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)

The effects and toxicities of interferon alfa are described, and the role of the pharmacist in making decisions and providing education about biologic response modifiers (BRMs) is discussed. Interferons have both direct antitumor activity and extensive effects on the immune system. Two recombinant interferon alfa products--interferon alfa-2a and interferon alfa-2b are available commercially. Indications in FDA-approved labeling for interferon alfa include the treatment of hairy-cell leukemia, acquired immunodeficiency syndrome-related Kaposi's sarcoma, and genital warts; however, it also is being used successfully against early chronic myelogenous leukemia, low-grade non-Hodgkin's lymphoma, cutaneous T-cell lymphoma, and previously untreated multiple myeloma. Other malignancies that respond to treatment with interferon alfa are malignant melanoma, ovarian carcinoma, and renal cell carcinoma. The toxic pattern of interferon alfa consists of flu-like symptoms, which are seen at all doses, on all schedules, and in virtually all patients. After repeated dosing, the chronic toxicities of anorexia, weight loss, and malaise and fatigue may develop. Myelosuppression, central nervous system toxicity, increased hepatic enzyme concentrations, nausea and vomiting, and cardiovascular toxicity also are possible. Serum neutralizing antibodies may be formed during therapy; this phenomenon may affect the clinical outcome. Numerous BRMs are being investigated for clinical use, and pharmacists must become conversant in the issues that surround these agents. Areas in which pharmacist involvement and knowledge are important include overall cost, product similarities and differences, dosing and scheduling, drug delivery systems, ways to minimize waste, adverse effects and their management, drug interactions, storage requirements, differences in production and purification techniques among manufacturers, and education of patients and staff.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Biologic response modifiers: the interferon alfa experience. 248 96

In order to obtain human monoclonal antibodies for immunodetection or treatment of ovarian carcinoma, we generated hybridomas by fusing peripheral blood lymphocytes of patients with ovarian carcinoma and the mouse myeloma cell line X63.Ag8.653. The patients were immunized prior to collection of peripheral blood lymphocytes with autologous tumor cells admixed with New Castle Disease Virus. Immunocytologic studies of hybridoma supernatant with tumor cells fixed with methanol and air-dried tumor cells indicated that all 14 antibodies reactive with tumor cells were directed against cytoplasmic or nuclear antigens. One hybridoma designated as 1B3 was very stable and secreted a specific IgM antibody. This cell line expanded in nude mice and the monoclonal antibody 1B3 was effectively purified from ascites or supernatant fluid. In experiments with tissue sections partly derived from the patient whose peripheral blood lymphocytes were used for fusion, biotinylated 1B3 recognized ovarian tumor cells. There was no significant cross-reaction against normal tissue from stomach, small intestine, colon, lung, kidney, endometrium, placenta, or lymph node. Mammary carcinoma preparations were also stained by 1B3 while normal breast tissue was negative.
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PMID:Human monoclonal antibodies directed against ovarian carcinoma. 266 83

The occurrence of treatment-related hematologic malignancies after adjuvant therapy with alkylating agents for gastrointestinal cancers, ovarian carcinoma, and breast cancer and after treatment for Hodgkin's disease, non-Hodgkin's lymphoma, germ-cell tumors, and multiple myeloma has been well documented. Adjuvant chemotherapy is frequently used for the treatment of early stage breast cancer, and to date there has been no increase in the incidence of secondary myelodysplastic syndromes or acute leukemia after cyclophosphamide-based regimens when compared with surgical controls. This report describes two patients who developed acute myelocytic leukemia only after exposure to cyclophosphamide, methotrexate, and 5-fluorouracil adjuvant therapy. These two cases of acute leukemia, which developed 3 years after diagnosis of breast cancer and initiation of chemotherapy, were characterized by trilineage dysplasia and pancytopenia, and had abnormalities of chromosomes 5 and 7: characteristics consistent with treatment-related leukemia. Many women are diagnosed with early stage breast cancer each year who are potential candidates for adjuvant therapy. Although certain subgroups of patients have been shown to benefit from adjuvant therapy, continued efforts must be directed at identifying responders so that others will not be exposed to the additional risks of chemotherapy.
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PMID:Secondary acute myelocytic leukemia after adjuvant therapy for early-stage breast carcinoma. A new complication of cyclophosphamide, methotrexate, and 5-fluorouracil therapy. 274 58

