Search

Objective: High-mobility group protein 2 (HMGA2) and epithelial-mesenchymal transition (EMT)-associated proteins play key roles in cancer progression and metastasis. However, the clinical significance of HMGA2 and its relationship with EMT markers in nasopharyngeal carcinoma (NPC) is unclear. This study aimed to assess the clinicopathological significance and prognostic value of HMGA2, E-cadherin, and vimentin in NPC., Methods: Using immunohistochemistry, HMGA2, E-cadherin, and vimentin expression levels were evaluated in NPC (n=124) and non-tumoral inflammatory nasopharynx (n=20) tissues. The association of HMGA2 and EMT markers with clinicopathological characteristics and relationships between the protein levels and overall survival were analyzed., Results: Compared with non-tumorous tissues, HMGA2 and vimentin levels were markedly increased in NPC tissues, whereas decreased E-cadherin levels were observed (P<0.001). Moreover, HMGA2 expression was positively correlated with vimentin levels (r=0.431, P<0.001) and negatively correlated with E-cadherin amounts (r=-0.413, P<0.001) in NPC tissues. The expression of all three proteins correlated significantly with tumor N stage, TNM stage, and 2-year metastasis. Furthermore, significant correlations were found for T stage, N stage, TNM stage, HMGA2, E-cadherin, and vimentin (all P<0.013) with poor prognosis (univariate analysis). However, multivariate analyses showed that only HMGA2 (hazard ratio [HR]: 2.683, 95% confidence interval [CI]: 1.185-6.077, P=0.018) and N stage (HR: 7.892, 95% CI: 2.731-22.807, P<0.001) were independent predictors of poor prognosis., Conclusion: These results demonstrated that HMGA2, an independent prognostic factor, may promote NPC progression and metastasis, and is significantly associated with EMT proteins. Therefore, HMGA2 may be considered a potential therapeutic target in NPC.

Objectives: The purpose of this study was to investigate the relationship between huntingtin-associated protein1 (HAP1) gene and radiation therapy of breast cancer cells., Methods: HAP1 gene was transfected into breast cancer MCF-7 cells, which was confirmed by quantitative reverse transcription-polymerase chain reaction analysis (qRT-PCR) and Western blot in vitro. The changes of cell radiosensitivity were assessed by colony formation assay. Apoptosis were examined by flow cytometry. The expressions of two radiation-induced genes were evaluated by Western blot. Tumor growth was investigated in nude mice xenograft models in vivo., Results: Our data showed that HAP1 gene expression was significantly increased in HAP1-transfected MCF-7 cells in comparison with the parental cells or negative control cells. The survival rate in MCF-7/HAP1 cells was significantly decreased after irradiation (0, 2, 4, 6, 8Gy), compared to cells in MCF-7 and MCF-7/Pb groups in vitro. HAP1 gene increased apoptosis in MCF-7 cells after irradiation. Additionally, the tumor volume and weight in MCF-7/HAP1+RT group were observably lower than in MCF-7/HAP1 group and MCF-7/Pb+RT group., Conclusion: The present study indicated that HAP1 gene expression was related to the radiosensitivity of breast cancer cells and may play an important role in the regulation of cellular radiosensitivity., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Magnetic resonance imaging of breast, reported to be a high sensitivity of 94% to 100%, is the most sensitive method for detection of breast cancer. The purpose of this study was to investigate our clinical experience in MRI-guided breast lesion wire localization in Chinese women., Materials and Methods: A total of 44 patients with 46 lesions undergoing MRI-guided breast lesion localization were prospectively entered into this study between November 2013 and September 2014. Samples were collected using a 1.5-T magnet with a special MR biopsy positioning frame device. We evaluated clinical lesion characteristics on pre-biopsy MRI, pathologic results, and dynamic curve type baseline analysis., Results: Of the total of 46 wire localization excision biopsied lesions carried out in 44 female patients, pathology revealed fourteen malignancies (14/46, 30.4%) and thirty-two benign lesions (32/46, 69.6%). All lesions were successfully localized followed by excision biopsy and assessed for morphologic features highly suggestive of malignancy according to the American College of Radiology Breast Imaging Reporting and Data System (BI-RADS) category of MRI (C4a=18, C4b=17, C4c=8,C5=3). Of 46 lesions, 37 were masses and 9 were non-mass enhancement lesions. Thirty-two lesions showed a continuous kinetics curve, 11 were plateau and 3 were washout., Conclusions: Our study showed success in MRI-guided breast lesion wire localization with a satisfactory cancer diagnosis rate of 30.4%. MRI-guided wire localization breast lesion open biopsy is a safe and effective tool for the workup of suspicious lesions seen on breast MRI alone without major complications. This may contribute to increasing the diagnosis rate of early breast cancer and improve the prognosis in Chinese women.

