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)

Paclitaxel is a new anticancer agent with a novel mechanism of action. It promotes polymerisation of tubulin dimers to form microtubules and stabilises microtubules by preventing depolymerisation. In noncomparative trials, continuous infusion of paclitaxel 110 to 300 mg/m2 over 3 to 96 hours every 3 to 4 weeks produced a complete or partial response in 16 to 48% of patients with ovarian cancer and 25 to 61.5% of patients with metastatic breast cancer, many of whom were refractory to treatment with cisplatin or doxorubicin, respectively. 23 to 100% of patients with ovarian cancer achieved complete or partial responses with paclitaxel in combination with cisplatin, carboplatin, cyclophosphamide, altretamine and/or doxorubicin. Similarly, response rates of 30 to 100% were observed with paclitaxel plus doxorubicin, cisplatin, mitoxantrone and/or cyclophosphamide in patients with metastatic breast cancer. Comparative trials in patients with advanced ovarian cancer showed paclitaxel therapy to produce greater response rates than treatment with parenteral hydroxyurea (71 vs 0%) or cyclophosphamide (when both agents were combined with cisplatin) [79 vs 63%]. Paclitaxel was also more effective than mitomycin in 50 patients with previously untreated breast cancer (partial response in 20 vs 4% of patients). Paclitaxel therapy also produced promising results in patients with advanced squamous cell carcinoma of the head and neck, malignant melanoma, advanced non-small cell lung cancer (NSCLC), small cell lung cancer (SCLC), germ cell cancer, urothelial cancer, oesophageal cancer, non-Hodgkin's lymphoma or multiple myeloma, and was successfully combined with cisplatin, carboplatin and/or etoposide in patients with NSCLC, SCLC or advanced squamous cell carcinoma of the head and neck. Hypersensitivity reactions were initially a concern with administration of paclitaxel, although current dosage regimens have reduced the incidence of these events to less than 5%. The major dose-limiting adverse effects of paclitaxel are leucopenia (neutropenia) and peripheral neuropathy. Other haematological toxicity was generally mild. Cardiac toxicity was reported in small numbers of patients and most patients developed total alopecia. Several aspects of paclitaxel use remain to be clarified, including the optimal treatment schedule and infusion time, confirmation of the tolerability profile and efficacy of combination regimens in an expanded range of malignancies. Long term follow-up of paclitaxel recipients will also allow the effects of the drug on patient survival to be determined. Nevertheless, paclitaxel is a promising addition to the current therapies available, with significant activity reported in patients with advanced ovarian or breast cancer or other types of tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
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PMID:Paclitaxel. A review of its pharmacodynamic and pharmacokinetic properties and therapeutic potential in the treatment of cancer. 753 Jun 32

Peripheral blood progenitor cells (PBPC) can be mobilized using cytotoxic chemotherapy and cytokines. There is a substantial variability in the yield of hematopoietic progenitor cells between patients. We were looking for predictive parameters indicating a patient's response to a given mobilization regimen. Multiparameter flow-cytometry analysis and clonogenic assays were used to examine the hematopoietic progenitor cells in bone marrow (BM) and peripheral blood (PB) before filgrastim (R-metHuG-CSF; Amgen, Thousand Oaks, CA)-supported chemotherapy and in PB and leukapheresis products (LPs) in the recovery phase. Fifteen patients (four with high-grade non-Hodgkin's lymphoma [NHL], two with low-grade NHL, two with Hodgkin's disease, two with multiple myeloma, three with breast cancer, one with ovarian cancer, and one with germ cell tumor) were included in this study. The comparison of immunofluorescence plots showed a homogenous population of strongly CD34+ cells in steady-state and mobilized PB whereas in steady-state BM, the CD34+ cells ranged from strongly positive with continuous transition to the CD34- population. Consistent with the similarity in CD34 antigen expression, a correlation analysis showed steady-state PB CD34+ cells (r = .81, P < .001) and colony-forming cells (CFCs; r = .69, P < .01) to be a measure of a patient's mobilizable CD34+ cell pool. Individual estimates of progenitor cell yields could be calculated. With a probability of 95%, eg, 0.4 steady-state PB CD34+ cells x 10(6)/L allowed to collect in six LPs 2.5 x 10(6) CD34+ cells/kg, the reported threshold-dose of progenitor cells required for rapid and sustained engraftment after high-dose therapy. For the total steady-state BM CD34+ cell population, a weak correlation (r = .57, P < .05) with the mobilized CD34+ cells only became apparent when an outlier was removed from the analysis. Neither the CD34+ immunologic subgroups defined by the coexpression of the myeloid lineage-associated antigens CD33 or CD45-RA or the phenotypically primitive CD34+/HLA-DR- subset nor the BM CFC count had a predictive value for the mobilization outcome. This may be caused by the additional presence of maturing progenitor cells in BM, which express lower levels of the CD34 antigen and do not circulate. Our results permit us to recognize patients who are at risk to collect low numbers of progenitor cells and those who are likely to achieve sufficient or high progenitor cell yields even before mobilization chemotherapy is administered.
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PMID:Peripheral blood progenitor cell (PBPC) counts during steady-state hematopoiesis allow to estimate the yield of mobilized PBPC after filgrastim (R-metHuG-CSF)-supported cytotoxic chemotherapy. 860 80