Purified, recombinant human gamma-interferon (rIFN-gamma) was tested at clinically achievable doses for direct and indirect antiproliferative activity against human tumor cell lines using a clonogenic assay. One-h treatment with rIFN-gamma showed direct dose dependent inhibition of tumor colony growth in cell lines established from human melanoma, myeloma, renal cell, and cervical cancers. Longer treatments resulted in suppression of ovarian and breast carcinoma clonogenicity. In order to test for indirect antiproliferative effects of rIFN-gamma, feeder cells were included in a separate agarose underlayer in the cloning assay. These feeder cells included mouse peritoneal macrophages, U-937 (human histiocytic lymphoma cell line), and adherent cells from human malignant ascites specimens. Colony growth of ovarian carcinoma and melanoma cell lines was stimulated by each of these feeder cell types. Cultures containing mouse peritoneal macrophages or U-937 cells showed the same antiproliferative responses to rIFN-gamma as did control cultures without feeder cells. In contrast, human adherent ascites cells (greater than 80% macrophages) became strongly inhibitory to tumor colony growth when treated with rIFN-gamma. These results suggest that human tumor associated macrophages may become tumoricidal under the influence of rIFN-gamma, producing a diffusable substance in agarose culture which causes the observed antiproliferative effects on tumor cells.
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PMID:Direct and indirect effects of human recombinant gamma-interferon on tumor cells in a clonogenic assay. 308 Feb 33

Fifty-seven patients with advanced malignant tumours were treated with ifosfamide (Holoxan) and mesna (Uromitexan) in our department from November 1979 to December 1984. This series comprised eight cases of soft tissue sarcoma, nine cases of ovarian carcinoma, five cases of non-seminomatous testicular tumour, 11 cases of bronchogenic carcinoma, three cases of renal carcinoma, seven cases of non-Hodgkin's lymphoma, two cases of skeletal fibrosarcoma, two cases of breast carcinoma, one case each of Ewing's tumour, prostatic carcinoma, seminoma, plasma cell tumour, multiple myeloma, malignant teratoma, nasopharyngeal carcinoma, Wilms's tumour, neuroblastoma and mycosis fungoides. Out of these 57 cases, 53 were evaluable. There were five complete remissions and 20 partial remissions, corresponding to a total response rate of 47%. The overall median survival time (MST) of the 53 evaluable patients was 7.5 months. The responders had a longer survival time (MST 10 months) than the non-responders (MST 4.75 months) (p greater than 0.05). Analysis of the results according to sex, age, dosage of ifosfamide and degree of histological differentiation of the tumour cells failed to show any influence of these factors on the therapeutic results. The response rate to ifosfamide found in this study might be related to the histological origin of the tumours and to whether the primary tumours had been resected. The non-seminomatous testicular tumours, non-Hodgkin's lymphomas and ovarian carcinomas showed a high response rate. The response rate was higher in the group in which the primary tumour had been resected (61%) than in the non-resected group (12%) (except the non-Hodgkin's lymphoma). The side-effects of this regimen were moderate. Dyspepsia, nausea, vomiting, myelodepression, dizziness, and alopecia were common. Cystitis could be prevented nearly completely by concomitant administration of mesna, when given correctly, for preventing side-effects of ifosfamide on the urinary system (haemorrhagic cystitis, etc.).
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PMID:Treatment of advanced malignancies with ifosfamide under protection with mesna. 313 Mar 16

Mouse monoclonal antibodies (OV-TL 3) were raised against human ovarian tumor-associated antigens for diagnostic purposes. A cloned hybridoma cell line was obtained by fusion of murine myeloma cells with spleen lymphocytes from BALB/c mice immunized with a tumor cell suspension prepared from an ovarian endometrioid carcinoma. The antibodies were initially screened for their ability to bind on frozen sections of human ovarian carcinoma tissue and a negative reaction on gastric carcinoma tissue by indirect immunofluorescence. The reactivity of the selected OV-TL 3 clone (IgG1 subclass) was studied on normal and neoplastic tissues as well as on a cell line derived from the original tumor cell suspension used for immunization. OV-TL 3 antibodies stained frozen sections of human ovarian carcinomas of the following histological types: serous, mucinous, endometrioid, and clear cell. No reaction was found with breast cancers or other nongynecological tumors. No differences in staining pattern were observed between primary and metastatic ovarian carcinomas. OV-TL 3 antibodies brightly stained ovarian carcinoma cell clusters in ascitic fluids and left unstained mesothelial cells and peripheral blood cells. The OV-TL 3-defined antigen also remained strongly expressed on a cell line derived from the endometrioid ovarian carcinoma originally used for generation of OV-TL 3 clone. Reactivity was weak and irregular in a few ovarian cysts, while traces of fluorescence were sometimes detected in epithelial cells lining the female genital tract. In only 3 specimens of 15 endometrium carcinomas was weak focal reactivity with OV-TL 3 antibodies observed. The results of the immunofluorescence study were confirmed by the more sensitive avidin-biotin method and by 125I-labeled OV-TL 3 antibodies. Thus OV-TL 3 recognizes a common antigen for most ovarian carcinomas and may be a useful tool for rapid diagnosis of ovarian carcinomas.
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PMID:Monoclonal antibody against human ovarian tumor-associated antigens. 351 52

