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

Utilizing the P388 murine leukemia cells sensitive (P388/S) and resistant (P388/ADR) to Adriamycin (ADR), we evaluated the effect of quinidine, an anti-arrhythmic agent, on the cytotoxic activity of ADR and Mitoxantrone (MITO), both in vitro as well as in vivo. Quinidine enhanced the cytotoxicity of both ADR and MITO in P388/S and P388/ADR cells, as assessed by the decrease in color intensity of formazan crystal in the MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay. A dose dependent inhibition of 3H-thymidine and 3H-uridine incorporation was observed when the P388/S and P388/ADR cells were exposed to quinidine alone. A non-toxic concentration of quinidine (5 microM) enhanced the DNA biosynthesis inhibition induced by ADR (55 to 65%) and MITO (37 to 44%) in P388/ADR cells, indicating reversal of resistance, while in P388/S cells only a minimal increase in DNA biosynthesis inhibition was observed. The combination of quinidine at doses of 50 to 100 mg/kg significantly potentiated the antitumor activity of ADR and MITO in P388/ADR bearing mice, whereas the potentiation of ADR and MITO antitumor response was lower in P388/S bearing mice. Quinidine increased the cellular levels of ADR by 53 to 126% in P388/ADR cells in vitro, but failed to indicate such elevated levels of cellular ADR in P388/S cells. This enhanced intracellular accumulation of ADR in P388/ADR cells, explains the therapeutic efficacy of ADR and MITO in P388/ADR, both in vitro as well as in vivo. Results suggest the efficacy of quinidine to ameliorate the antitumor effects of ADR and MITO in drug resistant tumor cells.
 ...
PMID:Evaluation of quinidine effect on the antitumor activity of adriamycin and mitoxantrone in adriamycin-sensitive and -resistant P388 leukemia cells. 236 55

Aliphatic triazenes, such as 1,3-dimethyltriazene, are potent biological alkylating agents because they form alkyldiazonium ions. They are also subject to very rapid proteolytic decomposition, even at physiological pH. The acylated analogues 1,3-dialkyl-3-acyltrizenes are much more stable in aqueous solution, but they also give rise to alkyldiazonium ions. Four acylated 1,3-dimethyltriazenes, where the acyl groups were diethylphosphoryl (DMP), carbethoxy (DMC), acetyl (DMA), and N-methylcarbamoyl (DMM), were studied kinetically. Rate-pH profiles indicated that the acyl group had a profound effect on the mechanism of decomposition. The cytotoxic potential of all four compounds was studied in vitro by using the MTT-tetrazolium assay. The compounds had fair-to-good activity against some cell lines, particularly those deficient in methylation repair. In vivo assays of DMC and DMM against several tumor xenografts in nude mice showed promising activity for some cancers, particularly in the case of DMM. In vitro assays were also carried out on three 1-(2-chloroethyl)-3-methyl-3-acyltriazenes. The acyl groups were carbethoxy (CMC), acetyl (CMA), and N-methylcarbamoyl (CMM). The activity of these compounds largely paralleled that of bis(2-chloroethyl)-N-nitrosourea (BCNU), except for those cell lines which exhibited the Rem phenotype; triazenes were more active in those lines than BCNU. The in vivo activity of CMC, CMA, and CMM was tested in the P388 leukemia assay. All three were active but CMC and CMA proved to be rather toxic. CMM was well tolerated and was examined in several tumor xenografts in nude mice. Significant activity was found against MX-1 mammary carcinoma, against LX-1 small cell lung carcinoma, and particularly against LOX amelanotic melanoma, where complete cures were effected. The antineoplastic activity of the acyltriazenes is well-correlated with their chemical behavior.
 ...
PMID:1,3-Dialkyl-3-acyltriazenes, a novel class of antineoplastic alkylating agents. 239 96

We have applied the MTT dye reduction assay to the anticancer drugs sensitivity test using short-term microplate cultures. The tumor cells were cultured with the anticancer drugs for 2 and 4 days. After culture, MTT dye was placed in each microwell and culture was carried out again for 4 more hours. The formazans generated by living cells were dissolved in acidified isopropyl alcohol and the absorbances of each well were measured at a wavelength of 540 nm. When tables of cytotoxicity indices classified into anticancer drugs, concentrations and durations of culture for each type of leukemic cell were made, it became possible to compare each drug and to select the effective ones. This assay is simple, precise, rapid, has no washing steps and is convenient for handling a large volume of material. We apply this assay in clinical practice.
 ...
PMID:[Anticancer drug sensitivity test using the short-term microplate culture and MTT dye reduction assay]. 243 30

