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Biomedical subjects

L Y Yang

Publications and source records attributed to L Y Yang.

At least 91 records · Page 5Linked to original sources
PubMed1980

Treatment of cultured human colon carcinoma cells with fluorinated pyrimidines.

The shape of the initial part of the dose-dependent response curve of LoVo cells, an established human colon carcinoma cell line, exposed for 1 hr to graded concentrations of 5-FU depended on the medium supplement, i.e., fetal calf serum (FCS), in which the cells were treated and subsequently incubated for colony-formation. At concentrations of 50--100 micrograms/ml (equivalent to peak plasma levels following an in vivo bolus dose of 15 mg/kg) cell kill was completely prevented by FCS. The serum did not contain thymidine (TdR) but had significant amounts of uridine (UR). When 5-FU was delivered in dialyzed FCS, concentrations of 50--100 micrograms/ml achieved only a modest 15% cell kill after 1 hour treatment. Regardless of medium supplement, the killing effect of 5-FU did not increase beyond concentrations greater than 2,000 micrograms/ml. Increasing the exposure interval dramatically increased the killing of LoVo cells by 5-FU, although the effects of medium supplement on the degree of cell survival persisted for about 12 hours. Virtually all of the incorporated 5-FU was transformed into 5-FUR, and a very small proportion eventually was incorporated into nucleic acids, suggesting that the killing effect of 5-FU on LoVo cells is mediated mostly by ribosidation and not by conversion into the deoxyribonucleoside. This conclusion is supported by the failure of 5-FUdR to kill LoVo cells after a treatment interval of one hour, even at concentrations of 5000 micrograms/ml; yet after the same exposure interval, 5-FUR effectively killed cells at concentrations of 50--100 micrograms/ml. TdR afforded no protection from cell kill by 5-FU. In contrast, UR was capable of protecting LoVo cells from the lethal effects of both 5-FU and 5-FUR even at concentrations as low as 10 micrograms/ml. Ftorafur exposed to LoVo cells for 1 hour had a slight killing effect (about 20--25%) at concentrations ranging up to 2000 micrograms/ml. Although the lethal effect of ftorafur was slightly increased after longer periods of incubation, it failed to reach 90% even after intervals of 48 hours. The results on cellular sensitivity that we obtained for LoVo cells treated with various fluorinated pyrimidines differ substantially from those of other investigators who used different methods to assess cell killing on nonhuman and noncolonic cell systems. The predictive relevance of these data as compared to those obtained in other systems is justified by the suboptimal results with these agents in clinical practice.

Cell Line↗
PubMed1980

Serum CEA levels in a human colonic adenocarcinoma (LOVO) xenograft system.

The relationship between tumor size and circulating CEA titers was examined for a human colonic adenocarcinoma xenografted in Balb/C athymic mice. Xenograft material was derived from line LoVo, which produces moderate amounts of CEA, both in vitro and in vivo. No correlation was found between tumor size and serum CEA levels.

Adenocarcinoma↗
PubMed1980

Observations on the synthesis of carcinoembryonic antigen by an established human colonic carcinoma cell line.

Some properties and kinetics of synthesis of the carcinoembryonic antigen (CEA-LoVo) produced by an established human colon carcinoma cell line were analyzed. CEA-LoVo was assayed by the method of Chu and Reynoso which was standardized against the activity of the First British Standard for CEA. CEA-LoVo was stable at -20 and 4 degrees C. At 37 degrees C, CEA-LoVo degraded at the rate of 1.4%/day in cell-free supernatants, and at the rate of 6.6%/day in the supernatants of monolayer cultures. CEA-LoVo was sensitive to enzymatic treatment ( approximately 55% loss) and extraction of PCA (greater than 70% loss). The elution profile of CEA-LoVo in concanavalin A-Sepharose B coincided with that of the First British Standard for CEA. No A or B blood group antigenic activity was noted. Studies employing immunofluorescent and horseradish peroxidase-labeled antibody techniques demonstrated heavy membrane and moderate intracytoplasmic localization. The greatest amount of net synthesis occurred for cells in stationary phase while CEA-LoVo release occurred maximally in lag phase.

Adenocarcinoma↗
PubMed1980

Observations on the synthesis of carcinoembryonic antigen by an established human colonic carcinoma cell line.