In the present paper, to fabricate electroluminescent devices CdSe QDs were used as active materials, TPD (N,N'-biphenyl-N,N'-bis-(3-methylphenyl)-1,1'-biphenyl-4,4'-diamine) was used as a hole transport layer, and ZnS was used as an electron transport layer. The electroluminescent properties of the organic/inorganic composite ITO/TPD/CdSe QDs/ZnS/Ag light emitting devices were studied. Both TPD and CdSe QDs thin films were spin-coated and ZnS thin films were deposited by magnetron sputtering. The surfaces of the devices are smooth. The luminescence (EL) peak of the CdSe QDs is at 580 nm which is assigned to the band-edge exciton emission. Compared to the previous EL device of ITO/ZnS/CdSe QDs/ZnS/Ag, it is seen that the new devices do not display surface state related emission peaks and EL intensity is about 10 folds that of the previous device. The enhancement of luminescence efficiency is attributed to both of the excitation of CdSe QDs by accelerated electron collision and carriers injection into QDs: (1) electrons are accelerated by the ZnS layer and collide with CdSe QDs, which excites electrons in QDs to excited states and allows them to emit photons; (2) the holes injected into QDs recombine with some of electrons excited in the QDs. The authors further studied the influence of thickness variation of ZnS on the luminescent properties. ZnS thin films are of 80, 120, and 160 nm thickness, respectively. It was found that as the thickness of ZnS increases the threshold voltage rises and EL intensity increases, but breakdown voltage decreases. The EL peak position blue shifts when the thickness of ZnS decreases. The explanation of underlying mechanism is given.

It has been previously reported that vascular endothelial growth factor (VEGF) and matrix metalloproteinase (MMP)-9 are important for the occurrence and development of non-small cell lung cancer (NSCLC). The present study was designed to detect the serum levels of VEGF and MMP-9 in NSCLC, and to explore their diagnostic and prognostic values. A total of 543 cases were involved, of which 332 were NSCLC (272 cases in the pretreatment group and 60 cases in the postoperative group), 91 were patients with benign lung diseases and 120 were healthy controls. The serum levels of VEGF and MMP-9 were determined by Luminex multiplex technology. The serum levels of VEGF and MMP-9 were found to be significantly higher in the pretreatment group than those in the patients with benign lung diseases and healthy controls (VEGF, P<0.0001; MMP-9, P<0.0001). Compared with the pretreatment group, the serum levels of VEGF and MMP-9 in the postoperative group were significantly decreased (VEGF, P=0.005; MMP-9, P=0.002), and the levels of VEGF and MMP-9 in the pretreatment group of patients with stages III and IV were higher than those with stages I and II (VEGF, P<0.0001; MMP-9, P=0.021). In addition, the levels of VEGF and MMP-9 were found to closely correlate with lymph node metastasis (VEGF, P<0.0001; MMP-9, P<0.0001) in the pretreatment group, while being independent of other clinicopathological parameters (P>0.05). Furthermore, a positive correlation was observed between the serum levels of VEGF and MMP-9 (r=0.159; P=0.009). A receiver operating characteristic curve analysis showed that the diagnostic value of MMP-9 was higher than that of VEGF in the pretreatment group. The log-rank test indicated that the inoperable NSCLC patients with low levels of VEGF exhibited a significantly longer overall survival time than those with high VEGF levels (P<0.0001). Additionally, the serum levels of VEGF and lymph node metastasis were identified as independent prognostic factors of the inoperable NSCLC patients in a multivariate Cox regression analysis (P<0.05). These results indicated that VEGF and MMP-9 may be potential biomarkers for the diagnosis and prognosis of NSCLC.