In the German Society of Pediatric Oncology (GPO) designed in 1982 a cooperative study to improve the outlook of patients with malignant testicular germ cell tumors. According to stage and histology of the tumor different surgical approaches to retroperitoneal lymphadenectomy are outlined. Local radiotherapy is not recommended. Adjuvant chemotherapy with Vinblastine, Bleomycin and CIS-Platinum is proposed. Up to 1987 27 YST, 3 MTI, 6 MTU, 1 MTT and 9 TD were treated. Only one patient with YST had a relapse; one patient died from candida septicemia. Alternative chemotherapy was given 3 times. Overall toxicity from treatment was mild. So far the combined modality therapy was found to be effective to increase the relapse free survival.
 ...
PMID:[Results of the cooperative Malignant Testicular Tumors 82 Study of the German Society of Pediatric Oncology on the therapy of malignant germ cell tumors in childhood]. 246 3

We investigated a new chemosensitivity test, MTT-hybrid assay, which was a hybrid of MTT colorimetric assay and double-layered soft agar colony assay, using human bone and soft tissue tumor cells. MTT formazan crystals produced by viable cells in the soft agar medium were solubilized by SDS at 60 degrees C. The absorbance (560 nm) is directly proportional to the cell number over a wide range. The absorbance increased in proportion to colonial growth of osteosarcoma cells, while it decreased in a human diploid cell strain in a few days. Drug sensitivity of tumor cells is supposed to be assessed without contaminating normal cells by MTT-hybrid assay in primary tumor samples. Good correlation of IC50 was observed between MTT-hybrid assay and colony assay. The MTT-hybrid assay shows potential value as a rapid predictive test for chemotherapeutic agents in an individual patient.
 ...
PMID:[A study of MTT-hybrid assay using human bone and soft tissue tumor cells]. 251 17

The 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) hybrid assay was developed by technically combining the human tumor clonogenic assay and the MTT assay to make the most of both assays. This assay was able to estimate the in vitro growth of cultured cell lines and of tumor cells in pleural effusion, suggesting the possibility of its use for assessment of chemosensitivity and radiosensitivity of fresh tumor samples. Multiple cell lines [including morphological and/or phenotypical in vitro converters and cisplatin (CDDP)-resistant lines] were established from three patients with small cell lung cancer at different stages of the disease. Chemosensitivity of these cell lines to four commonly used chemotherapeutic drugs was tested by the MTT hybrid assay. SK1 and SK3 lines were established from Patient S. K. before and after chemotherapy and radiotherapy, respectively. SK3/CDDP, a CDDP-resistant line derived from the SK3 line, was 30-fold more resistant to CDDP [50% inhibiting dose (IC50), 21.5 micrograms/ml] than the SK1 line. In Patient M. O., MOA2/CDDP, a CDDP-resistant line derived from MOA2 (an in vitro converter from the MO line), was 41-fold more resistant to CDDP (IC50, 37 micrograms/ml) than the parent MO line. From Patient T. M., TM1 and TM2 lines were established before and after chemotherapy, respectively. The latter showed 6-fold more resistance to CDDP than the former. Chemosensitivity of these lines to three other drugs, 4-hydroperoxycyclophosphamide, Adriamycin, and etoposide, suggested cross-resistance between CDDP and 4-hydroperoxycyclophosphamide. Radiosensitivity study was also carried out with the MTT hybrid assay. The MOA2 line was more resistant [Do, 3.0 Gy; extrapolation number (n), 4.0] than the parental MO line (Do, 1.6 Gy; n, 2.1). There was no clear difference in radiosensitivity between the cell lines established before and after radiation therapy in Patient S. K.
 ...
PMID:Chemosensitivity and radiosensitivity of small cell lung cancer cell lines studied by a newly developed 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) hybrid assay. 254 17