Some properties and kinetics of synthesis of the carcinoembryonic antigen (CEA-LoVo) produced by an established human colon carcinoma cell line were analyzed. CEA-LoVo was assayed by the method of Chu and Reynoso which was standardized against the activity of the First British Standard for CEA. CEA-LoVo was stable at -20 and 4 degrees C. At 37 degrees C, CEA-LoVo degraded at the rate of 1.4%/day in cell-free supernatants, and at the rate of 6.6%/day in the supernatants of monolayer cultures. CEA-LoVo was sensitive to enzymatic treatment with trypsin (approximately 55% loss)) and extraction of PCA (> 70% loss). The elution profile of CEA-LoVo in Concanavalin A-Sepharose B coincided with that of the First British Standard for CEA. No A or B blood group antigenic activity was noted. Studies employing immunofluorescent and horseradish peroxidase-labeled antibody techniques demonstrated heavy membrane and moderate intracytoplasmic localization. The greatest amount of net synthesis occurred for cells in the stationary phase while CEA-LoVo release occurred maximally in the lag phase.

Adenocarcinoma↗
PubMed1980

A method to measure carcinoembryonic antigen neosynthesis by cultured colon carcinoma cells.

A double-antibody radioimmunoprecipitation assay was used to measure the rate of incorporation of radioactive precursors into carcinoembryonic antigen (CEA) newly synthesized by cultured human colon carcinoma (LoVo) cells. Mixtures of 125I-labeled CEA and standard CEA were used to construct titration curves as a function of concentration, time of incubation, and temperature for goat anti-CEA serum and rabbit antigoat serum. In contrast to the zirconyl phosphate gel method, the double-antibody technique did not precipitate compounds with low molecular weights. Similar slopes were observed when standard CEA was used to inhibit immunoprecipitation of 125I-labeled CEA by both the zirconyl phosphate gel and the double-antibody techniques. When CEA produced by the colon carcinoma cells (CEA-LoVo) was used to inhibit immunoprecipitation of radioactive 125 I-labeled CEA, the curve was superimposed upon that elicited for standard CEA. CEA-LoVo incorporated significant amounts of [N-acetyl-3H]glucosamine, and chromatography of the 3H-labeled CEA-LoVo eluted with a peak superimposed upon that of the First British Standard for CEA. This method was subsequently used to estimate changes in the rate of CEA neosynthesis by LoVo cells as a function of culture age. The rate of incorporation of [N-acetyl-3H]glucosamine into CEA of LoVo cells in stationary phase was about three times that measured for cells in exponential growth. The technique described in this report has the advantage that labeling of CEA results from actual metabolic cellular activity. Therefore, it provides a tracer method to study the localization and kinetics of CEA synthesis by cultured colon cells.

Acetylglucosamine↗
PubMed1976

Establishment of a human carcinoembryonic antigen-producing colon adenocarcinoma cell line.

A human carcinoembryonic antigen-producing colon carcinoma cell line has been established. The cells form acinar structures and signet ring cells. The lumen of the acini presents microvilli and a glycocalyx. Neighboring cells show desmosomes and terminal bars. The cells present an aneuploid karyotype with a modal number of 49. No marker chromosomes are found, although a significant proportion of cells show an altered A2 chromosome and an extra B. Exponentially growing cultures produce 54 ng of carcinoembryonic antigen/10(6) cells. Kinetic parameters are as follows: doubling time, 37 hr; mitotic index, 0.8%; labeling index, 31%; generation time, 30 hr; G1 phase, 7 hr; S phase, 18 hr; G2 phase, 5 hr; growth fraction 90%. This cell line, designated line LoVo, represents an in vitro model for human colon carcinoma.

Adenocarcinoma↗
PubMedDate not supplied

Hepatic metastases from breast carcinoma: comparison of noncontrast, arterial-dominant, and portal-dominant phase spiral CT.

