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Mao-De Lai

Publications and source records attributed to Mao-De Lai.

18 recordsLinked to original sources

Expression of human DNA methyltransferase 1 in colorectal cancer tissues and their corresponding distant normal tissues.

BACKGROUND AND AIM: DNA methylation plays an important role during colorectal cancer (CRC) carcinogenesis. DNA methyltransferase 1 (DNMT1) is responsible for maintaining DNA methylation. We addressed the significance of DNMT1 expression in CRC. MATERIALS AND METHODS: We measured the expression of DNMT1 in CRC tissues and in their corresponding distal normal colorectal mucosa using reverse transcriptase-polymerase chain reaction and immunohistochemical analysis. RESULTS: The mean +/- SD of DNMT1 mRNA in CRC tissues was 1.04 +/- 0.36, which was significantly higher than that in their corresponding distal normal colorectal mucosa (0.58 +/- 0.44, P < 0.05). Fifty-eight out of 77 (75.3%) CRC tissues and only 30 out of 77 (39%) corresponding distant normal colorectal mucosa showed immunoreactivity (P < 0.001). We also found that the immunoreactivity of DNMT1 was higher in mucosa adjacent to cancer than in corresponding normal colorectal mucosa; high immunoreactivity was significantly correlated with poor differentiation in CRC tissues (P = 0.008). No significant associations were found between DNMT1 immunoreactivity and the following variables: age, sex, locations of cancer, Duke's phase, and the presence of lymph-node metastasis. CONCLUSION: These findings suggested that DNMT1 was associated with the malignant phenotype, and dysregulation of DNMT1 expression was present in tumor cells of CRC.

Adult↗

Identification of a novel VNTR polymorphism in C6orf37 and its association with colorectal cancer risk in Chinese population.

BACKGROUND: C6orf37 was a gene up-regulated in colorectal adenoma in our previous study. A variable region of C6orf37 sequence was found when we blasted its full sequence with NCBI nucleotide database. METHODS: RT-PCR and sequencing were conducted to identify the variable region of C6orf37 as VNTR. DHPLC was applied to detect the VNTR genotypes in 122 colorectal carcinoma patients and 166 healthy controls. RESULTS: A novel VNTR sequence found in C6orf37 second exon was composed of 15 base pair consensus sequence encoding 5-amino-acid (G-G-D-F-G). The repeat timePOST alleles contain three repeats (a), 4 repeats (b) and 5 repeats (c), respectively, which produced 3 homozygotes (a/a, b/b and c/c) and 3 heterozygotes (a/b, a/c and b/c). a, b, c allele frequencies were 0.145, 0.304, 0.551, respectively in Chinese population. Heterozygosity (H) was 0.583. Polymorphism information content (PIC) was 0.510. The distribution of genotypes and allele frequencies of the VNTR reached no significant difference between patients and healthy controls and there was no correlation between VNTR polymorphism and colorectal cancer clincopathological features. CONCLUSION: A novel VNTR polymorphism in C6orf37 exists in Chinese population and is not associated with colorectal cancer risk.

Adult↗

[Alternative splicing of insulin receptor mRNA in cancer and type 2 diabetes mellitus: a review].

The insulin receptor exists in two isoforms that result from alternative splicing of exon 11 in the primary transcript. The two isoforms have different affinities for insulin and insulin-like growth factors, and mediate different biological actions by different intracellular pathways. Differential expression of the two isoforms not only might contribute to insulin resistance in type 2 diabetes mellitus, but also play an important role in the pathogenesis of cancer. Alternative splicing can be regulated by metabolic and hormonal factors, such as hyperinsulinemia and hyperglycemia, but the precise mechanism is unknown. It has also been demonstrated that there are certain important nucleotide sequences in insulin receptor gene that can influence alternative splicing.

Alternative Splicing↗

[Bioinformatic analysis of adenoma-normal mucosa SSH library of colon].

We established a colonic adenoma-normal mucosa suppressive subtraction hybridization (SSH) library in 1999. In this study, we wanted to explore the expression profile of all candidate genes in this library. We developed an EST pipeline which contained two in-house software packages, nucleic acid analytical software and GetUni. The nucleic acid analytical software, an integrator of the universal bioinformatics tools including phred, phd2fasta, cross_match, repeatmasker and blast2.0, can blast sequences of differential clones with the downloaded non-redundant nucleotide (NR) database. GetUni can cluster these NR sequences into Unigene via matching with the downloaded Homo Sapiens UniGene database. Sixty-two candidate genes in A-N library were obtained via the high throughput automatic gene expression bioinformatics pipeline. Gene Ontology online analysis revealed that ribosome genes and immunity-regulating genes were the two most common categories in the KEGG or Biocarta Pathway. We also detected the expression of 2 genes with highest hits, Reg4 and FAM46A, by semi-quantitative RT-PCR. Both genes were up-regulated in 10 or 9 out of 10 adenomas in comparison with the paired normal mucosa, respectively. The candidate genes in A-N library would be of great significance in disclosing the molecular mechanism underlying in colonic adenoma initiation and progression.

