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 aim of study was to evaluate TF activity and TFPI concentration in patients with haematological malignancies and urinary tract tumors. TFPI concentration and activity and TF concentration were measured in 20 patients suffering from acute myeloblastic leukaemia (AML), 21 patients with chronic myelogenous leukaemia (CML), 17 patients with chronic lymphatic leukaemia (CLL), 16 patients with multiple myeloma (MM) and 65 healthy adults. TFPI and TF concentrations were measured also in patients with renal cell carcinoma (n = 12) and bladder cancer (n = 17) and patients with benign prostatic hyperplasia (BPH) (n = 15). Patients with AML, CML, CLL, and cancer revealed elevated TFPI concentrations. Patients with AML, CML, CLL, MM showed decreased TFPI activity. However TFPI concentration correlated inversely with TFPI activity only in the AML group. No significant changes were observed in TF concentrations in all investigated groups.
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PMID:[Tissue factor (TF) and inhibitor (TFPI) concentrations in patients with urinary tract tumors and haematological malignancies]. 1255 38

Allogeneic hematopoietic stem cell transplantation (HSCT) is used for the treatment of selected hematological malignancies. Its curative potential is based on two very different mechanisms, involving the conditioning regimen and the graft-versus-host reactions, respectively. The high-dose chemo-radiotherapy conditioning regimen is aimed at destroying tumor cells, ablating the host immune system (to prevent rejection) and eliminating the host bone marrow (to "make space" for donor stem cells). However, the definitive eradication of tumor cells is also largely mediated by an immune-mediated destruction of malignant cells by donor lymphocytes termed graft-versus-leukemia (GVL) or graft-versus-tumor (GVT) effect. However, because of its toxicity, conventional allogeneic HSCT is restricted to younger (< 55 years) and fitter patients. These observations led several groups to set up new (less toxic) transplant protocols based on a two step approach: first the use of immunosuppressive (but nonmyeloablative) conditioning regimens providing sufficient immunosuppression to achieve engraftment of allogeneic hematopoietic stem cells and, in a second step, destruction of malignant cells by the GVL effect. These transplants are called nonmyeloablative HSCT or reduced-conditioning HSCT or minitransplants. Preliminary results show that minitransplants are feasible with a relatively low transplant-related mortality (TRM) even in patients up to 70 years. In addition, strong anti-tumor responses are observed in several hematological malignancies as well as in some patients with renal cell carcinoma. As the benefits of minitransplants over alternative forms of treatment remain to be demonstrated, this strategy should be restricted to patients included in clinical trials.
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PMID:Minitransplants: allogeneic stem cell transplantation with reduced toxicity. 1272 60

The relative activities of interferon-alpha2b (IFN-alpha2b) and polyethylene glycol(12000)-IFN-alpha2b (PEG-IFN-alpha2b) were assessed in cell culture studies using WM9 melanoma or ACHN renal cell carcinoma cell lines. Interferon-alpha2b and PEG-IFN-alpha2b had identical antiproliferative activities when tested in cell proliferation studies conducted with equivalent antiviral units of each IFN preparation. Neither IFN formulation was effective in inducing apoptosis in WM9 melanoma cells, but both increased slightly the percentage of ACHN cells undergoing apoptosis as assessed by Annexin V staining. Interferon-alpha2b and PEG-IFN-alpha2b both activated signal transducer and activator of transcription complexes, and the duration of complex activation was similar for both IFN formulations. Induction of different IFN-stimulated genes was assessed by Northern blotting and the quantitative real-time reverse transcription-coupled polymerase chain reaction (RT-PCR) in WM9 melanoma, ACHN renal cell carcinoma, U937 lymphoma, and MOLT-4 and Mono Mac 6 leukemia cell lines. Interferon-alpha2b and PEG-IFN-alpha2b had equivalent gene-modulatory activities within each of these tumor cell lines, although cell line-specific induction patterns were observed. When compared with the antiviral 50% inhibitory concentration (IC(50)) values, the dose-dependent gene expression data correlated with cell sensitivity to IFN treatment. Together, the drug comparability and cell sensitivity data suggest a predictive relation between dose, time, antiviral activity, and gene transcription effects. Therefore, although the specific activity of IFN-alpha2b is approximately three times greater than PEG-IFN-alpha2b, the two preparations have identical in vitro biologic activities when applied to cells at equivalent antiviral units.
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PMID:Biologic activity of polyethylene glycol12000-interferon-alpha2b compared with interferon-alpha2b: gene modulatory and antigrowth effects in tumor cells. 1280 74