PURPOSE: The purpose of this work was to determine the relative value of noncontrast (NC), arterial-dominant (AD), and portal-dominant (PD) phase images in spiral CT of the liver for breast cancer metastases. METHOD: Forty-four spiral CT scans in 18 patients with hepatic metastases from breast cancer were retrospectively reviewed by three radiologists. Subjective evaluations of overall lesion conspicuity and margination were graded on a 5 point scale for NC, AD, and PD phase images, and the three phases were also ranked for demonstration of overall tumor volume. Those scans with hypervascular lesions were separately analyzed, resulting in three groups (all, hypervascular, hypovascular). RESULTS: For lesion conspicuity and margination for the entire study group, AD phase images showed the lowest grades (1.97 and 1.83), whereas the PD phase showed the highest grade (3.34 and 3.14; p < 0.0001) followed by NC (2.36 and 2.42; p < 0.0001). For the hypervascular subgroup, the AD phase also showed the lowest grades (2.39 and 2.24). In no case did the AD phase show more lesions than the combination of NC and PD phases. For depiction of overall tumor volume, the AD phase had the lowest ranking (2.51) compared with the NC and PD phases (1.71 and 1.78; p < 0.001). For the hypervascular subgroup, the AD phase had the lowest ranking (2.33) compared with the NC and PD phases (1.39 and 2.27; p < 0.0001). CONCLUSION: The AD phase is not required for lesion detection in spiral CT for hepatic metastases from breast carcinoma. The NC phase depicts the maximal tumor volume.

Adult↗
PubMedDate not supplied

Lumenal hydrolysis of menhaden and rapeseed oils and their fatty acid methyl and ethyl esters in the rat.

Simple alkyl (ethyl) esters of polyunsaturated fish oil fatty acids have been proposed as dietary supplements, but their relative efficiency of digestion and absorption have not been determined. Using stomach tubes, we gave rats menhaden or rapeseed oils, or the corresponding methyl and ethyl esters, and determined by chromatographic methods the lipid classes and molecular species recovered from the lumen of the jejunum during the first 1 to 2.5 h of digestion. Hydrolysis of menhaden oil resulted in a preferential retention of a high proportion of the polyunsaturated long chain acids in the sn-2-monoacylglycerols and in the residual triacyglycerols, while digestion of rapeseed oil led to a preferential release of free long chain monounsaturated fatty acids. In contrast, hydrolysis of the alkyl (methyl and ethyl) esters of the fatty acids of either menhaden or rapeseed oil resulted in a composition of free fatty acids which was much more representative of the original esters. It was therefore concluded that the differential lumenal liberation of the long chain and polyunsaturated (three or more double bonds) fatty acids from fish and rapeseed oil is largely due to their characteristic distribution between the primary and secondary positions in the glycerol molecule, and to a much lesser extent to a chain length discrimination by pancreatic lipase. This study also shows that the methyl and ethyl esters are hydrolyzed about 4 times more slowly than the corresponding triacylglycerols, which is sufficient to maintain a saturated micellar solution of fatty acids in the intestinal lumen during absorption.

Animals↗
PubMedDate not supplied

Further characterization of two distinct adriamycin-resistant sublines from LoVo human colon carcinoma cells.

We previously reported that two multidrug resistant sublines, AdR1.2 and SRA1.2, derived from LoVo human colon carcinoma cells, apparently expressed different resistance phenotypes including differential expression of p-glycoprotein (Pgp). Here, we further examined and compared other potential resistance mechanisms between AdR1.2 and SRA1.2 resistant cells. Our results showed that the Pgp-mediated AdR1.2 cells possessed an activated drug efflux pump and decreased nucleus binding of Adriamycin, while the non-Pgp-mediated SRA1.2 cells only held the second feature. Verapamil, however, partially reversed resistance in both sublines. Although glutathione-s-transferase was overexpressed in AdR1.2 but not in SRA1.2, both sublines had lower susceptibilities to drug-induced DNA strand breaks and greater capacities to repair such damage than did LoVo cells. These data suggest that, despite the differences in multidrug resistance phenotypes, the features of decreased susceptibility to DNA damage and enhanced DNA repair capacities may represent the common mechanisms responsible for drug resistance in both Pgp- and non-Pgp-mediated multidrug resistant cells.

ATP Binding Cassette Transporter, Subfamily B, Mem↗
PubMedDate not supplied

Heterogeneous effects of interferon on antitumor agents' cytotoxicities to human colon carcinoma cell lines.

Six established human colon carcinoma cell lines that segregated into three groups with different degrees of differentiation were treated using three subclasses of interferons as single agents and in combination with either 5-fluorouracil, cis-platinum, or adriamycin. The cytotoxicities of the combination treatments were heterogeneous and did not relate to the cell's levels of differentiation. Our data suggest that the optimal combinations of interferons and chemotherapeutic agents are independent of the differentiation state of the colon cancer cells.

Antineoplastic Agents↗
PubMedDate not supplied

Peplomycin and bleomycin effects on human colon cancer cells.

