Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0023418 (leukemia)
 93,477 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The in vitro production of beta 2-microglobulin (beta 2m) by leukaemic cells was studied in 22 patients with chronic B-lymphocytic leukaemia (CLL). In addition, the concentration of beta 2m in serum (S-beta 2m) was determined and expressed as percent of the upper normal limit, after a correction for elevated S-Creatinine values. Patients with progressive disease usually had CLL cells with a high rate of in vitro synthesis and an increased S-beta 2m. This was not found in patients with non-progressive disease. The in vitro synthesis of beta 2m X the lymphocyte count correlated with S-beta 2m in the total material (r = 0.65). The increased S-beta 2m frequently observed in CLL may therefore originate from the tumour cells. Hence, S-beta 2m is promising as a clinically useful tumour cell-associated marker in CLL.
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PMID:Production of beta 2-microglobulin by chronic lymphocytic leukaemia cells in vitro. 352 29

Gallium nitrate is the anhydrate salt of the naturally occurring heavy metal. It has demonstrated antitumor activity in a variety of murine tumor models, including Walker carcinosarcoma 256, fibrosarcoma M-89, leukemia K-1964, adenocarcinoma 755, mammary carcinoma YMC, reticulum cell sarcoma A-RCS, lymphoma P1798, and osteosarcoma 124F. Preclinical studies performed in rats, rabbits, dogs, and monkeys showed the dose-limiting toxicity to be renal. The hepatic, pulmonary, gastrointestinal, hematologic, and integumentary systems were also involved. The major route of elimination is the kidneys, with 35%-71% of the infused dose excreted within 24 hours. Three phase I studies suggested the following phase II doses: 700-750 mg/m2 by short infusion, once every 2-3 weeks; 300 mg/m2/day by short infusion for 3 consecutive days, to be repeated every 2 weeks; and 300 mg/m2/day by continuous infusion for 7 consecutive days, to be repeated every 3-5 weeks. The major organ toxicity reported was renal; however, this can be adequately controlled either by hydration and osmotic diuresis or by use of continuous schedule. (Either maneuver appears to allow delivery of the recommended phase II dose with a less than 30% risk of change in serum creatinine.) In limited phase II evaluation, the drug has shown antitumor activity in patients with either refractory lymphomas or small cell lung carcinoma, with total objective response rates of 28% and 11%, respectively. In addition, it has been effective in the treatment of patients with cancer-related hypercalcemia by having an inhibitory effect on calcium reabsorption from bone. Single-agent phase II studies are planned in all major tumor types. Some are already ongoing in patients with genitourinary malignancies (renal, bladder, prostate, testicular), small cell lung carcinoma, and multiple myeloma. Metabolic studies are in progress at Memorial Sloan-Kettering Cancer Center to further elucidate the mechanism or mechanisms of the hypocalcemic effects.
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PMID:Gallium nitrate: the second metal with clinical activity. 353 51

The antitumor activity of RA-700, a cyclic hexapeptide isolated from Rubia Cordifolia, was evaluated in comparison with deoxy-bouvardin and vincristine (VCR). As regards the proliferation of L1210 cultured cells, the cytotoxicity of RA-700 was similar to that of VCR but superior to that of deoxy-bouvardin. The IC50 value of RA-700 was 0.05 mcg/ml under our experimental conditions. RA-700 inhibited the incorporation of 14C-leucine at a concentration at which no effects were observed on the incorporation of 3H-thymidine and 3H-uridine in L1210 culture cells in vitro. The antitumor activity of RA-700 was similar to that of deoxy-bouvardin and VCR against P388 leukemia. Daily treatment with RA-700 at an optimal dose resulted in 118% ILS. As with deoxy-bouvardin and VCR, the therapeutic efficacy of RA-700 depends on the time schedule. RA-700 showed marginal activity against L1210 leukemia (50% ILS), similar to that of deoxy-bouvardin but inferior to that of VCR. RA-700 inhibited Lewis tumor growth in the early stage after tumor implantation, whereas deoxy-bouvardin and VCR did not. As regards toxicity, a slight reduction of peripheral WBC counts was observed with the drug, but no reduction of RBC and platelet counts. BUN, creatinine, GPT and GOT levels in plasma did not change with the administration of the drug.
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PMID:Antitumor activity and toxicity in mice of RA-700, a cyclic hexapeptide. 363 86

