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Bo Zhao

Publications and source records attributed to Bo Zhao.

36 records · Page 2Linked to original sources
PubMed2005

Temporal performance of amorphous selenium mammography detectors.

We investigated temporal performance of amorphous selenium (a-Se) detectors specifically designed for mammographic imaging. Our goal is to quantify the inherent lag and ghosting of a-Se photoconductor as a function of imaging conditions. Two small area electroded a-Se samples, one positively and the other negatively biased on the entrance side of x rays, were used in the experiments. The study of lag and ghosting was performed by delivering a number of raw exposures as experienced in screening mammography to the samples at different electric field strength E(Se) while measuring the current through the a-Se sample. Ghosting at different operational conditions was quantified as the percentage x-ray sensitivity (x-ray generated photocurrent measured from the sample) reduction compared to before irradiation. Lag was determined by measuring the residual current of a-Se at a given time after the end of each x-ray exposure. Both lag and ghosting were measured as a function of E(Se) and cumulative exposure. The values of E(Se) used in our experiments ranged from 1 to 20 V/microm. It was found that ghosting increases with exposure and decreases with E(Se) for both samples because of the dominant effect of recombination between trapped electrons and x-ray generated holes. Lag on the other hand has different dependence on E(Se) and cumulative exposure. At E(Se) < or = 10 V/microm, the first frame lag for both samples changed slowly with cumulative exposure, with a range of 0.2%-1.7% for the positively biased sample and 0.5%-8% for the negatively biased sample. Overall the positively biased sample has better temporal performance than the negatively biased sample due to the lower density of trapped electrons. The impact of time interval between exposures on the temporal performance was also investigated. Recovery of ghosting with longer time interval was observed, which was attributed to the neutralization of trapped electrons by injected holes through dark current.

Electrodes↗
PubMed2005

Epstein-Barr virus nuclear protein 3A domains essential for growth of lymphoblasts: transcriptional regulation through RBP-Jkappa/CBF1 is critical.

Experimental reverse genetic replacement of Epstein-Barr virus nuclear antigen 3A (EBNA3A) with a conditional mutant EBNA3A revealed that EBNA3A is critical for continued lymphoblastoid cell (LCL) growth. Wild-type (wt) EBNA3A expressed in the LCLs specifically sustained growth under nonpermissive conditions, whereas EBNA3B or EBNA3C expression had no effect (S. Mauro, E. Johannsen, D. Illanes, A. Cooper, and E. Kieff, J. Virol. 77:10437-10447, 2003). This genetic system and related biochemical assays have now been used to discover that EBNA3A lacking amino acid residues 170 to 240 (delta170-240), TLGC202 to AAGA202, or delta300-386, which are deficient in repression of EBNA2 activation of an RBP-Jkappa/CBF1-dependent EBV Cp enhancer, are null mutations for LCL growth, whereas EBNA3A delta2-124, delta410-439, delta440-470, delta470-500, delta500-523, delta523-612, and delta620-820, which are wt in repression are wt for LCL growth. Thus, EBNA3A regulation of transcription through RBP-Jkappa/CBF1 is critical for LCL growth. EBNA3A mutants deleted of amino acid residues 240 to 300, 386 to 410, or 827 to 944 were intermediate, null, or intermediate, respectively, for LCL growth despite being wt for RBP-Jkappa association and repression. Amino acid residues 240 to 300, 386 to 410, and, particularly, C-terminal residues 827 to 944 are therefore likely to contribute to LCL growth through RBP-Jkappa-independent mechanisms.

Cell Line, Transformed↗
PubMed2005

[Pathologic change of elastic fibers with difference of microvessel density and expression of angiogenesis-related proteins in internal hemorrhoid tissues].

