Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0007097 (carcinoma)
152,788 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The responses of cells to ionizing radiation include induction and/or suppression of the expression of genes and proteins. In our investigations of alterations in cellular protein expression in response to ionizing radiation, we have used the techniques of two-dimensional polyacrylamide gel electrophoresis and silver staining. We compared the nuclear protein profiles of control and irradiated (6 Gy, 4 h postirradiation) radioresistant squamous carcinoma cells (SQ-20B) and observed an alteration in the expression of a 40 kDa protein: control nuclei express a protein isoform with pI values between 5.4-5.8, while irradiated nuclei express a more acidic variant with pI values between 5.2-5.5. Using the cyanogen bromide/O-phthalaldehyde method followed by microsequencing analysis, we obtained an internal amino acid sequence and identified the 40 kDa protein as nucleolar protein B23. Western blotting experiments confirmed the internal amino acid sequencing results and showed both species (control, 5.4-5.8, irradiated, 5.2-5.5) to be recognized by an anti-B23 monoclonal antibody. Radiolabeling of control and irradiated samples with [32P]NAD or [32P]orthophosphoric acid revealed the acidic species of B23 to be both ADP-ribosylated and phosphorylated. Therefore, exposure of SQ-20B cells to radiation results in the increase in expression of an ADP-ribosylated and phosphorylated species of B23.
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PMID:Modification of nucleolar protein B23 after exposure to ionizing radiation. 763 Oct 8

Two non-transformed intestinal epithelial cell lines (RIE-1 and IEC-6) and three intestinal carcinoma cell lines (HT-29, T84 and MCA-38) were used to detect the toxic effects due to okadaic acid in the presence of mussel tissue homogenates. Cytotoxicity was assessed by measurement of the metabolic conversion of 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide to its corresponding formazan dye. All of the cell lines were sensitive to okadaic acid, with HT-29, RIE-1 and IEC-6 showing the greatest response. Dilutions of whole mussel tissue homogenates caused some loss of viability in most of the cell lines but had no significant effect on the viability of RIE-1 cells. In no case did the mussel homogenate compromise the dose-response curve to okadaic acid when data were normalized to the appropriate control value. These intestinal epithelial cell lines may prove useful in the bioassay of okadaic acid and related toxins.
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PMID:Use of cultured permanent lines of intestinal epithelial cells for the assay of okadaic acid in mussel homogenates. 767 65

Effects of gamma-irradiation, given in the range of 5 to 30 Gy on Caski cells (Epitheloid carcinoma from the cervix) were investigated by the MTT (3-(4,5-dimethylthiazol-2-yl) -2, 5-diphenyl tetrazolium bromide) method. Results were compared with data assessed simultaneously from cell number counts. The sizes of cells irradiated with 10 to 30 Gy were larger than those of unirradiated ones, and each irradiated cell reduced a larger amount of MTT than did each unirradiated cell. Irradiation in the above range, therefore causes Caski cells to lose their ability to divide, but the effect on the mitochondria was very slight. Application of the MTT method to the irradiated cells should be done with care. Because, in the irradiated cells depending on the irradiation dose, the MTT activity does not correlate to the cell number.
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PMID:Gamma irradiation effects on cultured cells: investigated by the MTT method. 775 4

There is a need to improve the selectivity of photodynamic therapy and for better targeting of tumor cells within specific tumor compartments. Selective in vitro phototoxicity of a human bladder carcinoma cell line 647V has been achieved by targeting sulfonated aluminum phthalocyanines (AlSPc) with monoclonal antibodies. Aluminum tetra-3 sulfonyl chloride phthalocyanine (PC) or rhodamine sulfonyl chloride were directly coupled to antibodies by a sulfonamide linkage and AlSPc or carboxyfluorescein were encapsulated in liposomes of the small unilamellar vesicle type (SUV) bearing antibody. Antibody E7 (IgM subclass), which recognized an antigenic determinant expressed on 647V but was absent on T24 a control human bladder carcinoma cell line, and a control IgM antibody were used. The effects of the two types of conjugate were compared. Immunofluorescence studies on living cells demonstrated specific cell surface localization of conjugates at 4 degrees C and internalization at 37 degrees C. Phototoxicity was measured by 3-(4,5-dimethylthiazol-2-5-diphenyltetrazolium) bromide assay after exposing AlSPc-sensitized cells to red light. Significant AlSPc dose-dependent phototoxicity of the order 4 degrees C < 4 degrees C plus 37 degrees C < 37 degrees C was observed with E7-SUV and E7-PC in the range 1-8 microM AlSPc. At equimolar AlSPc doses absolute toxicity was similar for the two conjugate types, but at equimolar antibody doses, the liposomal conjugate was more effective by up to 13-fold. Addition of urine during illumination decreased toxicity, which was attributed to the presence of protective elements. The results suggest that photosensitizers such as AlSPc could be used for antibody-directed therapy and in particular for selectively damaging tumor cells of the epithelial cell compartment in bladder carcinoma by intrabladder administration. The therapeutic ratio, which takes into account both specific and nonspecific toxicity, was greater for the liposome conjugate than for the direct conjugate indicating their greater suitability for in vivo instillation.
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PMID:A comparison of direct and liposomal antibody conjugates of sulfonated aluminum phthalocyanines for selective photoimmunotherapy of human bladder carcinoma. 780 Jul 20