Adenoma↗

[The expression of Staufen gene in colorectal cancer].

To study the expression of differential methylation-associated Staufen gene in colorectal cancer (CRC), we detected the expression of Staufen gene in adenocarcinoma, mucosa adjacent to colorectal cancer (MACC) and corresponding distant normal tissue using RT-PCR and immunohistochemistry. We found that the expression of Staufen gene in MACC and adenocarcinoma of CRC was significantly lower than that in corresponding distal normal tissue at mRNA level (P<0.05.No significant associations were found between age, sex, location of cancer (colon/rectal), degree of differentiation and metastasis of lymph node with expression of Staufen gene. Lower expression of Staufen protein in MACC was verified by comparing with matched normal tissue and adenocarcinoma (P<0.05). This study indicated low expression of Staufen gene in colorectal cancer and the Staufen gene might be involved in the development of colorectal cancer.

Adenocarcinoma↗

Autocrine stimulation in colorectal carcinoma (CRC): positive autocrine loops in human colorectal carcinoma and applicable significance of blocking the loops.

Many tumors co-express growth factors and their receptors; thus, the concept of autocrine secretion was proposed to explain the unrestrained growth of the malignant cells. Autocrine stimulation refers to positive autocrine secretion, which functions to stimulate cell growth. Many of the positive autocrine loops have been demonstrated in human colorectal carcinoma (CRC), which are considered to play an important role in the initiation and progression of the cancer. These autocrine loops provide information for prognostic markers and targets for biological therapies of CRC. Interruption of the autocrine loops could potentially inhibit malignant cell growth. The field is encouraging but further research is needed.

Autocrine Communication↗

[Microsatellite instability and relative gene expressions in sporadic and familial adenomatous polyposis adenomas].

In order to understand the role of mismatch repair (MMR) gene in colorectal carcinogenesis,microsatellite instability (MSI) status of 16 microsatellite loci of 62 adenomas from 59 patients, including sporadic and familial adeonmatous polyposis (FAP) adenomas were detected by microdissection-PCR-SSLP, and protein expressions of beta-catenin, P53, and BAX, etc. were assayed by immunohistochemistry. Results were as following: (1)The overall MSI alteration rate of the 16 loci was 14.4%. Different adenomas from the same patient showed different microsatellite alterations at the same loci; (2)All of the five FAP patients were MSI-L, three of which showed MSI at the locus of hMSH3; (3)The membrane expression rate of beta-catenin in adenomas and accompanied carcinomas was 42.9% and 11.4%, respectively (P<0.001); (4)Microsatellite alterations of the microsatellite loci of TP53, D5S346, TCF4(A)(9), TGFbetaRII(GT)(3) and TGFbetaRII(A)(10) were associated with the changes of their protein expressions. It could be concluded the following: (1)Microsatellite instability existed even in the early stage (adenomas) of colorectal tumorigenesis. The alterations of chromosome 1p, APC genes, and the TGFbeta signal transduction pathway could also be deduced; (2)In the progression of adenoma to carcinoma, the staining of beta-catenin would be transferred from membrane to cytoplasm and then nucleus, and the cytoplasm stain was stronger in carcinoma than that in adenomas. The abnormality of the signal transduction pathway of APC-beta-catenin-TCF4 could be concluded.

Adenocarcinoma↗

[A non-radioactive method used for Reverse Northern].

In this paper, a simple, rapid and safe method of Reverse Northern was introduced. A non-radioactive labeling system was used to label the probe. During the process, the quality of probe was normalized three times to rule out the possibility of false results. Samples were dotted as microarray and were hybridized effectively. The method is effective and expected to be widely used in laboratories.

Adenocarcinoma↗

[DHPLC analysis of microsatellite instability in gastric cancer].

To establish a fast, simple and solid method of studying microsatellite instability (MSI) in gastric cancer, a panel of 12 microsatellite sites, D1S548, D1S552, D5S346, TP53, IGF II R(G)(8), IGF II R(CT)(5), TGFbetaR II(GT)(3), TGFbetaR II(A)(10), hMSH3(A)(8), hMSH6(G)(8), BAX(G)(8) and Bat26, were detected by denatured polyacrymide gel electrophoresis-silver stain in 28 gastric cancers. Bat26 was also analyzed by denatured high performance liquid chromatograph (DHPLC) at 50 degrees in the DNASep Cartridge. Two MSI-H (7.14%) and 15 MSI-L cancers (53.6%) were identified in 28 gastric cancers. Bat26 was positive only in 2 MSI-H cancers. The alterations of Bat26 and MSI-H status were coincident (P<0.01). The two Bat26+ cancers were also confirmed by DHPLC. Results obtained from DHPLC and gel electrophoresis were completely consistent. Thus, DHPLC analysis of Bat26 site may be a favorable method of detecting MSI-H status in gastric cancer, and be of clinical importance.