OBJECTIVE: To investigate the pathological variations in internal hemorrhoid and evaluate the expression of nitric- oxide synthase(NOS),vascular endothelial growth factor(VEGF),matrix metalloproteinase- 2(MMP2) and MMP9. METHODS: Normal anal cushion and internal hemorrhoids tissue samples were obtained from 24 patients with iii degree hemorrhoids after procedure for prolapse and hemorrhoids(PPH) procedure. The expression of NOS, VEGF, MMP2, MMP9 and CD34 were detected by immunohistochemical staining; the microvessel density (MVD) was counted by anti- CD34 antibody; the elastic fibers were detected by orcein staining. RESULTS: There were statistically significant differences in the expression of MVD, VEGF, MMP9 between internal hemorrhoid tissue and normal anal cushions(P< 0.05). iNOS was significantly increased in hemorrhoid tissue, but no significant difference between normal anal cushions and hemorrhoid tissue. Morphological abnormalities such as breaking, distortion, mortality, hyaline degeneration were found in elastic fibers of internal hemorrhoid tissue, but not in normal anal cushions. CONCLUSION: Angiogenesis is evident in hemorrhoid tissue, suggesting the possible mechanism in the pathogenesis of hemorrhoids. The direct degeneration effect of MMP9 on supporting structure elastic fibers in anal cushion is another important mechanism. The high expression of iNOS suggests the inflammatory factors involve in the pathogenesis of hemorrhoids, and NO may be involve in pathological effect on hemorrhoids.

Adult↗
PubMed2005

[Treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury].

OBJECTIVE: To investigate the treatment and mechanism of compound carraghenates suppository to rat acute rectal mucous injury. METHODS: The model of rat acute rectal mucous injury was established by 3% acetic acid. Two hundred and forty rats were divided equally into control and experimental group. The rats of experimental group were administrated with 20 mg carraghenates suppository via rectum twice a day, but rats of control group were not administrated with carraghenates suppository. Thirty rats in both groups were executed at different time points. The pathologic changes were observed and the rectal mucous injury was scored. Immunohistochemical staining was used to evaluate the effect of carraghenates suppository on expression of VEGF, iNOS, IL-8, MMP9, HIF-1 alpha and PCNA in the two groups. RESULTS: The scores of rectal mucous injury was lower, the pathologic changes such as hyperaemia, edema, destroy of glands were less severe, and tissue repair time was shorter in experimental group compared with those in the control group at 24 h, 78 h and 120 h after administration of carraghenates suppository. No obvious cicatrisation was observed in experimental group. Expression of VEGF and MMP9 was significantly lower in experimental group compared with those in the control group at 24 h after administration. Expression of VEGF, iNOS, IL-8, MMP9, HIF-1alpha and PCNA were statistically decreased in experimental group than those in the control group at 72 h, 120 h after administration. MVD in experimental group was statistically decreased than that in the control group. CONCLUSION: The compound carraghenates suppository can reduce the rectal mucous injury from 3% acetic acid, and accelerate the wound healing without obvious cicatrisation. The compound carraghenates suppository can reduce the expression of MMP9, VEGF, IL-8, PCNA, iNOS and HIF-1 alpha, which may play a role in its protective mechanism.

Animals↗
PubMed2004

Clinical features and mismatch repair gene mutation screening in Chinese patients with hereditary nonpolyposis colorectal carcinoma.

AIM: Hereditary nonpolyposis colorectal cancer (HNPCC) is an autosomal dominantly-inherited cancer-susceptibility syndrome that confers an increased risk for colorectal cancer and a variety of other tumors at a young age. It has been associated with germline mutations in five mismatch repair (MMR) genes (hMSH2, hMLH1, hPMS1, hPMS2, and hMSH6/GTBP). The great majority of germline mutations were found in hMSH2 and hMLH1. The purpose of this study was to analyze the clinical features of Chinese HNPCC patients and to screen hMSH2 and hMLH1 gene mutations. METHODS: Twenty-eight independent Chinese families were collected, of which 15 met Amsterdam criteria I and 13 met the Japanese clinical diagnosis criteria. The data were recorded including sex, site of colorectal cancer (CRC), age of diagnosis, history of synchronous and/or metachronous CRC, instance of extracolonic cancers, and histopathology of tumors. Peripheral blood samples were collected from all pedigrees after formal written consents were signed. PCR and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding regions of hMSH2 and hMLH1 genes. The samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer. RESULTS: One hundred and seventy malignant neoplasms were found in one hundred and twenty-six patients (multiple cancer in twenty-three), including one hundred and twenty-seven CRCs, fifteen gastric, seven endometrial, and five esophageal cancers. Seventy-seven point eight percent of the patients had CRCs, sharing the features of early occurrence (average age of onset, 45.9 years) and of the right-sided predominance reported in the literature. In Chinese HNPCC patients, gastric cancer occurred more frequently, accounting for 11.9% of all cancers patients and ranking second in the spectrum of HNPCC predisposing cancers. Synchronous CRCs occurred less frequently, only accounting for 3.1% of the total CRCs. Twenty percent of the colorectal patients had metachronous CRCs within 10 years after operation. Eight hMSH2 or hMLH1 gene sequence variations were found in twelve families, including the first Mongolian kindred with a hMSH2 gene mutation. CONCLUSION: HNPCC is characterized by an early-age onset, proximal predominance of CRC, multiple metachronous CRCs, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous CRCs are the remarkable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening. hMLH1 gene mutations, especially of the first nine exons, have been found more common than hMSH2 gene mutations in Chinese patients. Three of seven mutations have been found to be novel, and the germline G204X nonsense mutation in the third exon of hMSH2 has become the first MMR gene mutation found in Chinese Mongolian people.

