Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0026764 (multiple myeloma)
 36,148 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lipophilic antitumor alkaloid acronycine (ACRO) was solubilized in the cosolvent system used for etoposide. ACRO in this etoposide diluent (VPD) was found to be cytotoxic (less than or equal to 50% colony formation in soft agar) in fresh human tumors from patients with renal cell cancer, ovarian cancer, uterine cancer, and metastatic tumors of unknown primary. In P-glycoprotein-positive, multidrug-resistant (MDR) cell lines, ACRO in VPD was active in MDR Chinese hamster ovary cells but not against MDR L1210 murine leukemia cells, 8226 human myeloma cells, or human CCRF-CEM lymphoblasts. In mice, ACRO in VPD was active in two solid tumor models and an i.p. MOPC-315 plasmacytoma model. ACRO i.p. in 10% VPD (v/v%) produced significant tumor growth delays in (a) nude mice bearing human MCF-7 breast cancer xenografts and (b) C57BL mice bearing colon 38 tumor. In MOPC-315-bearing mice, a single i.p. ACRO dose of 25 mg/kg was as effective as melphalan (15 mg/kg) at prolonging life span. Finally, ACRO pharmacokinetics was evaluated in mice given single 25-mg/kg doses i.p. or p.o. The oral bioavailability of an ACRO solution in VPD was only 50% but both i.p. and p.o. regimens achieved plasma levels greater than 1.0 micrograms/ml. The plasma half-life was just under 2 h. These results show that parenteral ACRO in VPD comprises a cytotoxic antitumor agent with improved bioavailability over p.o. administration. ACRO is active in vitro against several human solid tumors but is cross-resistant in 3 of 4 MDR tumor cell lines. The prior clinical activity of p.o. ACRO in myeloma and the new results in MOPC-315 plasmacytomas in mice suggest that ACRO in VPD could have activity against human multiple myeloma.
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PMID:Antitumor activity and murine pharmacokinetics of parenteral acronycine. 291 Apr 53

The risk of cancer associated with a broad range of organ doses was estimated in an international study of women with cervical cancer. Among 150,000 patients reported to one of 19 population-based cancer registries or treated in any of 20 oncology clinics, 4188 women with second cancers and 6880 matched controls were selected for detailed study. Radiation doses for selected organs were reconstructed for each patient on the basis of her original radiotherapy records. Very high doses, on the order of several hundred gray, were found to increase the risk of cancers of the bladder [relative risk (RR) = 4.0], rectum (RR = 1.8), vagina (RR = 2.7), and possibly bone (RR = 1.3), uterine corpus (RR = 1.3), cecum (RR = 1.5), and non-Hodgkin's lymphoma (RR = 2.5). For all female genital cancers taken together, a sharp dose-response gradient was observed, reaching fivefold for doses more than 150 Gy. Several gray increased the risk of stomach cancer (RR = 2.1) and leukemia (RR = 2.0). Although cancer of the pancreas was elevated, there was no evidence of a dose-dependent risk. Cancer of the kidney was significantly increased among 15-year survivors. A nonsignificant twofold risk of radiogenic thyroid cancer was observed following an average dose of only 0.11 Gy. Breast cancer was not increased overall, despite an average dose of 0.31 Gy and 953 cases available for evaluation (RR = 0.9); there was, however, a weak suggestion of a dose response among women whose ovaries had been surgically removed. Doses greater than 6 Gy to the ovaries reduced breast cancer risk by 44%. A significant deficit of ovarian cancer was observed within 5 years of radiotherapy; in contrast, a dose response was suggested among 10-year survivors. Radiation was not found to increase the overall risk of cancers of the small intestine, colon, ovary, vulva, connective tissue, breast, Hodgkin's disease, multiple myeloma, or chronic lymphocytic leukemia. For most cancers associated with radiation, risks were highest among long-term survivors and appeared concentrated among women irradiated at relatively younger ages.
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PMID:Radiation dose and second cancer risk in patients treated for cancer of the cervix. 318 29

Migration inhibition activity from ascitic fluids of ovarian cancer patients (OC-MIF) was used to develop monoclonal antibodies. The OC-MIF was purified about 10,000 fold by affinity chromatography on L-fucose-Sepharose 6B. Spleen cells from AB/Jena mice immunized with purified OC-MIF were hybridized with P3X63 Ag 8.653 myeloma cells. Supernatants of the hybridoma cultures were screened by solid-phase binding assay, direct neutralizing assay and solid-phase RIA. Several clones of these hybridomas secreted antibodies into the culture medium, which neutralized the biological activity of OC-MIF at dilutions as high as 10(-4) relative to the initial culture medium. After expansion and cloning one clone was selected for ascitic antibody production. This monoclonal antibody coupled to Sepharose 4B adsorbed OC-MIF. Most of the adsorbed biological activity could be eluted with 0.1 M acetic acid.
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PMID:Inhibition of macrophage migration by a factor from ascites fluids of ovarian cancer patients. III. Generation of monoclonal antibody specific for human MIF. 331 Oct 40

