Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001418 (adenocarcinoma)
 68,496 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Recombinant human-interferon-gamma (rH-IFN-gamma) and verapamil (VRP), either alone or in combination, were evaluated in MTT assay for their modification effects on adriamycin-induced cytotoxicity against MKN-45, human stomach adenocarcinoma cells. VRP as a single agent did not inhibit the survival of MKN-45 at doses of up to 5.0 micrograms/ml. The survival of MKN-45 was inhibited by rH-IFN-gamma dose-dependently and further inhibited by the addition of VRP. However, the maximum growth inhibition of MKN-45 in any combination treatment with rH-IFN-gamma and VRP was less than 50% except in the highest concentration combinations (% survival: 47.9% at 10(4) U/ml of rH-IFN-gamma and 3.0 micrograms/ml of VRP). Adriamycin caused a concentration-dependent cytotoxicity and its cytotoxicity was significantly enhanced by the addition of rH-IFN-gamma and further enhanced by the combined use of rH-IFN-gamma and VRP. The modification effects of rH-IFN-gamma and VRP on adriamycin-induced cytotoxicity were evaluated in terms of modification index (MI), demonstrating that rH-IFN-gamma significantly increased in adriamycin-induced cytotoxicity and that the combined use of rH-IFN-gamma and VRP enhanced the adriamycin-induced cytotoxicity to a greater extent than did rH-IFN-gamma alone: MI values at 10(2) U/ml and 10(3) U/ml of rH-IFN-gamma were 1.7 and 3.1, respectively; those at 1.5 micrograms/ml and 3.0 micrograms/ml of VRP in the presence of 10(3) U/ml of rH-IFN-gamma were 4.4 and 6.0, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Modification of adriamycin-induced cytotoxicity by recombinant human interferon-gamma and/or verapamil in human stomach cancer cells. 128 22

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.
 ...
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

The effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer was investigated in rats using magnetic resonance imaging. Experimental liver metastatic tumors were established in syngeneic BDIX rats after intrasplenic injection of DHD/K12 colon adenocarcinoma cells. Each rat with implanted liver tumors received s.c. injections of somatostatin analogue RC-160 (50 micrograms/kg) or the vehicle (control) twice a day for 4 weeks, starting 3 weeks after tumor inoculation. During the treatment with RC-160, the growth of liver tumors was studied quantitatively by measuring liver tumor volumes in vivo with magnetic resonance imaging at intervals of 7 days. Chronic administration of RC-160 inhibited the growth of hepatic metastases of colon cancer in rats. Significant inhibition of liver tumor growth in RC-160-treated rats was observed throughout the treatment. The final liver tumor volume in the treated rats was decreased by 56.1% as compared to the controls. The treatment with RC-160 reduced the percentage increase in liver tumor volume from 1575 +/- 674% (mean +/- SEM) for the control to 1034 +/- 727% in the treated group. The tumor volume doubling time in treated rats was 3.7 days longer than the controls. The liver tumor growth delay time was 15.1 days. At the end of the treatment, the incidence of ascites and the weights of tumorous livers were also decreased by RC-160 treatment. Administration of RC-160 prolonged the median survival time by 13 days in treated rats. In cell cultures, significant inhibitory effects of somatostatin-14 and RC-160 on the growth of DHD/K12 colon cancer cells were determined by MTT assay and [3H]-thymidine incorporation assay, indicating direct effects of these peptides on the growth of colon cancer cells in vitro. These data suggest that administration of RC-160 could inhibit the growth of colon cancer and their hepatic metastases in rats. Somatostatin analogue RC-160 might be considered as a potential new agent for the treatment of patients with hepatic metastases of colorectal cancers.
 ...
PMID:Inhibitory effect of somatostatin analogue RC-160 on the growth of hepatic metastases of colon cancer in rats: a study with magnetic resonance imaging. 135 23