Adaptor Proteins, Signal Transducing↗
PubMed2004

[Germline E-cadherin gene mutation screening in familial gastric cancer kindreds].

OBJECTIVE: To evaluate the frequency and nature of E-cadherin gene (CDH1) germline mutations in familial gastric cancer kindreds of china. METHODS: Five familial gastric cancer kindreds of Chinese origin were screened for germline CDH1 mutations, all of them meeting the clinical criteria for hereditary diffuse gastric cancer (HDGC), by PCR-DHPLC and direct sequencing. RESULTS: A new truncating mutation in exon 10 in B family was identified, producing a stop codon at position 503 (Q503X), resulting in a truncated protein. The proband of this family had metachronous development of lobular breast and diffuse type gastric carcinoma. No protein expression was detected in the lobular breast carcinoma, indicating complete inactivation of the gene. CONCLUSIONS: A Chinese gastric cancer family with CDH1 germline truncating mutation is described for the first time, and our findings suggest that lobular breast carcinoma might be part of the tumor spectrum of HDGC.

Adult↗
PubMed2004

Role of DNA polymerase eta in the bypass of abasic sites in yeast cells.

Abasic (AP) sites are major DNA lesions and are highly mutagenic. AP site-induced mutagenesis largely depends on translesion synthesis. We have examined the role of DNA polymerase eta (Poleta) in translesion synthesis of AP sites by replicating a plasmid containing a site-specific AP site in yeast cells. In wild-type cells, AP site bypass resulted in preferred C insertion (62%) over A insertion (21%), as well as -1 deletion (3%), and complex event (14%) containing multiple mutations. In cells lacking Poleta (rad30), Rev1, Polzeta (rev3), and both Poleta and Polzeta, translesion synthesis was reduced to 30%, 30%, 15% and 3% of the wild-type level, respectively. C insertion opposite the AP site was reduced in rad30 mutant cells and was abolished in cells lacking Rev1 or Polzeta, but significant A insertion was still detected in these mutant cells. While purified yeast Polalpha effectively inserted an A opposite the AP site in vitro, purified yeast Poldelta was much less effective in A insertion opposite the lesion due to its 3'-->5' proofreading exonuclease activity. Purified yeast Poleta performed extension synthesis from the primer 3' A opposite the lesion. These results show that Poleta is involved in translesion synthesis of AP sites in yeast cells, and suggest that an important role of Poleta is to catalyze extension following A insertion opposite the lesion. Consistent with these conclusions, rad30 mutant cells were sensitive to methyl methanesulfonate (MMS), and rev1 rad30 or rev3 rad30 double mutant cells were synergistically more sensitive to MMS than the respective single mutant strains.

Base Sequence↗
PubMed2004

[Clinical features and hMSH2/hMLH1 germline mutation screening of Chinese hereditary nonpolyposis colorectal cancer patients].

