Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
 152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The effects of the combination of genistein, a tyrosine kinase inhibitor, and adriamycin, an anthracycline anticancer drug, were studied in three human breast carcinoma cell lines (MCF-7/WT, MCF-7/ADR(R) and MDA-231) differing in estrogen receptor status and adriamycin sensitivity. Genistein inhibited cell proliferation in all three cell lines (IC50 between 7.0 and 37.0 microM). The combination produced additive to synergistic effects; epidermal growth factor receptor modulation by adriamycin does not seem to be involved in this interaction. The possible therapeutic advantage of this drug combination, especially on hormone-independent and multidrug resistant tumor cells, deserves further investigation.
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PMID:Antiproliferative effect of genistein and adriamycin against estrogen-dependent and -independent human breast carcinoma cell lines. 807 76

Doxorubicin is an anticancer agent widely used in the treatment of human cancer. The major limitation of this drug governing the cell-killing effect appears to be its poor penetration into a tumor mass. We have studied the effects of hyaluronidase on the penetration and cell-killing effect of doxorubicin using multicellular tumor spheroids (MTS). MTS approximately 500 microns in diameter were produced by a liquid-overlay culture technique from PC-10 lung and HEp-2 laryngeal squamous carcinoma cell lines. Cells in MTS and monolayer were exposed to hyaluronidase for various lengths of time; this was followed by a 1-h resting interval and a subsequent 1-h exposure to doxorubicin. MTS and monolayer cells were then trypsinized to a single-cell suspension and subjected to clonogenic assay. Hyaluronidase at a concentration of 25 U/ml or 250 U/ml was nontoxic to the monolayer cells. For PC-10 MTS, pretreatment with 25 U/ml hyaluronidase for 24 h and 72 h resulted in approximately 20% increases in Doxorubicin cell killing at the median (IC50) dose as compared to doxorubicin alone. HEp-2 MTS were more sensitive to the hyaluronidase pretreatment. Thus, a 1-h exposure to the enzyme produced a 40% increase in doxorubicin-induced cell death at the IC50 dose. A fluorescence microscopic study revealed that a 1-h exposure of MTS to doxorubicin produced doxorubicin fluorescence only in the one or two outer layers of MTS. When MTS were pretreated with hyaluronidase, there was enhanced penetration of doxorubicin fluorescence into the MTS core. Hyaluronidase-induced enhancement of Doxorubicin penetration and its cell-killing effect is dependent on the exposure time and tumor cell origin. These data suggest that anecdotal reports of hyaluronidase-enhanced activity of preclinical chemotherapy deserve a controlled trial.
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PMID:Effects of hyaluronidase on doxorubicin penetration into squamous carcinoma multicellular tumor spheroids and its cell lethality. 812 58

MA is an orally active PG derivative with an excellent safety profile that is used primarily for the treatment of carcinomas of the breast and endometrium. We investigated the potential application of MA as an MDR-reversal agent using cell culture and human tumor xenograft models. The reversing activity of MA in vitro was compared with that of PG and VER in two human MDR cell lines, the colon carcinoma HCT-116/VM46 and the breast carcinoma MCF-7/ADR, and in a murine cell line, J774.2. At concentrations as low as 3 microM, MA was capable of partially restoring sensitivity to Act D in the HCT-116/VM46 cells and sensitivity to DOX in the MCF-7/ADR cells. Although less effective than VER, MA was about 2.5 times more potent than PG in reversing MDR at equimolar concentrations. Increased accumulation of DOX in drug-resistant cells that were treated simultaneously with MA was observed by flow cytometry. In vivo, using established human colon and breast carcinoma xenografts implanted s.c. in athymic mice, the combined therapy with MA and DOX resulted in enhanced antitumor activity relative to that of DOX alone in the MDR sublines. These results suggest that MA may be a promising clinical MDR-reversing agent.
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PMID:Reversal of the human and murine multidrug-resistance phenotype with megestrol acetate. 819 72