The measurement of soluble transferrin receptor (sTfR) has been proposed as a novel approach to the diagnosis of iron deficiency, especially in anaemia of chronic diseases (ACD). Our aim was to study the utility of sTfR under 'everyday conditions' as seen in a geriatric hospital in the following groups of patients: First, in a pilot group of 99 multimorbid geriatric patients (85 women, 14 men; 82.00 +/- 6.32 years) admitted for rehabilitation after recent surgical treatment of a bone fracture; second, in 677 geriatric patients (506 women, 171 men; 79.17 +/- 11.47 years) with different diagnoses admitted to a department of internal medicine; third, in some remarkable clinical cases in order to illustrate the diagnostic limits of sTfR. In general, both genders showed a remarkable age-dependent decrease in erythropoiesis. In patients with haemoglobin levels below 12.0 mg/dL, this parameter correlated significantly with sTfR. However, this was seen only in women, not in men. Moreover, an age-dependent increase in sTfR was seen in women, while in men it remained almost constant. Based on these findings, we conclude that there is a different, gender-specific aetiology of iron deficiency in the elderly. About 30% of patients of both genders simultaneously had low haemoglobin levels and low sTfR. This was interpreted as 'adaptation' or 'tolerance' to the iron deficiency. This was illustrated by a clinical case of megaloblastic anaemia: Initially low sTfR rose only during the vitamin B12 substitution and normalized after recovery. We conclude that sTfR provides an insight into the 'dynamics' of iron metabolism: A rise in sTfR indicates an 'acute readiness to refill iron stores', while a low (non-stimulated) sTfR level corresponds to the quite frequent adaptation to iron deficiency and/or inhibition of resorption. Finally, extremely high sTfR levels were observed in some cases of malignancy such as in acute leukaemia and in hypernephroma. Thus, increased sTfR levels can be caused by paraneoplastic effects.
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PMID:Soluble transferrin receptor and iron status in elderly patients. 1283 62

Sixty-two congeners of vinblastine (VLB), primarily with modifications of the piperidine ring in the carbomethoxycleavamine moiety of the binary alkaloid, were synthesized and evaluated for cytotoxicity against murine L1210 leukemia and RCC-2 rat colon cancer cells, and for their ability to inhibit polymerization of microtubular protein at < 10(-6) M, and for induction of spiralization of microtubular protein, and for microtubular disassembly at 10(-4) M concentrations. An ID50 range of >10(7) M concentrations was found for L1210 inhibition by these compounds, with the most active 1000x as potent as vinblastine.
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PMID:Syntheses and biological evaluation of vinblastine congeners. 1294 3

We investigate the feasibility of CD34-selected peripheral blood stem cell (PBSC) transplantation followed by pre-emptive CD8-depleted donor lymphocyte infusions (DLI) after a minimal conditioning regimen. Six patients with advanced hematological malignancies ineligible for a conventional myeloablative transplant (n=5) or metastatic renal cell carcinoma (n=1), and with an HLA-identical (n=4) or alternative (n=2) donor were included. The nonmyeloablative conditioning regimen consisted in 2 Gy TBI alone (n=4), 2 Gy TBI and fludarabine (RCC patient, n=1) or cyclophosphamide and fludarabine (patient who had previously received 12 Gy TBI, n=1). Post transplant immunosuppression was carried out with cyclosporin (CyA) and mycophenolate mofetil (MMF). Initial engraftment was achieved in all patients. One out of six patients (17%) experienced grade > or =2 acute GVHD only after abrupt cyclosporin discontinuation and alpha interferon therapy for life-threatening tumor progression. T-cell chimerism was 23% (19-30) on day 28, 32% (10-35) on day 100, 78% (49-95) on day 180 and 99.5% (99-100) on day 365. Three out of four patients who had measurable disease before the transplant experienced a complete response. We conclude that CD34-selected NMSCT followed by CD8-depleted DLI is feasible and preserves engraftment and apparently also the graft-versus-leukemia (GVL) effect. Further studies are needed to confirm this encouraging preliminary report.
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PMID:Low T-cell chimerism is not followed by graft rejection after nonmyeloablative stem cell transplantation (NMSCT) with CD34-selected PBSC. 1452 Apr 30

