Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006142 (breast cancer)
 160,383 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autologous peripheral blood progenitor cells (PBPC) rescue after high-dose chemotherapy has been used progressively as a form of treatment in some solid and hematologic tumors. This increasing use can be explained by both advantages of PBPC rescue over bone marrow rescue (decrease in the duration of marrow aplasia, reduction of platelet transfusions, earlier discharge from hospital, potential use in patients with inadequate bone marrow reserve) and the low number of aphereses (one or two) needed to collect a sufficient number of progenitor cells for autografting. High-dose chemotherapy is likely to be increasingly used after the results of two recently reported studies in which treatment with high-dose compared with standard-dose chemotherapy increases overall survival in metastatic breast cancer patients and relapsed lymphoma patients. After the initial use of unselected mobilizing regimens regardless of the patient characteristics and the tumor type, now it seems more useful to optimize this approach. Mobilization of PBPC can be obtained by several approaches. Moderate or high doses of single agent alone (e.g. cyclophosphamide 4-7 g/m2) or some hematopoietic growth factors alone (e.g. G-CSF, GM-CSF) have been proven to be adequate mobilizing agents. However, the use of hematopoietic growth factors alone may disadvantageously delay the start of an effective chemotherapy. An efficient mobilizing regimen requires the use of both chemotherapy and hematopoietic growth factors: the efficiency of mobilization was greater and with less side effects than chemotherapy alone. It was postulated that PBPC mobilization could be achieved only at hematopoietic recovery following myeloablative chemotherapy. Recently, it has been demonstrated that some standard-dose chemotherapy regimens associated with hematopoietic growth factors are efficient priming agents. We reported that standard-dose CEF chemotherapy plus filgrastim is a disease specific regimen (breast cancer) allowing PBPC mobilization without any relevant toxicity. The maximum release of PBPC has been observed at day 11. The optimal time for PBPC collection is predictable and aphereses can be guided by WBC counts. In conclusion, both standard and high dose chemotherapy are effective priming regimens. So presently a mobilizing regimen should be an effective disease specific chemotherapy program and should contain a hematopoletic growth factor. The choice between standard and high-dose chemotherapy can be based on patients characteristic and disease status.
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PMID:[Mobilization of peripheral blood stem cells with conventional chemotherapy]. 892 33

Low-dose, subcutaneous recombinant human granulocyte colony-stimulating factor (rHuG-CSF, Lenograstim) was administered to 40 cancer patients (17 men, 23 women) enrolled from two medical centers to verify its clinical effectiveness and safety. The patients' mean age was 50.3 +/- 14.9 years. In this study, there were 20 patients with non-Hodgkin's lymphoma, 10 with breast cancer and 10 with various other solid tumors. The patients first received a course of chemotherapy without rHuG-CSF (control cycle). All patients had at least one episode of neutropenia or leukopenia during the control cycle. rHuG-CSF (2 micrograms/kg/day) was given subcutaneously for 10 days during the study cycle starting on the fourth day of chemotherapy. The nadirs of absolute neutrophil counts (ANC) were 1.8 +/- 0.25 x 10(9)/L and 0.27 +/- 0.05 x 10(9)/L for the rHuG-CSF cycle and pre-rHuG-CSF control cycle, respectively. The number of days of ANC < 1 x 10(9)/L were 1.03 +/- 0.29 and 7.38 +/- 0.58 for rHuG-CSF and control cycles, respectively. The duration from nadir to recovery of ANC (> or = 2 x 10(9)/L) was 9.68 +/- 1.15 days in the rHuG-CSF cycle, vs 22.53 +/- 1.03 days in the control cycle (p < 0.0001). No patient withdrew from the study. Adverse events were mild, with 12.5% to 40% of patients developing myalgia, general malaise, back pain, anorexia or fever. These side-effects were tolerable in all cases. The biochemical abnormalities were subtle and negligible. rHuG-CSF 2 micrograms/kg/day given subcutaneously for 10 days beginning on the fourth day of chemotherapy is very effective (90%), safe and convenient.
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PMID:Clinical trial of low-dose rHuG-CSF in neutropenic cancer patients following anti-cancer chemotherapy. 899 Jul 72

