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)

Tumour cell contamination of autologous peripheral blood stem cell samples (PBSC) and bone marrow (BM) is frequent. Enrichment of CD34+ stem cells is a promising approach to purging tumour cells from autografts without damaging progenitor cells. Breast cancer cells were seeded (10(-3)-10(-7)) into mononuclear cells from G-CSF-mobilised PBSC and BM harvests from patients without breast cancer. CD34+ cells were enriched from mixtures either by immunomagnetic separation (Isolex-50, and MiniMACS) or by biotin-streptavidin immunoaffinity columns (Ceprate-LC). CD34+ cell fractions were determined by FACS, cancer cells were detected immunocytochemically with an anti-pancytokeratin antibody. The CD34+ cells were enriched with a median purity of 92.2% (43.5-96.1) (n = 17) (Isolex-50), 96.5% (66.6-99.2) (n = 17) (MiniMACS) and 77.9% (31.4-93.6) (n = 15) (Ceprate-LC) from PBSC and BM harvests. The percentages of median recovery of CD34+ cells were 30.8% (18.6-71.8) (Isolex-50), 69.9% (39.1-100) (MiniMACS) and 42.9% (23.7-100) (Ceprate-LC). The median tumour cell reductions in log steps were 3.7 (2.9-4.3) (n = 13) (Isolex-50), 3.5 (2.6-4.3) (n = 13) (MiniMACS) and 1.5 (0.9-2.9) (n = 17) (Ceprate-LC). Results were compared statistically by univariate analysis. Purity was significantly (P < 0.05) better after MiniMACS selection. Recovery rates were significantly different between all devices tested. Tumour cell purging was superior after immunomagnetic separation (P < 0.001). Tumour cell purging is a main objective of CD34+ selection in the autologous setting. Our in vitro data clearly indicate that immunomagnetic separation is more efficient in the prevention of accidental reinfusion of contaminating tumour cells compared to immunoaffinity. However, it is not yet known if the same results can be obtained with fresh contaminating tumour cells.
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PMID:Purging and haemopoietic progenitor cell selection by CD34+ cell separation. 957 5

Vinorelbine (Navelbine) is a unique semi-synthetic vinca-alkaloid with a favorable safety profile that has demonstrated significant antitumor activity in patients with non-small cell lung cancer, advanced breast cancer, advanced ovarian cancer and Hodgkin's disease. The most common dose-limiting toxicity is neutropenia, while other reported toxicities are minimal. Mitoxantrone (Novantrone) is an anthracene derivative that has demonstrated antitumor activity in patients with breast cancer, ovarian cancer, acute leukemia, and lymphoma. Mitoxantrone also has a very favorable toxicity profile with significantly less nausea and vomiting, alopecia, and stomatitis as compared with anthracyclines. The dose-limiting toxicity for mitoxantrone is leukopenia. The study was designed to determine the safety and maximally tolerated dose of IV vinorelbine used in combination with a fixed dose of mitoxantrone for the treatment of patients with refractory solid tumors. Vinorelbine was administered on days 1 and 8 of the treatment regimen as a short IV infusion. The starting dose was 15 mg/m2. Mitoxantrone was administered as a 20-min infusion on day 1 only at a fixed dose of 10 mg/m2. Seventeen patients with solid malignancies were entered in the study. For personal reasons, one patient decided to discontinue the treatment after day 1 of cycle 1. Therefore, 16 patients were evaluable for toxicity. The main toxicity was myelosuppression which was dose-limiting and resulted in dose reductions and delays. The use of G-CSF had a minimal overall impact on this regimen. Stable disease was observed in three cases. In patients previously treated with chemotherapy, the maximally tolerated dose was defined as vinorelbine 20 mg/m2 on days 1 and 8 and mitoxantrone 10 mg/m2 on day 1 without growth factor support. These doses can be recommended for phase II study of the regimen as salvage treatment.
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PMID:A phase I trial of vinorelbine in combination with mitoxantrone in patients with refractory solid tumors. 974 May 42

