1.Detection and clinical significance of NTRK in digestive system neoplasms.
X J HOU ; Y FU ; X H PU ; X S FAN
Chinese Journal of Pathology 2023;52(8):876-880
2.Evaluation of allelic alterations in 13 CODIS STR loci in tumor tissues from human digestive system.
Jian-xin FANG ; Cheng-tao LI ; Li XIAO
Journal of Forensic Medicine 2007;23(4):280-282
OBJECTIVE:
To study genetic alterations in 13 CODIS STR loci in various tumor tissue samples from human digestive system.
METHODS:
Malignant tumor tissues and blood samples taken from 55 different unrelated individuals were collected. DNA samples were extracted using Chelex100 extraction kit, amplified using Profiler and Cofiler PCR amplification kit and analyzed using API 310 analyzer.
RESULTS:
Aberrant cell divisions were detected in all of the 55 tumor tissue samples, with STR alternations detected in two samples including allelic alteration, partial and complete loss or unbalance of heterozygosity. Moreover, the alternations might occur simultaneously at more than one loci.
CONCLUSION
Caution must be taken in STR analysis of tumor tissue samples since the exclusion loci in forensic identification or paternity testing may be resulted from mutations in the tumor tissue.
Alleles
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DNA, Neoplasm/analysis*
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Digestive System Neoplasms/genetics*
;
Gastrointestinal Neoplasms/genetics*
;
Genetic Variation
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Genotype
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Humans
;
Loss of Heterozygosity
;
Pancreatic Neoplasms/genetics*
;
Polymerase Chain Reaction
;
Tandem Repeat Sequences/genetics*
3.Evaluation of the criterion of partial loss of heterozygous in tumor tissues.
Cheng-Tao LI ; Shu-Min ZHAO ; Su-Hua ZHANG ; Li LI
Journal of Forensic Medicine 2009;25(6):417-420
OBJECTIVE:
To evaluate the applicability of partial loss of heterozygous (pLOH) criteria in tumor tissues with Identifiler system.
METHODS:
Eight thousand four hundred and twenty eight heterozygous loci of the 696 unrelated individuals (UIP) genotyped with Identifiler Kit were randomly paired by locus to construct odds ratio of allelic peak height (or area under allelic curve) according to the given formula. Similarly, odds ratios of allelic peak height (or area under allelic curve) of the 896 heterozygous loci of 77 pairs of tumor and homologous normal tissues (TNP) were also acquired. Curve fitting was performed to determine the distribution of the odds ratio. The proportion of pLOH in two groups was determined with odds ratio less than 0.5 or higher than 2.0. Compared the relevance ratio of allelic peak height and peak area by chi2 test.
RESULTS:
The odds ratio of both peak height and peak area presented normal distribution in UIP (4214 heterozygous loci pairs) and TNP group (896 heterozygous loci pairs). There was 0.12% of normal heterozygous in UIP group erroneously presumed as pLOH with current criteria (< 0.5 or > 2.0). There was no significantly difference between the calling rate based on two types of odd ratio (P = -0.5632).
CONCLUSION
It is feasible to determine the pLOH in tumor tissue with Identifiler system by both peak height and peak area according to the standards of the odds ratio less than 0.5 or higher than 2.0.
Alleles
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Digestive System Neoplasms/genetics*
;
Female
;
Gene Frequency
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Humans
;
Loss of Heterozygosity
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Male
;
Mutation
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Odds Ratio
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Polymerase Chain Reaction/methods*
;
Tandem Repeat Sequences/genetics*
4.Role of TROP2 in cancer and as potential therapeutic target.
Chinese Journal of Pathology 2013;42(12):860-863
Animals
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Antigens, Neoplasm
;
genetics
;
metabolism
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Biomarkers, Tumor
;
genetics
;
metabolism
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Brain Neoplasms
;
metabolism
;
Cell Adhesion Molecules
;
genetics
;
metabolism
;
Digestive System Neoplasms
;
metabolism
;
Female
;
Genital Neoplasms, Female
;
metabolism
;
Glioma
;
metabolism
;
Head and Neck Neoplasms
;
metabolism
;
Humans
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Immunotherapy
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Male
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Prostatic Neoplasms
;
metabolism
;
Signal Transduction
5.Microsatellite Instability of Gastric and Colorectal Cancers as a Predictor of Synchronous Gastric or Colorectal Neoplasms.