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

Using unfixed mouse bladder tumor cells (MBT) as target cells and a modified avidin-biotin-complex (ABC) method made it possible to detect a humoral immune response in C3H mice with growing MBT tumors. The rise of the serum levels is significant (p less than 0.005) when compared to control animals and correlates with the tumor size. Mice with recurrences after surgical removal of the primary tumor had significantly (p less than 0.05) higher serum values than animals without recurrence. Purulent or granulomatous inflammatory changes, muscle necrosis, growth of a lymphoma or an ovarian carcinoma did not significantly change the results (p less than 0.05). Injection of myeloma cells from a different strain of mice caused a minimal, but significant increase in the values when compared to controls (p less than 0.0001). However, the slope of the curve differed significantly (p less than 0.05) from that in mice with MBT tumors. Irradiated MBT cells or Corynebacterium parvum used as immunomodulators significantly increased the serum values (p less than 0.001). In the presence of a growing MBT tumor, however, the immunomodulation did not substantially falsify the results. The serum values were related to the corresponding tumor sizes.
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PMID:Quantitative measurements of humoral immune response in mice to a FANFT induced bladder tumor. 389 7

Three types of interferon preparation (alpha, beta and gamma) have been used in the treatment of tumours in vivo. At the time of writing no information is available on IFN-gamma treatment of tumour patients. Treatments with IFN-alpha and IFN-beta have been undertaken at many clinical centres. Both types of preparation can exert side effects. Both types have also been able to cause regression of certain tumours in individual patients. At our hospital, IFN-alpha has been given to tumour patients over the last decade. Antitumour effects have been registered on patients with juvenile laryngeal papillomatosis, Hodgkin's disease, myelomatosis, ovarian carcinoma, hypernephroma and glioblastoma. Further study is needed on how therapy with IFN should best be undertaken and also how such treatment compares with other treatments of various tumour diseases. IFN therapy should also be combined with other such treatments.
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PMID:Interferon therapy in neoplastic diseases. 618 85

Levels of intracellular glutathione (GSH) and the GSH-related enzymes gamma-glutamylcysteine synthetase (gamma-GCS) and gamma-glutamyltranspeptidase (gamma-GT) were measured in the melphalan-resistant human multiple myeloma cell line 8226/LR-5 and were compared to those measured in the drug-sensitive 8226/S and doxorubicin-resistant 8226/Dox40 cell lines. Both GSH and gamma-GCS activity, the rate-limiting step in the de novo synthesis of GSH, were elevated by a factor of approximately 2 in the melphalan-resistant 8226/LR-5 cells relative to the other two lines. gamma-GT activity was not elevated significantly in the /LR-5 cells. Northern analysis with a probe specific for the large subunit of human liver gamma-GCS identified two bands (3.2 and 4.0 kb), both of which were increased by a factor of 2-3 in the 8226/LR-5 line. Levels of gamma-GCS mRNA expression were comparable in the /S and /Dox40 cell lines. Levels of gamma-GT mRNA were similar in the /S and /LR-5 lines but were reduced in the /Dox40 cells. These data suggest that the increased GSH levels associated with resistance to melphalan in the 8226/LR-5 myeloma cells is attributable to up-regulation of gamma-GCS. This observation is consistent with recent demonstrations of up-regulation of gamma-GCS in melphalan-resistant prostate carcinoma cells and cisplatinum-resistant ovarian carcinoma cells, suggesting that increased expression of gamma-GCS may be an important mediator of GSH-associated resistance mechanisms.
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PMID:Up-regulation of gamma-glutamylcysteine synthetase activity in melphalan-resistant human multiple myeloma cells expressing increased glutathione levels. 751 21


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