While abundant data exist documenting variables associated with early platelet engraftment after autologous PBPC transplantation, data concerning later sustained platelet engraftment is sparse. We retrospectively examined a series of 80 patients undergoing autologous PBPC transplantation with respect to their platelet count 6 weeks after transplant. Underlying diagnoses included breast cancer (n = 33), non-Hodgkin's lymphoma (n = 32), Hodgkin's disease (n = 9), and other hematologic malignancies (n = 6). Patients received G-CSF for PBPC mobilization and collected a target threshold number of 2.0 x 10(6) CD34+ cells per kilogram. A univariate analysis revealed that a diagnosis of breast cancer, fewer courses of prior chemotherapy, younger age and complete remission were associated with a higher 6-week platelet count. Additionally, the ability to collect the threshold number of CD34+ with fewer sessions of leukapheresis was also associated with a higher 6-week platelet count. The platelet count and the white blood cell count at the initiation of PBPC collection was also associated with a higher 6-week platelet count. A multivariate analysis revealed a higher platelet count on the first day of pheresis, fewer phereses required to collect 2 x 10(6) CD34+ cells per kilogram, and a diagnosis of breast cancer were all associated with a higher 6-week post-transplant platelet count. Seven patients failed to reach a 6-week platelet count of 30 x 10(9)/l and an additional five patients had a platelet count of 30-50 x 10(9)/l. We conclude that underlying clinical characteristics, as well as hematologic variables at the time of PBPC collection, influence later, sustained platelet engraftment. A percentage of patients have poor sustained platelet engraftment and may be candidates for new cytokines that specifically target megakaryocyte growth and development.
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PMID:Variables associated with the platelet count 6 weeks after autologous peripheral blood progenitor cell transplantation. 975 41

High-dose therapy followed by peripheral blood stem cell (PBSC) support was performed in 29 patients with primary high-risk (Group I) or chemoresponsive metastatic (Group II) breast cancer patients. Group I patients had received PBSC mobilization within 4 weeks of modified radical mastectomy. Group II patients had to achieve minimal residual disease (MRD) by induction chemotherapy before being considered eligible for PBSC mobilization and high-dose therapy. An innovative FE120C regimen (5-FU 600 mg/m2, i.v., day 1; epirubicin 120 mg/m2, i.v., day 1; cyclophosphamide 600 mg/m2, i.v., day 1) plus G-CSF (300 microg/day, subcutaneous injection for 9 days, from day 4 post-FE120C) was used to mobilize PBSCs. After high-dose CTCb (cyclophosphamide 6,000 mg/m2, thiothepa 500 mg/m2, carboplatin 800 mg/m2, in 4 days), patients received PBSC infusion and daily C-CSF 300 microg subcutaneous injection. There were 19 and 16 patients enrolled into Group I and Group II, respectively. Ten of the Group II patients had achieved minimal residual disease (MRD) after induction chemotherapy. The median numbers of mobilized total CD34 + cells for Group I and Group II patients were 27.3 (9.2 to 114.1) x 10(6)/kg and 17.1 (5.9 to 69.1) x 10(6)/kg respectively. The median time to neutrophil recovery (ANC > or = 500/microL) was 8 and 9 days in Group I and II, respectively. The median time to platelet recovery (> or = 50,000/microL) was 10 and 15 days in Group I and II, respectively. No major treatment-related toxicities were noted. In Group I, 13 out of 19 patients (68.4%; 43-87%, 95% C.I.) remained recurrence-free with a median follow-up of 31 months (6 + to 55 + months). In Group II, 3 out of 10 patients (30%; 7-65%, 95% C.I.) remained progression-free at 33 +, 35 +, 39 + months from induction therapy. We suggest that the FE120C plus G-CSF is an effective and innovative regimen for PBSC mobilization in breast cancer patients, and high-dose CTCb therapy with PBSC support is a safe and well-tolerated treatment modality.
Breast Cancer Res Treat 1998 Jun
PMID:High-dose therapy with peripheral blood stem cell (PBSC) support using an innovative mobilization regimen in patients with high-risk primary or chemoresponsive metastatic breast cancers. 977 7