Risk of cancer mortality from 1973 to 1985 in persons born in the Indian subcontinent who migrated to England and Wales was analysed by ethnicity, and compared with cancer mortality in the England and Wales native population, using data from England and Wales death certificates. There were substantial highly significant raised risks in Indian ethnic migrants for cancers of the mouth and pharynx, gall bladder, and liver in each sex, larynx and thyroid in males, and oesophagus in females. There were also substantial raised risks in these migrants of each sex for non-Hodgkin's lymphoma and myeloma. For the mouth and pharynx, and liver in each sex, and gall bladder in females, there were also raised risks of lesser magnitude in British ethnic migrants. For colon and rectal cancer and cutaneous melanoma in each sex, ovarian cancer in women and bladder cancer in men, there were appreciable significantly reduced risks in the Indian ethnic migrants not shared by those of British ethnicity. Appreciable raised risks in British ethnic migrants not shared by those of Indian ethnicity occurred for nasopharyngeal cancer in males, soft tissue malignancy in both sexes and non-melanoma skin cancer in males. In migrants of both ethnicities there were appreciable significantly raised risks in each sex for leukaemia and decreased risks in each sex for gastric cancer, for lung cancer except in females of British ethnicity and in males for testicular cancer. The results suggest the need for public health measures to combat the high risks of oral and pharyngeal cancers and liver cancer in the Indian ethnic immigrant population of England and Wales, by prevention of betel quid chewing and hepatitis transmission respectively. The data also imply that early exposures or early acquired behaviours in India, or exposures during migration, may increase the risk of leukaemia and reduce the risks of gastric and testicular cancers in the migrants irrespective of their ethnicity. Aetiological studies would be worthwhile to investigate the reasons for the sizeable decreased risk of colon and rectal cancer and increased risk of gall bladder cancer in each sex and the increased risk of thyroid and laryngeal cancer in males and oesophageal cancer in females of Indian ethnicity but not of British ethnicity who have migrated from the Indian subcontinent.
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PMID:Cancer mortality in Indian and British ethnic immigrants from the Indian subcontinent to England and Wales. 757 89

