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Query: UMLS:C0027651 (tumor)
 685,946 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Fundamental concepts of combination multi-drug chemotherapy have not been well recognized from the aspects of chemo-sensitivity test upon malignant tumors. A chemo-sensitivity test by in-vitro bioassay for Dunn osteosarcoma and NR fibrosarcoma was developed by us to study the simultaneous interactions between two anticancerous agents. 0.1 ml of cell suspension of either mouse sarcoma was immersed in 0.4 ml of RPMI 1640 cell culture medium containing an anticancerous agent such as Mitomycin (MC), Cyclophosphamide (CPM), Vincristine (VC), Bleomycin (BM), 5-FU, Adriamycin (ADM), Cisplatin (CDDP) or Methotrexate (MTX) in a test-tube, and incubated at 37 degrees C for 3 or 6 hours. Then, the sedimented cell suspension of 0.1 ml was inoculated subcutaneously in the dorsum of C3H mouse which provided 4 sites for 4 different sensitivity tests. In 3 weeks, sensitivities of the anticancerous agents were evaluated as positive sensitivity if no growth of the tumor was observed, or negative sensitivity if the growth of more than 10 mm in diameter was observed. Then, the determination of antitumorous effect on 2-drug combination out of the 8 anticancerous agents, were performed on each mouse sarcoma by the same method. In Dunn osteosarcoma or NR fibrosarcoma, the combination of 2 sensitivity-positive agents revealed no apparent synergistic effects. In any combinations of one sensitivity-positive agent with the other sensitivity-negative agent, except the combinations with CPM which possessed mighty antitumorous effect, apparent reduction of antitumorous effects was observed. The combination of 2 sensitivity-negative agents never produced any antitumorous effects.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Consideration of simultaneous combination chemotherapy--employing a sensitivity test in Dunn osteosarcoma and NR fibrosarcoma by intra-test tube contact of tumor cell suspension, and subcutaneous inoculation]. 207 88

The ability of RO 11-2933 to modulate in vivo Doxorubicin and Cisplatin antitumor activity has been evaluated in sensitive and resistant P388 and L1210 murine leukemias. A reversal of both Doxorubicin or Cisplatin resistance has been observed when P388/Dx or L1210/CP tumor bearing mice received multiple treatments of the antitumor agent plus 30 mg/Kg of RO 11-2933. No modification of Doxorubicin or Cisplatin effect has been observed in sensitive tumors. The results obtained indicate that RO 11-2933 might represent a promising agent for the reversal of multidrug resistance.
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PMID:Reversal of doxorubicin and cisplatin resistance in vivo in murine leukemias by the calcium antagonist RO 11-2933. 209 36

The chemotherapeutic agent cisplatin, reported to be a complete carcinogen in rodents and a tumor initiator for mouse skin, was tested for activity to enhance the conversion of carcinogen-induced skin papillomas to carcinomas. Initiation of mouse skin by 7,12-dimethylbenz[a]anthracene followed by 12 weeks of promotion by 12-O-tetradecanoylphorbol-13-acetate produced seven to eight papillomas/mouse. Ten weekly injections of 100 micrograms of cisplatin into these papilloma-bearing mice induced a 2.3-fold enhancement of conversion relative to the spontaneous rate of 1.9%. Even a single exposure to cisplatin in tumor-bearing mice increased the carcinoma incidence to the same extent as 10 exposures to urethane, an agent previously shown to enhance malignant conversion. At the dose tested, cisplatin was inactive as a complete carcinogen or a tumor promoter. Cisplatin-DNA adducts, measured in samples from skin, liver, and kidneys, were persistent for at least 4 weeks after the last exposure to cisplatin. Thus cisplatin is a relatively potent inducer of the putative genotoxic changes required for conversion of skin tumors from a benign to a malignant phenotype. The activity of cisplatin in the initiation and malignant conversion stages in this animal model for carcinogenesis suggests that patients given cisplatin-based chemotherapy are at increased risk for the development of treatment-induced second cancers.
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PMID:Enhanced malignant conversion of benign mouse skin tumors by cisplatin. 211 Feb 67