Adult↗

Reg gene family and human diseases.

Regenerating gene (Reg or REG) family, within the superfamily of C-type lectin, is mainly involved in the liver, pancreatic, gastric and intestinal cell proliferation or differentiation. Considerable attention has focused on Reg family and its structurally related molecules. Over the last 15 years, 17 members of the Reg family have been cloned and sequenced. They have been considered as members of a conserved protein family sharing structural and some functional properties being involved in injury, inflammation, diabetes and carcinogenesis. We previously identified Reg IV as a strong candidate for a gene that was highly expressed in colorectal adenoma when compared to normal mucosa based on suppression subtractive hybridization (SSH), reverse Northern blot, semi-quantitative reverse transcriptase PCR (RT-PCR) and Northern blot. In situ hybridization results further support that overexpression of Reg IV may be an early event in colorectal carcinogenesis. We suggest that detection of Reg IV overexpression might be useful in the early diagnosis of carcinomatous transformation of adenoma. This review summarizes the roles of Reg family in diseases in the literature as well as our recent results of Reg IV in colorectal cancer. The biological properties of Reg family and its possible roles in human diseases are discussed. We particularly focus on the roles of Reg family as sensitive reactants of tissue injury, prognostic indicators of tumor survival and early biomarkers of carcinogenesis. In addition to our current understanding of Reg gene functions, we postulate that there might be relationships between Reg family and microsatellite instability, apoptosis and cancer with a poor prognosis. Investigation of the correlation between tumor Reg expression and survival rate, and analysis of the Reg gene status in human malignancies, are required to elucidate the biologic consequences of Reg gene expression, the implications for Reg gene regulation of cell growth, tumorigenesis, and the progression of cancer. It needs to be further attested whether Reg gene family is applicable in early detection of cancer and whether Reg and Reg-related molecules can offer novel molecular targets for anticancer therapeutics. This has implications with regard to prognosis, such as in monitoring cancer initiation, progression and recurrence, as well as the design of chemotherapeutic drugs.

Diabetes Mellitus↗

Aberrant crypt foci as microscopic precursors of colorectal cancer.

Since the first detection of aberrant crypt foci (ACF) in carcinogen-treated mice, there have been numerous studies focusing on these microscopically visible lesions both in rodents and in humans. ACF have been generally accepted as precancerous lesions in regard to histopathological characteristics, biochemical and immunohistochemical alterations, and genetic and epigenetic alterations. ACF show variable histological features, ranging from hyperplasia to dysplasia. ACF in human colon are more frequently located in the distal parts than in the proximal parts, which is in accordance with those in colorectal cancer (CRC). The immunohistochemical expressions of carcinoembryonic antigen (CEA), beta-catenin, placental cadherin (P-cadherin), epithelial cadherin (E-cadherin), inducible nitric oxide synthase (iNOS), cyclooxygenase (COX-2), and P16INK4a are found to be altered. Genetic mutations of K-ras, APC and p53, and the epigenetic alterations of CpG island methylation of ACF have also been demonstrated. Genomic instabilities due to the defect of mismatch repair (MMR) system are detectable in ACF. Two hypotheses have been proposed. One is the "dysplasia ACF-adenoma-carcinoma sequence", the other is "heteroplastic ACF-adenoma-carcinoma sequence". The malignant potential of ACF, especially dysplastic ACF, makes it necessary to reveal the nature of these lesions, and to prevent CRC from the earliest possible stage. The technique of magnifying chromoscope makes it possible to detect "in vivo" ACF, which is beneficial to colon cancer research, identifying high-risk populations for CRC, and developing preventive procedures.

Adenomatous Polyposis Coli↗

Neuroendocrine markers in adenocarcinomas: an investigation of 356 cases.

