Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0006826 (cancer)
 1,092,456 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Rats used were W/Fu strain with a reported incidence of spontaneous mammary tumors (MTs) of 17%. Most of these have been benign fibroadenomas in older females. X-ray or fast neutron irradiations were given in subthreshold doses, some as low as 10 rads. Also, low doses (150 mg) of a chemical carcinogen (N-nitroso-N-butylurea; NBU) prolactin (MtH). The prolactin was provided by grafting a syngeneic mammatropic pituitary tumor (MtT.W95 or MtT.W98). Tumors developing at the implantation site were chormophobe adenomas. The latent period of tumor induction decreased after the 4th generation of animal passage of the tumors. In some rats, ovariectomy was done 1 week before X-irradiation. No MT was found in 18 untreated controls during 1 year of observation. No MT developed in 32 rats having only the grafts for 9-12 months. Total-body-X-irradiation with 25 or 50 rads alone elicited no MT for 1 year. Among 27 rats exposed to 200 rads of X-rays 2 developed MT fibroadenomas after 5 and 7 months. The supplemental administration of prolactin greatly increased and accelerated the occurrence of MTs in irradiated rats. Most of these were adenocarcinomas. Ovariectomized rats had fewer MTs than intact females. A correlation was found between dose and MT incidence. The persistence of chemically transformed MT cells was shown by the addition of prolactin several months after NBU therapy. MTs developed in 8 of 10 rats within 3 months after the MTT graft became palpable. All but 1 of these were adenocarcinomas. Apparently there had been no repair or elimination of damaged cells in the dormant state. It is suggested that progressive growth of MTs may depend on the hormonal milieu of the host.
J Natl Cancer Inst 1977 Jun
PMID:Role of prolactin in rat mammary carcinogenesis: detection of carcinogenicity of low-dose carcinogens and of persisting dormant cancer cells. 32 20

Cancer chemotherapy has witnessed a great deal of progress since the introduction of the nitrogen mustards in the 1940s. Unfortunately, individual patients with apparently identical tumour histologies do not always respond identically to the same drug regimen. Determining the sensitivity and resistance of an organism before treatment has been the standard of care in infectious diseases for many years, while in oncology treatment has been initiated according to tumour histology rather than the tumour's sensitivity to a given agent. Attempts to individualise therapy have been the goal of oncologists since the 1950s. Since that time a number of in vitro assays have been developed to predict therapeutic outcome prior to the start of therapy. In the 1970s, with the introduction of the human tumour stem cell assay, it was generally believed that oncology was on the threshold of entering an era of predictive in vitro chemosensitivity testing. Unfortunately, this assay was shown to have a number of technical drawbacks including the low plating efficiencies of many primary tumour samples which thus limits the percentage which can be evaluated, leaving us still at this threshold today. Several recent developments, such as the Kern assay, which measures inhibition of radioactive precursors into tumour cells in the presence of antineoplastic agents, ATP bioluminescence assays, and the fluorescent cytoprint assay offer the promise of rapid and sensitive results. Other assays, such as the tetrazolium-based MTT and the sulphorhodamine blue assay appear to hold more promise in the screening and evaluation of potential new agents in established tumour cell lines than for evaluating chemosensitivity of clinical specimens. However, before a particular assay can be considered as an in vitro test of chemosensitivity or resistance, controlled prospective studies must be carried out to validate the assay in a number of different tumour types.
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PMID:Prediction of response to drug therapy of cancer. A review of in vitro assays. 128 May 62

Chemosensitivity testing of adenocystic, tongue and gingiva cancer cell lines to 14 antitumor drugs using a tetrazolium-based colorimetric assay (MTT assay) was carried out and the values of the relative antitumor activity (RAA) of the drugs were compared. Adriamycin (ADM), methotrexate (MTX) and fluorouracil (5-FU) showed the most potent RAA against the cell lines while Cantharidin (CTD) did not show RAA. The rank orders of other 10 drugs against each cell line differed from each another.
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PMID:[Chemosensitivity testing of adenocystic tongue and gingival cancer cell lines]. 128 86