Resistance of a rat ovarian tumor cell line (O-342/DDP) to cisplatin was induced in vitro by stepwise increase of cisplatin concentrations. Both chemosensitive parental cells (O-342) and resistant O-342/DDP cells grow in a monolayer and enter log-phase growth about 24 h after seeding (cell population doubling time in log-phase growth is about 24 h). O-342/DDP cells show a 33-fold resistance to cisplatin as compared to O-342 cells (ID50 = 33 microM in O-342/DDP vs 1 microM in O-342 cells). The intracellular total glutathione (GSH + GSSG) of O-342/DDP cells was twice as high as that of O-342 cells (3.04 vs 1.37 nmol/10(6) cells), while the intracellular GSSG was increased by 26% in O-342/DDP cells compared to O-342 cells. DNA interstrand crosslinks were found to be 8.5 times higher in O-342 cells than in O-342/DDP cells (204 vs 24 rad equiv.), following cisplatin treatment. DNA single-strand breaks were approximately doubled in the sensitive line as compared to the resistant line following exposure to cisplatin. Chromosome analysis uncovered a change in the karyotype of O-342/DDP cell as compared to O-342 cells. In the sensitive line hyperploid (3n) clones, in the resistant line near-diploid clones predominated. Both DL-buthionine-(S,R)-sulfoximine and 3-aminobenzamide were able to sensitize the resistant line towards cisplatin. Thus, the present results suggest that mechanisms for cisplatin resistance in this tumor line apparently are multi-factorial, and include a higher intracellular GSH content and an increased repair activity.
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PMID:In vitro investigations on induction and reversal of cisplatin resistance in a rat ovarian tumor cell line. 212 38

Murine peritoneal macrophages were rendered tumoricidal to Dalton's lymphoma (DL) cells on incubation with recombinant tumor necrosis factor alpha (rTNF-alpha), recombinant interleukin-1 (rIL-1) and cisplatin in vitro. Simultaneous treatment of macrophages with suboptimal doses of rTNF-alpha and rIL-1 had additive effect on the activation of macrophages. Priming of macrophages with recombinant interferon gamma (rIFN-gamma) significantly enhanced the rTNF-alpha and rIL-1-induced macrophage cytotoxicity. Cisplatin was found to up-regulate rIL-1-induced macrophage activation but inhibited the activation of macrophages with rTNF-alpha. These studies indicate the potential of appropriate combination of these Biological Response Modifiers (BRMs) against neoplasia.
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PMID:Activation of murine macrophages by tumor necrosis factor, interleukin-1, interferon-gamma and cisplatin. 212 75

Human natural killer (NK) cells and monocytes treated in vitro concomitantly with cisplatin and rIFN-gamma enhanced lysis of K562 cells. Lysis was dependent upon the duration of treatment. Cisplatin and rIFN-gamma treated monocytes were equally cytotoxic to NK sensitive (K562) and NK resistant (Daudi & Raji) cell lines whereas NK cells were not rendered cytotoxic against NK resistant tumor cells. NK- and monocyte-mediated cytotoxicity against K562 cells was further enhanced when the effector cells were primed with rIFN-gamma and were subsequently treated with cisplatin.
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PMID:Activation of human NK cells and monocytes with cisplatin in vitro. 212 63

Primitive neuroectodermal tumors/medulloblastoma (PNET/MB) are the most common posterior fossa tumors in childhood. Despite surgery and radiation therapy, 40% to 50% of children with PNET/MB will have recurrent disease. Various chemotherapeutic agents are transiently effective in recurrent PNET/MB, but long-lasting responses are rarely attainable. To increase the rate and duration of response in children with recurrent PNET/MB, the authors treated seven patients (ages 2-18 years; median, 10 years) with lomustine (CCNU) (100 mg/m2), cisplatin (CPDD) (90 mg/m2) and vincristine (VCR) (1.5 mg/m2; maximum, 2 mg) in a 6-week cycle for a maximum of eight cycles. Six of six evaluable patients responded to chemotherapy. Four patients had a complete response; three with complete disappearance of tumor by imaging studies; and one with eradication of extraneural disease for a median of 24 months from relapse (13-29 months). Overall disease-free survival was 18.5 months. All six patients have subsequently died of recurrent tumor. Major toxicities consisted of reversible bone marrow suppression (six of six), high frequency hearing loss (six of six) and decreased renal function (three of six). All patients required dosage modification for toxicity. A regimen of CCNU, VCR, and CPDD is effective therapy in children with relapsed PNET/MB and can produce relatively long-term disease control with good quality of life. Further investigation into the efficacy of this combination as adjuvant chemotherapy in newly diagnosed high-risk PNET/MB is now being performed.
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PMID:Results of treatment of children with recurrent medulloblastoma/primitive neuroectodermal tumors with lomustine, cisplatin, and vincristine. 215 28