Young Beak KIM ; Sun Young LEE ; Jeong Hwan KIM ; In Kyung SUNG ; Hyung Seok PARK ; Chan Sup SHIM ; Hye Seung HAN
Gut and Liver 2016;10(2):220-227
BACKGROUND/AIMS: Microsatellite instability (MSI) plays a crucial role in gastrointestinal carcinogenesis. The aim of this study was to clarify whether MSI is a useful marker for predicting synchronous gastric and colorectal neoplasms. METHODS: Consecutive patients who underwent both esophagogastroduodenoscopy and colonoscopy before the resection of gastric or colorectal cancers were included. MSI was analyzed using two mononucleotide and three dinucleotide markers. RESULTS: In total, 434 gastric cancers (372 microsatellite stability [MSS], 21 low incidence of MSI [MSI-L], and 41 high incidence of MSI [MSI-H]) and 162 colorectal cancers (138 MSS, 9 MSI-L, and 15 MSI-H) were included. Patients with MSI gastric cancer had a higher prevalence of synchronous colorectal cancer, colorectal adenoma, and gastric adenoma than those with MSS gastric cancers (4.8% vs 0.5%, p=0.023; 11.3% vs 3.2%, p=0.011; 3.2% vs 1.2%, p=0.00, respectively). The prevalence of synchronous colorectal adenomas was highest in MSI-L gastric cancers (19.0%), compared with MSI-H (7.3%) or MSS (3.2%) gastric cancers (p=0.002). In addition, there were no significant differences in the prevalence rates of synchronous colorectal adenoma among the MSI-H (13.3%), MSI-L (11.1%), and MSS (12.3%) colorectal cancers (p=0.987). CONCLUSIONS: The presence of MSI in gastric cancer may be a predictor of synchronous gastric and colorectal neoplasms, whereas MSI in colorectal cancer is not a predictor of synchronous colorectal adenoma.
Adenoma/*genetics/surgery
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Aged
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Colonoscopy
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Colorectal Neoplasms/*genetics/surgery
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Endoscopy, Digestive System
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Female
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Humans
;
Male
;
*Microsatellite Instability
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Middle Aged
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Neoplasms, Multiple Primary/*genetics/surgery
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Predictive Value of Tests
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Stomach Neoplasms/*genetics/surgery
6.Nrf2 as a chemoprevention target in gastrointestinal carcinoma.
Peng GAO ; Xiu-wen TANG ; Xiu-jun WANG
Journal of Zhejiang University. Medical sciences 2012;41(4):453-463
Gastrointestinal tract carcinoma is one of the leading causes of cancer-related death in China. Chemoprevention has been considered as a potential approach to control this type of disease. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a redox-sensitive transcription factor that protects cells from oxidative/electrophilic stresses by activating the expression of a battery of cytoprotective genes through the antioxidant response element (ARE). Recently, Nrf2 has emerged as a novel target for chemoprevention. Several natural or synthetic chemicals, which activate Nrf2/ARE signaling pathway, have showed effect in animal models, and promises in many ongoing clinical trials. This review summarizes the recent findings on the regulation of Nrf2/ARE signaling pathway, and the developments in both preclinical and clinical studies.
Animals
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Anticarcinogenic Agents
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pharmacology
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Antioxidants
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metabolism
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Chemoprevention
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Digestive System Neoplasms
;
genetics
;
metabolism
;
prevention & control
;
Humans
;
NF-E2-Related Factor 2
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genetics
;
metabolism
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Oxidative Stress
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drug effects
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Response Elements
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genetics
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Signal Transduction
;
drug effects
7.Expression of hMSH2 gene and mutant p53 in sporadic digestive tract tumors.
Yanjie KANG ; Zhenke ZHANG ; Junxia WANG ; Jing CHEN ; Bo PENG ; Ping KANG
Chinese Medical Journal 2003;116(1):53-56
OBJECTIVETo investigate the role of mutated mismatch repair gene hMSH2 and mutant p53 gene in the carcinogenesis and development of sporadic digestive tract tumors.