Recent interest in site-selective cAMP analogs has focused on the role of 8-chloro-adenosine (8-Cl-adenosine) in the inhibition of tumor cell growth by 8-chloro-cAMP (8-Cl-cAMP) (Van Lookeren Campagne, et al. Cancer Res 1991; 51: 1600-5). We have evaluated 8-Cl-cAMP and 8-Cl-adenosine for their growth inhibitory activity against two human colon adenocarcinoma cell lines, HCT116 and FET. Because these cell lines have been adapted to grow in chemically defined medium we were able to evaluate the effect of serum on 8-Cl-cAMP's growth inhibitory activity. In addition, cells grown in serum-free medium were tested for their sensitivity to 8-Cl-cAMP, serum-activated 8-Cl-cAMP and 8-Cl-adenosine. IC50 values, determined by measuring cell growth using a MTT colorimetric assay, showed that 'serum activation' of 8-Cl-cAMP was required to achieve inhibition of HCT116 (IC50 = 1.3 +/- 0.1 microM) and FET (IC50 = 2.0 +/- 0.1 microM) cell growth. IC50 values were not reached at the highest concentrations tested (IC50 > 500 microM) in the absence of serum, permitting us to conclude that 8-Cl-cAMP does not have growth inhibitory activity between 1.0 and 500 microM doses. HCT116 and FET cells grown in media containing serum and in the presence of 8-Cl-adenosine had IC50 values of 0.6 +/- 0.1 and 0.9 +/- 0.2 microM, respectively. HCT116 and FET cells grown in chemically defined medium containing 8-Cl-adenosine exhibited IC50 values of 1.0 +/- 0.1 and 3.1 microM, respectively.(ABSTRACT TRUNCATED AT 250 WORDS)
 ...
PMID:Inhibition of colon tumor cell growth by 8-chloro-cAMP is dependent upon its conversion to 8-chloro-adenosine. 145 Apr 43

Antineoplastic ether lipids have entered phase I clinical trial and, although their mechanism of action remains unclear, it is widely believed that the plasma membrane is the primary cellular drug target. In the present study the hypothesis was tested that metabolism of ether lipids acts as a detoxification process. [31P]-nuclear magnetic resonance (NMR) spectroscopy was used to study the metabolism of the ether lipid SRI 62-834 (SRI) and the phosphate ester hexadecylphosphocholine (HPC) in the presence of both isolated phospholipases C and D and post-mitochondrial rat liver homogenate. Both SRI and HPC were slowly metabolised by phospholipase D to their alkyl phosphates and choline, and the alkyl phosphates were subsequently metabolised by phosphatase to yield the alcohols and inorganic phosphate. These studies failed to detect any metabolism of either SRI or HPC by phospholipase C, and the metabolism of platelet-activating factor (PAF) by this enzyme was not inhibited by the addition of either compound. The cytotoxicity of SRI, the related compound HPC and their metabolites was determined in vitro using three cell lines. Cytotoxicity was measured by analysis of cell growth kinetics, MTT assay and lactate dehydrogenase release. Closely similar results were obtained in the JB1 rat hepatoma cell line, in the non-transformed BL8 rat hepatocyte cell line, and in A549 human lung adenocarcinoma cells. SRI was the most toxic of the compounds analysed, the concentration required to produce 50% toxicity or growth inhibition (IC50) being 6-9 microM. The putative metabolite of SRI, 2,2'-bis(hydroxymethyl)tetrahydrofuran, and the known metabolites [2'-(octadecyloxymethyl)tetrahydrofuran-2'-yl]methyl phosphate and 2-hydroxymethyl-2-octadecyloxymethyltetrahydrofuran exhibited IC50 values of > 200, > 100 and 40-70 microM, respectively, consistent with metabolic detoxification. HPC was more cytotoxic (IC50, 37 microM) than its phosphate metabolite (IC50, 140 microM), but its toxicity was similar to that of its metabolite hexadecanol (IC50, 28 microM), suggesting that only the former metabolic route leads to detoxification.
 ...
PMID:Is metabolism an important arbiter of anticancer activity of ether lipids? Metabolism of SRI 62-834 and hexadecylphosphocholine by [31P]-NMR spectroscopy and comparison of their cytotoxicities with those of their metabolites. 145 Dec 37

The chemosensitivities of squamous cell carcinoma (SCC) tissues from the head and neck area were compared to findings of adenocarcinoma, mainly from digestive organs. The sensitivity of each tissue was determined using the in vitro succinate dehydrogenase (SD) inhibition test, which shares a common principle with the 3-(4,5-dimethyl-thiazolyl)-2,5-diphenyl-2H-tetrazolium bromide (MTT) assay. Tumor tissues were obtained at surgery or biopsy. Anticancer drugs tested were carboquone, Adriamycin, mitomycin C, cisplatin (CDDP), aclacinomycin A, 5-fluorouracil and 1-hexylcarbamoyl-5-fluorouracil with 10 times the peak plasma concentration, respectively. The means +/- standard deviations of SD activities in SCC tissues were significantly lower than those in adenocarcinoma tissues (p less than 0.001), and the sensitivity rates of SD activity in SCC tissues had a higher value than those in adenocarcinoma tissues (p less than 0.05), against each drug. Our study showed that CDDP-based combination regimens might be effective for SCC tissues. The chemosensitivity of each excised tissue should be tested, in order to prescribe sensitive, effective drugs for each patient.
 ...
PMID:Comparison of in vitro anticancer chemosensitivity between human squamous cell carcinoma and adenocarcinoma. 152 69

