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Biomedical subjects

S H Lu

Publications and source records attributed to S H Lu.

At least 37 records · Page 2Linked to original sources
PubMed1989

Rapid detection of ras oncogenes in human tumors: applications to colon, esophageal, and gastric cancer.

We have developed a rapid, nonradioactive large scale method for the detection of ras oncogenes in human tumors. DNA is amplified by the polymerase chain reaction (PCR), and then digested with specific restriction enzymes to detect either endogenous or primer-mediated Restriction Fragment Length Polymorphisms (RFLPs). We report here that three of 15 colon tumors tested contain K-ras codon 12 aspartic acid mutations and one, along with the HCT 116 colon carcinoma cell line, contains a K-ras codon 13 aspartic acid mutation. On the other hand, we did not detect H- or K-ras codon 12 mutations or the K-ras codon 13 aspartic acid mutation in 25 esophageal and 27 gastric cardia tumors isolated from patients in Lin-xing County, China. By incorporating nucleotide substitutions in PCR primers, this method can be applied towards the rapid, non-radioactive screening of virtually any genetic disease caused by known point mutations.

Codon↗
PubMed1989

A study of sex identification of trace, dried bloodstains using a Y-chromosome-specific deoxyribonucleic acid (DNA) probe.

A new method is discussed which examines trace, dried bloodstains by gel in situ hybridization using a Y-chromosome-specific deoxyribonucleic acid (DNA) probe to determine the sex of the bloodstain for forensic medicine application. The complete DNA is transferred directly by electrophoresis onto the gel intact, bypassing the possibilities of impurities contaminating the sample and of DNA degradation. The method has proven accurate for small (2.5-mm-diameter) samples aged up to eight years and is quick, simple, and easily read.

Adult↗
PubMed1988

Amplification of the EGF receptor and c-myc genes in human esophageal cancers.

The incidence of esophageal cancer is extremely high in Linxian County and certain other regions of the People's Republic of China. Epidemiologic and laboratory studies suggest that N-nitroso carcinogens and other environmental factors play a causative role. In the present study, employing over 100 DNA samples obtained from Lin-xian patients who underwent surgery for esophageal cancer, we have found a significant frequency of amplification of either the human epidermal growth factor receptor (HER-I) gene or the c-myc oncogene. These changes were found not only in tumor specimens, but also in adjacent non-tumor (grossly normal) tissue specimens obtained from patients with esophageal cancer. RNA samples were also obtained from over 30 tissue samples. These revealed considerable variation in the abundance of HER-I and c-myc transcripts in both the tumor and adjacent non-tumor specimens. A few samples revealed extremely high levels of these transcripts. Thus, changes in gene copy number or level of expression of HER-I or c-myc DNA sequences may play an important role in the pathogenesis of esophageal cancer in this high-risk region.

Blotting, Northern↗
PubMed1988

Effect of A-nor steroids and oestradiol on progesterone production by human luteal cells.

Cell suspensions were prepared from human corpora lutea obtained during the mid-luteal phase. Progesterone production was assessed after short-term incubation of luteal cell suspensions. Luteal cells were very sensitive to hCG, the concentration required for 50% maximum response being 0.01 i.u./ml, and the response was 5 times higher than the basal production. Oestradiol (1-100 microM) induced a significant dose-related decrease in both basal and hCG-stimulated progesterone production. The A-nor steroidal compounds anordrin and AF-45 reduced hCG-stimulated progesterone production only at the high concentration of 100 microM. The ED50 values were approximately 3 microM, 75 microM and 100 microM for oestradiol, AF-45 and anordrin respectively. Anordrin showed no significant effects on basal progesterone production. In addition, oestradiol markedly inhibited the activity of 3 beta-hydroxysteroid dehydrogenase in luteal cells, expressed by the conversion of pregnenolone to progesterone, but the inhibitory effects of anordrin and AF-45 were negligible or relatively low. The effects of anordrin and AF-45 were different from those of oestradiol on progesterone production by human luteal cells in vitro, indicating that neither substance is likely to be a useful luteolytic agent in women.

Cells, Cultured↗
PubMed1987

Radioimmunoassay used to detect DNA alkylation adducts in tissues from populations at high risk for oesophageal and stomach cancer.

N-Nitrosamines are alkylating agents capable of forming various covalent adducts with DNA in vivo. Since formation of promutagenic DNA adducts, particularly O6-methyldeoxyguanosine (O6-medGuo), has been implicated as an initiating event in nitrosamine-induced carcinogenesis, we have used radioimmunoassay (RIA) to probe for such damage in surgical tissue samples from cancer patients in populations likely to be exposed environmentally to nitrosamines.

Alkylation↗
PubMed1987

Determination of N-nitrosamines in gastric juice and urine and a comparison of endogenous formation of N-nitrosoproline and its inhibition in subjects from high- and low-risk areas for oesophageal cancer.