Since July 1979 all patients transplanted in Basle have been treated with Cyclosporin-A (CyA) as prophylaxis against Graft-versus-Host-Disease (GvHD). Currently CyA is given as a continuous infusion for 3-4 weeks, followed by an oral once-daily-therapy for one year. The daily dose is adjusted depending on the serum creatinine. Patients with acute GvHD during CyA therapy are treated with high dose bolus-steroid therapy. 83 patients with leukemia were treated in these 5 years. All were conditioned with 2 X 60 mg/kg Cyclophosphamide and 10 Gy total body irradiation. 78 had an HLA-identical, 5 an HLA-haploidentical family donor. The median age is 28 years (5-42 y). 20 patients had AML in 1. CR, 9 patients AML not in 1. CR (2nd, 3rd CR or relapse), 11 ALL in 1. CR, 19 not in 1. CR, 20 CML in chronic and 4 CML in accelerated phase. 40 patients are actually alive, well and without any signs of their disease; 9 are living in relapse. Major cause of death is relapse and GvHD. CyA does not reduce the incidence, it does reduce the severity of GvHD. The only long-term side-effects of bone marrow transplantation seen are cataracts and sterility. The major factors influencing outcome is the time of transplant. 31/51 patients transplanted in 1. CR or in chronic phase of CML are alive compared to only 9/32 transplanted in later stages. We conclude that bone marrow transplantation should be performed early in the disease and that CyA eases the procedure.
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PMID:Cyclosporin-A in allogeneic bone marrow transplantation for leukemia: Basle experience 1979 to 1984. 391 37

The records of 59 immunocompromised patients with fever and pulmonary infiltrates who underwent open lung biopsy, were reviewed. A specific diagnosis was made by lung biopsy in 49 (83%) patients, and in 32 instances (54%) the diagnosis was a treatable infection. Only two (3.4%) false-negative biopsies occurred. Transplant recipients were more likely to have a specific, treatable pneumonia (74%) than patients with a reticuloendothelial malignancy (42%, P less than 0.05). This was due to a greater frequency of bacterial pneumonias, primarily due to Legionella, in transplant recipients (P less than 0.01). However, obtaining a specific diagnosis by lung biopsy did not appear to improve outcome. Seventeen of 32 (53%) patients with treatable infections survived, compared to 8 of 16 (50%) with specific, but untreatable, diagnosis and 6 of 11 (55%) with nondiagnostic biopsies. Advanced age and a low platelet count were predictive of death in both transplant recipients and patients with leukemia and lymphoma (P less than 0.05); a high serum creatinine was an additional predictor in renal transplant recipients.
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PMID:Diagnosis of pneumonitis in immunocompromised patients by open lung biopsy. 634 79

23 patients undergoing marrow transplantation for leukemia or aplastic anemia were given cyclosporin A (CyA) for graft-versus-host disease (GvHD) prophylaxis. A radioimmunoassay was used to monitor CyA serum levels in 13 patients and whole blood levels in 10. Serum creatinine levels were recorded daily until day 30 and then weekly. The severity of acute GvHD was recorded daily for a total of 1,738 patient days. CyA dose was then correlated with CyA serum or blood levels, serum creatinine levels and severity of acute GvHD. The daily dose of administered CyA correlated with serum CyA levels (p = 0.001) but not with whole-blood CyA levels. The cumulative CyA dose correlated with serum creatinine. There was an inverse correlation between the daily CyA dose and the severity of acute GvHD (p = 0.05). On the other hand the total amount of CyA given within 10 days after bone marrow transplantation had no influence on the severity of acute GvHD developing after day 10. Serum and whole-blood levels did not correlate with severity of GvHD nor with creatinine levels. The results of this study point out the nephrotoxicity of CyA, and a low GvHD score with high doses of administered CyA, at least on a daily basis. Serum but not blood levels reflect the dose of CyA given, but are not correlated with nephrotoxicity or GvHD.
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PMID:Cyclosporin A serum and blood levels in marrow graft recipients: correlation with administered dose, serum creatinine and graft-versus-host disease. 643 79

