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Biomedical subjects

C C Cheng

Publications and source records attributed to C C Cheng.

At least 109 records · Page 6Linked to original sources
PubMed1983

Characterization of an antigen present on testicular cells and preimplantation embryos whose expression is modified by the t12 haplotype.

In attempts to identify cell surface molecules specified by lethal genes in the T/t-complex, we prepared a rabbit antiserum that has cytotoxic activity against testicular cells from males heterozygous for t12, but not against wild type cells. However, anti-t12 serum immunoprecipitates the same major component, a glycoprotein of mol. wt. 87,000 daltons, from galactose-labelled C3H. +/t12 testicular cell lysate and from congenic C3H. +/+ lysate, although the gp87 molecule precipitated from +/t12 cells appears to be more highly galactosylated than the +/+ form. The antigen is heavily glycosylated in both genotypes, since when testicular cells are treated with tunicamycin before immunoprecipitation, a protein of 40,000-42,000 daltons is obtained. Gp87 is also present on pre-implantation embryos, and on teratocarcinoma cells, but is barely detectable on any adult somatic cells examined. Its expression is developmentally regulated during pre-implantation stages, but the temporal pattern of its expression appears to be different between wild type and t12 embryos. Thus, we believe we have identified a molecule that may play a role in the differentiation of testicular cells and pre-implantation embryos, and that is either specified by genes in the t12 haplotype, or responsive in some way to the effects of t12.

Animals↗
PubMed1982

Structure-activity relationship study of anthraquinones: 1,4-dihydroxy-5,8-bis[[2-(2-hydroxyethoxy)ethyl]amino]-9,10-anthracenedione, an analog of an established antineoplastic agent.

An oxygen analog of the antineoplastic anthraquinone, 1,4-dihydroxy-5,8-bis[[2-(2-hydroxyethyl)amino]ethyl]amino - 9,10-anthracenedione, was synthesized. This compound, 1,4-dihydroxy-5,8-bis[[2-(2-hydroxyethoxy)ethyl]amino] - 9,10-anthracenedione, was found to be inactive against P-388 lymphocytic leukemia. A comparative structure-activity study of these two anthraquinones in terms of previously postulated N--O--O triangulation hypothesis was discussed.

Animals↗
PubMed1982

Sister-chromatid exchange and chromosomal aberrations by DHAQ and related anthraquinone derivatives in Chinese hamster ovary cells.

The induction of sister-chromatid exchanges (SCEs) and chromosomal aberrations in Chinese hamster ovary cells by doxorubicin (adriamycin), DHAQ and several related anthraquinone derivatives was investigated. Doxorubicin, DHAQ and some of its analogues exhibited genotoxic effects at 1 nM concentration. Among them, DHAQ possessed the strongest activity. The DNA-damaging action of these substituted anthraquinone compounds correlated well with their antiproliferative effect on cells, and this action was detectable at concentrations significantly below that which caused inhibition of cell proliferation. Our data suggest that the genotoxic effects of the compounds occur prior to manifestation of their antiproliferative activity.

Animals↗
PubMed1982

Effect of dihydroxyanthraquinone (NSC 279836) and thoracic irradiation on long-term survival of rats.

Dihydroxyanthraquinone (DHAQ; NSC 279836) is a recently synthesized compound that is structurally similar to Adriamycin and produces greater antitumor effects in murine model systems. We compared DHAQ to Adriamycin in rats, with and without irradiation of the chest at various intervals after drug treatment. A single injection of Adriamycin (1 mg/kg i.p.) had little effect on animal survival, even if combined with radiation (12 Gy 25 MV X-rays), greater than 90% being alive at 1 year. A single injection of DHAQ (3 mg/kg i.p.) was equally uneffective up to 200 days after treatment (survival, greater than 90%). However, between 200 and 370 days after treatment, all animals died, producing a median survival time of 280 days. Further, when DHAQ was combined with radiation, there was an increase in animal deaths between Days 300 and 200. For animals irradiated on Days 0, 43, and 93 after DHAQ treatment, only 50, 75, and 80%, respectively, survived to Day 200. All animals that survived past Day 200 subsequently died by 1 year, displaying the same kinetics of lethality as those animals that had received DHAQ only. A repeat experiment using DHAQ at 1 mg/kg produced similar results. Based on these findings, we conclude that DHAQ produces a long-term (greater than 200 days) toxicity in rats that is not detectable by short-duration toxicity screening. In addition, radiation enhances short-term (less than 200 days) lethality, with the degree of enhancement decreasing as the interval between drug and radiation is increased.