Forty-one patients with operable breast cancer and >/=10 positive axillary lymph nodes were treated with 6 cycles of dose-dense adjuvant chemotherapy consisting of epirubicin (100 mg/m2) every 2 weeks with G-CSF support. A total of 240 cycles were administered, all of them at full dose and 19 (8%) with a delay. Thirty-eight (93%) patients completed the treatment according to the protocol. The relative dose intensity of epirubicin was 0.99. Grade 3 toxicities included anemia (3%), nausea and vomiting (5%) and alopecia (71%). After a median follow-up of 40 months, 16 (39%) patients were free of relapse. In conclusion, the present study has shown that the administration of dose-dense chemotherapy with epirubicin is feasible in the adjuvant setting with minimal toxicity.
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PMID:Dose-dense adjuvant chemotherapy with epirubicin monotherapy in patients with operable breast cancer and >/=10 positive axillary lymph nodes. A feasibility study. 977 14

We treated 20 women with locally advanced breast cancer between January 1991 and September 1996. The treatment regimen included 4 cycles of intensive doxorubicin (30 mg/m2/d on 3 consecutive days every 2 weeks with G-CSF support), followed by appropriate surgery, followed by high dose therapy with cyclophosphamide, carboplatin and thiotepa (STAMP V, CTCb). Of the 20 patients, seven presented with inflammatory breast cancer, three with Stage IIIB, seven with stage IIIA, one with multifocal Stage IIB and two with Stage IV M1 (ipsilateral supraclavicular lymph node involvement) (including one who had an inflammatory primary) disease. Six patients had not undergone mastectomy at the time of entering the protocol. These six received the doxorubicin in a neoadjuvant fashion and were thus evaluable for tumor response. The remaining 14 received doxorubicin as adjuvant therapy prior to intensification and transplantation. All patients underwent local-regional radiation therapy and were placed on oral tamoxifen. Doxorubicin was well tolerated in this schedule with all but three patients receiving all their cycles on schedule. Both BM and PBPC were easily collected after this regimen and, when reinfused, resulted in the prompt recovery of granulocytes (median 11 days to 500 absolute granulocyte count) and platelets (median 13 days to 20,000 platelets). The six patients who received doxorubicin prior to mastectomy all had major clinical responses, but were found to have microscopic focii of breast cancer in the mastectomy specimens. The overall treatment was well tolerated with the exception of one treatment-related death (5%). The overall and relapse free survival are 70% and 58% respectively with a median follow-up of 40 months (range 12-74 months). When the Stage IV patients are censored, the relapse-free survival rate is 69%. In the bone marrow transplant phase of treatment, the major non-hematologic toxicities were stomatitis (70%) and anorexia requiring parental nutrition (75%).
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PMID:Durable remission of locally advanced breast cancer with multimodality management. 978 15

Using an Isolex 300 immunomagnetic cell separator, we carried out CD34+ cell selection in samples from 4 patients with solid tumors: 2 patients with relapsed breast cancer, 1 post-operative patient with advanced breast cancer, and 1 post-operative patient with advanced ovarian cancer. Peripheral blood stem cells were mobilized by G-CSF and high-dose chemotherapy (CAF or VIC-E regimen). The mean recovery rate for CD34+ cells was 62.0% and the mean purity was 89.5%. However, the mean recovery for colony-forming cells (CFC) was only 10.9%, suggesting that recovered CD34+ cells may be damaged during the separation of immunomagnetic beads by releasing peptide or by 4 cycles of cytocentrifugation (at 800 G for 10 min). Approximately 30% of the CFC, consisting largely of BFU-E, had been recovered in the CD34- cell fraction. Recently, it has been reported that primitive long-term hematopoietic repopulating cells may express weakly or not at all for CD34 antigen. This suggests that careful follow-up monitoring is necessary for long-term hematopoietic reconstitution after CD34+ cell transplantation.
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PMID:[CD34-positive cell selection using an Isolex 300 system in patients with solid tumors and its application for autologous peripheral blood stem cell transplantation]. 979 98