The antitumor activity of a new highly water-soluble platinum derivative, (1,2-diaminocyclohexane)(isocitrato)platinum(II) (NSC 350602; PHIC), was studied in L1210 leukemia cells inoculated into mice. PHIC was found to be active for i.p. graft-i.p. treatment, i.p. graft-i.v. treatment, and i.v. graft-p.o. treatment. A significant activity was observed on early and advanced L1210 leukemia even when the treatment was delayed 6 days after the graft. A comparison between the activities of PHIC, cisplatin (NSC 119875), and (4-carboxyphthalato)(1,2-diaminocyclohexane)-platinum(II) (NSC 271674; DACCP) for i.p. graft-i.p. treatment indicated that the highest activity was observed for divided doses rather than single dose in the case of PHIC and DACCP and not for cisplatin. Under these conditions, PHIC gave larger treated versus control survival time values or a greater number of surviving animals than did cisplatin and DACCP. No cross-resistance between PHIC and cisplatin could be detected in L1210 leukemia cells resistant to cisplatin. Mutagenicity studies on Salmonella typhimurium revealed that PHIC is far less mutagenic than cisplatin on TA100 and TA98 strains. Other pharmacological parameters, such as growth inhibition rate of cultured L1210 cells, penetration, and DNA binding in L1210 cells inoculated in mice, were compared for PHIC and cisplatin together with their in vitro rates of hydrolysis and platinum:DNA adducts. No nephrotoxicity was detected with PHIC at the maximum nonlethal dose level in mice in contrast to results with cisplatin. A preclinical study was conducted in baboons at 100, 150, and 200 mg/kg. No nephrotoxicity could be detected at a dose of 100 mg/kg without prehydration for six courses at 3-week intervals. At 200 mg/kg, an increase of blood creatinine was controlled by prehydration. Gastrointestinal toxicity was mild during the three regimens. Phase I clinical trials are under way.
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PMID:Pharmacological and preclinical toxicological studies of 1,2-diaminocyclohexane(isocitrato)platinum(II). 654 Jan 42

Using a single dose, [15N]glycine turnover technique, whole body rates of proteins synthesis and breakdown were assessed in six healthy children and in eight children with newly diagnosed leukemia (DeWys, W. D. Cancer Res., 42: 721s-726s, 1982) or lymphoma (Baracos, V., Rodemann, H. P., Dinarello, C. A., and Goldberg, A. L. N. Engl. J. Med., 308: 553-558, 1983). Based on excretion of 15N as urinary ammonia, synthesis (g protein per kg body weight per day) was significantly (p less than 0.025) higher in the cancer patients [5.4 +/- 1.5 (S.D.)] compared to the controls (3.6 +/- 0.9); breakdown was also higher (p less than 0.02) in the patients (5.5 +/- 1.8) compared to the controls (3.1 +/- 1.1). When only the seven patients with leukemia were considered, there also were significant increases in synthesis (5.4 +/- 1.6, p less than 0.05) and breakdown (5.4 +/- 1.9, p less than 0.025) compared to controls. Increases in both synthesis and breakdown were also observed in the patients when the protein turnover data were expressed as a function of the rate of creatinine excretion or the calculated lean body mass. We conclude that whole body protein turnover is increased in sick children at the time of diagnosis with some forms of newly diagnosed cancer.
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PMID:Increased whole-body protein turnover in sick children with newly diagnosed leukemia or lymphoma. 657 52

Pretreatment of Swiss mice and Sprague-Dawley rats with glutathione (GSH) reduced the acute lethal toxicity of cis-dichlorodiammine platinum (II) (cis-DDP) in a dose-dependent manner. The protection was accompanied by reduction of both body weight loss and by reduction of nephrotoxicity, as measured by a rise in serum blood urea nitrogen (BUN), creatinine levels and by histopathologic changes, which occurred 4 days following cis-DDP treatment. The antitumor effects of cis-DDP on experimental tumor models (P388 and Gross leukemia) were not significantly altered by GSH treatment. It is suggested that the partial protection by GSH from acute toxicity of the antitumor drug is directly related to protection of renal function.
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PMID:Protective effect of reduced glutathione against cis-dichlorodiammine platinum (II)-induced nephrotoxicity and lethal toxicity. 668 12

A murine monoclonal antibody directed against a normal T-cell differentiation antigen was given to a patient with adult T-cell leukemia. Immunofluorescence staining showed increased amounts of this antigen on the patient's leukemia cells. Using a competition radioimmunoassay, free antigen was not detectable in the serum prior to therapy. Two courses of in vivo therapy were given using a 1-mg dose. Each produced a prompt and dramatic fall in WBC with return to pretreatment levels over the ensuing 24 hr, a pattern similar to that seen with leukopheresis. After the first dose of antibody, circulating free antigen became detectable in the serum and a transient decline in creatinine clearance was noted. A 5-mg dose of antibody given at that time was ineffective, presumably because it was blocked by free antigen. Antigenic modulation by leukemia cells was found transiently following each course of antibody. A weak and clinically insignificant host antimouse antibody response was found 5 days after the first treatment. The patient tolerated antibody therapy without difficulty. Monoclonal antibodies offer promise as an immunotherapeutic approach to cancer but problems encountered here must be addressed.
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PMID:In vivo effects of murine hybridoma monoclonal antibody in a patient with T-cell leukemia. 678 95


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