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The main target of the thesis was to investigate the drug resistance reversal on prokaryotic and eukaryotic model organisms. Based on DNA and protein complex formation properties of the given compounds the plasmid elimination of bacteria and the modification of the drug transporter proteins various experimental systems have been studied in bacteria and tumor cells.It was found that E. coli cells isolated from clinical specimen were less sensitive for the plasmid elimination than the laboratory strain carrying F prime plasmid, however, there was a complex formation between the antiplasmid compounds and the plasmid DNA isolated from both the clinical and laboratory strains. In addition there was a difference between the curing effect of two phenothiazines – the PMZ and TFP – on some E. coli strains in this study. The mechanism of action of different antiplasmid compounds was investigated on model nucleic acids such as calf thymus DNA and plasmid DNA. The pyrido[3,2-g] quinoline and phenothiazine derivatives seemed to have a complex formation with the model nucleic acids. Some of the compounds modified the activity of membrane efflux proteins. Based on the effect of trifluoromethyl ketones earlier studied my attention was focused on the combination of the trifluoromethyl ketone proton pump inhibitor TF18 with well-known antiplasmid compounds such as promethazine, trifluoperazine and 9-aminoacridine. In checkerboard studies the interaction between proton pump inhibitor and tricyclic compounds has been examined and it turned out that the interaction of proton pump inhibitor and trifluoperazine exerted synergistic antibacterial and plasmid curing effect on E. coli doxycycline resistant clinical strain due to the alteration of activity of membrane transporters. The role of proton pump system of the bacterial membrane was studied on Helicobacter pylori strains. The trifluoroketone proton pump inhibitor was able to block the proton motive forces and the activity of flagellar motor of both clarithromycin sensitive and resistant isolates of Helicobacter pylori . Since swimming was more sensitive to the inhibition than tumbling, I can suppose that TF18 works as an un-coupler in biological motor. The sensitivity of MDR1 type of eukaryotic ABC-transporter to resistance modifiers was studied on cancer cells. The synthetic benzo[b]-1,8-naphthyridine, pyridoquinoline, aza-oxafluorene and pregnane derivatives exerted reversing action of P-glycoprotein. Furthermore natural compounds, like coumarin derivatives and some fractions of persimmon extracts have been found to be potent resistance reversal agents against tumour cells.

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microgravity experiments in tumor research. Several tumor cell lines have shown significant alterations in their properties, including proliferation, apoptosis, and migration ( 6 ). Thyroid cancer cells have been shown to be transformed into a less malignant

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Milacic V, Banerjee S, Landis-Piwowar KR, Sarkar FH, Majumdar AP, Dou QP: Curcumin inhibits the proteasome activity in human colon cancer cells in vitro and in vivo. Cancer Res 68(18), 7283–7292 (2008) Dou Q

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, it is necessary to consider the drug-resistant cells in the tumor. The fact that the chemotherapeutic doses used in the treatment of cancer are capable of killing the drug-resistant cells among the cancer cells is a desirable treatment. There is no

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Authors: Chao-Chuan Chi, Chiang-Ting Chou, Chun-Chi Kuo, Yao-Dung Hsieh, Wei-Zhe Liang, Li-Ling Tseng, Hsing-Hao Su, Sau-Tung Chu, Chin-Man Ho and Chung-Ren Jan

JS, Chai KL, Cheng HH, Fang YC, Chi CC, Su HH, Chou CT, Jan CR: Tamoxifen-induced [Ca 2+ ] i rises and Ca 2+ -independent cell death in human oral cancer cells. J. Receptor Signal Transduction Res. 27, 353–367 (2007

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lymphoma and human colon cancer cell lines. In Vivo, 2006, 20 , 119–124. Lóránd T. Cinnamylidene ketones as potential modulators of multidrug resistance in mouse lymphoma and human

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Abstract  

Radiolabeled molecules have an important role to evaluate tumor characteristics such as aggressiveness, and to identify the effectiveness of cancer treatments such as chemotherapy and radiotherapy. Various radionuclide (18F, 99mTc, 124I) labeled molecules can be used apoptosis detection by estimating decrescendos cell viability after therapy. 99mTc-tetrofosmin which is used as a myocardial perfusion imaging agent in routine and at the same time is known to accumulate in various tumors including breast tumor. The aim of this study was to assess the utility of 99mTc-tetrofosmin for monitoring the early response of MCF-7 breast cancer to chemotherapy. To evaluate the role of 99mTc-tetrofosmin in vitro chemotherapy, the uptake ratio was determined using MCF-7 breast cancer line after the cells had been treated with cisplatin. When we examined the apoptotic ratios which induced with different dose of cisplatin in MCF-7 breast cancer cells by using Annexin V and TUNEL methods, it was observed that the rate of apoptosis increased with soaring dose. The uptake rates of 99mTc-tetrofosmin in MCF-7 cell line in the chemotherapeutic groups were lower than it is in the control group (p < 0.01). The negative correlation between uptake ratios and apoptotic rates shows that 99mTc-tetrofosmin may be used a radiopharmaceutical for evaluating chemotherapy response. 99mTc-tetrofosmin might be probably useful as an imaging agent for estimation of early chemotherapy response in breast cancer.

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Abstract  

An antigastric cancer monoclonal antibody, 3H11 and its Fab fragment, were labeled with #-emitter 211At using p-[211At] astatobenzoic acid (PAtBA) intermediate. The astatinated antibodies had conspicuous cytotoxic effect on human gastric cancer cell M85 in vitro. Tissue distribution of the astatinated antibodies were investigated in nude mice with subcutaneous tumor xenografts by i.v. injection. The astatinated Fab fragment was better suitable for 7.2-hour half life of 211At, since its tumor uptake remained higher (9.48–8.42 I.D%/g) than the astatinated intact antibody (~4.0 I.D%/g) from 3 to 14-hour post injection. However, the undesired high 211At uptake of the astatinated antibodies in some normal tissues, such as stomach, kidney and lung, suggested that the 211At labeled antibodies should be further explored.

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Engi, H., Gyémánt, N., Lóránd, T. és mtsai: Cinnamylidene ketones as potential modulators of multidrug resistance in mouse lymphoma and human colon cancer cell lines. In Vivo, 2006, 20 , 119–124. Lóránd T

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