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)

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

In extracorporeal circulation, blood is affected by artificial biomaterials and shear forces. We investigated the effects of peripheral blood progenitor cell (PBPC) apheresis on the kinetics and level of platelet membrane antigen expression in 11 breast cancer and 13 testicular cancer patients. After mobilization with rhG-CSF, continuous-flow apheresis was performed. Expression of structural antigens CD41a and CD42b and activation-dependent antigens CD62p, CD63, and fibrinogen was analyzed by flow cytometry at fixed time intervals. Initial changes occurred in all of the antigens within minutes, followed by a progressive increase in the mean channel fluorescence intensities (MCFI) of CD62p from 26 +/- 8 (mean +/- SD) to 73 +/- 29 (p < 0.05), CD63 from 22 +/- 5 to 51 +/- 16 (p < 0.05) and antifibrinogen from 120 +/- 20 to 356 +/- 154 (p < 0.05). In contrast, CD41a and CD42b fluorescence decreased during apheresis (p < 0.05 for both). The more rapid sequestration of P-selectin-expressing platelets known to occur during extracorporeal PBPC apheresis suggests that platelet activation may be associated with the loss of platelets during this procedure. In addition, alteration of platelet surface antigens increases thrombogenic potential and may reduce the in vivo efficacy of the platelet hemostatic potential.
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PMID:Alteration of platelet-associated membrane glycoproteins during extracorporeal apheresis of peripheral blood progenitor cells. 937 70

Thirty-four patients diagnosed with breast cancer were included in a prospective study evaluating the bone marrow (BM) CD34+/CD71- cell content, as a predictive parameter of the CD34+ cell mobilization after rG-CSF administration. Analysis of the concentration of medullary CD34+/CD71- cells before priming schedules was significantly related with the collection of CD34+ cells in apheresis day 1 (P = 0.03, r = 0.36), apheresis day 1 + day 2 (P = 0.01, r = 0.42) or the total CD34+ cells collected (P = 0.005, r = 0.47). A BM CD34+/CD71- cell concentration greater than or less than a cut-off value of 30/microl was significantly associated with the yield of CD34+ cells collected by cytapheresis procedures (mean values 3.12 x 10(6)/kg, and 2.19 x 10(6)/kg, respectively, P = 0.013). These results suggest that in breast cancer patients undergoing priming with rG-CSF, steady-state BM CD34+/CD71- measurement is a relevant predictive parameter of CD34+ mobilization.
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PMID:Bone marrow steady-state CD34+/CD71- cell content is a predictive value of rG-CSF-mobilized CD34+ cells. 963 70

Discussion of the total costs and cost-effectiveness ratios of patients receiving high-dose chemotherapy (HDC) and peripheral blood stem cell support (PBSCS) is controversial. In Germany, no reliable data are available, whereas in other countries this issue has been extensively studied. We performed a pharmacoeconomic evaluation on all patients (n = 37) treated with HDC and PBSCS at our institution between July 1994 and June 1997. Patients suffered from high-risk or poor-prognosis breast cancer (n = 24), Hodgkin's disease (n = 3), high-grade non-Hodgkin's lymphoma (n = 4), multiple myeloma (n = 2), small-cell cervical cancer (n = 1), malignant hystiocytosis (n = 1) and testicular cancer (n = 2). For pharmacoeconomic evaluation, the period from initiation of induction chemotherapy (IC) until reconstitution after the last course of HDC and PBSCS was considered. A total of 18 patients received IC/HDC/PBSCS for locally advanced or systemic disease, and 19 patients received adjuvant or consolidation IC/HDC/PBSCS. Treatment protocols were heterogeneous. Patients were treated with two to five courses (median two) respectively of IC and sequential mono-HDC (n = 26), tandem-HDC (n = 10) or triple-HDC (n = 1). All patients received granulocyte/macrophage-colony-stimulating factor (G-CSF) for stem cell mobilisation and for amelioration of neutropenia after HDC. The relative costs (based on supplier prices) for the total amount of drugs prescribed during the in-patient period was 29.8% for G-CSF, 35.8% for blood products 18.5% for chemotherapy, 2.4% for antiemetics, 5.9% for antimicrobial drugs and 7.6% for other drugs. Contrary to expectations, antimicrobial drugs had only a minor pharmacoeconomic impact during IC/HDC/PBSCS in patients with high-risk or poor-prognosis malignancies, indicating that prolonged septic complications were uncommon in our institution. We conclude that pharmacoeconomic evaluations in IC/ HDC/PBSCS might be integrated into the effort to ensure quality control and monitoring.
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PMID:Pharmacoeconomic evaluation of high-dose chemotherapy and peripheral blood stem cell support in high-risk or poor-prognosis malignancies. 964 62