Doxorubicin (DOX) has been incorporated into five different formulations of protein microspheres, each altering tumour drug disposition in a characteristic manner. There was no correlation between the stimulation in anaerobic quinone bioreduction over the levels produced by free DOX and tumour growth delay against the Sp 107 rat mammary carcinoma. A strong correlation (r2 = 0.948, P < 0.01, two-tailed t statistic) was observed between a slower decline in parent drug levels and antitumour activity. These data support the view that free radical processes are not involved in the mechanism of action of DOX and suggest that the optimum way to delivery the drug to the Sp 107 tumour is through sustained release of lower concentrations (approximately 2 microM) from a large extracellular pool.
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PMID:Correlation between tumour drug disposition and the antitumour activity of doxorubicin-loaded microspheres: implications for the drugs' in vivo mechanism of action. 832 91

Multidisciplinary treatment is necessary for esophageal carcinoma. Radio-chemo-immunotherapy and aggressive chemotherapy with large doses of 5-FU, CDDP, ADR and VDS, were performed postoperatively from 1975. From 1975 to 1990, operations were performed on 456 patients with thoracic esophageal carcinomas. Postoperative radio-chemo-immunotherapy improved the 5-year survival rate of patients without lymph-node metastasis to 74.6% compared with 55.3% for patients not receiving any postoperative therapy. In the case of n1(+) and n2(+), the five-year survival rate of patients treated with aggressive chemotherapy (32.7%) was similar to the rate (34.8%) for patients treated with radio-chemo-immunotherapy. In cases of n3(+) and n4(+), improvement of the two-year survival rate of patients who received aggressive chemotherapy (37.0%) was noted compared with the rate of patients who received radio-chemo-immunotherapy (20.9%). However, there was no difference in five-year survival rate between the two groups. More effective multidisciplinary treatment based on randomized study will improve the therapeutic outcome.
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PMID:[Multidisciplinary treatment of cancer of the esophagus]. 833 41

The patient was a 40-year-old female (154 cm, 45 kg). Several months after receiving radiotherapy, surgery and chemotherapy (Epi-ADR, CDDP, PEP) for an undifferentiated carcinoma of the left parotid gland, she had multiple pulmonary metastases without local recurrence. Following 2 cycles of combination chemotherapy with CDDP (30 mg/1 hr, days 1 approximately 5) and 5-FU (1,000 mg/24 hrs, days 2 approximately 6), most pulmonary nodules disappeared. For the remaining pulmonary nodules, one cycle of combination chemotherapy with 5-FU (850 mg/24 hrs, days 1 approximately 5), leucovorin (9 mg x 3/day, days 1 approximately 5) and CDDP (110 mg/2 hrs, day 7) was added, but further improvement was not obtained on chest CT. Side effects were tolerable in both regimens. It was suggested that the combination chemotherapy with CDDP and 5-FU might be useful for the treatment of advanced parotid gland carcinomas.
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PMID:[A combination chemotherapy with CDDP and 5-FU effective for pulmonary metastases in a case of parotid gland carcinoma]. 868 22

We investigated the effect of hypoglycemic treatment on the activation of the AP-1 transcription factors and the regulation of basic fibroblast growth factor (bFGF) gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. Northern blot and gel mobility shift assays showed that hypoglycemic treatment induced c-jun and c-fos gene expression, AP-1 binding activity, as well as bFGF gene expression. Moreover, transfected cells expressing high levels of abnormal c-Jun protein exhibited a reduction in the bFGF protein levels compared to parental cells. A potent protein kinase C (PKC) inhibitor, H-7 (60 micrograms/ml) suppressed the stress-induced bFGF gene expression. Our study also demonstrated that H-7 did not facilitate the decay of bFGF mRNA. Thus, the suppression of bFGF gene expression by treatment with H-7 was due to the effect of the drug on the synthesis of bFGF mRNA rather than the stability of bFGF mRNA. Our data suggest that hypoglycemia-induced bFGF gene expression is mediated through the activation of PKC and the AP-1 transcription factors.
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PMID:Hypoglycemia-induced AP-1 transcription factor and basic fibroblast growth factor gene expression in multidrug resistant human breast carcinoma MCF-7/ADR cells. 870 Jan 61