METHODShMSH2 gene in normal and tumor tissue of 30 digestive tract tumor specimens was examined using polymerase chain reaction-single strand conformation polymorphism (PCR-SSCP) silver staining. The PCR product with an abnormal strand was sequenced directly. Mutant p53 protein in the tumor tissue was analyzed immunohistochemically.
RESULTSSix patients were identified as having mutated strands, three on hMSH2 exon 1 and three on hMSH2 exon 5. DNA sequencing revealed that all 6 patients had mutated basic groups that led to decrease in function of the hMSH2 protein. Forty percent (12/30) of patients were p53 positive. The frequency of mutated hMSH2 in p53 positive patients (41.7%) was significantly higher than in p53 negative patients (5.6%, P < 0.05).
CONCLUSIONThe mutation of hMSH2 plays an important role in the carcinogenesis and development of digestive tract tumors through stimulating p53 mutation.
DNA-Binding Proteins ; Digestive System Neoplasms ; genetics ; Genes, p53 ; Humans ; Immunohistochemistry ; MutS Homolog 2 Protein ; Mutation ; Polymerase Chain Reaction ; Polymorphism, Single-Stranded Conformational ; Proto-Oncogene Proteins ; genetics ; Tumor Suppressor Protein p53 ; analysis
8.Experimental study on anti-neoplastic activity of epigallocatechin-3-gallate to digestive tract carcinomas.
Zhi-hua RAN ; Jian ZOU ; Shu-dong XIAO
Chinese Medical Journal 2005;118(16):1330-1337
BACKGROUNDEpigallocatechin-3-gallate (EGCG) has been demonstrated to have anti-neoplastic activity, but the effective concentration of EGCG and its possible mechanisms are uncertain. The study on the killing effects of EGCG on different digestive tract cancer cell lines can find target sites of its anti-neoplastic effect and provide a theoretical basis for its clinical application in the treatment of cancers.
METHODSMethyl thiazolyl tetrazolium (MTT) analysis was made to detect the differential sensitivities of eight digestive tract cancer cell lines to EGCG. The effect of EGCG on cell cycle distribution of sensitive cancer cell line was measured by flow cytometry. By polymerase chain reaction (PCR)-enzyme linked immunosorbent assay (ELISA) protocol, the influence of EGCG on telomerase activity of sensitive cancer cell line was also investigated. RT-PCR method was employed to detect the influence of EGCG on the expressions of hTERT, c-myc, p53 and mad1 genes in sensitive cancer cell line.
RESULTSEGCG exhibited dose-dependent killing effects on all eight digestive tract cancer cell lines. The 50% inhibitory concentration (IC50) of SW1116, MKN45, BGC823, SGC7901, AGS, MKN28, HGC27 and LoVo cells were 51.7 micromol/L, 55.9 micromol/L, 68.5 micromol/L, 79.1 micromol/L, 83.8 micromol/L, 119.8 micromol/L, 183.2 micromol/L and 194.6 micromol/L, respectively. There were no apparent changes in cell cycle distribution of sensitive cancer cell line MKN45 48 hours after incubating with three different concentrations of EGCG compared with the controls. It was found that EGCG could suppress the telomerase activity of MKN45 cells, and the effects were dose- and time-dependent. After EGCG administration, the expression of hTERT and c-myc genes in MKN45 cells was decreased, that of the mad1 gene increased, and that of the p53 gene unchanged.
CONCLUSIONSEGCG has dose-dependent killing effects on different digestive tract cancer cell lines. Administration of EGCG has no obvious effect on cell cycle distribution of sensitive cancer cell line MKN45. The anti-neoplastic activity of EGCG might be due to the inhibition of telomerase activity by means of its influence on hTERT and the up-stream regulation genes.
Antineoplastic Agents ; pharmacology ; Catechin ; analogs & derivatives ; pharmacology ; Cell Cycle ; drug effects ; Cell Line, Tumor ; DNA-Binding Proteins ; genetics ; Digestive System Neoplasms ; drug therapy ; metabolism ; pathology ; Dose-Response Relationship, Drug ; Genes, myc ; Genes, p53 ; Humans ; Telomerase ; genetics ; metabolism
9.Phenotypic heterogeneity of mutations in androgen receptor gene.