OBJECTIVE: To analyze the clinical features of hereditary nonpolyposis colorectal cancer (HNPCC) among Chinese and report the results of screening of hMSH2 and hMLH1 gene mutations. METHODS: The data concerning sex, site of colorectal cancer (CRC), age of diagnosis, history of synchronous and/or metachronous colorectal cancer, instance of extracolonic cancers, and histopathology of tumors of 126 patients from 28 independent families of HNPCC in China were collected, of which 15 met the Amsterdam criteriaI and 13 met the Japanese clinical diagnosis criteria. The genomic DNA was extracted from the peripheral lymphocytes. Polymerase chain reaction (PCR) and denaturing high-performance liquid chromatography (DHPLC) were used to screen the coding region of hMSH2 and hMLH1 genes. Samples showing abnormal DHPLC profiles were sequenced by a 377 DNA sequencer. RESULTS: One hundred and seventy malignant neoplasms were found in the 126 patients, in which 23 of multiple cancers were found. Ninety-eight of the 126 patients (77.8%) had colorectal cancers, with an average age of onset of 45.9 years and a right-sided predominance. Eight hMSH2 or hMLH1 gene sequence variations were found in 12 families, and a germline G204X nonsense mutation in the third exon of hMSH2 was found for the first time, the first mismatch repair gene (MMR) mutation ever found in Chinese Mongolian people. CONCLUSIONS: HNPCC is a typical auto-dominant hereditary disease, characterized by early onset, proximal predominance of colorectal cancer, multiple synchronous and metachronous colorectal cancers, and an excess of extra-colonic cancers. Frequent gastric cancer occurrence and less synchronous colorectal cancers are notable features in Chinese HNPCC patients. DHPLC is a powerful tool in hMSH2 and hMLH1 gene mutation screening. Three novel mutations have been found. hMLH1 gene mutations, especially those of the first nine exons, are more common than hMSH2 gene mutations in Chinese patients.

Adaptor Proteins, Signal Transducing↗
PubMed2004

Translesion synthesis of acetylaminofluorene-dG adducts by DNA polymerase zeta is stimulated by yeast Rev1 protein.

Translesion synthesis is an important mechanism in response to unrepaired DNA lesions during replication. The DNA polymerase zeta (Polzeta) mutagenesis pathway is a major error-prone translesion synthesis mechanism requiring Polzeta and Rev1. In addition to its dCMP transferase, a non-catalytic function of Rev1 is suspected in cellular response to certain types of DNA lesions. However, it is not well understood about the non-catalytic function of Rev1 in translesion synthesis. We have analyzed the role of Rev1 in translesion synthesis of an acetylaminofluorene (AAF)-dG DNA adduct. Purified yeast Rev1 was essentially unresponsive to a template AAF-dG DNA adduct, in contrast to its efficient C insertion opposite a template 1,N6-ethenoadenine adduct. Purified yeast Polzeta was very inefficient in the bypass of the AAF-dG adduct. Combining Rev1 and Polzeta, however, led to a synergistic effect on translesion synthesis. Rev1 protein enhanced Polzeta-catalyzed nucleotide insertion opposite the AAF-dG adduct and strongly stimulated Polzeta-catalyzed extension from opposite the lesion. Rev1 also stimulated the deficient synthesis by Polzeta at the very end of undamaged DNA templates. Deleting the C-terminal 205 aa of Rev1 did not affect its dCMP transferase activity, but abolished its stimulatory activity on Polzeta-catalyzed extension from opposite the AAF-dG adduct. These results suggest that translesion synthesis of AAF-dG adducts by Polzeta is stimulated by Rev1 protein in yeast. Consistent with the in vitro results, both Polzeta and Rev1 were found to be equally important for error-prone translesion synthesis across from AAF-dG DNA adducts in yeast cells.

2-Acetylaminofluorene↗
PubMed2004

Direct interactions between Epstein-Barr virus leader protein LP and the EBNA2 acidic domain underlie coordinate transcriptional regulation.

The Epstein-Barr virus nuclear leader protein LP (EBNALP) and EBNA2 are expressed first in lymphocyte infection, coordinately regulate cell and viral gene transcription, and are critical for lymphocyte outgrowth into lymphoblastoid cell lines (LCLs). We have now found that EBNALP readily associated with EBNA2 or with the EBNA2 C-terminal acidic activation domain (E2AD) when both components were expressed by bacteria. In lymphoblasts, EBNALP and EBNA2 did not stably associate. However, EBNALP deleted for only 10 C-terminal amino acids stably associated with EBNA2 in lymphoblasts or with EBNA2 acidic activating domain from bacteria. The E2AD was essential for EBNALP coactivation of the latent membrane protein 1 promoter in lymphoblasts; EBNALP could coactivate with a deficient mutant EBNA2, EBNA2W(454)T, but not with EBNA2 deleted for E2AD. Moreover, EBNALP 31 amino acids (dW2Y1) with 24 C- or N-terminal amino acids was a specific and efficient affinity matrix for EBNA2 or EBNALP. Even an EBNALP 22-aa peptide, dW2, specifically bound EBNALP or EBNA2. These biochemical interactions between EBNALP and EBNA2 enable coordinated transcriptional regulation of cell and viral gene expression in lymphoblasts only when the interaction is unstable; deletion of the EBNALP C-terminal 10 aa stabilized association with EBNA2 and prevented coactivation. Because EBNALPd10 dominantly inhibited EBNALP coactivation with EBNA2, EBNALPd10 expression in LCLs may be useful in assessing the role of EBNALP coactivation in LCL growth or survival.

