01) and CA199 (P<0.01), but not CA125 (P>0.05), among the seven groups. Receiver operator characteristic analysis showed that, compared with other four tumor markers, CA153 was the best biomarker in diagnosing malignant pleural effusions of lung adenocarcinoma (area under curve (AUC): 0.838 (95%confidence interval: 0.787, 0.888); cut-off value: 10.2U/ ml; sensitivity: 73.2% (64.4-80.8)%, specificity: 85.2% (77.8-90.8)%), lung squamous cell carcinoma (AUC: 0.716 (0.652, 0.780); cut-off value: 14.2U/ml; sensitivity: 57.6% (50.7-64.3)%, specificity: 91.2% (76.3-98.0)%), and small-cell lung cancer (AUC: 0.812 (0.740, 0.884); cut-off value: 9.7U/ml; sensitivity: 61.5% (55.0-67.8)%, specificity: 94.1% (71.2-99.0)%); CEA was the best biomarker in diagnosing MPEs of mesothelioma (AUC: 0.726 (0.593, 0.858); cut-off value: 1.43ng/ml; sensitivity: 83.7% (78.3-88.2)%, specificity: 61.1% (35.8-82.6)%) and lymphoma/leukemia (AUC: 0.923 (0.872, 0.974); cut-off value: 1.71ng/ml; sensitivity: 82.8% (77.4-87.3)%, specificity: 92.3% (63.9-98.7)%). Thus CA153 and CEA appear to be good biomarkers in diagnosing different causes of malignant pleural effusion. Our findings implied that the two tumor markers may improve the diagnosis and treatment for effusions of unknown primaries.
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PMID:CEA, AFP, CA125, CA153 and CA199 in malignant pleural effusions predict the cause. 2452 57