To evaluate the relationship between alcohol drinking, XRCC1 codon 194 and 399 polymorphisms and risk of colorectal cancer, we conducted a case-control study with 315 colorectal cancer cases (105 colon, 210 rectal) and 439 population-based controls in Jiangsu Province of China. The XRCC1 codon 194 and 399 genotypes were identified using polymerase chain reaction and restrictrion fragment length polymorphism methods (PCR-RFLP). A structured questionnaire was used to elicit detailed information. Odds ratios (ORs) were estimated with an unconditional logistic model. In this study no significant differences were observed among the studied groups with regard to the genotype distribution of the XRCC1 codons 194 and 399 and the risk of colorectal cancer did not appear to be significantly influenced by genotype alone, whereas alcohol consumption showed a positive association (P for trend <0.01). When combined effects of XRCC1 polymorphisms and alcohol consumption were analyzed, we found that the 194Trp or 399Gln alleles further increased the colorectal cancer risk due to high alcohol intake. These findings support the conclusion that colorectal cancer susceptibility may be altered by gene-environment interactions.

Background: The aim of the research was to explore a cost effective, fast, easy to perform, and sensitive method for epidermal growth factor receptor (EGFR) mutation testing., Methods: High resolution melting analysis (HRM) was introduced to evaluate the efficacy of the analysis for dectecting EGFR mutations in exons 18 to 21 using formalin-fixed paraffin-embedded (FFPE) tissues and plasma free DNA from 120 patients., Results: The total EGFR mutation rate was 37.5% (45/120) detected by direct sequencing. There were 48 mutations in 120 FFPE tissues assessed by HRM. For plasma free DNA, the EGFR mutation rate was 25.8% (31/120). The sensitivity of HRM assays in FFPE samples was 100% by HRM. There was a low false-positive mutation rate but a high false-negative rate in plasma free DNA detected by HRM., Conclusions: Our results show that HRM analysis has the advantage of small tumor sample need. HRM applied with plasma free DNA showed a high false-negative rate but a low false-positive rate. Further research into appropriate methods and analysis needs to be performed before HRM for plasma free DNA could be accepted as an option in diagnostic or screening settings.

5,6-Dioxo-1,10-phenanthroline-2,9-dicarboxylic acid dihydrate (H(2)pdda·2H(2)O), C(14)H(6)N(2)O(6)·2H(2)O, was obtained by carbonylation of 1,10-phenanthroline-2,9-dicarboxylic acid. Its first coordination compound, [MnCl(C(14)H(6)N(2)O(6))(H(2)O)(2)]Cl·2H(2)O, in which the H(2)pdda ligand remains protonated, was synthesized in aqueous acetic acid. H(2)pdda chelates one water molecule via hydrogen bonds in H(2)pdda·2H(2)O, whereas in the coordination compound it chelates one heptacoordinate Mn(II) atom via coordination bonds. The N atoms in H(2)pdda·2H(2)O and the Cl atoms in the coordination compound are also involved in hydrogen bonds. Extensive hydrogen bonding results in supramolecular networks in both compounds.

Background: Dihydropyrimidine dehydrogenase (DPD), a key enzyme involved in the catabolism of 5-fluorouracil (5-FU), is the attractive candidate for pharmacogenetic research on efficacies and toxicities of 5-FU. The aim of this study is to explore the association between polymorphisms of dihydropyrimidine dehydrogenase gene (DPYD) and clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in the Chinese population., Methods: Three hundred and sixty-two patients with gastric cancer in the Chinese population were treated with fluorouracil-based adjuvant chemotherapy. The single nucleotide polymorphic genotypes of DPYD were determined by matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry (MALDI-TOF-MS) using DNA samples isolated from peripheral blood collected before treatment., Results: The average response rate for chemotherapy was 46.7%. A significantly different distribution of the rs1801159 (c2=8.76, P=0.012) genotypes was observed. Homozygous genotype rs1801159A/A was over-represented in responsive patients. Conversely, carriers of the rs1801159A/G genotype were prevalent in non-responsive patients. In the haplotype association analysis, there was significant difference in global haplotype distribution between the groups (c2=3.96, P=0.0465)., Conclusions: These results suggest that polymorphisms of rs1801159 in DPYD may be used as valuable predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in the Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of DPYD as predictive markers for gastric cancer in response to fluorouracil-based therapies are warranted.