We have shown previously that the flavonoid quercetin (3,3',4',5,7-pentahydroxyflavone) enhances the antiproliferative activity of cis-diamminedichloroplatinum(II) (cis-DDP) in vitro. In order to investigate whether this observation could be exploited in cancer treatment, we tested this drug combination in human tumor xenografts. The established human large-cell cancer of the lung (LXFL 529) was implanted s.c. into nude mice. Tumors were allowed to grow to a mean diameter of approximately 5 mm and the animals were subsequently treated intraperitoneally with quercetin, cis-DDP or a combination of both. Treatment was given 3 times at 3-day intervals. Twenty milligrams quercetin per kg body weight caused no inhibition in tumor growth compared to untreated controls; 3 mg cis-DDP per kg body weight with the same time schedule reduced tumor growth, compared to quercetin-treated and control animals. Concomitant treatment with 20 mg quercetin and 3 mg cis-DDP per kg body weight reduced tumor growth to a significantly greater degree than cis-DDP alone. Toxicity of this treatment was relatively low as determined by measurements of the body weight of the mice. A combination of 4 mg or 5 mg cis-DDP with 20 mg quercetin per kg body weight also reduced tumor growth compared to single cis-DDP treatment. The toxicity of treatment with these increased doses was high, as shown by the high lethality and the loss of body weight of surviving animals.
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PMID:Enhancement of the antiproliferative activity of cis-diamminedichloroplatinum(II) by quercetin. 215 85

There is increasing interest in compounds which show selective toxicity to the resistant hypoxic portions of tumors. Cisplatin does not generally show preferential toxicity in hypoxic cells, as do nitroimidazoles. It is proposed that attachment of a nitroimidazole could add a degree of hypoxic selectivity to Pt agents. Platinum complexes containing one nitroimidazole ligand bind to DNA and show higher toxicity in hypoxic than aerobic CHO cells. Cis and trans isomers of complexes with misonidazole (a 2-nitroimidazole) and metronidazole (a 5-nitroimidazole) are compared with respect to binding to DNA (approximately the same), reduction potential (trans miso greater than cis miso greater than cis metro greater than trans metro), and toxicity (trans greater than cis miso, cis greater than trans metro, with trans miso approximately cis metro in hypoxia, despite significantly different reduction potentials). The effect of platination on nitroimidazole toxicity is not entirely explained by DNA binding and increased reduction potential. These compounds do not exhibit cross resistance with cisplatin in L1210 resistant cells. This factor, their selectivity for hypoxia, and preliminary results in vivo indicating potentiation of anti-tumor activity by the vasoactive compound, hydralazine, which increases tumor hypoxia, suggest further development of these compounds for use in tumors with resistant hypoxic portions.
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PMID:Toxicity of [PtCl2(NH3)L] in hypoxia; L = misonidazole or metronidazole. 215 14

During the period 1978-1987, 255 patients with pathologically proven hepatocellular carcinoma (HCC) were assessed to be unresectable by laparotomy. Of them 155 had their tumors chiefly confined in the right or left lobe. Second stage resection was performed in 26 (16.8%) after marked reduction of the tumor by combination treatment with hepatic artery ligation (HAL) + hepatic artery infusion chemotherapy (HAI) + multifractionated radiotherapy (MFD) with linear accelerator, or radioimmunotherapy using 131I-anti human HCC ferritin antibody (131I-FtAb), which yielded the highest second stage resection rate (29.8%, 14/47) as compared to HAL + HAI or HAL + cryosurgery (16.9%, 12/71), HAL or HAI (0%, 0/37) alone. The 3 year survival rate of the 26 patients with second stage resection was 74.3%, comparable with those of small HCC resection (82.7%, n = 111) and radical resection of large HCC (56.1%, n = 122) in the same period. Experimental study using nude mice bearing human HCC also showed the superiority of triple (MFD or 131I-FtAb + Cisplatin PDD + mixed bacterial vaccine MBV) versus double (MFD or 131I-FtAb + PDD, or MFD or 131I-FtAb + MBV) and double versus single treatment modality. Both experimental and clinical data indicated that immunosuppression after radiotherapy was prevented by adjuvant immunotherapy (MBV). Thus, this treatment model provides an opportunity for resection or even cure in a part of patients with unresectable HCC confined in one lobe.
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PMID:[Multimodality treatment and two-stage resection for unresectable hepatocellular carcinoma--experimental and clinical studies]. 216 21


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