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)

Preliminary clinical observations have suggested that low cellular glucocorticoid receptor (GR) levels might have been connected with multidrug resistance in children with acute myeloblastic leukaemia (AML). To test this possibility, we have developed glucocorticoid resistant subclones of two recently established human myeloid leukaemic cell lines. The cause of glucocorticoid resistance was GR negativity in these subclones. GR positive parent cell lines or GR negative subclones were incubated for 1 h in the presence of Adriamycin, Cytosine-arabinosid, Etoposide or Vincristine, respectively. After short-term (1 h) incubation in suspension cultures cells were washed and plated in clonogenic agar cultures. Each anticancer drug was more potent against both GR positive parent cell lines than against the GR negative subclones. The results of this study suggest that the absence of GRs is a useful marker of multidrug resistance in childhood AML.
 ...
PMID:Decreased sensitivity of cytostatic drugs in glucocorticoid receptor-free acute myeloid leukaemia cells. Clinical and experimental observations. 186 89

Fourteen patients (M/F, 6/8; age, 48/23-64 yrs) with relapsing or primary resistant intermediate-high grade non-Hodgkin lymphomas were treated with ARA-C (2 g/m2 x 4 on days 1 and 2), DDP (100 mg/m2 96 hr infusion) and VP-16 (150 mg/m2 on days 1, 2 and 3). GM-CSF or placebo was administered from the 5th day until neutrophil count reached greater than or equal to 1000/microliters on 2 consecutive days. Three PR and 6 CR were documented. Two CR pts are still in CR at 19 and 23.5 months. With the exception of one case of cerebral haemorrhage, life-threatening liver toxicity, exfoliative colitis, capillary leak syndrome and anaphylactoid reaction, the protocol regimen provoked only modest haematological and extra-haematological toxicities.
Leukemia 1991
PMID:GM-CSF: clinical trials in non-Hodgkin's lymphoma patients with chemotherapy induced leucopenia. 189 Aug 60

Antitumor effect of CPT-11 in combination with cyclophosphamide (CY), nimustin hydrochloride (AC-NU), thio-TEPA (TESPA), methotrexate (MTX), 5-fluorouracil (5-FU), cytosine arabinoside (ara-C), thioinosine (6-MPR), adriamycin (ADM), bleomycin (BLM), mitomycin C (MMC), actinomycin D (ACT-D), vincristine sulfate (VCR), etoposide (VP-16) or cisplatin (CDDP) against L 1210 murine leukemia was investigated. The combination treatment of CPT-11 with CY, ACNU, ADM, CDDP, TESPA and ACT-D showed synergistic effects and significantly prolonged the survival time of L 1210-inoculated mice compared with CPT-11 alone or antitumor drug alone. Although the combination with 5-FU, 6-MPR, VP-16, MMC or VCR had synergistic effect for some schedules exceptionally with ara-C, MTX or BLM had slight synergistic effect against L 1210.
 ...
PMID:[Combination therapy of CPT-11, a camptothecin derivative, with various antitumor drugs against L 1210 leukemia]. 190 Jun 84

We investigated the efficacy of oral etoposide (VP-16) for the patients with acute non-lymphocytic leukemia (ANLL) in relapse or refractory to the standard chemotherapy. Patients were given etoposide orally at the dose of 50 mg/body/day on consecutive days until the leukemic cells in the bone marrow were reduced less than 5%. The duration of administration of oral etoposide ranged from 16 days to 50 days (average 30 days). Seven patients were given very low dose cytosine arabinoside (5 approximately 10 mg X 2/day i.s.c.) combination with oral etoposide. Six patients (66.7%) out of 9 achieved complete remission (CR) and 3 patients had no response. Adverse effects such as abdominal discomfort and appetite loss were observed in 3 patients, but they were mild and tolerable. The duration of CR ranged from 2 to 24 (+) months, and the median CR duration is 7 months. The over all CR rate (66.7%) in this group of patients with refractory or relapsed ANLL were encouraging. Further studies, however, are needed to evaluate the efficacy of long term oral administration of etoposide for the patients with leukemia.
 ...
PMID:[Long-term oral administration of etoposide (VP-16) for the patients with refractory or relapsed acute non-lymphocytic leukemia]. 192 Aug 37

