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)

A prospective randomized study was conducted to compare the adjuvant efficacy of 12 cycles of low-dose CMF (cyclophosphamide: CPA, methotrexate; MTX, 5-fluorouracil; 5-FU) with that of orally administered CPA plus FT (futraful) in premenopausal patients with stage I-II and one- to three-node-positive breast cancer. The 12-cycle CMF group (91 patients) received, 100 mg CPA orally on days 1 to 14 plus 20 mg MTX and 500 mg 5-FU intravenously (iv) on days 1 and 8 of each cycle. The CPA plus FT group (85 patients) received 100 mg CPA and 600 mg FT orally each day for one year. The background characteristics of the two groups were comparable. At 5 and 10 years, there were non-significant trends towards better disease-free and overall survival rates in the CMF group. Both treatments were well tolerated, but more patients in the CPA plus FT group refused to continue chemotherapy because of continuous gastrointestinal disturbances. No clear benefit of adding low-dose MTX to CPA and fluoropyrimidines was observed in this subgroup of Japanese patients. Further studies will be required to clarify the superiority of conventional-dose of CMF treatment to orally administered CPA plust FT treatment.
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PMID:Adjuvant cyclophosphamide, methotrexate and 5-fluorouracil versus cyclophosphamide plus futraful for premenopausal patients with stage I-II and one- to three-node-positive breast cancer: results of a prospective randomized study. 888 69

Cyclophosphamide is one of the alkylating agents and is a masked from compound. Combination chemotherapy with CMF or CAF has been commonly used as a first-line chemotherapy for recurrent and advanced breast cancer. The clinical efficacy of CMF chemotherapy (CPA + MTX + 5-FU) was evaluated on advanced and recurrent breast cancer. It is considered to be one of the most useful treatments. CAF chemotherapy (CPA + ADM + 5-FU) is also thought to be effective against breast cancers.
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PMID:[CMF or CAF combination chemotherapy for breast cancer]. 897 91

In a prospective multi-centre collaborative study, 516 patients with advanced cancer were treated by epirubicin (pararubicin, EPI) containing regimens. After CEOP (cyclophosphamide CTX, EPI, vincristine VCR and prednisone PDN) was used in the treatment of 213 patients with non-Hodgkin's lymphomas, 87 patients had complete remission (CR) and 99 partial remission (PR). Their response rate was 87.3%. However, there were 2 CR and 71 PR in 161 patients with non-small cell lung cancer treated by CEP regimen (CTX, EPI and cisplatin PDD), with a response rate of 45.3%. In 70 breast cancer patients treated by EMF regimen (EPI, Methotrexate MTX and 5-fluorouracil 5-FU), 8 had CR and 28 PR, with a response rate of 51.4%. The EPI containing regimens were also effective in dealing with gastro-intestinal tract and nasopharyngeal cancers. Adverse effects of epirubicin containing regimens were mainly nausea and vommiting, and the dose-qlimit toxicity was leucopenia. Hepatic, cardiac and renal toxicities were rather mild. The current phase III study revealed that the effect of epirubicin is similar to that of adriamycin, but the cardiac toxicity is relatively mild. So the effects can be improved by increasing the dose-intensity.
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PMID:[Epirubicin containing regimens in advanced malignant tumors report of 516 cases. Epirubicin Collaborative Study Group]. 1037 13

Human tumor cells have markedly elevated activity of enzymes of the purine and pyrimidine de novo and salvage pathways. Our therapy protocol is based on these findings. Different antimetabolites (MTX, 5-FU, dFdC, AZT) were administered to hit key enzymes. Vindesine and ifosfamide were aimed to block macromolecules. Repair mechanisms were impaired by hydroxyurea and topotecan. DNA transcription was blocked by actinomycin. IFNs (alpha, gamma) and IL-2 served as immuno-modulators. 47 patients (age 61.5 years, Karnowsky score 85%) were treated in an out-patient-setting. Median number of cycles was 3. General toxicity was low. Leucocytes, platelets, and monocytes were significantly reduced during therapy, but returned to normal on day 29. Lymphocyte subtypes did not show significant changes. 3 complete clinical responses, 22 partial responses, 9 progressive diseases were observed. CR occurred in 1/4 patients with kidney, in 1/1 with bladder, and in 1/5 with breast cancer.
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PMID:"Multi-enzyme-targeted" immunochemotherapy: a salvage therapy protocol. 1062 34