10 patients were subjected to tandem transplantation for breast cancer (n = 3), ovarian cancer (n = 2) and multiple myeloma (n = 5), at the Second Department of Medicine, Donauspital, Vienna. The breast cancer patients were in stages 2 and 3, respectively, at diagnosis and entered complete remission thereafter. 2 of them developed lymph node metastasis and additional local recurrence, the 3rd patient presented with distant metastasis. The 2 patients with ovarian cancer were in stages Figo III and IV, respectively, at the time of diagnosis, and showed minimal residual disease at second-look-operation. 5 patients with multiple myeloma were in stage 3 pretransplant. Peripheral stem cells were obtained after either high-dose cyclophosphamide or FEC induction and application of cytokines. In 4 patients, tandem transplantation has been completed. 1 patient with multiple myeloma, who had received total body irradiation in combination with chemotherapy for the 2nd transplant, succumbed from idiopathic interstitial pneumonia. No severe clinical complications were observed in all other patients. All patients with solid tumors entered complete remission after the 1st transplantation. 3 of them completed tandem transplantation. Of these, 2 remain in continuous complete remission, the 3rd patient relapsed in lymph nodes day 485. In patients who received only 1 course of high dose chemotherapy with stem cell transplantation, relapses occurred on days 29 and 75, respectively. All patients with multiple myeloma entered only partial remission. We conclude that supralethal chemotherapy with peripheral blood stem cell support is a safe procedure that may at least induce prolonged remissions in solid tumors and hematologic malignancies.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Tandem transplantation with peripheral autologous hematopoietic blood stem cells in treatment of oncologic and hematologic malignancies. Initial results of the Donauspital, Vienna]. 776 51

A novel vector pMH-gpt, which is proved useful for cloning mouse immunoglobulin heavy and light chain V genes and for expressing mouse-human chimeric antibody, was constructed. The vector contains human genomic C gamma 1 and C kappa genes, cloning sites for immunoglobulin V region genes, murine Ig promoters, a human Ig heavy chain enhancer, and the selection marker gene Eco-gpt. Because VH and V kappa genes can be cloned into a single vector, a chimeric antibody gene is easily constructed by this simple insertion procedure. The usefulness of the vector was confirmed by construction of two mouse-human chimeric antibodies. Mouse monoclonal antibody (MAb) 196-14 recognizes the ovarian cancer-associated antigen (CA125), and MoAb 2-18 reacts with carcinoembryonic antigen (CEA). Mouse-human chimeric 196-14 and 2-18 antibodies were readily constructed and efficiently produced in a mouse myeloma cell line by utilizing the vector. Both chimeric antibodies retained binding activity to their respective antigens. In biodistribution and immunoscintigraphy studies, specificity of radiolabeled chimeric 196-14 antibody was identical to that of its murine counterpart and significant accumulation at the tumor site was observed. The pMH-gpt vector is useful for constructing and producing mouse-human chimeric antibodies.
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PMID:Construction and expression of chimeric antibodies by a simple replacement of heavy and light chain V genes into a single cassette vector. 786 92

A retrospective study was undertaken to evaluate the efficacy of autologous blood stem cell transplantation (ABSCT) in terms of haemopoietic reconstitution after ablative chemotherapy or chemo-radiotherapy. 55 patients with malignancies, observed in four Italian institutions from January 1987 to June 1991, were eligible for evaluation. This series included 19 non-Hodgkin's lymphoma, 11 multiple myeloma, nine ovarian cancer, seven Hodgkin's disease, seven non-lymphocytic leukaemia, one acute lymphoblastic leukaemia, one neuroblastoma. 522 PBSC collections were performed on 55 patients. Following ABSCT, the rate of engraftment was positively related to the dose of CFU-GM infused and negatively to the presence of bone marrow involvement at conditioning. 48 patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant-related complications. Considering that 60% of the patients in this series were in partial remission or in progressive disease at the time of ABSCT, we conclude that ABSCT is a safe approach for the use of ablative conditioning therapy in patients with a wide scope of malignancies, provided that a large number of CFU-GM have been collected after mobilizing treatment.
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PMID:Haemopoietic reconstitution after autologous blood stem cell transplantation in patients with malignancies: a multicentre retrospective study. 791 99

A retrospective study was undertaken to assess the factors affecting the yield of peripheral blood stem cell (PBSC) collections after chemotherapy. Fifty-five patients with malignancies, observed in 4 Italian Institutions from January 1987 to June 1991 were eligible for evaluation. This series included 19 non-Hodgkin lymphoma, 11 multiple myeloma, 9 ovarian cancer, 7 Hodgkin disease, 7 acute non-lymphocytic leukemia, 1 acute lymphoblastic leukemia, 1 neuroblastoma. Five hundred and twenty two PBSC collections were performed on 55 patients after a median of 18 days after the start of chemotherapy. The yields of PBSC collections were related to the dose of cytoreductive chemotherapy exploited for PBSC mobilization and to the number of circulating white blood cells, colony forming unit granulocyte/macrophage (CFU-GM) and the percentage of monocytes at the time of collection. Forty-eight patients out of 55 transplanted (87%) had rapid, complete and sustained engraftment. Three patients (5%) died of transplant related complications.
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PMID:Autologous blood stem cell collection after chemotherapy in patients with sensitive and refractory malignancies: a multicenter retrospective study. 791 30