Epstein-Barr Virus Nuclear Antigens↗
PubMed2004

Four EBNA2 domains are important for EBNALP coactivation.

EBNA2 transcriptional activation and regulated EBNALP coactivation are critical for Epstein-Barr virus-infected primary B-lymphocyte growth transformation. EBNALP coactivation requires the EBNA2 acidic activation domain (E2AD); EBNALP can bind to E2AD. EBNALP has now been found to bind less well to EBNA2 amino acids 1 to 58, which has been identified to be a second transcriptional activation domain, E2AD2. E2AD2 was specifically coactivated by EBNALP. Moreover, E2AD, E2AD2, EBNA2 RG domain, and the intermediate domain between RG and E2AD had significant roles in EBNA2-mediated activation and EBNALP coactivation.

B-Lymphocytes↗
PubMed2003

Mutagenesis of benzo[a]pyrene diol epoxide in yeast: requirement for DNA polymerase zeta and involvement of DNA polymerase eta.

Benzo[a]pyrene is a potent environmental carcinogen, which can be metabolized in cells to the DNA damaging agent anti-benzo[a]pyrene-7,8-dihydrodiol-9,10-epoxide (anti-BPDE). We hypothesize that mutations induced by BPDE DNA adducts are mainly generated through an error-prone translesion synthesis that requires a specialized DNA polymerase (Pol). Using an in vivo mutagenesis assay in the yeast model system, we have examined the potential roles of Pol(zeta) and Pol(eta) in (+/-)-anti-BPDE-induced mutagenesis. In cells proficient in mutagenesis, (+/-)-anti-BPDE induced 85% base substitutions with predominant G --> C followed by G --> T transversions, 9% deletions of 1-3 nucleotides, and 6% insertions of 1-3 nucleotides. In rad30 mutant cells lacking Pol(eta), (+/-)-anti-BPDE-induced mutagenesis was reduced and accompanied by a moderate decrease in base substitutions and more significant decrease in deletions and insertions of 1-3 nucleotides. In rev3 mutant cells lacking Pol(zeta), (+/-)-anti-BPDE-induced mutagenesis was mostly abolished, leading to a great decrease in both base substitutions and deletions/insertions of 1-3 nucleotides. In contrast, large deletions/insertions were significantly increased in cells lacking Pol(zeta). Consistent with the in vivo results, purified yeast Pol(zeta) performed limited translesion synthesis opposite (+)- and (-)-trans-anti-BPDE-N(2)-dG DNA adducts with predominant G incorporation opposite the lesion. These results show that (+/-)-anti-BPDE-induced mutagenesis in yeast requires Pol(zeta) and partially involves Pol(eta) and suggest that Pol(zeta) directly participates in nucleotide insertions opposite the lesion, while Pol(eta) significantly contributes to deletions and insertions of 1-3 nucleotides.

7,8-Dihydro-7,8-dihydroxybenzo(a)pyrene 9,10-oxide↗
PubMed2003

Transcriptional regulatory properties of Epstein-Barr virus nuclear antigen 3C are conserved in simian lymphocryptoviruses.

