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

Mitoxantrone is an anthraquinone antineoplastic agent with structural similarities to doxorubicin. It has a mechanism of action similar to the anthracyclines. Its primary elimination route is hepatic metabolism (only seven percent renal excretion) and it has a terminal half-life of approximately 40 hours. Mitoxantrone has significant activity in the treatment of metastatic breast cancer, acute leukemias, and non-Hodgkin's lymphoma. Some activity is reported in head and neck cancer, Hodgkin's, myeloma, bladder cancer, prostate cancer, non-small-cell lung cancer, and liver cancer. There is a suggestion of incomplete cross-resistance between mitoxantrone and the anthracyclines in certain neoplasms. Some activity is reported with mitoxantrone in patients refractory to the anthracyclines in breast cancer, acute leukemias, and non-Hodgkin's lymphomas. The usual doses used in solid tumors and in lymphomas are mitoxantrone 12-14 mg/m2 iv q3-4wk and in leukemias is mitoxantrone 12 mg/m2/d X 5 d iv for initial induction.
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PMID:Mitoxantrone. 351 24

Although age may reduce the physiologic reserve of many systems, elderly patients with good performance status may receive chemotherapy without undue toxicity. Both survival and quality of life may be improved by treatment of responsive neoplasms, such as acute leukemia, multiple myeloma, small cell cancer of the lung, lymphomas and breast cancer. Age-related decrements in glomerular filtration rate and cardiac reserve suggest that doses of renally excreted drugs and cardiotoxic anthracyclines should be reduced in the elderly.
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PMID:Cancer chemotherapy in the elderly. 354 92

The glutathione (GSH) synthesis inhibitor, buthionine sulfoximine (BSO) was tested for cytotoxicity and thiol depletion in murine and human tumor cells in vitro, and for its antitumor activity and toxicity in vivo. The cell lines used in these studies included murine L-1210 leukemia, human RPMI 8226 myeloma, MCF-7 breast cancer and WiDr colon carcinoma. Soft agar colony forming assays showed that BSO was most effective at reducing tumor colony formation when exposed continuously to cells in vitro. Drug concentrations which inhibited colony formation to 50% of control levels ranged from 2.0-6.2 mM (for 1 hour exposures), 2-100 mM for 24 hour exposures and 0.4-1.40 microM (for continuous BSO exposures). Human myeloma cells proved most sensitive to BSO. In vitro cytotoxicity correlated with depletion of intracellular nonprotein sulfhydryls to less than or equal to 10% of control values in both L-1210 and 8226 cells. This was routinely achieved with prolonged exposures to mM BSO concentrations for greater than 24 hours. Normal mice tolerated high BSO doses (up to 5.0 g/kg) without evidence of acute toxicity. BSO was not active against L-1210 leukemia-bearing DBA/2 mice. When tested in vivo against MOPC-315 plasmacytoma-bearing BALB/c mice, BSO was not active at doses up to 4.0 g/kg. In contrast, the bifunctional alkylating agent melphalan (L-PAM) was active against MOPC-315 and this activity was enhanced by a 24 hour pretreatment of mice with 50 mg/kg of L-BSO.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Cytotoxic effects of glutathione synthesis inhibition by L-buthionine-(SR)-sulfoximine on human and murine tumor cells. 358 42

Natural interferon-alpha preparation "Sumiferon" was recently developed in Japan. This is a human lymphoblastoid interferon (HLBI) preparation. Like other interferon preparations, this preparation showed both direct and indirect antitumor effect and the toxicities were moderate. The phase I-II studies were carried out in 38 major institutions in Japan. In the phase I study in 5 patients with advanced breast cancer, the maximum tolerated dose (MTD) was found to be 12 X 10(6) units/day given for 1 month. In the phase II study, HLBI was given in at 3 approximately 6 X 10(6) units/day. Out of 391 cases, 280 were evaluable. Complete and partial responses (CR and PR) were observed in 40 (14.3%) out of 280 evaluable cases, including 11 (19.6%) out of 56 renal cell cancer, 14 (19.2%) out of 73 multiple myeloma, and 9 (17.3) out of 52 malignant lymphoma among others. Major side effects observed were: fever (69.8%), gastrointestinal disturbances (31.4%), leukopenia (30.7%), thrombocytopenia (27.8%), hepatotoxicities (23.6%) and general fatigue (22.1%). Sumiferon seemed to be one of useful antitumor drugs effective against renal cancer.
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PMID:[Introduction of natural interferon-alpha "Sumiferon"]. 363 77