The purpose of this study was to determine the toxicities and potential effectiveness of high-dose busulfan, melphalan and thiotepa (Bu/Mel/TT) followed by autologous peripheral blood stem cell (PBSC) infusion in patients with a variety of diseases. A phase II clinical trial of Bu (12 mg/kg), Mel (100 mg/m2) and TT (500 mg/m2) followed by PBSC infusion in 104 patients with breast cancer (n = 48), malignant lymphoma (n = 25), ovarian cancer (n = 13), multiple myeloma (n = 7) and other malignancies (n = 11) was performed. Sixty-two patients were treated in an academic medical center and 42 in a community cancer center. Grade 3-4 regimen-related toxicities occurred in 14% of patients, causing regimen-related mortality in six (6%) patients with an overall transplant-related mortality of 9%. Transplant-related deaths occurred in 6/62 patients (10%) treated in an academic medical center and in 3/42 (7%) treated in a community cancer center. Complete remissions (CR) were achieved in 1/17 (6%) patients with refractory stage IV breast cancer, 4/4 patients with responsive stage IV breast cancer, 6/13 (46%) with more-advanced lymphoma and 4/4 with less-advanced lymphoma. These patients are alive and disease-free a median of 712, 279, 461 and 404 days after transplant, respectively. Nineteen of 22 patients with stage II-III breast cancer remain alive and disease-free a median of 365 days after transplant. Complete remissions were also seen in 4/9 patients with ovarian cancer and 3/7 with multiple myeloma. The Bu/Mel/TT regimen followed by autologous PBSC infusion is associated with acceptable morbidity and mortality, appears to have significant activity in patients with breast cancer and is well tolerated in the adjuvant setting of stage II-III breast cancer. Bu/Mel/TT also appears to have significant activity in patients with lymphoma, multiple myeloma and possibly ovarian cancer. Further phase II-III studies are warranted in patients with these and other malignancies.
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PMID:Phase II study of high-dose busulfan, melphalan and thiotepa with autologous peripheral blood stem cell support in patients with malignant disease. 880 98

High-dose chemotherapy with haematopoietic stem cell rescue has proven to be an effective treatment in relapsed lymphoma and neuroblastoma. This treatment approach should be considered also in selected patients with leukaemia, multiple myeloma, breast cancer, ovarian cancer and testicular cancer. Relative contraindications include progression of the disease on appropriate conventional treatment, poor performance status, active infection as well as serious renal, pulmonary, liver and cardiac dysfunction. Increasing age should also be taken into consideration when autologous stem cell transplantation is planned. Every effort should be made to eliminate malignant cells that can be present in the stem cell containing population, which will be infused to the patient following myeloablative treatment.
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PMID:Autologous stem cell transplantation in the treatment of cancer. 893 7

Autologous transplantation uses high dose chemotherapy (with or without radiation therapy) followed by hematopoietic stem cell support in an attempt to cure certain malignant conditions. Autotransplantation can be considered as a treatment modality, if the tumor demonstrates a steep dose-response curve, marrow toxicity is the major dose limiting side effect of the active chemotherapeutic agents, and the source of the cells used for hematopoietic reconstitution is free of viable tumor cells. Hematopoietic stem cells can be obtained from peripheral blood after recovery from chemotherapy induced neutropenia or following treatment with hematopoietic growth factors and these peripheral blood stem cells are the predominant product used for autologous transplants at the present time. Autotransplantation has been shown to be useful in the treatment of certain patients with lymphomas, leukemias, myeloma, breast cancer, testicular cancer, ovarian cancer, and selected other tumors.
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PMID:The use of autologous transplantation in the treatment of malignant disorders. 915 Jan 16


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