Epstein-Barr virus (EBV) nuclear antigen 3C (EBNA-3C) is a large transcriptional regulator essential for EBV-mediated immortalization of B lymphocytes. We previously identified interactions between EBNA-3C and two cellular transcription factors, J kappa and Spi proteins, through which EBNA-3C regulates transcription. To better understand the contribution of these interactions to EBNA-3C function and EBV latency, we examined whether they are conserved in the homologous proteins of nonhuman primate lymphocryptoviruses (LCVs), which bear a strong genetic and biological similarity to EBV. The homologue of EBNA-3C encoded by the LCV that infects baboons (BaLCV) was found to be only 35% identical in sequence to its EBV counterpart. Of particular significance, this homology localized predominantly to the N-terminal half of the molecule, which encompasses the domains in EBNA-3C that interact with J kappa and Spi proteins. Like EBNA-3C, both BaLCV and rhesus macaque LCV (RhLCV) 3C proteins bound to J kappa and repressed transcription mediated by EBNA-2 through its interaction with J kappa. Both nonhuman primate 3C proteins were also able to activate transcription mediated by the Spi proteins in the presence of EBNA-2. Like EBNA-3C, a domain encompassing the putative basic leucine zipper motif of the BaLCV-3C protein directly interacted with both Spi-1 and Spi-B. Surprisingly, a recently identified motif in EBNA-3C that mediates repression was not identifiable in the BaLCV-3C protein. Finally, although the C terminus of BaLCV-3C bears minimal homology to EBNA-3C, it nonetheless contains a C-terminal domain rich in glutamine and proline that was able to function as a potent transcriptional activation domain, as does the C terminus of EBNA-3C. The conservation of these functional motifs despite poor overall homology among the LCV 3C proteins strongly suggests that the interactions of EBNA-3C with J kappa and Spi do indeed play significant roles in the life cycle of EBV.

Amino Acid Sequence↗
PubMed2003

Tricuspid valve detachment in closure of congenital ventricular septal defect.

From January 1991 through December 2001, 600 patients underwent closure of a perimembranous ventricular septal defect through a right atrial approach at our institution. In 122 of these patients, the operation included temporary detachment of a tricuspid valve septal leaflet from the annulus to allow complete visualization of a perimembranous ventricular septal defect The mean age of the patients at surgery was 4.6 years in those who underwent leaflet detachment and 4.7 years in the 478 patients who did not (P > 0.05). Preoperatively, all patients were in sinus rhythm. Echocardiography showed trivial tricuspid regurgitation in 21 of the patients undergoing detachment and in 39 of the non-detachment patients. There was no difference in bypass time or aortic cross-clamp time between the 2 groups. Postoperatively, 3 patients in the non-detachment group had heart block; all other patients were in sinus rhythm. Echocardiograms on the 7th postoperative day showed small residual ventricular septal defects in none of the patients who underwent valve detachment and in 10 of the non-detachment patients; mild tricuspid regurgitation was present in 12 non-detachment patients only; and trivial tricuspid regurgitation was present in 19 patients who underwent valve detachment and in 29 who did not. There was no hospital death in either group. Long-term follow-up showed no progression of tricuspid regurgitation or tricuspid stenosis. All patients remained in sinus rhythm. This study suggests that tricuspid valve detachment is a safe, effective technique that improves exposure for ventricular septal defect repair and does not adversely affect valve competence.

Cardiac Surgical Procedures↗
PubMed2002

Cholangiocarcinoma cells express somatostatin receptor subtype 2 and respond to octreotide treatment.

BACKGROUND/PURPOSE: We investigated the in vitro and in vivo inhibitory effects of a somatostatin analogue (octreotide, OCT) on cholangiocarcinoma cell lines. METHODS: The reverse transcriptase-polymerase chain reaction (RT-PCR) was employed to detect the gene expression of five somatostatin receptor (SSTR) subtypes in four cholangiocarcinoma cell lines (RBE, NEC, QBC939, and SSP-25). The antiproliferative effects of OCT on these cell lines were determined by means of an MTT assay in vitro, as well as in a nude mouse tumor heterograft model in vivo. Apoptosis and cell cycles in the cholangiocarcinoma cell lines after OCT administration were evaluated by flow cytometry; and the effects of OCT on the expression of cyclin E, cyclin-dependent kinase 2 (CDK2), and p27kipl were evaluated by Western blots. RESULTS: Only SSTR2 mRNA was detected in these four cholangiocarcinoma cell lines. OCT significantly inhibited the proliferation of the four cholangiocarcinoma cell lines in vitro ( P < 0.05 vs control), and the weights of the QBC939 xenografts in the OCT-treated group were lower than those in the control group, but there was no significant difference between them. After 48-h exposure to 10(3) ng/ml OCT, flow cytometric analysis demonstrated an increased number of cells in G0/G1 phase associated with a decreased number of cells in G2/M and S phases ( P < 0.01 vs control). Apoptosis was not observed in any samples. The expression of p27kipl was promoted by OCT administration, while that of cyclin E and that of CDK2 were inhibited. CONCLUSIONS: The results proved that OCT inhibits the proliferation of cholangiocarcinoma cells through G0/G1 cell cycle arrest rather than through the process of apoptosis. These effects are partially mediated by enhancing the expression of p27kipl, and decreasing the amounts of cyclin E-CDK2 complex.