The German society of Pediatric Oncology (GPO) designed in 1982 a cooperative study to improve the outlook of patients with malignant testicular germ cell tumors (MAHO 82). So far the combined modality therapy was effective to increase the relapse free survival (Haas et al. 1988). From the data the MAHO 88 protocoll was outlined as follows: Yolk sac tumor: Unilateral orchiectomy; Stage I A - wait and see. Stage I B/C-IV 4 courses standard chemotherapy. If alpha-feto-protein after 2 courses is still positive explorative laparatomy has to be performed. Malignant teratoma (MTI, MTU, MTT), seminoma: Unilateral orchiectomy. Stage I: 4 courses standard chemotherapy. Stage II-IV: 2 courses standard chemotherapy, explorative laparatomy. During explorative laparatomy 3 different approaches are recommended: Modified lymphadenectomy, radical lymphadenectomy or removal of "bulky disease". In case of presence of vital tumor cells patients with teratoma receive "salvage therapy", patients with seminoma receive instead x-irradiation. If only differentiated teratoma cells are found in addition 2 courses of standard chemotherapy are administered. Standard chemotherapy consists of Vinblastine, Bleomycine and Cis-platinum, salvage therapy of VP 16, Ifosfamide and Cis-platinum.
 ...
PMID:[Malignant testicular tumors in children. Concept of the cooperative therapy study MAHO 88 based on MAHO 82]. 267 31

Several in vitro chemosensitivity assays have been developed for predicting clinical response to chemotherapeutic and biologic agents, alone and in combinations. The most widely accepted assay is the colony forming assay (CFA) which assesses the clonogenic capability of stem cells. Other methods include growth inhibition assays by evaluating cell number; thymidine incorporation; or amino acid uptake. More recently an automatic colorimetric technique utilizing crystal violet dye or a tetrazolium (MTT) vital dye has been developed for more rapid assessment of cytotoxic or growth inhibitory activity in vitro. Several reports have compared the results of in vitro tests with patients' clinical response. Two major problems affect the predictive value of in vitro chemosensitivity tests. The foremost is cellular heterogeneity which exists within a single tumor as well as between tumors. Artificial selective pressure inherent to tissue culture system is the other problem. In general, in vitro tests predict clinical resistance more consistently than clinical sensitivity. However, chemosensitivity assays remain useful in screening new agents and preclinical modeling of clinical trials.
 ...
PMID:In vitro chemosensitivity testing and its clinical application in human gliomas. 268 52

The hypoxic cytotoxicities of misonidazole and pimonidazole (Ro 03-8799) towards the human tumor cell lines HT-1080 and LoVo have been compared with those seen with Chinese hamster V79-379A cells. Survival was assayed using two colorimetric assays, either a tetrazolium salt (MTT) or methylene blue, and by conventional colony scoring. The drugs were more cytotoxic towards HT-1080 and LoVo cells than V79 cells. The times taken for 10 mmol dm-3 misonidazole to reduce survival to 0.1 surviving fraction (SF) using colony formation as the end point were 2.6 hr for HT-1080, 2.4 hr for LoVo, and 3.5 hr for V79; using the MTT assay these times were 3.5 hr, 2.1 hr, and 2.9 hr, respectively. The times for 2 mmol dm-3 pimonidazole to reduce survival to 0.1 SF using colony formation as the end point were 2.0 hr for HT-1080, 1.7 hr for LoVo, and 3.7 hr for V79; using the MTT assay these times were 2.5 hr, 1.4 hr, and 2.5 hr, respectively.
 ...
PMID:A comparison of colorimetric and clonogenic assays for hypoxic-specific toxins with hamster and human cells. 270 1

Claims of synergy between etoposide and cisplatin have been based upon preclinical in vivo murine P388 models or upon human clinical trials in tumors such as lung cancer. Such in vivo studies are useful in exploring therapeutic synergy, i.e., an improved therapeutic strategy. The term "synergy" in this context is sometimes, however, taken to imply greater than additive kill of tumor cells. Unfortunately, it is virtually impossible to document supra-additive tumor cell kill in vivo, since in vivo curves of therapeutic effect are not linear and drugs are therefore not additive with themselves. Therapeutic synergy may, in fact, occur when two drugs are merely additive (or even antagonistic) with regard to cytotoxicity if the drugs have nonoverlapping host toxicity. The demonstration of true supra-additive cell kill would imply an interaction of the two agents at a cellular level and would have profound implications for biochemical studies. In order to determine whether the reported therapeutic synergy of etoposide and cisplatin is due, in part, to supra-additive cell kill, we used an in vitro tetrazolium-based colorimetric assay for cytotoxicity (MTT assay) and an isobologram analysis to test combinations of the two drugs against four human small cell and four human non-small cell lung carcinoma lines. Using a rigorous test for in vitro synergy, we could not establish a greater than additive cytotoxic effect on our cell lines. It thus appears that the clinical synergy between etoposide and cisplatin is not due to a supra-additive effect at the cellular level. Our results have implications for a variety of fields in which claims of "synergy" often appear.
 ...
PMID:Lack of in vitro synergy between etoposide and cis-diamminedichloroplatinum(II). 270 26


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>