Because the great majority of patients with advanced breast cancer have been traditionally placed under the care of surgeons, therapeutic planning is usually done by making operative management the key even at the present time when operable breast cancer is appropriately recognized to represent a systemic disease. For advanced breast cancer to be treated more effectively, systematically planned multimodality treatment must be undertaken. The development of G-CSF and stem cell transplantation to counter hematopoietic toxicity have allowed the safe use of high-dose intensity chemotherapy, which has also been applied in the neoadjuvant setting. Recent experience with neoadjuvant chemotherapy (NACT) has shown promise and indeed some good responders have been offered breast conserving surgery. NACT also serves as an in vivo chemosensitivity test, the results of which are to be exploited in chemo-hormonal therapy after locoregional treatment. Although further studies are required to evaluate this treatment more precisely, multicycle dose-intensified chemotherapy can now be safely and liberally incorporated into systematically planned multimodality treatment for advanced breast cancer.
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PMID:[Treatment of advanced breast cancer: current issues]. 979 5

In order to evaluate the mobilization of peripheral blood progenitor cells (PBPC) after an effective induction regimen in breast cancer, we performed a study on 15 breast cancer patients. Between January 1995 and June 1996, these patients received TNCF (THP-doxorubicin. vinorelbine, cyclophosphamide, fluorouracil for four days, every 21 days) with G-CSF support (5 microg/kg for 10 days after chemotherapy) to reduce aplasia. This regimen is known to result in a complete pathological response in 30% of patients. Between two cycles of TNCF treatment, hematological recovery was observed. Progenitor cells (CFU-GM and CD34+ cells) and mononuclear cells in DNA synthesis (MCDS) counts were performed daily, between the 12th and 17th post-chemotherapy days (81 samples). The results showed a similarity for hematological recovery and PBPC mobilization kinetics depending on the number of treatment cycles. The three methods used for PBPC evaluation were well correlated (P < 0.01) with an optimal mean PBPC recruitment by the last day of G-CSF administration: respectively, 11 520 (1729-26539) CFU-GM/ml of blood, 249 (14-1160) CD34+ cells/microl of blood and 211 (21-554) MCDS/microl of blood. These results suggested that a daily injection of G-CSF after one or two TNCF cycles will produce an effective PBPC mobilization in comparison with currently used regimens.
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PMID:Mobilization of peripheral blood progenitor cells after induction chemotherapy (THP-doxorubicin-vinorelbine-cyclophosphamide-fluorouracil) and granulocyte colony-stimulating factor in breast cancer. 982 11

Colony-stimulating factors (CSFs) are commonly used for the treatment of neutropenia following chemotherapy and for the mobilization of peripheral blood stem cells (PBSC). We recently experienced a rare case of a new onset of psoriasiform eruption by GM-CSF (granulocyte-macrophage colony-stimulating factor) which was exacerbated by G-CSF (granulocyte colony-stimulating factor) in a patient with breast cancer. A 36-year-old woman had received neoadjuvant chemotherapy (cyclophosphamide, epirubicin and 5-fluorouracil), modified radical mastectomy and adjuvant chemotherapy with paclitaxel and mitoxantrone followed by GM-CSF administration for the treatment of locally advanced breast cancer. She had developed a psoriatic skin lesion on face and both upper arms during leukocyte recovery in spite of no previous history of psoriasis. Next, the chemotherapy course was complicated by a flare of mild psoriatic skin lesion, although CSF was changed into G-CSF due to GM-CSF-associated psoriasis. Subsequently, she had had high-dose chemotherapy and autologous peripheral blood stem cell transplantation for consolidation therapy. GM-CSF was administered for the mobilization of PBSC and post-transplant period, but psoriatic skin lesion did not appear. During 6 months after PBSCT, psoriasiform eruption did not appear.
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PMID:Psoriasiform eruption triggered by recombinant granulocyte-macrophage colony stimulating factor (rGM-CSF) and exacerbated by granulocyte colony stimulating factor (rG-CSF) in a patient with breast cancer. 988 82


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