Since interferon alfa-2b (Intron A) is useful as a single agent, it is important to determine if interferon can be combined with standard chemotherapy to improve both response and survival in patients with cancer. Using clonogenic assays, interferon was tested alone and in combination with cyclophosphamide (Cytoxan) or melphalan (Alkeran) using several dose and exposure schedules to evaluate cytotoxicity. In vitro, continuous-exposure interferon produced optimal cell kill. Maximum enhancement of cytotoxicity occurred with cyclophosphamide or melphalan pretreatment (1 hour) and/or simultaneous interferon treatment. Based upon these data, a phase I-II study was designed to determine the tolerance of cancer patients to a fixed dose of cyclophosphamide (150 mg/m2 p.o. daily X 4 days [days 2 to 5]) combined with increasing doses of interferon. Interferon was administered subcutaneously on treatment cycle days 1 to 5, plus days 8, 10, 12, 15, 17, and 19 of the 21-day regimen. Three patients had partial responses: one breast cancer, one angiosarcoma, and one myeloma (mixed). All patients reported mild flu-like symptoms, fatigue, and anorexia. Leukopenia occurred in all patients; three required treatment interruption to allow recovery. Eight patients had a fall in hemoglobin (mean decrease 1.4 g/dL). The combination of cyclophosphamide and interferon was safe and deserves further trial in cancer treatment. However, using this combination schedule, interferon doses greater than or equal to 5 X 10(6) IU were poorly tolerated and compromised administration of full-dose cyclophosphamide.
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PMID:Interferon alfa-2b-cyclophosphamide combination studies: in vitro and phase I-II clinical results. 376 44

Spleen cells from rats bearing syngeneic metastatic 13762NF mammary adenocarcinoma clone MTLn3 tumors were fused with the rat myeloma Y3 Ag1.2.3 to generate a panel of monoclonal antibodies (MAbs). The MAbs could be divided into three groups: those cross-reactive with all 13762NF cells; those reactive with cloned MTLn3 and MTC cells; and those predominantly reactive with the highly metastatic MTLn3 cells. One of these MAbs, MT10:21 (an immunoglobulin G2a), binds predominantly to highly metastatic MTLn3 cells and has a high tumor-cell affinity as determined by its saturation kinetics. MAb MT10:21 has a 6-h half-life on the MTLn3 cell surface and a 24-h half-life in the blood of syngeneic rats. Immunoblotting experiments using lysates from the cloned 13762NF sublines revealed that MAb MT10:21 binds to several proteins having relative molecular weights of 72,000, 73,000, and 120,000. Using an immunohistochemical procedure with frozen tissue sections, MAb MT10:21 shows little reactivity with normal rat mammary tissue, irrespective of the stage of the estrous cycle, and it failed to react with a number of other normal fetal and adult tissues. Furthermore, MAb MT10:21 is heterogeneous in its reactivity to cloned sublines of the 13762NF mammary adenocarcinoma, on both tissue cultured cells and tissue sections prepared from tumors growing in situ in the mammary fat pads of syngeneic rats. MAb MT10:21 reacted with certain human breast cancer cell lines and with a subpopulation of metastatic human breast cancer cells in frozen tissue sections from biopsies and autopsies. Metastases from breast cancers reacted more intensely than the primary tumors from which they were derived.
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PMID:Monoclonal antibodies against cell-surface antigens of the metastatic rat 13762NF mammary adenocarcinoma and their cross-reactivity with human breast carcinomas. 377 54

A hypercalcemia frequency of 1.5% was found in patients with malignant disease attending a large oncological center. Eighty per cent of hypercalcemias were of obvious malignant etiology. Hypercalcemia was most frequent in multiple myeloma, renal carcinoma, squamocellular carcinomas of different sites and breast cancer. Most patients had advanced metastasized disease. In 80% of those with solid tumors malignant hypercalcemia was associated with bone metastases. Serum calcium could almost invariably be reduced by treatment, and active treatment was associated with a more favorable prognosis. One year actuarial survival of patients with malignant hypercalcemia was 31%.
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PMID:Malignant hypercalcemia--a hospital survey. 381 29