The lethal effects of peplomycin and bleomycin on cultured human colon cancer cells (LoVo) were compared by using the technique of inhibition of colony formation. The survival of LoVo cells after treatment for 1 h with either peplomycin or bleomycin was characterized by a biphasic exponential curve. When the exposure time was extended to 24 h, both drugs produced much greater cytotoxic effects, with survival decreased to less than 0.10% for bleomycin and less than 0.02% for peplomycin. Both peplomycin and bleomycin, in a dose-dependent manner, inhibited the incorporation of thymidine into cells. On an equal-weight basis, the cytotoxicity of peplomycin (24-h exposure) was similar to that of bleomycin. Both agent also inhibited the incorporation of leucine and uridine after 24 h of drug exposure, but to a lesser extent than inhibition of thymidine incorporation. However, after 1 h of exposure, such inhibitory effects were minimal. These results demonstrate that prolonged peplomycin or bleomycin exposure produces greater cell-kill than shorter drug exposure. Schedules with continuous drug administration should be explored clinically.

Bleomycin↗
PubMedDate not supplied

Metronidazole enhances the cytotoxic synergism produced by the combination of 1-beta-arabinofuranosylcytosine and cis-diamminedichloroplatinum.

Metronidazole (MZ) was evaluated as a single agent or in combination with CDDP and araC for its cytotoxic effects on five established human colon carcinoma cell lines. MZ alone produced little cytotoxicity at 1 h drug incubation. The cytotoxicity was detectable only after 2 h incubation and increased as a function of duration of treatment, suggesting a time-dependent rather than a dose-dependent cytotoxic effect. MZ had no effect on CDDP- or araC-induced cytotoxicity, whereas MZ enhanced the synergism resulting from the combination of two antitumor agents on the human colon tumor cell lines tested. Such enhancement was more pronounced on cells growing in stationary rather than in exponential phase. MZ not only produced a reversible S-phase arrest but also lessened the CDDP-produced inhibition on the incorporation of araC into DNA. However, it did not enhance CDDP-induced DNA cross-linkings, with or without araC. Our results indicated that MZ enhanced the synergism produced by two antitumor drugs in combination and that enhancement was accompanied by an increase in S-phase population and of the incorporation of araC into nucleic acids.

Cell Line↗
PubMedDate not supplied

Synergism of 1-beta-D-arabinofuranosylcytosine and cis-diamminedichloroplatinum in their lethal efficacies against seven established cancer cell lines of gastrointestinal origin.

We previously reported that the combination of cis-diamminedichloroplatinum (CDDP) and 1-beta-D-arabinofuranosylcytosine (ara-C) induced a remarkable synergistic killing effect on an established human colon carcinoma cell line, LoVo. The current study investigated whether this effect was LoVo specific or could be extended to other colon cancer cell lines as well as to cell lines of different histological origins, including an estrogen receptor-positive breast cancer cell line (MCF7), an ovarian cancer cell line (OV1225), and an esophageal cancer cell line (Hcu18). The six human colorectal cancer cell lines included in this study represent three biological groups with distinct phenotypic properties. Group 1 (well-differentiated) consisted of LoVo and SW48; group 2 (intermediately differentiated) comprised SW480 and SW620; and group 3 (undifferentiated) was represented by SW403 and SW1116. No significant synergistic cytotoxicity was noted after the breast and ovarian cancer cells were treated. However, synergistic lethal effects were observed in all of the six colon cancer cell lines as well as the esophageal cancer cell line. The synergistic effect on the gastrointestinal cancer cell lines was related to the concentration of ara-C and CDDP during treatment. Our results suggest that the cytotoxic synergism between ara-C and CDDP may be tissue-type specific and that synergism may depend on the histological origin of the cancer.

Cell Survival↗
PubMedDate not supplied

The heterogenous cytotoxic response of colon cancer cells is unrelated to phenotypic differentiation characteristics.

Six colon cancer cell lines segregated into three groups with distinct biological properties (i.e., morphological differentiation, DNA content, carcinoembryonic antigen production, etc.) were treated with ten antitumor drugs. Cytotoxic responses were heterogenous and not associated to biological grouping, in fact, for some drugs, the response of one member of the group resembled that of a member of another group rather than its group counterpart. Thus the most common phenotypic characteristics that identify colon cancer cells did not predict the cytotoxic response and do not appear useful for stratifying patients into categories with distinct responses to currently available chemotherapeutic agents.

Antineoplastic Agents↗