Animals↗
PubMed1982

Comparison of the effects of dihydroxyanthraquinone and adriamycin on the survival of cultured Chinese hamster cells.

Dihydroxyanthraquinone [1,4-dihydroxy-5,8-bis ((2-([(2-hydroxyethyl)amino)ethyl)amino))-9,10-anthracenedione (DHAQ) (NSC 279836)] is currently being tested as a cancer chemotherapeutic agent because of its structural similarity to Adriamycin (ADR) and other DNA-intercalating antibiotics. We have therefore studied the effect of DHAQ on the survival of cultured Chinese hamster cells in direct comparison to ADR. Both DHAQ and ADR produced cytotoxicity that was dependent upon the concentration and duration of drug exposure. For 1-hr pulse exposures of asynchronous populations of exponentially growing cells, a 5- to 10-fold greater concentration of ADR than of DHAQ was required to produce the same level of cell killing. There were also differences in the cell cycle age specificity demonstrated by treating at various times before or after selection of cells in mitosis. DHAQ produced the greatest cytotoxicity in cells treated while in G1 or G2; ADR was more effective on cells located in S phase or mitosis. Overall, DHAQ was found to be similar to ADR and other DNA-intercalating antibiotics with regard to the induction of cell lethality. The only differences were those of the concentration required to produce a certain level of effect and of the cell cycle phase specificities for maximum effect.

Animals↗
PubMed1981

Synthesis of new polyamine derivatives for cancer chemotherapeutic studies.

Selected homologs, analogs, and acylated derivatives of spermine and spermidine, together with several heterocyclic and aromatic compounds containing a novoldiamine side chain, were prepared and evaluated biologically. Several compounds possessed activity against B-16 melanoma and human epidermoid carcinoma of the nasopharynx.

Animals↗
PubMed1981

Antiproliferative activity of doxorubicin and aminoanthraquinone derivatives on Chinese hamster ovary cells.

A study of the antiproliferative activity of doxorubicin and several substituted aminoanthraquinone derivatives on Chinese hamster ovary cells was conducted. Doxorubicin and a derivative each inhibited cell proliferation at low concentrations, the latter being more potent than doxorubicin. A structure-activity relationship of these compounds is discussed in connection with an earlier postulated N-O-O triangulation hypothesis.

Animals↗
PubMed1981

Synthesis and antimalarial activity of 8-[(1-alkyl-4-aminobutyl)amino]-6-methoxy-4-methylquinolines.

Three analogues of the causal prophylactic antimalarial primaquine were prepared and their antimalarial activity was evaluated. 8-[(1-Ethyl-4-aminobutyl)amino]-6-methoxy-4-methylquinoline (2a) demonstrated activity against Plasmodium berghei in mice at 20 mg/kg, with all animals cured at 320 mg/kg, and is without toxicity at 640 mg/kg. It also possessed outstanding causal prophylactic activity against Plasmodium cynomolgi in rhesus monkeys at very low dosages.

Animals↗
PubMed1980

Nature of the antigenic determinants of T locus antigens.

The nature of the antigenic specificities of several antigens associated with the T/t complex in the mouse were analyzed by means of glycosidase and haptene inhibition studies. Results indicate that on testicular cells sugar residues are involved in at least six different T/t antigenic determinants. The immunodominant sugar appears to be different for each of the specificities. The specificity for the following T/t antigens resides predominantly in the sugars indicated: T:sialic acid; t12:beta-D-galactose; tw32:beta-D-galactose; t0:L-fucose; tw1:N-acetyl-D-galactosamine; tw18:L-fucose. It seems probable that these sugars are found at the terminal reducing ends of the carbohydrate portion of T/t-bearing moleculse. These studies imply that at least some of the genes in the T locus code for glycosyltransferases or regulators of glycosyltransferases which modigy oligosaccharide structures and impart specificity to the T/t antigens by alteration of their terminal sugar residues.