46 patients (17 myelomas, 11 malignant lymphomas, 8 mammary carcinomas, 7 head and neck carcinomas, 2 gastrointestinal carcinomas and 1 ovarian carcinoma) were treated with Permease prepared of bovine testes by Sanabo. 7500 i.u. were given either intramuscular one hour before cytostatic chemotherapy or intraperitoneally with cytostatic agents. There were 2 cases of local irritation on the site of injection and 1 case of reversible anaphylactoid reaction. Results achieved in patients treated with the same chemotherapy in spite of resistance, but with addition of Permease: myeloma CR 2/9, subjective improvement 7/9; 5 patients expired, median observation time: 13 months; non-Hodgkin-lymphomas CR 2/5, PR 2/5; 2 patients expired, median observation time: 9 months; breast cancer PR 2/4, 2 patients expired, median observation time: 5 months, 1 patient with Morbus Hodgkin CR, expired after 24 months. The other patients who received systemic treatment had either primary chemotherapy with addition of Permease, or chemotherapy was altered because of resistance against the prior therapy before Permease was applied. Intraperitoneal application of Permease together with cytostatic agents, usually not used for local therapy because of high rate of irritation like cis-platin, was well tolerated. Complete regression of ascites was achieved in all cases. In 1 of the 4 patients duration of remission was 7 months. Hypotheses concerning the mechanism of action of hyaluronidase in malignant diseases are discussed. The effectiveness of Permease might be related to resistance phenomenon of tumor cells or to alteration of pharmacokinetics of cytostatic agents.
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PMID:[Results of a pilot study of hyaluronidase as an adjunct to cytostatic therapy in malignant diseases]. 383 6

The numbers of second cancers among 182,040 women treated for cervical cancer that were reported to 15 cancer registries in 8 countries were compared to the numbers expected had the same risk prevailed as in the general population. A small 9% excess of second cancers (5,146 observed vs. 4,736 expected) occurred 1 or more years after treatment. Large radiation doses experienced by 82,616 women did not dramatically alter their risk of developing a second cancer; at most, about 162 of 3,324 second cancers (approximately equal to 5%) could be attributed to radiation. The relative risk (RR = 1.1) for developing cancer in organs close to the cervix that had received high radiation exposures--most notably, the bladder, rectum, uterine corpus, ovary, small intestine, bone, and connective tissue--and for developing multiple myeloma increased with time since treatment. No similar increase was seen for 99,424 women not treated with radiation. Only a slight excess of acute and non-lymphocytic leukemia was found among irradiated women (RR = 1.3), and substantially fewer cases were observed than expected on the basis of current radiation risk estimates. The small risk of leukemia may be associated with low doses of radiation absorbed by the bone marrow outside the pelvis, inasmuch as the marrow in the pelvis may have been destroyed or rendered inactive by very large radiotherapy exposures. There was little evidence of a radiation effect for cancers of the stomach, colon, liver, and gallbladder, for melanoma and other skin cancers, or for chronic lymphocytic leukemia despite substantial exposures. An excess of thyroid cancer possibly was related to the low dose received by this organ. Ovarian damage caused by radiation may have been responsible for a low breast cancer risk (RR = 0.7), which was evident even among postmenopausal women. A substantial excess of lung cancer (RR = 3.7) largely may be due to misclassification of metastases and the confounding influence of cigarette smoking. Women who were under 30 or over 50 years of age when irradiated were at greatest absolute risk for developing a second cancer. The RR, however, was higher among those under age 30 years at exposure (RR = 3.9) than among older women. The expression period for radiation-induced solid tumors appeared to continue to the end of life.
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PMID:Second cancers following radiation treatment for cervical cancer. An international collaboration among cancer registries. 385 84

Five patients with multiple cancers that included hematologic malignancies are described. The incidence of multiple cancers in hematologic malignancies has been 8.8% in the past two and a half years at our hospital. The combinations were: 1) primary bilateral breast cancers and acute monocytic leukemia; 2) breast cancer, malignant lymphoma and gastric cancer; 3) malignant lymphoma and gastric cancer; 4) malignant lymphoma and prostate cancer, and 5) colon cancer and multiple myeloma. Our experience suggests an increasing incidence of multiple cancer in hematologic malignancies.
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PMID:[A report of five cases of multiple cancer with hematologic malignancies]. 386 85


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