Samples of gastric juice were collected from a high-risk area for oesophageal cancer in China and analysed for N-nitroso compounds. N-Nitrosodimethylamine (NDMA), N-nitrosodiethylamine (NDEA), N-nitrosomethylbenzylamine (NMBzA), N-nitrosopyrrolidine (NPYR) and N-nitrosopiperidine (NPIP) were identified in descending order of concentration. Several unknown compounds were also detected in the fasting gastric juice. A positive correlation was found between the amount of nitrosamines in gastric juice and the degree of severity of lesions of the oesophageal epithelium: the amounts of nitrosamines in gastric juice from subjects with a normal oesophageal epithelium were lower than those in subjects with marked dysplasia or carcinoma of the oesophagus. In addition, 1500 samples of 24-h urine were collected from various communes in six high-risk areas and two low-risk areas for this cancer in China and analysed for N-nitrosamino acids. Subjects in high-risk areas excreted higher levels than those in low-risk areas. Intake of L-proline resulted in marked increases in levels of urinary N-nitrosoproline (NPRO) in inhabitants from both high- and low-risk areas. Intake of moderate doses of vitamin C, alpha-tocopherol and zinc by high-risk subjects reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in low-risk areas, suggesting a rational basis for prevention in high-risk areas.

China↗
PubMed1986

Relevance of N-nitrosamines to esophageal cancer in China.

Studies on the relevance of the N-nitrosamines to esophageal cancer in China are reviewed. Esophageal cancer is a complex and multifactorial problem. Although a causal association between nitrosamines exposure and esophageal cancer in China has not yet been rigorously established, exposure of Lin-Xian subjects to nitrosamines either directly or as a result of their in vivo formation has been detected in our study. Several N-nitrosamines (NDMA, NDEA, NMBzA, NPyr, NPip, and NSAR) in gastric juice collected from Lin-Xian inhabitants have been detected. A correlation was found between the lesions of esophageal epithelium and the amount of nitrosamines present. In addition, the amounts of N-nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, NSAR, and nitrates) excreted in 24-hr urine of subjects in Lin-Xian were significantly higher than those in Fan-Xian, indicating a higher exposure to N-nitroso compound and their precursors of the inhabitants in the high-risk area. The effect of nitrosamines on human esophagus has been investigated at the cellular levels. The amounts of O6-MedG in DNA of esophageal or stomach mucosa of patients from Lin-Xian were higher than that from Europe (Lyon and Essen). The presence of O6-MedG in the human fetal esophagus cultured with NMBzA was also detected. These findings indicate that the elevated levels of O6-MedG in esophageal DNA could be the result of a recent exposure to N-nitroso compounds or a genetically determined reduced cellular capacity for repair of O6-MedG from DNA. The hyperplasia was induced in the esophagus of human fetus that cultured with NMBzA for 2 weeks to 2 months. The intervention studies of esophageal cancer in Lin-Xian have been pursued. Intake of moderate doses of ascorbic acids by Lin-Xian subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in un-dosed subjects in the low-risk area. If N-nitroso compounds are formed in vivo and are among the causative factors of esophageal cancer in Lin-Xian, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds. Thus, the plan of chemoprevention is carried out in Lin-Xian.

Ascorbic Acid↗
PubMed1986

Urinary N-nitrosamino acids as indices of endogenous formation of N-nitroso compounds.

Exposure to their precursors (e.g., amines, nitrate/nitrite, NOx) can lead to formation in the human body of N-nitroso compounds (NOC), a class of potent animal carcinogens, which are also suspected of being carcinogenic in man. A non-invasive method, the 'N-nitrosoproline (NPRO) test', for estimating endogenous nitrosation in man was developed in our laboratory. This test, which monitors 24-hr-excretion of urinary N-nitrosamino acids, is now applied in clinical and field studies, with the aim of measuring nitrosamine exposure and of identifying dietary, life-style, and host factors, or disease states, that affect nitrosation in man. Results from such studies are used to identify populations/individuals at high risk for cancers of the stomach, oesophagus, and oral cavity possibly caused by endogenous nitrosamines, and to indicate preventive measures by which the body burden of endogenous nitroso carcinogens can be lowered efficiently.

Amino Acids↗
PubMed1986

Urinary excretion of N-nitrosamino acids and nitrate by inhabitants of high- and low-risk areas for esophageal cancer in Northern China: endogenous formation of nitrosoproline and its inhibition by vitamin C.