A problem in evaluating different therapies from a review of clinical trials is that the published clinical trial literature may be biased in favor of positive or promising results. In this report, a model is proposed for reviewing clinical trial results which is free from publication bias based on the selection of trials registered in advance in a registry. The value of a registry is illustrated by comparing a review of published clinical trials located by a literature search with a review of registered trials contained in a cancer trials registry. Two therapeutic questions are examined: the survival impact of initial alkylating agent (AA) v combination chemotherapy (CC) in advanced ovarian cancer, and the survival impact of AA/prednisone v CC in multiple myeloma. In advanced ovarian cancer, a pooled analysis of published clinical trials demonstrates a significant survival advantage for combination chemotherapy (median survival ratio of CC to AA, 1.16; P = .02). However, no significant difference in survival is demonstrated based on a pooled analysis of registered trials (median survival ratio, 1.05; P = .25). For multiple myeloma, a pooled analysis of published trials also demonstrates a significant survival advantage for CC (median survival ratio, 1.26; P = 04), especially for poor risk patients (ratio, 1.66; P = .002). A pooled analysis of registered trials also shows a survival benefit for patients receiving combination chemotherapy (all patients, P = .06; poor risk, P = .03), but the estimated magnitude of the benefit is reduced (all patients: ratio, 1.11; poor risk: ratio, 1.22). These examples illustrate an approach to reviewing the clinical trial literature, which is free from publication bias, and demonstrate the value and importance of an international registry of all clinical trials.
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PMID:Publication bias: the case for an international registry of clinical trials. 376 Sep 20

Melphalan (MEL) is an aromatic alkylating agent which is useful for the treatment of a number of human cancers, including myeloma and ovarian cancer. However, like most cytotoxic drugs, MEL has side effects, due to its nonspecific effects on all or most cells. To overcome these nonspecific effects N-acetyl melphalan (N-AcMEL) was synthesized and found to be 75 times less toxic to tumor cells in vitro. However, when N-AcMEL was conjugated to monoclonal antibodies (MoAbs) to form N-AcMEL-MoAb conjugates the cytotoxic effect of MEL was restored, but with a difference in that the MEL could only act on cells which bound antibody. It was shown that, for N-AcMEL-MoAb conjugates, the N-AcMEL entered cells via the MoAb, by endocytosis, and not by the phenylalanine amino acid transport system. In addition, N-AcMEL-MoAb conjugates more effectively erradicated tumors in vivo than does free MEL or N-AcMEL. The N-AcMEL-MoAb conjugates therefore have high specific activity both in vitro and in vivo and a markedly reduced nonspecific toxicity, as N-AcMEL is relatively nontoxic to cells unless conveyed there by MoAb. In these respects the study offers a new approach to the use of chemotherapeutic agents in patients with cancer.
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PMID:Selective enhancement of antitumor activity of N-acetyl melphalan upon conjugation to monoclonal antibodies. 379 Dec 21

Marrow transplantation is effective treatment for a number of hematological diseases in patients under the age of 50 who have an HLA-identical sibling donor. It is successful in the treatment of aplastic anemia with 70-85% long-term survival. It offers 10-30% apparent cures for patients with acute leukemia who have relapsed at least once, and for those with chronic myelocytic leukemia in blast crisis. Although still somewhat controversial, it appears to be the treatment of choice for patients with acute nonlymphoblastic leukemia in first chemotherapy induced remission, and for those with chronic myelogenous leukemia in the chronic phase since approximately 50-60% of these patients experience long-term, disease-free survival. Patients with acute lymphoblastic leukemia grafted in second or subsequent remission may expect a 30% "cure" of their disease. Marrow grafting is the only effective treatment for many patients with inherited immunologic deficiencies and certain genetic storage diseases. Cures of congenital Fanconi's anemia, Blackfan-Diamond anemia, osteopetrosis, paroxysmal nocturnal hemoglobinuria and thalassemia major have been achieved. Marrow transplantation is being explored for the therapy of patients with lymphoma, Hodgkin's disease, preleukemia, multiple myeloma, hairy cell leukemia, small cell lung cancer, testicular cancer, ovarian cancer and neuroblastoma. Marrow transplantation has been limited by the fact that many patients do not have HLA-identical siblings and very few have monozygotic twins. More recently, marrow transplants from HLA-nonidentical family members and even from unrelated donors have been successfully explored.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Marrow transplantation: the Seattle experience. 391 47