The title compound, C(14)H(12)N(2)O(4)Se(2), is not chiral, but the mol-ecules assume a chiral conformation in the solid state and crystallize as an aggregate. The central C-Se-Se-C torsion angle is 90.4 (2)°, while the two Se-Se-C-C fragments assume gauche conformations with values of -59.4 (5) and 67.5 (4)°. The dihedral angle between the two benzene rings is 80.74 (14)°.

To evaluate the relationship between physiological, reproductive factors and risk of breast cancer, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. All subjects completed an in-person interview. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as measures of risk for breast cancer. The results have revealed that there was an increasing risk of breast cancer, include early age at menarche(≤ 13 year), late age at menopause(< 50 year) and older age at first pregnancy (≤ 30 year). Breastfeeding was associated significantly with a reduced risk of breast cancer. Women who had history of breastfeeding were at significantly decreased OR (0.44, 95%CI: 0.27-0.73). The protective effects of breastfeeding for breast cancer seemed greater for women who had extended duration of breastfeeding during their lifetime (p for linear trend: 0.0095). These results suggested that physiological and reproductive factors may play important roles in the development of breast cancer among Jiangsu' women of China.

Neuregulin-1 (NRG-1) is a member of the epidermal growth factor family. Our previous study showed that NRG-1 protected neurons from apoptosis following focal cerebral ischemia by the inhibition of caspase-3 and TNF-alpha expression. However, the molecular signaling mechanisms for this action of NRG-1 following cerebral ischemia are not fully understood. Presently, activation of the PI3K/Akt pathway has been implicated as a major contributor to neuronal survival after an ischemic insult. In the present study, we investigated whether NRG-1 modulates the activation of Akt and its downstream targets Bad and Bcl-2 expression after transient focal cerebral ischemia by intraluminal blockade of the middle cerebral artery. Western blot was employed to analyze the change of phosphorylated Akt (p-Akt) expression; reverse transcription and polymerization chain reaction (RT-PCR) were used to measure changes of Bcl-2 mRNA. The level of phosphorylation of Bad (p-Bad) was determined using an enzyme-linked immunosorbent assay (ELISA). Our results showed that recombinant human NRG-1(3.0 ng.kg-1) significantly increased the expression of p-Akt protein, Bcl-2 mRNA, and the level of p-Bad, respectively, whereas administration of LY294002, a specific inhibitor of PI3K, significantly decreased the expression of p-Akt, p-Bad, and Bcl-2 induced by NRG-1 after a 60 min ischemic insult, followed by 24 h of reperfusion. These results indicate that NRG-1 may be involved in regulating the expression of Bcl-2 and p-Bad through the PI3K/Akt pathway after transient focal cerebral ischemia.

Aim: To observe the effect of heat shock protein 27 (Hsp27) on nitric oxide synthase (NOS) of spinal cord anterior horn after brachial plexus roots avulsion., Methods: Sixty male adult Wistar rats were divided into control and experiment groups at random. The experiment group subjected to heat shock under 45 degrees C for 15 min, and maintained under 42 degrees C for 20 min subsequently. After recovering 24 h under the room temperature, the nerves of brachial plexus were avulsion with microhemostatic forcep. In a span from 12 h to 7 d, these animals were killed at different time. But the control group only received the surgery of the nerve roots of brachial plexus avulsion. The freeze sections of spinal cord were stained by NADPH-d histochemistry, HSP27 immunohistochemical., Results: (1) In experiment group, the motoneuron began to express NOS abundantly at 12 h after avulsion (A=0.13625). Then the NOS-positive neurons declined quickly, but in control group, the motoneuron began to express NOS at the 5th day after lesion. (2) Hsp27 begin to show the peak at 1 d in experiment and control groups, but the experiment group were more strong than the control group., Conclusion: Hsp27 inhibited NOS of motoneuron after avulsion and brought into full play the cytoprotection.