We have studied the ability of cyclosporin A (CsA) and a non-immunosuppressive analogue, O-acetyl cyclosporin A (OACsA, B3-243) to inhibit the growth of human lung cancer cells in vitro. Using continuous drug exposure and the MTT colorimetric assay to determine cell growth we found that CsA produced partial growth inhibition at doses ranging from 0.5 to 3.0 micrograms ml-1 (0.4-2.4 microM). At progressively higher doses, complete growth inhibition and in situ cell lysis were seen. The P-glycoprotein expressing multidrug resistant (MDR) variant H69/LX4 of the small cell line H69/P was less sensitive to cyclosporins than the parent line, but this was not true of the non-P-glycoprotein expressing MDR variants of large cell line COR-L23 or adenocarcinoma line MOR. Sensitivity to OACsA was approximately 2-fold higher than that to CsA in most of the lines although not in the most sensitive line, COR-L88. Even in COR-L88, exposed to CsA or OACsA for 24 h, clonogenic cell survival was reduced only to 50%. There was no reduction in polyamine content of COR-L23 or COR-L88 cells following 48 h of exposure to CsA or OACsA. The effects on cell growth could not be inhibited by the addition of exogenous putrescine, nor could they be enhanced by the addition of alpha-difluoromethylorthinine. It does not appear therefore that inhibition of polyamine synthesis is the basis of the observed growth inhibition.
Br J Cancer 1992 Mar
PMID:Effects of cyclosporin A and a non-immunosuppressive analogue, O-acetyl cyclosporin A, upon the growth of parent and multidrug resistant human lung cancer cells in vitro. 131 90

Because most small-cell lung cancers (SCLC) are initially chemosensitive and express neuroendocrine (NE) cell markers and most non-SCLC tumors (NSCLC) are chemoresistant and do not express NE cell markers, we investigated the association between morphological type and NE cell differentiation with in vitro chemosensitivity. We tested a panel of 55 lung cancer cell lines established from previously untreated patients. These were tested against five cytotoxic drugs commonly used in the therapy of lung cancer, using the MTT assay. For comparative purposes, we also tested cell lines established from previously treated patients with SCLC and from colorectal tumors. The logarithms of the IC50 values of all of the cell lines were normally distributed, permitting the use of Student's t-test for assessment of differences. In general, the in vitro sensitivities of SCLC, NSCLC, and colorectal cell lines mirrored the clinical experience with these tumor types. Cell lines started from previously treated patients with SCLC were more resistant than those from previously untreated patients who responded to initial therapy. For all of the cell lines, the sensitivities to the five drugs tested were highly significantly correlated with each other. Thus, for comparative purposes, each group could be assigned an average standardized mean rank. About 15% of NSCLC tumors express multiple neuroendocrine (NE) cell markers and 4 of 5 lines from these NSCLC-NE tumors were relatively chemosensitive, similar to SCLC lines and significantly different from other NSCLC lines. Other NE cell lines tested included bronchial carcinoids and cell lines from small-cell carcinomas arising in extra-pulmonary locations (ExPuSC).(ABSTRACT TRUNCATED AT 250 WORDS)
J Natl Cancer Inst Monogr 1992
PMID:Association between histological type and neuroendocrine differentiation on drug sensitivity of lung cancer cell lines. 132 32

Two kinds of immunoconjugate (T-3M and T-11M) of murine monoclonal antibody with mitomycin C (MMC) were developed using spacers containing a disulfide (T-3M) or thiocarbamate (T-11M) bond. A murine monoclonal antibody (NCC-LU-243) raised against a human small cell lung carcinoma cell line, Lu-24, in nude mice, is an IgG2a monoclonal antibody that recognizes a 145-kDa protein on the cell surface membrane. T-3M and T-11M showed affinity for the LU-243 antigen-positive H-69 cell line but not for the antigen-negative Lu-65 cell line in vitro. In the in vitro MTT assay, the order of efficacy of these compounds was T-11M > T-3M > MMC against antigen positive H-69 and T-11M = MMC > T-3M against antigen-negative K562. When antigen-positive H-69 was transplanted into nude mice for in vivo assay, the maximum tolerated dose of T-3M was twice as high than that of the parent compound MMC. Furthermore, T-3M showed higher antitumor activity against antigen-positive H-69 than MMC conjugated with a non-specific rabbit IgG in vivo. When the maximum tolerated doses of T-3M and MMC were administered to H-69-bearing nude mice, the effect of T-3M was superior to that of MMC, whereas no differences were observed between the antitumor activity of T-3M and MMC against antigen- negative MX-1, a human breast carcinoma. These two immunoconjugates of monoclonal antibody with mitomycin C are thought to be useful for targeting cancer chemotherapy against human small cell lung carcinomas.
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PMID:Targeting cancer chemotherapy using a monoclonal antibody (NCC-LU-243) conjugated with mitomycin C. 132 68

Selective toxicity against cancer cells is a most important determinant for anticancer agents. Therefore, we have preferably evaluated anticancer effects in vivo using murine tumor models for several decades. Approximately 50 anticancer agents are currently available for clinical therapy, but very few agents are effective against some types of cancer. Much progresses in cell culture techniques resulted in establishment of various human tumor cell lines. Currently, we are able to use human tumor lines as well as murine ones for the examination of drug sensitivity. A number of assay methods to evaluate anticancer activity have been developed. In the beginning, growth inhibitory activity was evaluated by counting cell numbers after drug exposure. Then, human tumor clonogenic assay (HTCA) was designed to measure only proliferative cells. Recently colorimetric MTT assay and SRB assay in 96-well microplates were developed, which were adopted in the screening system in the NCI, based on a new idea, that is, disease-oriented screening (DOS) using about 60 human tumor cell lines. In this paper outline of each method was described, adding especially several comments on disease-oriented screening.
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PMID:[Cell culture and its application--in vitro evaluation of anticancer activity using human tumor cell lines]. 132 72

