Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Combinations of drugs are used clinically for the therapeutic advantages they may provide over single agents. We have studied the cytotoxic interaction between four either phospholipids ET-18-OCH3, BM 41.440, BN 52205 and BN 52211, and several chemotherapeutic drugs (ADM, CDDP, VLB, VP-16, MMC, BLM and MTX) on two human tumor cell lines, A427 (lung) and HT29 (colon). We have used the MTT colorimetric assay to evaluate growth inhibition and performed isobologram analysis on the IC50 data. For both cell lines a synergistic effect has been found between each of the four ether phospholipids in association with CDDP and ADM. In both cell lines only BM 41.440 and BN 52211 act synergistically with VLB while, in A427 cells, only BN 52205 behaves similarly with MMC. These results show that a positive interaction exists between ether phospholipids, spindle poisons and DNA-interactive drugs.
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PMID:Evaluation of combinations of antineoplastic ether phospholipids and chemotherapeutic drugs. 128 28

A carcinogen-transformed rat hepatoma cell line (Reuber H-35) was utilized as a model system for investigation of the biochemical factors which may limit the effectiveness of chemotherapy in intrinsically resistant tumors such as hepatocellular carcinoma. Northern blotting demonstrated expression of mRNA coding for the P-170 membrane-glycoprotein associated with the multi-drug resistance phenotype, while Western blotting identified the P-170 glycoprotein in the hepatoma cell membrane. Consistent with these observations, tumor cell sensitivity to the vinca alkaloids, vincristine and vinblastine, to the anthracycline antibiotics, Adriamycin and daunorubicin, and to the demethylepipodophyllotoxin derivative, VM-26, was enhanced by continuous incubation in the presence of the calcium channel antagonist, verapamil. Verapamil produced a minimal change in cell sensitivity to the demethylepipodophyllotoxin derivative, VP-16, and to the aminoacridine, m-AMSA. Relatively high detoxification potential via the glutathione metabolic pathway was also observed in the hepatoma cell. The capacity of topoisomerase II in nuclear extracts from the hepatoma cell to mediate cleavable complex formation stimulated by VM-26, VP-16 and m-AMSA appeared to be at least comparable to, if not greater than that from drug-sensitive HL-60 cells, suggesting that drug resistance may not occur at the level of this enzyme. Consistent with findings in a number of tumor cell lines resistant to antineoplastic drugs, the antiproliferative activity of the topoisomerase II inhibitors VM-26, VP-16 and m-AMSA appeared to be dissociable from the induction of DNA strand breaks, suggesting that such lesions in DNA may fail to fully account for the antiproliferative activity of these agents in the hepatoma cell.
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PMID:Components of intrinsic drug resistance in the rat hepatoma. 131 Aug 53

A 53-year-old man who suffered from advanced hepatocellular carcinoma (HCC) was treated with hepatic arterial infusion (HAI) of Etoposide, Epirubicin and CDDP. Treatment consisted of a continuous HAI of Epirubicin (50 mg/body, day 1.7), CDDP (75 mg/body, day 2.8) and Etoposide (80 mg/body, day 4-6). He had two series of infusions and was treated by transarterial embolization using CDDP powder (100 mg) added to lipiodol and aluminum stearate as suspension following HAI. The tumor regression rate was about 60% after HAI, but the remaining tumor seemed to be almost necrotic. AFP and PIVKA-II reached the normal range after TAE. We could not find lipiodol accumulated in tumor on CT carried out eight weeks after TAE. No recurrence has been noticed in the following 8 months. Toxicity was not so severe and was well tolerated.
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PMID:[A case with hepatocellular carcinoma effectively treated by continuous hepatic arterial infusion of etoposide, epirubicin and CDDP]. 131 15

Chemotherapy was given as initial therapy to 23 patients with previously untreated early and advanced cervical carcinoma. A combination of cisplatin and VP-16 was given in squamous cell carcinoma, and cisplatin, epirubicin and cyclophosphamide in adenocarcinoma in one to three courses at 4-week intervals. The overall clinical response rate to initial chemotherapy was 78% (80% in early and 78% in advanced disease). A complete response was achieved in 3 (13%) and a partial response in 15 (65%) patients. To obtain independent information on treatment response serial tumor marker determinations were used in patients with elevated pretreatment levels. Squamous cell carcinoma antigen (SCC) responded to chemotherapy by decreasing levels in 91% of the cases, carcinoembryonic antigen (CEA) in 33%, CA 125 in 83%, and tumor-associated trypsin inhibitor (TATI) in 50%, respectively. These results show that cervical carcinoma is a drug-responsive tumor and that SCC and CA 125 can be used as an aid in the evaluation of response to chemotherapy. Initial chemotherapy appears be of value by reducing tumor volume thus providing better conditions for surgery and radiotherapy.
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PMID:Chemotherapy as initial treatment for cervical carcinoma: clinical and tumor marker response. 132 23