Singh RAJENDER ; Lalji SINGH ; Kumarasamy THANGARAJ
Asian Journal of Andrology 2007;9(2):147-179
Androgen receptor (AR) gene has been extensively studied in diverse clinical conditions. In addition to the point mutations, trinucleotide repeat (CAG and GGN) length polymorphisms have been an additional subject of interest and controversy among geneticists. The polymorphic variations in triplet repeats have been associated with a number of disorders, but at the same time contradictory findings have also been reported. Further, studies on the same disorder in different populations have generated different results. Therefore, combined analysis or review of the published studies has been of much value to extract information on the significance of variations in the gene in various clinical conditions. AR genetics has been reviewed extensively but until now review articles have focused on individual clinical categories such as androgen insensitivity, male infertility, prostate cancer, and so on. We have made the first effort to review most the aspects of AR genetics. The impact of androgens in various disorders and polymorphic variations in the AR gene is the main focus of this review. Additionally, the correlations observed in various studies have been discussed in the light of in vitro evidences available for the effect of AR gene variations on the action of androgens.
Androgen-Insensitivity Syndrome
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genetics
;
physiopathology
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Bone Diseases, Metabolic
;
genetics
;
physiopathology
;
Breast Neoplasms
;
genetics
;
physiopathology
;
Cognition Disorders
;
genetics
;
physiopathology
;
Digestive System Diseases
;
genetics
;
physiopathology
;
Female
;
Genital Neoplasms, Female
;
genetics
;
physiopathology
;
Genital Neoplasms, Male
;
genetics
;
physiopathology
;
Humans
;
Infertility, Male
;
genetics
;
Male
;
Muscular Atrophy, Spinal
;
genetics
;
physiopathology
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Phenotype
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Point Mutation
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Polycystic Ovary Syndrome
;
genetics
;
physiopathology
;
Polymorphism, Genetic
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Pre-Eclampsia
;
genetics
;
physiopathology
;
Pregnancy
;
Receptors, Androgen
;
genetics
;
physiology
;
Schizophrenia
;
genetics
;
physiopathology
;
Testosterone
;
deficiency
;
Trinucleotide Repeats
10.Study on the relationship between genetic polymorphism Val384Asp in hMLH1 gene and the risk of four different carcinomas.
Xiao-Mei ZHANG ; Jin-Tian LI ; Ming ZHU ; Xiao-Liu WU ; Ping GAO ; Ping ZHOU ; Ya-Ping WANG
Chinese Journal of Epidemiology 2004;25(11):978-981
OBJECTIVETo investigate the association of genetic polymorphism Val384Asp in hMLH1 gene with the risk of colorectal, gastric, esophageal and breast carcinomas.
METHODSA case-control study was taken to investigate the role of Val384Asp in hMLH1 gene in developing these four carcinomas. 233 colorectal, 273 gastric, 90 esophageal and 111 breast cancer patients were included, as well as 268 healthy individual served as controls. Peripheral white blood cell DNA was obtained from all subjects. hMLH1 gene Val384Asp was analysed using a PCR-based DHPLC while the existence of Val384Asp were verified by DNA sequencing.
RESULTS6.34% of the healthy individuals were identified as Val384Asp carriers and significant differences existing between colorectal cancer patients or gastric cancer patients and controls, especially between young aged patients and controls.
CONCLUSIONDetermination of Val384Asp in hMLH1 gene single nucleotide polymorphism seemed to be suitable for identifying individuals with increased risk of gastrointestinal cancer in the Chinese population.
Adaptor Proteins, Signal Transducing ; Adult ; Aged ; Asian Continental Ancestry Group ; Breast Neoplasms ; etiology ; genetics ; Carrier Proteins ; genetics ; Digestive System Neoplasms ; etiology ; genetics ; Female ; Genetic Predisposition to Disease ; genetics ; Humans ; Male ; Middle Aged ; MutL Protein Homolog 1 ; Mutation, Missense ; Nuclear Proteins ; genetics ; Polymorphism, Genetic ; Risk Factors