Primary manifestation of malignant lymphoma and/or leukaemia rarely occurs in the kidney. It can be the cause of a hitherto unexplained acute renal failure or it is incidentally detected as shown in the three cases under report.1.A 68-year-old man was operated on because of a symptomatic tumour in his right kidney. At nephrectomy, a conventional (clear cell) renal cell carcinoma was found simultaneously with an occult mantle cell lymphoma infiltrating the adjacent renal and extrarenal tissue. Clinical follow-up uncovered nodal and bone marrow involvement, so that a primary renal manifestation of mantle cell lymphoma was apparent.2.A 69-year-old man with suspected vertebral metastasis underwent partial renal resection because of a mass in his left kidney. Histologically and immunohistochemically, the renal infiltration was diagnosed as a precursor B-lymphoblastic lymphoma. After chemotherapy and irradiation, leukaemic blood cell counts with 50% lymphoblasts proved a primary renal manifestation of precursor B-lymphoblastic leukaemia/lymphoma.3.A 13-year-old boy presented clinically with renal failure, enlarged kidneys, and normal urinalysis. Renal biopsy showed a diffuse interstitial infiltration with atypical T-lymphoblasts compressing tubules and surrounding preserved glomeruli. Subsequent clinical bone marrow smears presented 60% T-lymphoblasts, so that the final diagnosis of a primary renal manifestation of acute T-lymphoblastic leukaemia of mature thymic cortex type was made. Immediate chemotherapy resulted in total recovery of renal function and bone marrow findings.
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PMID:[Primary renal manifestation in malignant lymphomas and leukemia]. 1460 52

Pentostatin (2'-deoxycoformycin, dCF) is a purine nucleoside analog and a product of the fermentation of Streptomyces antibioticus. It is a tight-binding inhibitor of adenosine deaminase (ADA), an enzyme essential in the cellular metabolism of purines. Children with congenital absence of ADA suffer from atrophy of lymphoid tissues and severe combined immune deficiency (SCID) syndrome. It was hypothesized that pentostatin would be lymphocytotoxic and this proved to be true; this finding prompted its investigation in lymphoid neoplasms. It was anticipated that pentostatin would be most active in neoplasms with high intracellular concentrations of ADA, e.g. acute lymphocytic leukemia (ALL), particularly of the T-cell variety. Although pentostatin proved to be active in ALL, large doses were required and major toxic effects outweighed therapeutic benefits. By contrast, pentostatin proved to be exceptionally active in hairy cell leukemia (HCL), a B-cell neoplasm with low intracellular concentrations of ADA. Pentostatin has since been shown to possess activity in chronic lymphocytic leukemia, prolymphocytic leukemia, cutaneous T-cell lymphomas, adult T-cell lymphoma-leukemia, and low grade non-Hodgkin's lymphomas. It potentiates the activity of vidarabine against viruses and against the cells of acute myeloid leukemia. Pentostatin is inactive in melanoma and renal carcinoma, but has not been adequately evaluated in other solid tumors. The toxic effects of pentostatin include renal failure, central nervous system (CNS) depression, immunosuppresion, keratoconjunctivitis, and opportunistic infections. In the absence of pre-existing bone marrow compromise, pentostatin produces only mild myelosuppression. Aside from its use as an antineoplastic agent, pentostatin has potential applications as an immunosuppressive drug, as an antiviral agent, as an antimalarial compound, and in the protection of cells of the CNS from damage induced by ischemia and anoxia. Clinical studies with pentostatin are ongoing, and its roles in the management of neoplastic and non-neoplastic diseases have yet to be fully defined.
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PMID:Deoxycoformycin (pentostatin): clinical pharmacology, role in the chemotherapy of cancer, and use in other diseases. 1465 Dec 24

Authors present a case of three asynchronous malignancies in man working life-long in chemical industry. Course of diseases and their treatment are described: B chronic lymphatic leukaemia (B-CLL) (age of 55), conventional clear cell renal carcinoma (CRCC) (age of 61) and adenocarcinoma of prostate (CaP) (age of 72). B-CLL treatment was chlorambucil for 2 years and follow-up subsequently. CRCC treatment was radical transperitoneal nephrectomy. Due to locally advanced CaP bilateral orchiectomy and radical external beam radiotherapy were performed. Patients is alive 30 months without any signs of any malignity. Incidence of multiple malignancies and particularly triplicities are discussed in this article. Authors point out pertinence of radical therapeutic approach also in multiple malignancies and oncological screening not only in patients with heamatological malignancy, but considering it in all tumours.
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PMID:[Asynchronous occurrence of three neoplastic diseases: chronic B-cell lymphatic leukemia, renal carcinoma and prostatic adenocarcinoma]. 1468 58

Intracranial metastases represent 7-17% of all brain tumors. Renal cell carcinoma, thyroid cancer, choriocarcinoma, melanoma, retinoblastoma, lung cancer and breast cancer have a propensity for producing hemorrhagic brain metastases. Leukemias have also been rarely reported to cause hemorrhagic brain metastases. We describe an 18-year-old girl diagnosed as acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases. MRI demonstrated high signal intensity lesions on both T1- and T2-weighted images which were characteristic for extracellular methemoglobin and consistent with hemorrhagic metastases.
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PMID:[Acute lymphoblastic leukemia presenting with multiple hemorrhagic brain metastases (case report)]. 1523 25


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