We used the PCR technique to detect the Epstein-Barr virus (EBV) and human papillomavirus (HPV) DNA in paraffin-embedded tissues from Greek patients with nasopharyngeal carcinoma (NPC). The oligonucleotide primers used for the detection of EBV amplify a 375-bp long sequence from the EcoRI B fragment of the viral genome, whereas for HPV the primers amplify a 151-bp long sequence of the viral genome. The PCR products were analysed by agarose gel electrophoresis and visualised by UV illumination after staining with ethidium bromide. Sixty-three specimens were examined. EBV specific sequence was amplified in 20 (32%) and HPV in 12 (19%) out of the 63 samples. There was no co-infection with EBV and HPV. Although there is a high correlation of EBV infection with poorly differentiated NPC in patients from Southern China and South-East Asia, the restricted distribution suggests genetic or environmental cofactors in the development of the neoplasm. Our results confirm this suggestion since there was only a 32% correlation of EBV with NPC in Greece. HPV may also be involved in the carcinogenesis of EBV-negative squamous cell nasopharyngeal carcinomas.
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PMID:Detection of Epstein-Barr virus and human papillomavirus in nasopharyngeal carcinoma by the polymerase chain reaction technique. 788 26

The role of estrogenic hormones on the induction of drug resistance was studied in cervical cancer cell lines, SiHa and Caski. After the cells were inoculated with estradiol (E2) or diethylstilbestrol (DES) in various dosages, the cell survival rates with adriamycin treatment were examined by MTT (3-[4,5-dimethyl-thiazole-2-yl]-2,5-diphenyl-tetrazolium-bromide) test and the intracellular accumulation of adriamycin was evaluated by flow cytometry. In the same condition, the expression of multidrug resistance gene-1 (mdr-1 gene) was detected either by Northern blot hybridization for mdr-1 mRNA or by immunoblot for P-glycoprotein 170. The data in this study indicated that estrogenic hormones had the capacity to induce drug resistance in cervical carcinoma cell lines. When cells were treated with estrogenic hormones and adriamycin simultaneously, the intracellular accumulation of adriamycin declined and corresponded with the drug resistance. Since the expression of the mdr-1 gene induced by E2 or DES results in drug resistance, it is suggested that the mdr-1 gene in SiHa cells may contain the estrogenic responsive element (ERE) in its regulatory region. However, the mechanism of drug resistance induced by estrogenic hormones in Caski cells is different from SiHa cells due to the absence of mdr-1 gene expression. Despite that, this experiment may provide a model to investigate the relationships between estrogenic hormones and drug resistance in other female genital cancers.
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PMID:The induction of multidrug resistance in human cervical carcinoma cell lines by estrogenic hormones. 791 38

Using 3-(4,5-dimethythiazole)-2,5-diphenyltetrazolium bromide (MTT) method, the effect of probimane (Pro) on doxorubicin (Dox) cytotoxicity was studied. Pro 0.313, 0.625, and 1.25 micrograms.ml-1 potentiated cytotoxicity of Dox in Ehrlich ascites carcinoma (EAC) cells. Incubation of EAC cells with Dox 10 micrograms.ml-1 and Pro 116.5, 233, and 466 micrograms.ml-1 resulted in an increase in intracellular drug accumulation from 0.69 +/- 0.06 to 1.08 +/- 0.10 micrograms/10(7) cells. In S37-bearing mice, Pro 23.3, 46.6, and 116.5 micrograms.ml-1 enhanced the malondialdehyde (MDA) formation in tumor and liver mitochondria and decreased MDA formation in liver mitochondria. These results suggested that the increases of Dox accumulation and MDA formation in tumor cells by Pro might be the reasons for synergistic effect of Pro on Dox cytotoxicity.
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PMID:Synergistic effect of probimane on anticancer cytotoxicity of doxorubicin in vitro. 801 87