Cytotoxic T-cell (CTL) cultures were generated from five ovarian cancer patients (OvCTL) and from three breast cancer patients (BrCTL). All CTL lines were T-cell receptor (TcR) alphabeta+ and predominantly CD8+ (73 +/- 13%). These CTL lines preferentially recognized autologous tumor cells in an HLA class I-restricted, and in part HLA-A2-restricted, manner. In addition, the CTL lines recognized allogeneic HLA-A2+ ovarian and breast tumor cells. Specific recognition was determined by T-cell-mediated cytotoxicity as well as cytokine release. Coculture of irradiated autologous tumor cells with OvCTL induced secretion of IFN-gamma, GM-CSF and TNF-alpha, but not IL-4, indicating a T helper-1-type response. Similar results were obtained when OvCTL and BrCTL were stimulated with histologically matched HLA-A2+ tumor cells. Also, BrCTL stimulated with HLA-A2+ but not HLA-A2- ovarian tumor cells produced significant levels of GM-CSF and TNF-alpha. Finally, the Her2/neu peptide p654-662, earlier identified as a tumor antigen in both ovarian and breast cancer, induced cytotoxicity as well as the specific release of IFN-gamma and TNF-alpha but not IL-4 by OvCTL and BrCTL. Thus, tumor-specific recognition by CTL was verified by cytotoxicity and cytokine release. The secretion of Th1-like cytokines as opposed to Th2-like cytokines suggest that therapeutically OvCTL and BrCTL could potentially enhance the endogenous immune response to tumor.
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PMID:Simultaneous production of T helper-1-like cytokines and cytolytic activity by tumor-specific T cells in ovarian and breast cancer. 902 20

Thirty patients diagnosed with breast cancer were included in a prospective randomized study comparing the in vivo priming effect of bioequivalent doses of glycosylated (lenograstim) and nonglycosylated (filgrastim) rG-CSF administration. Analysis of the efficacy of equivalent biological doses of both rG-CSFs showed no significant differences either in the mobilization of the subpopulations of PBPC considered (CD34+, CD34+/38-, CD34+/DR-), the content of such CD34+ cell subsets in the leukapheresis product, or the cost of the mobilization and collection procedures between both recombinant molecules. These results suggest that priming with bioequivalent doses of the two commercially available forms of glycosylated or nonglycosylated rG-CSF has a similar in vivo effect on PBPC mobilization.
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PMID:Prospective randomized study comparing the efficacy of bioequivalent doses of glycosylated and nonglycosylated rG-CSF for mobilizing peripheral blood progenitor cells. 902 36

We report on an 66-year old female in whom we diagnosed uterine carcinosarcoma and concurrent breast cancer. As first-line treatment the patient received ifosfamide 4.8 mg/m2 body surface. During her second course of chemotherapy she developed sequentially life-threatening toxicities; severe emesis followed by nephrotoxicity, neurotoxicity and myelosuppression. Early prophylactic administration of rhG-CSF (Filgrastim) helped to overcome severe, potentially fatal myelosuppression. The course of severe toxicities following high doses of ifosfamide might reflect a dependent sequence, where one organ failure causes a subsequent organ failure. Prophylactic treatment of anticipated toxicity should be considered for the management of severe ifosfamide-induced toxicity. Such treatment may consist of sufficient antiemesis, sufficient hydration, as well as a therapy with methylene blue in case of severe neurotoxicity.
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PMID:[Sequential course and prospective management of ifosfamide-induced multi-organ toxicity]. 903 65

The generation of megakaryocytes (MK) from cultured peripheral blood progenitor cells (PBSC), harvested via apheresis, from 18 female breast cancer patients treated with either PIXY321 or GM-CSF was compared. Nonadherent mononuclear cells (MNC) were cultured in liquid suspension with 50 U/ml thrombopoietin (TPO) and 2.5% autologous heparinized plasma for 12 days. Flow cytometric analysis was used to measure the percentage of CD34+ on day 1 and CD41+ cells on day 12. The frequency of CD34+ cells was greater in GM-CSF-mobilized samples than in PIXY321-mobilized samples, and MK/MNC yields correlated directly with the number of CD34+ cells seeded, PIXY321-mobilized samples produced more MKs per CD34+ cell than GM-CSF-mobilized samples. Overall, there was no significant difference in the MK/MNC yield between PIXY321- and GM-CSF-mobilized samples. Cyclophosphamide (CY) increased the frequency of CD34+ cells and the corresponding MK/MNC yield for both cytokines, but had no effect on the MK/CD34+ yield. Compared to GM-CSF, PIXY321 mobilization resulted in increased CD34+ cell commitment to the MK lineage.
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PMID:In vitro production of megakaryocytes from PIXY321 versus GM-CSF-mobilized peripheral blood progenitor cells. 909 Jul 87