FK973 (11-acetyl-8-carbamoyloxymethyl-4-formyl-14-oxa-1, 11-diazatetracyclo [7.4.1.0.0] tetradeca-2, 4, 6-trien-6, 9-diyl diacetate), an analogue of mitomycin C (MMC), was tested against human oral squamous cancer cell lines Ca 9-22, HSC-2, HSC-3, breast adenocarcinoma cell lines MCF-7, BT-20 and breast ductal carcinoma cell line T-47D using MTT assay. FK973 showed cytotoxic effects against six tested cell lines and much wider effective dose range than MMC, adriamycin (ADM), and cisplatin (CDDP). FK973 was the most potent of the four drugs tested against the growth of the three squamous cancer cell lines derived from oral cavity. However, in breast cancer cell lines, FK973 was less potent than MMC and ADM. FK973 was time and dose dependent. The combination effects of FK973 with 5-Fluorouracil (5FU) or CDDP were synthetical. It may be a promising candidate for the treatment of oral and breast cancer.
 ...
PMID:Cytotoxic activity of FK973 against human oral and breast cancer cells. 166 Dec 25

We have derived sublines of three human lung cancer cell lines with acquired resistance to cisplatin. The cisplatin resistant sublines of NCI-H69 (small cell), COR-L23 (large cell), and MOR (adenocarcinoma) show 5.3 fold, 3.1 fold, and 3.8 fold resistance, respectively, determined in a 6-day MTT assay. Although the parent lines show a wide range of glutathione content per cell, the sublines each show similar values to their corresponding parent line. Radiation response curves have been obtained using a soft agar clonogenic assay. Values obtained for the parent lines (95% CL in parentheses) were: NCI-H69: Do = 0.99 Gy (0.87-1.16), n = 2.9 (1.6-5.2), GSH = 14 ng/10(4) cells; COR-L23: Do = 1.23 Gy (1.05-1.49), n = 1.3 (0.7-2.2), GSH = 47 ng/10(4) cells; MOR: Do = 1.66 Gy (1.48-1.88), n = 3.0 (1.9-4.8), GSH = 86 ng/10(4) cells. The cisplatin resistant variants of NCI-H69 and COR-L23 showed 31% and 63% increases, respectively, in Do compared to their parent lines, whereas no change in radiation response was seen in MOR. In this panel of lines, therefore, although there is a correlation between glutathione content and radiosensitivity of the parent cell lines, acquired resistance to cisplatin is not accompanied by increased glutathione content. However, two of the three cisplatin resistant lines do show a significantly reduced radiosensitivity.
 ...
PMID:Radiation response of human lung cancer cells with inherent and acquired resistance to cisplatin. 184 46

Because of conflicting reports of clinical synergy, we used the tetrazolium-based colorimetric (MTT) assay to test in vitro combination effects of methotrexate (MTX) plus 5-fluorouracil (FUra) in 4 schedules on 2 human non-small-cell lung cancer cell lines (adenocarcinoma, NC1-H23; bronchio-alveolar-cell carcinoma, NC1-H358), and 1 human colorectal adenocarcinoma cell line (SNU-C1). The complete 3 dimensional set of isoboles in the dose range under study was generated by a microcomputer-based method. We found that the combination effects of 8-hr sequential FUra-MTX, simultaneous administration of MTX-FUra, and 8-hr sequential MTX-FUra were clearly antagonistic for all 3 cell lines. In contrast, the combination cytotoxic effects of 24-hr sequential MTX-FUra were much more active. Our in vitro model thus clearly shows that MTX-FUra interactions are highly schedule-dependent. This provides a rational basis for testing sequential MTX-FUra with a longer administration interval than usually employed clinically.
 ...
PMID:Schedule-dependent in vitro combination effects of methotrexate and 5-fluorouracil in human tumor cell lines. 184 23

The effects of human recombinant granulocyte-macrophage colony-stimulating factor (GM-CSF) 1-1000 U/ml on the growth of human lung cancer cell lines have been studied in vitro. A panel of 10 small cell, 1 adenocarcinoma and 1 large cell lines was used with multidrug resistant sublines of 3 of the panel. The MTT assay was used to quantify cell numbers after 6-8 days' growth in the presence of GM-CSF. Neither growth inhibition nor stimulation of any of the cell lines in the presence of GM-CSF was observed. Any effects of this agent on residual tumour cells may not therefore present a problem during its clinical use to stimulate marrow regeneration after high-dose chemotherapy for lung cancer.
 ...
PMID:Failure of GM-CSF to influence the growth of small cell and non-small cell lung cancer cell lines in vitro. 184 14


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