AIM: To investigate the incidence of neuroendocrine (NE) cells and their hormone products in adenocarcinomas and evaluate their significance in clinical pathology and prognosis. METHODS: By using tissue sectioning and immunocyto-chemistry, 356 cases of adenocarcinomas were studied to examine the presence of chromorgranin and polypeptide hormones in adenocarcinoma samples from our hospital. RESULTS: The positive rate of NE cells and hormone products was 41.5 % (54/130) and 59.3 % (32/54), respectively in large intestinal adenocarcinoma cases; 39.6 % (38/96) and 36.8 % (14/38), respectively in gastric cancer cases; 38.1 % (8/21) and 50.0 % (4/8), respectively in prostatic cancer cases; 21.0 % (17/81) and 17.6 % (3/17), respectively in breasr cancer cases; 17.9 % (5/28) and 60.0 % (3/5), respectively in pancreatic cancer cases. Among carcinomas of large intestine, pancreas and breast, the highly differentiated NE cell numbers were higher than the poorly differentiated NE cell numbers; while the gastric carcinoma cases had more poorly differentiated NE cells than highly differentiated NE cells. The higher detection rate of NE cells and their hormone products, the higher 5-year survival rate among the large intestine cancer cases. CONCLUSION: Close correlation was observed between NE cells and their hormone products with the cancer differentiations. For colorectal carcinomas, there is a close correlation of the presence of NE cells and their hormone products with the tumor staging and prognosis.

Adenocarcinoma↗

[Advances in the studies of Reg family].

Since the first member of Reg gene was discovered in 1988, it has been verified that Reg genes play important roles in diabetes, inflammation and injury, and tumors. More members were cloned and their application in treatment was studied. With the development of related research, there is a great potential of Reg family in biomedical field.

English Abstract↗

Less cytotoxicity to combination therapy of 5-fluorouracil and cisplatin than 5-fluorouracil alone in human colon cancer cell lines.

AIM: Our previous studies showed increased sensitivity to 5-FU in colon cancer cell lines with microsatellite instability, and considered that mutations of TGFbeta-R II, IGF IIR, RIZ gene might enhance the potentials of cell growth and proliferation, which increased the sensitivity to 5-FU. Here we compared the distribution of cell cycle and P53 status between two human colon cancer cell lines with different sensitivity to 5-FU. Because mechanistic differences exist between 5-FU and CDDP, we also analyzed the efficacy of CDDP and combination therapy on two human colon cancer cell lines. METHODS: We compared the sensitivity to CDDP of these two cell lines by MTT assay. Distribution of cell cycle under treatment of 5-FU, CDDP alone or both was analyzed by Flow Cytometry, and expression of P53 was detected by immunocytochemical staining. RESULTS: SW480 cells were more sensitive to CDDP than LoVo cells at the concentrations above 16 micromol/l (Ratio of absorption is 0.64 and 0.79 at 16 micromol/l, respectively; P<0.01). Efficacy of combination therapy was conversely lower than that of single-therapy of 5-FU (Ratio of absorption in LoVo+5-FU, SW480+5-FU, LoVo+5-FU+CDDP and SW480+5-FU+CDDP is 0.53, 0.54, 0.72, 0.78, respectively; P<0.01). LoVo cells were negative whereas SW480 cells positive in P53 expression. 5-FU induced G1-phase arrest in both cell lines, but LoVo cells peaked 24 hours earlier than SW480 cells, and 48 hours earlier for an apparent hypodiploid DNA. However, CDDP showed the contrary, inducing S-phase arrest, and SW480 cells peaking 36 hours earlier. Both cell lines showed hypodipliod nuclei 48 hours after CDDP treatment. Percentage of cells in G1-phase and S-phase dominated alternatively under combination therapy in both cell lines. CONCLUSION: These results suggest that colon cancer cells with microsatellite instability are more sensitive to 5-FU, whereas more resistant to CDDP. Combination therapy of 5-FU and CDDP shows fewer efficacies than 5-FU single-therapy, although it can render a cell cycle arrest. P53 may be involved in the shift of G1-phase to S-phase, but inessentially.

Adenocarcinoma↗

Anal cancer in Chinese: human papillomavirus infection and altered expression of p53.

AIM:To detect the presence of HPV DNA and study the alteration of p53 expression in anal cancers in Chinese.METHODS:HPV DNA was amplified by PCR.The amplified HPV DNA was classified by DBH. HPV antigen and p53 expression were respectively detected by immunohistochemistry.RESULTS:HPV DNA was amplified only in one case of squamous cell carcinoma of the 72 Chinese anal cancers and further classified as HPV type 16. Others were all HPV negative. HPV antigen and p53 expression were also detected in this case. Positive stainings with anti-p53 antibody were seen in 61.2% anal cancers.There were no statistically significant differences between anal squamous cell carcinomas and adenocarcinomas and between anal adenocarcinomas and rectal adenocarcinomas.p53 protein expression was observed in the basal cells of squamous epithelium of condyloma acuminatum and morphologically normal squamous epithelium in 2 cases invaded by anal adenocarcinoma.CONCLUSION:HPV infection was not associated with these cases of anal cancer.p53 alteration was a common event. Positive p53 immunostaining can not be regarded as a marker for differentiating benign from malignant lesions.

Journal Article↗