High-dose chemotherapy (HDC) supported by autologous transplantation of blood stem cells (BSC) is used increasingly for patients with poor-risk malignancies. We report our experience with 93 consecutive patients who were mobilized with recombinant human granulocyte colony-stimulating factor (rhG-CSF) alone. They received a fixed dose of G-CSF for 5 or 6 days, and BSC were collected by leukapheresis. Aphereses were evaluated for MNC, CD34+ cells, and CFU-GM counts and cryopreserved. All patients received a conditioning regimen without TBI. Engraftment was assessed as the first of 2 consecutive days on which patients achieved 0.5 and 1 x 10(9)/L neutrophils and an unsupported platelet count of 25 x 10(9)/L. Multivariate analysis was performed to study patients and graft characteristics that could influence reconstitution. The G-CSF priming regimen was well tolerated and allowed collection of BSC for all patients, 66% of them achieving >3 x 10(6)/kg CD34+ cells, and 86% achieving >10 x 10(4) CFU-GM/kg. The numbers of collected CD34 and CFU-GM cells were highly correlated. The number of courses of chemotherapy prior to collection, a diagnosis of breast cancer, the use of rhG-CSF posttransplant, and the numbers of CFU-GM and CD34+ cells reinfused were correlated with hematologic recovery. In a multivariate analysis, however, the number of CD34+ cells was the only factor independently influencing both granulocyte and platelet recovery. Patients who received at least 3 x 10(6)/kg CD34+ cells achieved granulocyte reconstitution on day 11 after reinfusion (range 8-15) and an unsupported platelet count of 25 x 10(9)/l on day 14 (range 12-180), significantly earlier than patients who received fewer cells (p < 0.001). In addition, G-CSF administration postreinfusion independently enhanced granulocyte reconstitution but not platelet recovery. In conclusion, CD34+ cell number appears to be the only factor predicting both granulocyte and platelet reconstitution. Based on this study, the collection of a minimal number of 3 x 10(6)/kg CD34+ cells appears desirable.
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PMID:Autologous transplantation of blood stem cells mobilized with filgrastim alone in 93 patients with malignancies: the number of CD34+ cells reinfused is the only factor predicting both granulocyte and platelet recovery. 911 55

High-dose chemotherapy often requires hematopoietic progenitor cell reinfusion, but drugs with extramedullary dose-limiting toxicity may be administered in the high-dose range by simple growth factor support. In this study, we evaluated the feasibility and toxicity of a three-drug high-dose regimen supported by recombinant human granulocyte colony-stimulating factor (rhG-CSF). Ten patients with histologically proven malignancy were enrolled. Eight had breast cancer, one non-Hodgkin's lymphoma, and one a mediastinal tumor of unknown origin. The regimen included cyclophosphamide (C) 5 g/m2, etoposide (E) 1.5 g/m2, and cisplatin (P) 150 mg/m2 (CEP), administered in a 3-day schedule followed by rhG-CSF, 300 micrograms once a day, beginning from day +5 (36 h after the end of chemotherapy). The cycle was repeated as clinically needed up to three times. After the first course, hematologic recovery was rapid and complete without documented infections, and no relevant extramyeloid toxicities were observed. Eight of 10 patients received a second course with comparably low toxicity, and three of them received a third course. We concluded that CEP therapy can be administered safely and even repeatedly, by simple growth factor support, in good performance status cancer patients.
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PMID:Standard-dose recombinant human granulocyte colony-stimulating factor (rhG-CSF) allows safe and repeated administration of high-dose cyclophosphamide, etoposide, and cisplatin (CEP). 916 51

A 66-year-old woman with medically treated hypertension and a recent operation for breast cancer was admitted because of burning pain localized between her shoulder blades and a paretic, dysaesthetic right arm. CSF examination revealed lymphocytic pleocytosis and specific IgM Borrelia burgdorferi antibodies. CT was normal. The patient was treated intravenously with high doses of penicillin for 14 days, and within one month of admission she had recovered completely neurologically. During the first days of treatment a drop in blood pressure, ECG changes, and further neurological changes were observed, but disappeared spontaneously within three days. The patient did not recall a tick bite, and the case illustrates that neuroborreliosis may be a differential diagnosis to stroke or cerebral neoplasms in elderly patients.
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PMID:[Lyme neuro-borreliosis in a 66-year old women. Differential diagnosis of cerebral metastases and cerebral infarction]. 919 7

Leptomeningeal (LM) cancer spread from either a primary brain tumor or a systemic cancer is rapidly fatal. Current therapies are ineffective and highly toxic to normal nervous system tissues. A xenograft model of LM neoplasia in nude rats using a diversity of tumor cell types was established in order to evaluate new treatment strategies and to study the pharmacokinetics and biological effects of treatments administered into the subarachnoid space. Consistent leptomeningeal engraftment and progressive tumor growth was seen after intrathecal injection of 9 of 13 tumor cells lines, including 2 melanomas, 2 neuroblastomas, 2 medulloblastomas, 2 gliomas, and 1 breast cancer. Clinical signs ranged from steady weight loss commencing from the day after tumor implantation to absence of any signs for three weeks until the sudden occurrence of major neurological deficits or death. Pathologic examination showed only leptomeningeal tumor growth with some cell lines and severe parenchymal invasion with others. CSF cytology consistently demonstrated tumor cells in animals with LM disease. Cranial magnetic resonance (MR) following intravenous (i.v.) administration of a contrast agent revealed enhancing lesions one week following melanoma tumor implantation. Reliable ventricular puncture was demonstrated by radiography following intraventricular (IVent) injection of an iodinated contrast material. IVent instillation of saline, albumin, or antibodies did not provoke clinical toxicity or an inflammatory response.
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PMID:A rat model of leptomeningeal human neoplastic xenografts. 925 14


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