This study was undertaken to evaluate the colorimetric MTT [3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2H tetrazolium bromide] assay as a means of testing the sensitivity of gliomas to chemotherapeutic agents in vitro. Eight human glioma established cell lines were plated in 96-well tissue culture plates and incubated for 4 days with 10 different anti-cancer agents; 5 different concentrations of each drug were tested. The MTT dye was then added to the wells, and the resulting formazan precipitate was solubilized with dimethylsulfoxide (DMSO). The spectrophotometric absorbance (measured at 570 nm) of control and experimental wells was used to calculate the cytotoxicity index (CI). Values with a CI greater than 50% growth inhibition indicated cytotoxic efficacy (sensitivity to the chemotherapeutic drug). Six of the seven (85.7%) glioma cell lines were highly sensitive at varying concentrations to mitomycin C, cisplatin, and doxorubicin. Four of the seven (57.1%) cell lines demonstrated intermediate sensitivity to mitoxantrone and vinblastine. Five of the seven (71.4%) cell lines exhibited resistance to etoposide, bleomycin, cosmegen, and BCNU. One of the cell lines tested, U-138MG, failed to produce the MTT formazan precipitate, so that the sensitivity of this cell line to the panel chemotherapeutic drugs could not be determined. The variability of the results indicates the need for an in vitro screening method to evaluate the effectiveness of clinical and experimental chemotherapeutic agents. The MTT assay provides a rapid method of screening antineoplastic agents against gliomas for cytotoxicity.
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PMID:Test for chemotherapeutic sensitivity of cerebral gliomas: use of colorimetric MTT assay. 812 70

A cell line (GZL-8) was established by cloning from ascitic fluid of an untreated ovarian carcinoma patient. The cells grew rapidly, accumulated lipids and showed chromosomal alterations. One of the marker chromosomes showed characteristics of a Y-like chromosome. This unusual finding was confirmed by DNA hybridisation using specific probes to the Y chromosome. The cells stained with fluorescent antibodies to desmoplakin and cytokeratins 8, 18, 19, and weakly with vimentin but not with desmin. The presence of epithelial membrane antigen, human milk fat globulin, alpha-lactalbumin, alpha-fetoprotein, placental alkaline phosphatase and oestrogen receptor-related antigen was demonstrated by indirect immunoperoxidase staining, but no CA-125 antigen could be detected. The cells showed positive reaction with antibodies to P-glycoprotein. The function of the P-glycoprotein transport system was demonstrated by the rhodamine-123 release test. The cells were initially responsive to doxorubicin, and to high concentrations of cisplatin. Growth inhibition by doxorubicin, especially at low doses was enhanced by the addition of verapamil or tamoxifen. This was shown by the soft agar clonogenic assay, by direct cell counting and by the MTT reducing test. Our results show that combination between drug and sensitivity modulators may be of potential clinical value in ovarian cancer.
Eur J Cancer 1992
PMID:A cell line with unusual characteristics from an ovarian carcinoma patient: modulation of sensitivity to antitumour drugs. 134 52

We evaluated the multidrug resistance (MDR)-modulating effects of progesterone (PRG) and an orally active, structurally related compound, megestrol acetate (MA), in several MDR human cell lines. At 100 microM, both steroids inhibited the binding of a Vinca alkaloid photoaffinity analog to P-glycoprotein (P-gp) in MDR human neuroblastic SH-SY5Y/VCR cells [which show greater than 1500-fold resistance to vincristine (VCR) in the tetrazolium dye (MTT) assay]. However, 100 microM MA markedly enhanced the binding of [3H]-azidopine to P-gp in both SH-SY5Y/VCR cells and the MDR human epidermoid KB-GSV2 cell line (which displays 250-fold resistance to VCR in the MTT assay). PRG had little effect on the binding of [3H]-azidopine to P-gp. MA at low doses was more effective than PRG in sensitizing cells to VCR and enhancing their accumulation of [3H]-VCR. The highly resistant SH-SY5Y/VCR subline exhibited significant collateral sensitivity to both steroids. These data suggest that MA may be a clinically useful modulator of MDR.
Cancer Chemother Pharmacol 1992
PMID:Megestrol acetate reverses multidrug resistance and interacts with P-glycoprotein. 134 73


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