Animals↗
PubMed2002

Report of 16 kindreds and one kindred with hMLH1 germline mutation.

AIM: To analyze the diagnosis and treatment of 16 hereditary nonpolyposis colorectal cancer (HNPCC) kindreds, and to report the first kindred with hMLH1 germline mutation in Mainland China. METHODS: The diagnosis, treatment and follow-up study of 16 HNPCC kindreds were retrospectively reviewed. Data concerning site of the malignant tumor, age at the diagnosis, history of synchronous and/or metachronous cancer, and histopathology of tumors were recorded. All treatments had won formal consent. PCR and SSCP were used to screen the coding region of hMLH1 and hMSH2 genes. Variant bands were sequenced by a 377 DNA sequencer. RESULTS: Among sixteen kindreds, sixty-eight patients had a mean age of 50.8 years, including twenty-one multiple cancer patients and forty-six colorectal cancer patients (metachronous colorectal cancers in sixteen). A total of one hundred and one malignant neoplasms were found in these sixty-eight patients, including 50 colonic, 17 rectal, 11 gastric, 7 endometrial, and 4 esophageal cancers. 39.5% colorectal patients had metachronous cancers within ten years who needed reoperations. A germline G265T nonsense mutation was found in the third exon of hMLH1, resulting in a stop codon and truncated protein. Three phenotypically normal family members were also found to carry the mutated gene. CONCLUSION: HNPCC is a typical auto-dominant hereditary disease, the main characteristics include early onset and frequency of cancers; predominance of colorectal, especially right-sided colon cancers; frequency of multiple primary cancers (especially colorectal cancers). Segmental resection for colorectal cancers is not eligible for colorectal cancer patient in HNPCC kindreds. Intensive follow-up is essential for all patients and possible gene carriers. The first HNPCC kindred with hMLH1 gene germline mutation was identified in Mainland China, and three phenotypically normal family members were found to be carriers of the mutated gene. The G265T germline (nonsense) mutation in the third exon of hMLH1 found here had not been reported previously in the literature.

Adaptor Proteins, Signal Transducing↗
PubMed2002

[Genealogical research of hereditary nonpolyposis colorectal cancer].

OBJECTIVES To analyse the diagnosis and treatment of 24 hereditary nonpolyposis colorectal cancer (HNPCC) kindreds and report mismatch repair gene mutations. METHODS The diagnosis, treatment and follow-up of 24 HNPCC kindreds were reviewed retrospectively, cancer incidence and spectrum were recorded. Clinical characteristics and treatment were analyzed. Peripherial blood and genomic DNA were extracted from family members who had provided informed consent. PCR and SSCP were used to screen coding regions of the hMLH1 and hMSH2 genes. Variant bands were sequenced by 377 DNA sequencer after purification. RESULTS One hundred and 25 malignant neoplasms were diagnosed in 75 patients (multiple cancers in 24) with an average age of 51 years in 24 pedigrees. The onset of the disease occurred earlier than expected with the passing of each generation within large kindreds. The neoplasm mainly included colonic cancer (63 patients), rectal cancer(21), stomach cancer(13), endometric cancer(7), and esophageal cancers(6). 84% patients received radical operations. Of 64 patients with colorectal cancer 16 had metachronous colorectal cancer. 24% colorectal patients developed metachronous cancer within 10 years after initial operation and received re-operation. In 3 detected families with germline hMSH2 and hMLH1 mutations resulting in truncated protein, 12 carriers were found. CONCLUSIONS The main characteristics of hereditary nonpolyposis colorectal cancer include early onset and frequence of cancer; predominance of colorectal cancer, especially right-sided colonic cancer; frequency of multiple primary cancer, especially colorectal cancer; and age anticipation in large HNPCC pedigrees. Segmental resection of colorectal cancer is not suitable for colorectal cancer patient in HNPCC kindred. Intensive follow-up is important for all patients and possible gene carriers.

Adaptor Proteins, Signal Transducing↗