A myelo dysplastic syndrome (MDS), refractory anemia with excess of blasts (RAEB), that occurred in a patient with small cell lung cancer (SCLC) during a period of complete response (CR) was reported. A 66-year-old female patient was diagnosed as SCLC in March, 1985. Induction chemotherapy (CDDP, ADM, VCR, VP-16) achieved CR in May, 1985. She had received maintenance chemotherapy (CDDP, ADM, VCR (or VDS), VP-16) and chest irradiation (48.6 Gy) until May, 1988. The hematologic findings revealed MDS and she was admitted in June, 1989. She died one month after onset of MDS because of pneumonia. An autopsy showed no evidence of recurrence of small cell carcinoma in the primary site and other organs. There is a possibility of the risk of secondary leukemia following long term chemotherapy and irradiation in patients with SCLC, and the role of treatment after the achievement of CR in patients with SCLC remains to be clarified.
 ...
PMID:[A myelo dysplastic syndrome (refractory anemia with excess of blasts) occurred in a patient with small cell lung cancer during complete response]. 196 99

This paper describes the cellular and tissue distribution of P-glycoprotein (P-GP) (mdr1 gene product), the role of P-GP in vivo and immunodiagnosis of multi-drug-resistant cancers. We mainly used MRK 16 monoclonal antibody (MAb) reactive with P-GP. P-GP was found to be expressed very strongly in the adrenal cortex of adults and strongly in the renal tubules of the kidney, capillary blood vessels of the brain, and also in placenta. Interestingly, P-GP was not distributed in fetal and neonatal adrenals, and thus may be closely related to adrenal maturation. A high level of P-GP expression was also seen in all cases of functional hormone-producing adrenal tumor, one case of insulinoma, two cases of untreated colonic cancer, one case each of untreated lung cancer, gastric cancer and breast cancer, six cases of renal cell carcinoma and 17 cases of bladder cancer. Using flow cytometry and immunocytochemistry, we investigated the reactivity of MRK 16 MAb with peripheral human mononuclear cells (mainly blastic cells and lymphocytes) from 31 patients with leukemia or malignant lymphoma. Reactivity with MRK 16 MAb was observed in five cases. Some cases reflected the prior administration of adriamycin, vincristine and VP-16, which are known to induce P-GP expression. P-GP-MRK 16-protein A-Sepharose complex derived from human adrenal possessed marked ATPase activity. These data suggest that P-GP may play a physiological role in the human adrenal. Finally, diagnostic criteria of multi-drug-resistant cancers are presented.
 ...
PMID:Expression and functions of P-glycoprotein (mdr1 gene product) in normal and malignant tissues. 197 61

Etoposide (VP-16-213) is an antineoplastic agent with demonstrated efficacy against a broad spectrum of human malignancies, including testicular, germ cell, lung, and other cancers. Etoposide can be synergistic with other agents. As part of combination chemotherapy, etoposide has become a so-called standard in therapies for testicular cancer and small cell lung cancer. Its activity in tumors such as lymphoma and leukemia, as well as solid tumors, identifies etoposide as a highly important chemotherapeutic agent. Cellular and animal models have shown that the cell kill and tumor response depend on both dose and time of exposure. Recent clinical studies again show that dose and schedule of etoposide can have important effects on clinical response to the drug. Further research should now continue: (1) on the use of etoposide as part of initial therapy in several cancers, and (2) in higher doses and prolonged schedules to optimize this agent's potential.
 ...
PMID:Etoposide. Current and future status. 198 22

Pharmacologic and immunologic methods of ex-vivo bone marrow (BM) purging for acute nonlymphocytic leukemia (ANLL) were combined to augment the effect of either method alone. Etoposide (VP16; 20 to 30 micrograms/mL) with or without cytosine arabinoside (Ara C; 10 mg/mL) was used in tandem with the anti-CD33 monoclonal antibody (MoAb), MY9, chosen because CD33 is found on the stem cell pool in the majority of patients with ANLL. The agents were tested singly or sequentially, with a 1-hour incubation of the drugs preceding complement-mediated lysis using MY9. VP16 combined with Ara C killed up to 3.9 +/- 0.3 and 5.11 +/- 0.4 logs of the human ANLL cell lines HL60 and K562 at drug concentrations that killed only 1.2 +/- 0.1 logs of normal committed granulocyte/macrophage stem cells (CFU-GM). Adding a single exposure of the MY9 and complement (C') to the drug-treated cells, greater than 5.4 logs of HL60 were killed. Similar to other pharmacologic agents, no differential kill for clonagenic leukemic cells (colony-forming unit-leukemia; CFU-L) from patients with ANLL was seen for drug only treated blasts versus normal CFU-granulocyte-macrophage (CFU-GM), with less than 1 log CFU-L kill at drug concentrations that spared 1 log of CFU-GM. Similarly, only 1.1 +/- 0.3 logs of ANLL CFU-L were eliminated using MY9 and C'. However, with the sequential VP16/Ara C----MY9 + C' treatment, synergy was demonstrated and 2.6 +/- 0.3 logs of CFU-L were eliminated. Because CD33 is also found on the normal CFU-GM pool, two-stage long-term BM cultures were performed to determine pluripotent stem cell elimination by the drug/MoAb purging combination. No difference of CFU-GM or BFU-E production at 4 to 6 weeks of culture for VP16/Ara C, MY9 + C', or VP16/AraC----My9 + C' treated cells was seen compared with untreated controls indicating sparing of early progenitor cells. Sequential ex vivo treatment of human ANLL CFU-L with VP16/Ara C followed by complement-mediated lysis using MY9 synergistically kills CFU-L while sparing early normal hematopoietic progenitor cells, and thus may be a more effective way to purge BM than either alone.
 ...
PMID:Anti-CD33 monoclonal antibody and etoposide/cytosine arabinoside combinations for the ex vivo purification of bone marrow in acute nonlymphocytic leukemia. 198