A 46-year-old woman presented with paraplegia and severe lumbago. She had had a radical mastectomy for left breast cancer 10 years earlier, and 6 months prior to presentation she completed CMF chemotherapy for treatment of retroperitoneal metastasis. CT and MRI to identify potential causes of the paraplegia and lumbago showed leptomeningeal carcinomatosis due to dissemination from invasive recurrence of the retroperitoneal tumor. An Ommaya reservoir was inserted, and infusion of intrathecal methotrexate (MTX; 5 mg twice weekly) began. Her clinical symptoms improved after receiving 53 mg MTX. However, after receiving 83 mg MTX, the patient became dizzy from leukoencephalopathy. Although administration of prednisolone mostly resolved her symptom, the patient died 9 months after the diagnosis of carcinomatous meningitis.
Breast Cancer 2000
PMID:Interventricular methotrexate therapy for carcinomatous meningitis due to breast cancer: a case with leukoencephalopathy. 1102 6

Methotrexate covalently bound to human serum albumin in a 1:1 molar ratio (MTX-HSA) is a new macromolecular drug which is currently being studied in phase I clinical trials by the German Association for Medical Oncology (AIO) Phase I/II study group. Previous studies have shown that MTX-HSA differs favorably from unbound MTX in terms of plasma half-life time, tumor accumulation of albumin and uptake mechanisms into cancer cells. To achieve optimal drug efficacy, repeated treatment cycles were necessary. To evaluate the anti-tumor activity of MTX-HSA and MTX in pre-clinical in vivo models, we selected 7 solid human tumor xenografts growing s.c. in nude mice and administered drug either i.p. or i.v. weekly for 3 weeks. The maximal tolerated dose (MTD) of MTX-HSA in nude mice was 12.5 mg/kg given i.p. on days 1, 8 and 15, whereas the MTD for free MTX was 100 mg/kg given i.v. MTX-HSA was significantly more active (p > 0.01) than MTX in 3 models. In the soft tissue sarcoma SXF 1301, MTX-HSA effected complete remission/cure after a single injection, whereas free MTX resulted in short-lasting, partial tumor regression. In the prostate-cancer model PRXF PC3M, MTX-HSA produced growth inhibition of 92.8% of control or an optimal test/control (T/C) of 7.2% compared to a T/C of 20.8% for MTX (p = 0.05). In the osteosarcoma model SXF 1410, optimal T/C values were 10.2% and 14.5%, respectively (p = 0.025). In lung cancers LXFE 409 and LXFL 529, bladder cancer BXF 1258 and breast cancer MAXF 449, both compounds were inactive. The improved therapeutic effects seen in 3 xenograft models under MTX-HSA treatment are promising and might be due to specific accumulation of the compound in solid tumors owing to their enhanced permeability and retention effect. Thus, clinical development of MTX-HSA will continue and sarcomas as well as prostate cancers will be included as potential target tumors for upcoming clinical phase II trials.
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PMID:Pre-clinical evaluation of a methotrexate-albumin conjugate (MTX-HSA) in human tumor xenografts in vivo. 1134 May 78

The establishment of two new breast cancer cell lines, MXT(+) and MXT(-), derived from the murine breast cancer models MXT-M-3, 2 MC (hormone-sensitive) and MXT-M-3, 2 (ovex) MC (hormone-insensitive), is described. Characterization of the cell lines was performed by investigation of morphology, steroid hormone receptor state, growth kinetics, and drug response as well as by cytogenetic analysis. MXT(+) contains estrogen receptors (ER; 6.9 fmol/mg protein) as well as progesterone receptors (PgR; 9.2 fmol/mg protein) and therefore is inhibited by tamoxifen (Tam). MXT(-) proved to be ER(-) but PgR(+) (23.4 fmol/mg protein) and, as expected, resistant against Tam.The sensitivity of MXT(+) and MXT(-) against a pattern of therapeutically established anti-breast cancer drugs (cDDP, cisplatin; JM-8, carboplatin; DX, adriamycin; 5-FU, 5-fluorouracil; MTX, methotrexate; VLB vinblastine) was studied by use of a computerized, kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. For each compound the inhibition profile reflecting cytostatic, transient cytotoxic, or cytocidal drug effects as well as development of resistance was evaluated. The following order of activity was found: MTX >, VLB >/= DX > cDDP >/= 5-FU > JM-8. The test data of 5-FU, VLB, cDDP, and Tam on MXT(+) as well as on MXT(-) were compared with those from studies on ER(+) and ER(-) human breast cancer cell lines (MCF-7, ZR-75-1, T-47-D, and MDA-MB-231, respectively). They revealed comparable inhibition profiles and sensitivities of human and murine breast cancer cell lines, an indication that the results achieved in combined in vitro-/in vivo tests by use of the murine test models MXT(+), MXT(-), MXT-M-3, 2 MC, and MXT-M-3, 2(ovex) MC are relevant for therapy in humans.
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PMID:Establishment and Characterization of New Murine Breast Cancer Cell Lines. 1200 8