Meningeal metastasis occurs in 3-8% of all cancer patients, producing neurologic morbidity and a high mortality. Diagnosis is best established by the demonstration of malignant cells in the cerebrospinal fluid. However, in patients with known cancer, MR scan with gadolinium may be diagnostic when subarachnoid nodules can be demonstrated in the head or spine. Therapy usually involves radiotherapy to symptomatic sites, often followed by intrathecal chemotherapy. Intrathecal chemotherapy is best delivered by an intraventricular reservoir system but can also be delivered by repeated lumbar puncture. Methotrexate, cytarabine and thiotepa are the most common agents instilled into the subarachnoid space. Their limited efficacy can be explained by their restricted spectrum of antitumor activity. Patients with leptomeningeal metastasis from leukemia, lymphoma or breast cancer tend to respond best and this may, in part, be attributed to the relative sensitivity of these primary tumor types to the agents administered intrathecally. Systemic chemotherapy may prove a more attractive alternative to intrathecal drugs since it can penetrate into bulky disease, reach all areas of the subarachnoid space, and not be restricted by CSF bulk flow. The prognosis for patients with leptomeningeal metastasis is poor, most individuals surviving a median of only about four months. Occasional patients do have prolonged survival and improvement of their neurologic function.
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PMID:Current diagnosis and treatment of leptomeningeal metastasis. 969 79

The macrophage colony-stimulating factor receptor (CSF-1R), the product of the c-fms proto-oncogene, regulates normal proliferation and differentiation of macrophages and trophoblasts. Recent research found abnormal expression of CSF-1R in human carcinomas of the breast, endometrium, and ovary. Furthermore, activation of CSF-1R by its ligand has been shown to regulate invasiveness and anchorage-independent growth in breast carcinoma cells. To study the significance of CSF-1R expression in breast cancer, we designed a case-controlled immunohistochemical study. We chose 80 patients from a database of 1200 early stage I or II breast cancer patients treated with conservative surgery and radiation therapy. Expression of CSF-1R in the tumors of 40 patients who experienced an ipsilateral breast tumor recurrence (IBTR) as a primary site of relapse were compared with 40 patients who had not experienced an IBTR. The index and control patients were matched by age, clinical stage, nodal status, and follow-up. Paraffin-embedded sections were immunostained with antibodies directed toward CSF-1R. For the CSF-1R antibody, a total of 28 index cases (70%) demonstrated strong staining, whereas only 16 control cases (40%) demonstrated high immunoreactivity (P = 0.007). The CSF-1R antibody showed a positive correlation for local relapse, but no correlation was found between CSF-1R expression and distant metastasis. In summary, our findings provide evidence for the poor prognostic role of CSF-1R in IBTR.
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PMID:Prognostic significance of colony-stimulating factor receptor expression in ipsilateral breast cancer recurrence. 971 11

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

Colony stimulating factor (CSF-1) and its receptor (CSF-1R, product of c-fms proto-oncogene) were initially implicated as essential for normal monocyte development as well as for trophoblastic implantation. However, recent findings have suggested that CSF-1 and CSF-1R might have additional roles in mammary gland development during pregnancy and lactation. Studies with osteopetrotic (op-/op-) mice, which bear a specific mutation that inactivates the CSF-1 gene, demonstrated that op-/op- mothers are incapable of normal milk production due to the incomplete development of their mammary glands during pregnancy. Also, significant increases in the levels of CSF-1 and CSF-1R proteins are observed in the epithelial cells of mammary gland during pregnancy and lactation. In vitro studies investigating the effect of the three major lactogenic hormones (prolactin, insulin, and glucocorticoids) on the expression of CSF-1 and CSF-1R have demonstrated that expression of CSF-1 can be regulated by prolactin and insulin whereas CSF-1R expression is regulated by glucocorticoids. This apparent role for CSF-1/CSF-1R in normal mammary gland development is very intriguing because this receptor/ligand pair has also been found to be important in the biology of breast cancer, where they regulate tumor cell invasion by a urokinase-dependent mechanism. This review aims to summarize recent findings on the role of CSF-1 and its receptor in normal and neoplastic mammary development which may elucidate potential relationships of growth factor-induced biological changes in the breast during pregnancy and tumor progression.
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PMID:The role of CSF-1 in normal and neoplastic breast physiology. 989 62