The present study demonstrated that poly(oxypropylene) and poly(oxyethylene) block copolymer pluronic L61 (L61)-hypersensitized multidrug-resistant CHRC5 Chinese hamster ovary cells and MCF-7/ADR human breast carcinoma cells to the cytotoxic action of doxorubicin (Dox). CHRC5 and MCF-7/ADR cells manifested 290- and 700-fold increases, respectively, in their sensitivity to Dox/L61 formulation compared with free Dox. Their sensitive counterparts Aux-B1 and MCF-7 displayed only marginal or no increase at all in their response to Dox/L61. The study of the drug transport performed by flow cytometry showed that L61 enhanced the drug uptake and reduced the P-glycoprotein-mediated drug efflux. Visualization of Dox subcellular distribution in CHRC5 cells by fluorescent microscopy revealed that Dox was sequestered in cytoplasmic vesicles, whereas incubation of the cells with Dox/L61 altered the drug compartmentalization by releasing the drug from these vesicles and shifting it to the nucleus. These findings suggested that the hypersensitive response of multidrug-resistant cells to the action of Dox/L61 was caused by an increase in the drug accumulation and changes in its subcellular distribution.
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PMID:Hypersensitizing effect of pluronic L61 on cytotoxic activity, transport, and subcellular distribution of doxorubicin in multiple drug-resistant cells. 870 95

Cytochalasins are a family of structurally related natural product cytotoxins that selectively depolymerize microfilaments. In this study, the interaction between several cytochalasins and the drug transporter P-glycoprotein was investigated. Dihydrocytochalasin B and cytochalasin E consistently sensitized P-glycoprotein-overexpressing human breast carcinoma cells (MCF-7/ADR) to daunomycin, vinblastine, and actinomycin D without affecting the cytotoxicity of cisplatin. These compounds did not affect the sensitivities of the parental MCF-7 cells to anticancer drugs, indicating that their effects are due to P-glycoprotein inhibition. Effects of dihydrocytochalasin B and cytochalasin E were observed at concentrations as low as 2.5 and 5 microM, respectively. In contrast, cytochalasins A, B, C, D, H, and J did not sensitize MCF-7/ADR cells to any of the drugs. The accumulation of [3H]-vinblastine by MCF-7/ADR cells and by drug-resistant human ovarian carcinoma cells (SKVLB1) was increased to the greatest extent by verapamil, followed by dihydrocytochalasin B > cytochalasin E > cytochalasin B, whereas cytochalasins A, C, D, H, and J did not alter intracellular accumulation of the drug. Similarly to verapamil, dihydrocytochalasin B significantly stimulated the ATPase activity of P-glycoprotein, while other cytochalasins were ineffective. These results demonstrate that very closely related compounds can differentially interact with P-glycoprotein. For example, the only difference between cytochalasin B and dihydrocytochalasin B is the saturation of a carbon-carbon double bond in dihydrocytochalasin B. These structural differences may provide important insight into chemical determinants for drug interaction with P-glycoprotein.
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PMID:Differential interactions of cytochalasins with P-glycoprotein. 883 87

From 1991 to 1996, 11 eligible patients (median age 50.4 years, range 33-71 years) with over Stage III and inflammatory breast carcinoma have been treated with neoadjuvant intra-arterial infusion chemotherapy. There were three Stage III a, one III b, three IV and four inflammatory carcinoma. Patients were treated with Epirubicin (10) and Doxorubicin (1), with a total amount of 120-190 mg. Three cases were combined with endocrine therapy (MPA 1,200 mg). In terms of morphological efficacy, 10 of 11 achieved PR, and three of those with endocrine therapy had over Grade 2 in histological efficacy. Carcinoma cells were especially deceased in one inflammatory carcinoma with MPA. Three of 11 died of liver metastasis, the others are still alive (median 24.5 months, range 7-51 months). Combined endocrine therapy should be considered applicable for the treatment strategy of the breast carcinoma.
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PMID:[Neoadjuvant intra-arterial infusion chemotherapy in over stage III and inflammatory carcinoma of the breast]. 885 99


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