Acetylgalactosamine↗
PubMed1980

Formation and reactions of negative ions relevant to chemical ionization mass spectrometry. I. CL mass spectra of organic compounds produced by F- reactions.

A systematic study of the negative-ion chemical ionization mass spectra produced by the reaction of F(-) with a wide variety of organic compounds has been accomplished. A time-of-flight mass spectrometer fitted with a modified high pressure ion source was employed for these experiments. The F(-) reagent ion was generated from CF(3)H or NF(3), typically at an ion source pressure of 100 mum. In pure NF(3), F(-) is the major ion formed and constitutes more than 90% of the total ion intensity. While F(-) is also the major primary ion formed in pure CF(3)H, it undergoes rapid ion-molecule reactions at elevated source pressures, yielding (HF)(n)F(-) (n = 1-3) ions, which makes CF(3)H less suitable as a chemical ionization reagent gas. Among the organic compounds investigated were carboxylic acids, ketones, aldehydes, esters, alcohols, phenols, halides, nitriles, nitrobenzene, ethers, amines and hydrocarbons. An intense (M - 1)(-) ion was observed in the F(-) chemical ionization mass spectra of carboxylic acids, ketones, aldehydes and phenols. Alcohols yield only (M + F)(-) ions upon reaction with F(-). A weaker (M + F)(-) ion was also detected in the F(-) chemical ionization spectra of carboxylic acids, aldehydes, ketones and nitriles. The F(-) chemical ionization mass spectra of esters, halides, nitriles, nitrobenzene and ethers are characterized primarily by the ions, RCOO(-), X(-), CN(-), NO(2) (-), and OR(-), respectively. In addition, esters show a very weak (M - 1)(-) ion (except formates). In the F(-) chemical ionization spectra of some aliphatic alkanes and o-xylene, a very weak (M + F)(-) ion was observed. Amines and aliphatic alkenes exhibit only insignificant fragment ions under similar conditions, while aromatic hydrocarbons, such as benzene and toluene are not reactive at all with the F(-) ion. The mechanisms of the various reactions mentioned are discussed, and several experimental complications are noted. In still other studies, the effects of varying several experimental parameters, including source pressure, relative proportions of the reagent and analyte, and other ion source parameters, on the observed chemical ionization mass spectra were also investigated. In a mixture of NF(3) and n-butanol, for example, the ratio of the intensities of the ions characteristic of the alcohol to that of the (HF)(n)F(-) ion was found to decrease with increasing sample pressure, with increasing NF(3) pressure, and with increasing electron energy. No significant effects on the spectra were observed to result from variation of the source repeller field or the source temperature. The addition of argon to the source as a potential moderator did not alter the F(-) chemical ionization spectrum significantly, but the use of oxygen appears to inhibit formation of the (HF)(n)F(-) cluster ion. The advantages of using F(-) as a chemical ionization reagent are discussed, and comparisons are made with other reagent ions.

Anions↗
PubMed1980

The search for new hypoxic cell radiosensitizers.

A number of newly synthesized compounds whose chemical structure suggested possible or remotely possible ability to radiosensitize hypoxic mammalian cells were studied in an in-vitro system. Those compounds that were not excluded because of insolubility or extreme cytotoxicity were tested for radiosensitizing ability. The correlation between chemical structure and radiosensitizing ability will be used for the rational design of additional compounds with a high probability of being effective hypoxic cell radiosensitizers. It is hoped that this will contribute to attempts to improve the cure rate of patients with malignant tumors through the use of radiation therapy and hypoxic cell radiosensitizers.

Cell Survival↗
PubMed1979

The structure of the capsular polysaccharide of Klebsiella K-type 31.

The structure of the Klebsiella K31 capsular polysaccharide has been elucidated by periodate oxidation, methylation analysis, characterization of oligosaccharides obtained by partial, acid hydrolysis, and proton magnetic resonance. The polymer consists of pentasaccharide repeating-units having the following structure (1).

Carbohydrate Conformation↗