We have examined the contribution of the mitochondrial genome to the tumorigenic phenotype expressed by human cell lines derived from an ovarian and a cervical carcinoma and from an osteogenic sarcoma. All these continuous cell lines are anchorage-independent in soft agar and form tumors in athymic nude mice. Long-term exposure of the cells to ethidium bromide, an intercalating agent which inhibits mitochondrial DNA replication, gave rise to subclones depleted of mitochondrial DNA and RNA molecules and displaying either anchorage independence or dependence. These respiratory-deficient subclones contain disorganized and enlarged mitochondria, are auxotrophic for uridine and pyruvate, and grow in vitro at a rate nearly identical or moderately slower than their respective parent. The tumor-forming ability of both anchorage-independent and -dependent cell lines was tested by s.c. and intramuscular implantation of the cells in nude mice. We found that the tumorigenic capacity was influenced by the route of inoculation. Subcutaneously, mitochondrial DNA-less cell lines are either poorly or nontumorigenic, while all but one cell line form tumors when implanted into the hind leg muscle. The relative in vivo growth rate of the parent and the mitochondrial DNA-less subclones reflects their respective in vitro rate of growth. All intramuscular tumors introduced into culture mimic the molecular and phenotypic traits of the injected cells, with the exception of the anchorage-dependent cell lines which give rise to anchorage-independent tumor cell lines. The present observations indicate that human cells without mitochondrial DNA have the capacity to proliferate and form tumors in vivo.
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PMID:Tumor-forming ability in athymic nude mice of human cell lines devoid of mitochondrial DNA. 803 12

We previously found that human cervix carcinoma HeLa cells irradiated with multiple fractions of gamma rays (0.5 Gy daily, five times per week over 6 weeks) become resistant to cis-dichlorodiammineplatinum(II) (cis-DDP), methotrexate (MTX) and vincristine (VCR), but retain the same sensitivity to gamma rays or UV light. In the present report attempts were made to elucidate the mechanisms by which these cells have acquired resistance to cis-DDP and VCR. The sensitivity to different drugs was measured by modified MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) method. Neither buthionine sulfoximine (BSO) nor ethacrinic acid were able to reverse the resistance of preirradiated cells to cis-DDP. Therefore, neither the increased levels of glutathione nor glutathione transferase seem to be involved in resistance to cis-DDP. Preirradiated cells did show resistance to cadmium, indicating the increased levels of metallothioneins in these cells. Resistance of preirradiated cells to vincristine was abolished by the addition of verapamil, indicating that resistance to this drug may depend on the increased expression of plasma membrane P-glycoprotein. It was concluded that mechanisms of resistance of preirradiated cells to cytostatics are multifactorial and involve at least the increased levels of metallothioneins and changes in the plasma membrane. Acquired resistance to cytotoxic drugs induced by preirradiation may be the reason for the reduced response to these drugs after radiation treatment of certain tumors.
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PMID:Multifactorial molecular mechanisms are involved in resistance of preirradiated human cervix carcinoma cells to cis-dichlorodiammineplatinum (II) and vincristine. 810 78

The present study was designed to analyze the growth-inhibitory effects of the combination of fluorouracil (FUra), cisplatin (CDDP), and dipyridamole (DP). These toxic effects were assessed on the human breast-carcinoma cell line MCF-7 using the MTT (tetrazolium bromide) assay in 96-well culture dishes. Data were analyzed using the median-effect principle. The drug combinations tested included FUra concentrations ranging from 0.8 to 800 nmol/l, CDDP concentrations of 0.3-30 mumol/l, and DP concentrations of 2-200 mumol/l. A total of 189 different experimental conditions were tested, including different sequences of administration, with being DP applied before, simultaneously with, or after the two antitumor drugs. Synergistic cytotoxic interactions were found between FUra and CDDP, FUra and DP, and CDDP and DP as well as when the three drugs were combined. The sequence of exposure did not influence the growth-inhibitory activity of the combination FUra-CDDP but altered the effect of combinations of either FUra or CDDP with DP, since at lower concentrations the effect shifted from synergism to antagonism when DP was added simultaneously with CDDP and after the two antitumor drugs. However, the interaction was shown to be truly synergistic by median-effect analysis when the two antitumor drugs were simultaneously associated, with no change in the synergistic effect being observed for the three DP administration sequences.
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PMID:Sequence-dependent growth-inhibitory effects of the in vitro combination of fluorouracil, cisplatin, and dipyridamole. 826 77


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