A 29-year-old-woman with recurrent cancer of rectum was treated with Etoposide, cis-platinum and external irradiation. Previous postoperative chemotherapies consisted of MMC, CPA, VCR and HCFU. Histologically, the tumor invaded in sheets and nests, and consisted of round to ovoid malignant cells with high nuclear/cytoplasmic and hyperchromatic nuclei with a coarse, clumped, or stippled chromatin pattern. Most cells demonstrated a positive reaction by Grimelius and NSE staining. Eight months after surgery, we switched to Etoposide cis-platinum and external irradiation, because of local recurrence. Etoposide (total 725 mg) and cis-platinum (total 100 mg) were injected into bilateral iliac artery and 60 Gy radiotherapy was performed. The patient showed a good response, and a complete response (CR) was evident for the following 42 months. Thus, Etoposide, Cis-platinum and radiotherapy are considered an effective combination therapy for a patient with small cell undifferentiated carcinoma.
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PMID:[A case of small cell undifferentiated carcinoma (SCUC) of the rectum treated with etoposide, cis-platinum and radiotherapy]. 133 27

Taxol has been demonstrated in numerous laboratories worldwide to have broad-spectrum antitumor activity against many tumor models. The susceptible tumors include murine leukemias and solid tumors, and human solid tumor xenografts. The initial findings of taxol's ineffectiveness against most distal site tumor models was probably a consequence of the insolubility of taxol in nearly all the vehicles used in those early studies. On the occasions when an ethanol-based vehicle was used to dissolve taxol, substantial distal site antitumor activity was observed. Although no definitive schedule dependency data have evolved, once-a-day or every-other-day i.v. injections for several treatments have proved to be reproducibly effective in stringent s.c. tumor models. Attempts to discern a therapeutically synergistic cytotoxic drug combination was made on two occasions without success. In the manner evaluated, taxol plus either adriamycin, cisplatin, cyclophosphamide or etoposide (VP-16) were not meaningfully more efficacious than the more effective drug in each of those combination settings.
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PMID:Taxol: a review of its preclinical in vivo antitumor activity. 135 64

Etoposide and teniposide are closely related derivatives of podophyllotoxin, and both have a phase-specific action in the late S and early G2 phases of the cell cycle. Etoposide has attracted more widespread use and study, although no evidence suggests a differing mode of action or spectrum of anticancer activity. The drugs have significant differences in their clinical pharmacology, however. Teniposide exhibits greater protein-binding affinity, has a longer plasma terminal elimination half-life, and has reduced plasma and renal clearances. Little is accurately known about the metabolism of either drug, but the fact that 40% to 60% of administered etoposide is accounted for by excretion or metabolism, whereas the range is only 10% to 25% for teniposide, reflects a further difference between the drugs. Renal dysfunction impairs etoposide excretion, but the effect of hepatic impairment on drug clearance is unclear. A specific oral formulation exists only for etoposide, although the unpalatable intravenous preparations of both drugs can be taken orally. The bioavailability of oral etoposide is about 50% at doses of 200 mg or less and decreases as drug doses increase. There is considerable intrapatient and interpatient variation in etoposide absorption, but the reasons for this are unknown. In vitro, the efficacy of etoposide is highly dependent on the schedule of administration. The superior efficacy without increased toxicity of more prolonged schedules of etoposide administration has been demonstrated recently in patients with small cell lung cancer (SCLC). Although the optimal schedule in any specific tumor is not known, current pharmacodynamic evidence suggests that the efficacy of etoposide, at least in SCLC, is related to the maintenance of prolonged low blood concentrations of drug.
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PMID:Clinical pharmacology and schedule dependency of the podophyllotoxin derivatives. 141 35

Two human ovarian carcinoma cell lines (JA-T/P and SK-OV-3/P) were exposed to 10 fractions of 5 Gy X-irradiation in vitro. Surviving populations generated sublines designated DXR-10 which expressed significant resistance to etoposide (VP-16) and vincristine (VCR), but not to adriamycin (ADR) or acute X-irradiation, as judged by clonogenic assays. JA-T/P and JA-T/DXR-10 tumor cells were xenografted into nude mice and treated with a single dose of VCR (1.8 mg/kg), VP-16 (24.5 mg/kg) or ADR (10.0 mg/kg) and 48 h later the surviving clonogenic cells in each tumor were quantitated. Significantly fewer colonies grew from the JA-T/P xenografts treated with either VCR or VP-16, as opposed to the JA-T/DXR-10 tumors, whilst comparable colony numbers were recorded after ADR treatment. These data suggest that the resistant phenotype following exposure to fractionated X-irradiation in vitro is also expressed in vivo.
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PMID:Expression of resistance to etoposide and vincristine in vitro and in vivo after X-irradiation of ovarian tumor cells. 142 36