A total of 238 samples of 24-h urine were collected from inhabitants of high-risk (Lin-xian) and low-risk (Fan-xian) areas for esophageal cancer in northern China, according to three protocols: (a) from undosed subjects; (b) from subjects who had ingested 100 mg L-proline three times a day 1 h after each meal; and (c) from subjects in Lin-xian who had ingested 100 mg ascorbic acid together with 100 mg L-proline three times a day 1 h after each meal. As an index of individual exposure to N-nitroso compounds or their precursors, ingested in food and/or formed endogenously, the levels of four urinary N-nitrosamino acids and nitrate were determined. The amounts of N-nitrosoproline, N-nitrosothiazolidine 4-carboxylic acid, N-nitrososarcosine, and nitrate excreted in the 24-h urine of undosed subjects in Lin-xian were significantly higher than those in Fan-xian, indicating a higher exposure of the inhabitants in the high-risk area to N-nitroso compounds and their precursors. Ingestion of L-proline resulted in a marked increase in urinary N-nitrosoproline levels in inhabitants from both areas, suggesting that endogenous nitrosation may occur to a larger extent when appropriate amine precursors are ingested in foods. Intake of moderate doses of ascorbic acid by high-risk subjects effectively reduced the urinary levels of N-nitrosamino acids to those found in undosed subjects in the low-risk area. If N-nitroso compounds formed in vivo are among the causative factors for esophageal cancer in this area of northern China, ascorbic acid appears to be effective in lowering the body burden of these carcinogenic compounds, thus offering a rational basis for long-term intervention studies in this area.

Adult↗
PubMed1985

O(6)-methyldeoxyguanosine in oesophageal DNA among individuals at high risk of oesophageal cancer.

A radioimmunoassay using monoclonal antibodies (MAb) against 0(6)-medGuo and 0(6)-etdGuo enabled the presence of these DNA adducts to be detected in human tissues. With this methodology and with 1 mg of hydrolysed DNA it is possible to detect approximately 25 fmol 0(6)-medGuo or 12.5 fmol 0(6)-etdGuo per mg DNA. The analysis comprised a total of 37 human tissue specimens derived from patients who underwent surgery for cancer of the oesophagus in Linxian County (People's Republic of China); for comparison 12 tissue samples obtained from hospitals in Europe were similarly analysed. Seventeen samples from Linxian County showed a level of 0(6)-medGuo ranging from 15 to 50 fmol/mg DNA, 10 showed higher levels up to 160 fmol/mg DNA, and the remaining 10 samples were below the limit of detection. All the tissue samples from Europe showed levels below 45 fmol 0(6)-medGuo/mg DNA, 7 being below the limit of detection. No 0(6)-etdGuo was detected in any of the samples. 0(6)-alkylguanine DNA alkyltransferase activity observed in tissue extracts from Linxian County ranged from 190 to 326 fmol (mean values) of 0(6)-medGuo removed per mg protein and lower values were obtained for the removal of 0(6)-etdGuo. The findings obtained using this approach appear promising in assessing the role of alkylating agents, e.g. nitrosamines, in the aetiology of human cancer.

China↗
PubMed1985

Proliferative abnormalities of the oesophageal epithelium of Chinese populations at high and low risk for oesophageal cancer.

Studies on the pattern of proliferation of epithelial cells from the oesophagus of 33 individuals from Linxian, a high-risk area for oesophageal cancer in China, and of 22 subjects from Jiaoxian, a low-risk area for the same cancer in China, were performed using thymidine labelling. Oesophageal biopsies were obtained during endoscopic surveys carried out in these 2 populations. A clear difference was observed between the 2 groups; the high-risk group showed cell proliferation in the upper layers of the epithelium more often than the low-risk group. No difference was found in the cell proliferation patterns of subjects with oesophagitis and those without oesophagitis in the high-risk area. This finding could suggest that the tritiated thymidine assay may be a more sensitive method to characterize the precancerous lesions of the oesophagus in high- and low-risk populations than simple histological evaluation.

Adult↗
PubMed1985

Repair of DNA alkylation adducts in mammalian cells.

Carcinogenic alkylating agents, including nitrosamines, are able to alkylate DNA at various sites. This review presents evidence of the high degree of specificity in the type of DNA damage induced by various N-nitroso compounds and in the DNA repair processes among tissues or cells of different species. The O6-alkylguanine DNA alkyltransferase activity in various human and rodent tissues is discussed as well as the detection of O6-methylguanine in human DNA, using monoclonal antibodies and radioimmunoassay. The relevance of these findings to the mechanisms of cancer induction by nitrosamines is discussed.

Alkylating Agents↗
PubMed1984

Recent studies on N-nitroso compounds as possible etiological factors in oesophageal cancer.

Possible etiological factors involved in oesophageal cancer in various parts of the world and in certain provinces in Northern China are summarized. Evidence is accumulating that N-nitroso compounds and their precursors are involved in the disease in Northern China, as shown in a recent study: excretion of urinary N-nitrosamino acids by inhabitants living in a high- (Linxian) and in a low-risk area (Fanxian) for oesophageal cancer was compared. Linxian subjects excreted significantly more nitrate and nitrosamino acids (N-nitrosoproline, N-nitrosothiazolidine-4-carboxylic acid, N-nitrososarcosine) than those in Fanxian. When Linxian subjects were given 100 mg vitamin C three times a day (after each meal) together with proline, the level of urinary N-nitrosamino acids was reduced to that found in Fanxian. Thus, vitamin C, an efficient inhibitor of endogenous nitrosation, should now be examined in intervention trials in subjects in whom endogenous formation of N-nitroso compounds is elevated.

Africa↗