Erythrocyte mean corpuscular volume (MCV) evolution during cytotoxic therapy of Hodgkin's disease, lymphoma, multiple myeloma, ovarian cancer, and breast cancer was studied. The fastest and the highest MCV increases were observed in the diseases and with the therapies the most frequently involved in secondary leukemia: Hodgkin's disease treated with MOPP (mechlorethamine, vincristine, procarbazine, prednisone), and multiple myeloma and ovarian cancer treated with melphalan. On the contrary, with cytotoxic regimens not linked to a high frequency of secondary leukemia such as CMF (cyclophosphamide, methotrexate, 5-fluorouracil) used in ovarian or breast cancer, MCV increase was moderate. As the MCV increase reflects the bone marrow reaction to cytotoxic therapy, an unusually high increase could indicate bone marrow damages which could lead to secondary leukemia.
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PMID:Erythrocyte mean corpuscular volume during cytotoxic therapy and the risk of secondary leukemia. 403 78

Among 4,184 patients with cancer of the esophagus, 55 second primary cancers were observed, whereas 64 were expected [relative risk (RR) = 0.86]. The absence of an excess risk of alcohol- and tobacco-related cancers was not anticipated. A significant 19% deficit of second cancers was found among 30,843 patients with stomach cancer. Cancer of the rectum, kidney, and lung all occurred significantly below expectation. An excess risk of ovarian cancer (RR = 1.9) was seen in women. Reasons for these findings are not entirely clear. Cancer of the small intestine is rare, and despite a relatively short survival expectation, a moderate excess of second cancers was seen among 868 patients (36 vs. 26.8). Only cancers of the liver and gallbladder were significantly elevated, and the possibility of misclassified metastases is discussed. Colon cancer is one of the most common cancers in Denmark, and 29,490 patients with this disease were at slightly lower risk for development of second cancer (RR = 0.96; 95% confidence interval = 0.9-1.0) than the general Danish population, excluding secondary colon cancers. Esophageal, stomach, and liver cancers occurred less frequently than expected. That cancers of the uterine corpus and ovary were significantly increased supports the notion that common risk factors, such as diet and endogenous hormones, influence the development of these cancers. A significant 23% deficit of second cancers was also found among 26,597 patients with cancer of the rectum, excluding secondary rectal cancer. Significant deficits were seen for cancers of the stomach (RR = 0.5), lung (RR = 0.8), and brain (RR = 0.5), and for multiple myeloma (RR = 0.4). The likelihood of underreporting of second cancers, especially of the digestive system, is discussed. However, cancer of sites previously reported to be associated with rectal cancer, e.g., the colon, breast, and uterus, did not occur below expectation. Cancers of the liver and biliary tract occurred in 4,453 patients; their average survival was only 1 year. Except for a slight excess of cancer of the ovary (5 vs. 1.6), the risk of second cancer development for all sites was consistent with unity (RR = 0.90). The risk of second cancers among 7,752 persons with cancer of the pancreas was not greater than expected (88 vs. 85.2). Males were at significant risk of kidney cancer (RR = 3.2), whereas females showed elevated rates of cancers of the uterine corpus (RR = 3.2) and ovary (RR = 3.1). No site occurred significantly below expectation.
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PMID:Second cancer following cancer of the digestive system in Denmark, 1943-80. 408 3

Four cases of acute myelodysplastic-non-lymphocytic leukemia secondary to cytotoxic agents were reported. Primary diseases were breast cancer (1 patient), ovarian cancer (2 patients) and multiple myeloma (1 patient). All except one (with multiple myeloma) were in clinical remission of their primary diseases. Common cytotoxic agent used was melphalan. Median total drug dose and median latent period from diagnosis of primary diseases were 1299 mg and 63 months respectively. None with the exception of one received specific treatment. All died except one who is in a very poor condition. Survival from the diagnosis of hematologic diseases ranged from 3-9 months. Clinical features, cytogenetic findings, pathogenetic mechanism and risk of the disease were briefly discussed.
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PMID:Therapy related acute non-lymphocytic leukemia: report of 4 cases. 409 7

Changes in mean corpuscular volume (MCV) were studied in cancer patients. Vitamin B12 or erythrocyte folate deficiencies were observed in only 9% of macrocytic patients (MCV greater than or equal to 100 fl). Bone marrow study in seven macrocytic patients with normal hemograms and normal levels of vitamin B12 and folic acid, on per os daily cyclophosphamide single agent therapy, showed myelodysplastic features. The highest MCV and MCV increases during therapy among 203 patients were observed in those cancers and cytotoxic therapies most commonly followed by secondary leukemia: Hodgkin's disease treated with MOPP and radiotherapy, and multiple myeloma and ovarian cancer treated with Melphalan. 21 patients who developed secondary leukemia had a higher MCV and a greater MCV increment than the control patients. Differences were significant in Hodgkin's disease. This preliminary report strongly supports monitoring MCV changes during cytotoxic therapy to attempt identification of patients at high risk of secondary leukemia.
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PMID:[Changes in the mean corpuscular volume during the cytotoxic treatment of cancer and risk of secondary leukemia. Preliminary results]. 632 84


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