The characteristic of malignant pleural mesothelioma is a tumor that grows by plate-like extension over the pleura, and invades adjacent tissues and organs. Radical surgical removal of the tumor is generally not possible, and most treatment regimens involve combined chemotherapy and radiotherapy, as well as debulking surgery. We have prospectively evaluated five locally-aggressive multi-modality treatment programs, using different hemithorax irradiation schedules and chemotherapy regimens. One hundred patients with confirmed malignant pleural mesothelioma entered the study between 1977 and 1989. The treatment programs, which can consecutively, were: I, 20 Gy (10 x 2 Gy) to the hemithorax + CYVADIC (cyclophosphamide 500 mg/m2 d 1, vincristine 1 mg/m2 d 1 and 5, adriamycin 40 mg/m2 d 1 and dacarbazine 200 mg/m2 d 1 and 5, several cycles before and after irradiation); II, 55 Gy (25 x 2.2 Gy) to the hemithorax + 15 Gy (6 x 2.5 Gy) to the tumor + CYVADIC (2 cycles before, 1 cycle during, and 2 cycles after irradiation); III, Mitoxantrone (14 mg/m2 q 28 d, < or = 6 cycles) followed by 70 Gy (56 x 1.25 Gy, twice a day); IV, 4-Epirubicin (110-130 mg/m2 q 28 d, < or = 6 cycles) followed by 35 Gy (28 x 1.25 Gy twice a day) to the hemithorax + 36 Gy (9 x 4 Gy every 2 days) to the tumor; V, Etoposide (150 mg/m2 1, 3, 5 q 28 d) followed by 38.5 Gy (11 x 3.5 Gy) to the hemithorax. A new system for evaluating tumor response in pleural mesothelioma was applied. None of the combined treatment programs prevented local invasive growth or the spread of mesothelioma outside the hemithorax. The median survival time was slightly increased from 8 to 12 months for those patients who completed the protocol treatments, but progressive disease was the invariable outcome. Radiation pneumonitis and fibrosis were severe and compatible with results of total loss of lung function on the irradiated side. We conclude that data relating to therapeutic responses and treatment programs in malignant mesothelioma should be better correlated internationally, if the problems associated with the evaluation of treatment and the management of patients with mesothelioma are to be improved.
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PMID:Multimodality treatment programs for malignant pleural mesothelioma using high-dose hemithorax irradiation. 142 86

Twenty patients, aged 6 months to 20 years, with low-grade astrocytoma (LGA) participated in a chemotherapy trial of vincristine (VCR) and etoposide (VP-16). Fourteen children had recurrent progressive disease at entry on study. Prior treatment consisted of surgical resection alone (6), surgical resection and irradiation (4), surgical resection, irradiation and chemotherapy (2), surgery and chemotherapy (1), and irradiation and chemotherapy (1). Six patients were treated at initial diagnosis of LGA because they were less than 5 years old (5) or for a second primary tumor (1). Four recurrent patients and 3 newly diagnosed patients underwent surgical debulking of their tumors immediately prior to study entry. Tumors were located in the optic nerve/chiasm/hypothalamus (8), brain stem/cerebellum (4), cerebral hemispheres (3), midline structures (3), and spinal cord (2). The treatment plan administered in an out-patient setting consisted of weekly VCR 1.5 mg/m2 for 7 to 8 weeks and VP-16 100 mg/m2 for 5 days repeated every 6 weeks for a total of 18 months of therapy. Responses were evaluated by computerized tomography or magnetic resonance imaging. Of the 20 patients, 1 exhibited a partial response maintained for 12+ months, 3 exhibited minor responses maintained for a period of 10+ to 35 months, and 11 maintained stable disease for 10 to 42 months. Of the 11 patients with stable disease, 2 were withdrawn early from the study without further therapy. Five of the 20 patients developed progressive disease; for 4 of these 5, this occurred during the first course of therapy. Subsequently, these 5 died due to tumor.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Chemotherapy with vincristine (VCR) and etoposide (VP-16) in children with low-grade astrocytoma. 143 38


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