Escalating doses of cyclophosphamide were given every 3 weeks as adjuvant treatment for women operated for breast cancer to determine the maximum tolerated dose of cyclophosphamide that can be given with constant doses of methotrexate (40 mg/m2) and 5-FU (600 mg/m2; CMF) as an outpatient treatment without the routine use of granulocyte colony-stimulating growth factor (G-CSF). The dose of cyclophosphamide was increased by 250 mg/m2 starting from the dose of 1,000 mg/m2. Mesna was given to prevent cystitis. The criteria for dose-limiting toxicity were grade IV granulocytopenia lasting for longer than 48 h, granulocytopenic infection or other grade IV toxicities. G-CSF and ofloxacin were used if grade IV granulocytopenia continued for longer than 48 h or if granulocytopenic infection occurred. At the dose level of 1,500 mg/m2 (500 mg/m2/week) 22 (92%) of the 24 patients had grade IV granulocytopenia during the 6 CMF cycles given, but only 3 (13%) had granulocytopenic fever. G-CSF was used in 28% of the cycles at this dose level. Other toxicities included complete alopecia (79%), nausea and vomiting. Sixteen (80%) of the premenopausal women became postmenopausal. At the dose level of 1,750 mg/m2 all 3 patients treated had to be hospitalized after the first cycle due to neutropenic infection (n = 2) or intractable vomiting even though prophylactic G-CSF was used. We conclude that intravenous CMF with a cyclophosphamide dose of 1,500 mg/m2 given at 3-week intervals with the selective use of prophylactic G-CSF is feasible as adjuvant treatment for patients with breast cancer.
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PMID:Intensified adjuvant cyclophosphamide, methotrexate and 5-fluorouracil therapy: a dose-finding study for ambulatory patients with breast cancer. 994 94

The circulating blood cells show highly reproducible circadian rhythms. However, the factors that regulate these rhythms are not well understood. In the current study, we examined the diurnal variations of peripheral blood cells (white blood cells, neutrophils, lymphocytes), granulocyte-macrophage-colony stimulating factor (GM-CSF), and melatonin levels, and considered the role of melatonin on these rhythms in healthy volunteers and in patients with early breast cancer. Fourteen premenopausal patients with early stage breast cancer (T2, N1 tumors) and 10 premenopausal healthy volunteers were included in the study. Blood samples were taken every 4 hr for a period of 24 hr. Peripheral blood cells were counted by automated analyser and also from peripheral blood films. GM-CSF levels were measured by ELISA and melatonin levels by radioimmunoassay (RIA). Serum melatonin, cortisol, and GM-CSF levels, and peripheral blood cell counts showed significant circadian rhythms in healthy volunteers. Except for GM-CSF, these circadian rhythms were found not to be suppressed in early breast cancer patients. While there were significant correlations of serum GM-CSF and cortisol levels with peripheral blood cell counts in healthy volunteers, only lymphocyte counts were found to be significantly correlated with serum GM-CSF and cortisol levels in patients with breast cancer. Serum melatonin levels were found to be significantly correlated with lymphocyte counts in both groups. Our results suggest that peripheral blood cells show significant circadian rhythms in both healthy volunteers and in patients with stage II (T2, N1) breast cancer, and GM-CSF, cortisol, and melatonin may have a role in the regulation of peripheral blood cell counts.
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PMID:The role of granulocyte-macrophage-colony stimulating factor, cortisol, and melatonin in the regulation of the circadian rhythms of peripheral blood cells in healthy volunteers and patients with breast cancer. 1010 54


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