Murine leukemia L1210 cells selected for progressive resistance to doxorubicin (DOX) display both the multidrug resistant (MDR) phenotype and reductions in drug induced topoisomerase II-mediated DNA cleavage in nuclear extracts (Ganapathi, R.; Grabowski, D.; Ford, J.; Heiss, C.; Kerrigan, D.; Pommier, Y., Cancer Commun. 1:217-224; 1989). The present study was performed to characterize the results of exposure of the sensitive (S) and progressively DOX-resistant (10-fold, R1, and 40-fold, R2) L1210 cells to the topoisomerase II inhibitor, etoposide, and to investigate the modulating effects of the calmodulin inhibitor, trifluoperazine (TFP). Immunoblotting experiments indicated no apparent decrease in the p170 or p180 isoforms of topoisomerase II in the resistant sublines versus parental sensitive cells. Cross-resistance to etoposide (VP-16) was similar to that of DOX (10- and 40-fold). A non-cytotoxic concentration of 5 microM TFP enhanced cell kill 1.5- fold in the sensitive and 3- to 5-fold in the progressively DOX-resistant cells. Accumulation of VP-16 was 30% to 50% lower in the resistant sublines versus similarly treated sensitive cells, and a marked enhancement of drug uptake in the presence of TFP was observed in the sensitive but not in the resistant cells exposed to equivalent extracellular levels of VP-16. Although equimolar concentrations of VP-16 produced fewer DNA single strand breaks (SSB) and DNA protein crosslinks (DPC) in the resistant versus sensitive cells, similar DNA damage was apparent when S and R1, but not R2, cells were treated at VP-16 concentrations that produced equivalent cell death.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Trifluoperazine modulation of resistance to the topoisomerase II inhibitor etoposide in doxorubicin resistant L1210 murine leukemia cells. 199 27

Acute lymphoblastic leukemia (ALL) is conventionally treated in three phases: remission induction, consolidation and maintenance. In adults initial remission rates of nearly 80% can be achieved. The 3 to 5 year leukemia free survival is 20 to 40%. Most relapses occur during maintenance, despite continuous therapy for 2 to 3 years. The value of maintenance therapy following intensive induction in adults is not documented. In this pilot study we treated 34 patients with ALL in five Swiss centers between 1986 and 1989 with intensive induction/consolidation therapy alone. Three induction/consolidation courses were applied: course I, 43 days, consisting of daunomycin, vincristine, prednisone, methotrexate, L-asparaginase and intrathecal CNS prophylaxis; course II, 6 days, consisting of high dose cytosine arabinoside and VP-16; course III, three non randomized arms, either allogeneic or autologous bone marrow transplantation (BMT) or high dose cyclophosphamide and repeated intrathecal therapy alone. 32 patients (94%) reached complete remission (CR): 24 after course I (71%), 7 after course II (cumulative 91%) and one after course III only (cumulative 94%). 3 patients had early, relapses before course III, 3 died of infection, and 2 of graft-versus-host disease. One patient had refractory leukemia in all three courses. 26 patients (76%) were in CR after completion of therapy. 16 relapsed within 1 to 17 months (median 5). 10 patients are free of disease after 10 to 44 months (median 24): 5 had had allogeneic BMT, 3 autologous BMT and 2 cyclophosphamide in course III.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:[The treatment of acute lymphatic leukemia in adults: pilot project with intensive early therapy without a maintenance phase]. 200 99


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>