The establishment of two new breast cancer cell lines, MXT+ and MXT-, derived from the murine breast cancer models MXT-M-3,2 MC (hormone-sensitive) and MXT-M-3,2 (ovex) MC (hormone-insensitive), is described. Characterization of the cell lines was performed by investigation of morphology, steroid hormone receptor state, growth kinetics, and drug response as well as by cytogenetic analysis. MXT+ contains estrogen receptors (ER; 6.9 fmol/mg protein) as well as progesterone receptors (PgR; 9.2 fmol/mg protein) and therefore is inhibited by tamoxifen (Tam). MXT- proved to be ER- but PgR+ (23.4 fmol/mg protein) and, as expected, resistant against Tam. The sensitivity of MXT+ and MXT- against a pattern of therapeutically established anti-breast cancer drugs (cDDP, cisplatin; JM-8, carboplatin; DX, adriamycin; 5-FU, 5-fluorouracil; MTX, methotrexate; VLB vinblastine) was studied by use of a computerized, kinetic chemosensitivity assay based on quantification of biomass by staining cells with crystal violet. For each compound the inhibition profile reflecting cytostatic, transient cytotoxic, or cytocidal drug effects as well as development of resistance was evaluated. The following order of activity was found: MTX > VLB > or = DX > cDDP > or = 5-FU > JM-8. The test data of 5-FU, VLB, cDDP, and Tam on MXT+ as well as on MXT- were compared with those from studies on ER+ and ER- human breast cancer cell lines (MCF-7, ZR-75-1, T-47-D, and MDA-MB-231, respectively). They revealed comparable inhibition profiles and sensitivities of human and murine breast cancer cell lines, an indication that the results achieved in combined in vitro-/in vivo tests by use of the murine test models MXT+, MXT-, MXT-M-3,2 MC, and MXT-M-3,2(ovex) MC are relevant for therapy in humans.
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PMID:Establishment and characterization of new murine breast cancer cell lines. 1204 56

Thiamine (vitamin B(1)) was investigated as a tumor-specific ligand for gadolinium nanoparticles. Solid nanoparticles containing gadolinium hexanedione (1.5 mg/mL) were engineered from oil-in-water microemulsion templates and coated with thiamine ligands. Thiamine ligands were synthesized by conjugating thiamine to either distearoylphosphatidylethanolamine (DSPE) or fluorescein via a poly(ethylene glycol) (PEG) spacer (Mw 3350). The efficiency of thiamine ligand attachment to nanoparticles was evaluated using gel permeation chromatography (GPC). Cell association studies were carried using a methotrexate-resistant breast cancer cell line, MTX(R)ZR75, transfected with thiamine transporter genes (THTR1 and THTR2). Thiamine-coated nanoparticle association with THTR1 and THTR2 cells was significantly greater than that with control breast cancer cells (MTX(R)ZR75 transfected with the empty expression vector pREP4) (p < 0.01; t-test). The nanoparticle cell association was significantly dependent on the extent of thiamine ligand coating on nanoparticles, expression of thiamine transporters in cells, temperature of incubation, and the concentration of competitive inhibitor (free thiamine). Further studies are warranted to assess the potential of the engineered thiamine-coated gadolinium (Gd) nanoparticles in neutron capture therapy of tumors.
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PMID:Specific association of thiamine-coated gadolinium nanoparticles with human breast cancer cells expressing thiamine transporters. 1264 51

Sialyl-Tn antigen (STn) is a cancer associated carbohydrate antigen over-expressed in several cancers including breast cancer, and currently associated with more aggressive diseases and poor prognosis. However, the commonly used breast cancer cell lines (MDA-MB-231, T47-D and MCF7) do not express STn antigen. The key step in the biosynthesis of STn is the transfer of a sialic acid residue in alpha2,6-linkage to GalNAc alpha-O-Ser/Thr. This reaction is mainly catalyzed by a CMP-Neu5Ac GalNAc alpha2,6-sialyltransferase: ST6GalNAc I. In order to generate STn-positive breast cancer cells, we have cloned a cDNA encoding the full-length human ST6GalNAc I from HT-29-MTX cells. The stable transfection of MDA-MB-231 with an expression vector encoding ST6GalNAc I induces the expression of STn antigen at the cell surface. The expression of STn short cuts the initial O-glycosylation pattern of these cell lines, by competing with the Core-1 beta1,3-galactosyltransferase, the first enzyme involved in the elongation of O-glycan chains. Moreover, we show that STn expression is associated with morphological changes, decreased growth and increased migration of MDA-MB-231 cells.
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PMID:Expression of sialyl-Tn antigen in breast cancer cells transfected with the human CMP-Neu5Ac: GalNAc alpha2,6-sialyltransferase (ST6GalNac I) cDNA. 1282 Jul 22


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