To investigate the relationship among alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genetic polymorphisms, alcohol consumption and the susceptibility to esophageal cancer in a Chinese population, we conducted a case-control study with 221 cases and 191 population-based controls in the Taixing city of Jiangsu Province of China. ADH2 and ALDH2 genotypes were examined using PCR and denaturing high-performance liquid chromatography. Alcohol drinkers with the ALDH2 A allele showed a significantly increased risk of esophageal cancer compared with drinkers with the ALDH2 G/G genotype (odds ratio (OR)=3.08, 95% confidence interval (CI): 1.65-5.78) or nondrinkers with any genotype (OR=3.05, 95% CI: 1.49-6.25). Drinkers with the ALDH2 A allele and a cumulative amount of alcohol consumption > or =2.5 (kg * years) were at a significantly higher risk of developing esophageal cancer (OR=11.93, 95% CI: 3.17-44.90) compared with individuals with ALDH2 G/G genotypes and a cumulative amount of alcohol consumption <2.5 (kg * years). A dose-dependent positive result was found between cumulative amount of alcohol consumption and risk of esophageal cancer in individuals carrying the ALDH2 A allele (P=0.023) and the homozygous ALDH2 G allele (P=0.047). Compared with individuals carrying both ALDH2 G/G and ADH2 A/A alleles and with a cumulative amount of alcohol consumption <2.5 (kg * years), drinkers carrying both ALDH2 A and ADH2 G alleles and with a cumulative amount of alcohol consumption > or =2.5 (kg * years) showed a significantly elevated risk of esophageal cancer (OR=53.15, 95% CI: 4.24-666.84). This result suggests that to help lower their risk for esophageal cancer, persons carrying the ALDH2 A allele should be encouraged to reduce their consumption of alcoholic beverages.

Several publications have showed that the number of metastatic lymph node (LN) should be taken into consideration in nodal category of esophageal cancer, but seldom considered extent of involved regional LNs. The aim of this study is to evaluate the significance of the extent of regional LN metastasis on survival in patients with esophageal cancer. A total of 245 thoracic esophageal cancer patients underwent transthoracic esophagectomy with standard lymphadenectomy between January 2000 and December 2006 were included in the study. Data including demographic factors, pathologic findings, LN parameters and survival outcomes were collected. The survival experience was depicted using Kaplan-Meier method. A multivariate Cox proportional hazard model was used to screen the significant prognostic factors. The univariate analysis to further explore the significant prognostic factor was done by log-rank test. After a median follow-up of 53.2 months, the 5-year survival rate was 46.3% for the entire cohort. Cox model regression indicated that the LN status and perigastric nodal status, aside from residual tumor status, histological tumor type and depth of invasion, were the independent prognostic factors. Patients without LN metastasis had better 5-year survival than those with positive nodes (64.2% vs. 18.9%, X2=35.875, P<0.001). However, For those patients with nodal involvement, there was no difference in 5-year survival between patients with involved nodes<3 and >or=3 (27.8% vs. 0%, X2=0.925, P=0.336). When considering the location of LN metastasis, patients could be further stratified according to whether the perigastric nodes were involved or not (37.5% vs. 10.0%, X2=4.295, P=0.038). In conclusion, involved LN number had no prognostic implication in nodal involved patients based on our data. Whereas, perigastric nodal involvement should be used to refine the N category (N0, no nodal metastasis, N1, non-perigastric node metastasis, N2, perigastric node metastasis) for the future esophageal cancer staging criteria.

Objective: To investigate the relationship among alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) genetic polymorphisms, alcohol consumption, and the susceptibility of stomach cancer in Chinese males., Methods: Three hundred and eighty-two stomach cancer patients and 382 healthy controls from Taixing and Changshu city of Jiangsu province were enrolled in this study. ADH2 and ALDH2 genotypes were examined by PCR and denaturing high-performance liquid chromatography (DHPLC). Unconditional logistic regression was used to calculate the odds ratios (OR) and 95% confidence intervals (95% CI)., Results: (1) In no drinkers, compared with ALDH2G/G carriers, ALDH2 G/A (OR=1.67, 95%CI: 1.01-2.78) carriers showed a significantly elevated risk of developing stomach cancer. No association was found between ADH2 genotypes and risk of stomach cancer. (2) ALDH2 A allele carriers with cumulative amount of alcohol consumption≥2.5 (Kg*years) were at a higher risk of developing stomach cancer compared with those with cumulative amount of alcohol consumption<2.5 Kg (Kg*years) (OR=2.72, 95%CI:0.89-8.31) and ALDH2 G/G carriers with cumulative amount of alcohol consumption<2.5 (Kg*years) (OR=2.46, 95%CI=0.90-6.72) or≥2.5 (Kg * years) (OR=2.53, 95%CI=0.86-7.49). (3) Compared with individuals with ADH2 A/A and ALDH2 G/G genotypes, ADH2 G and ALDH2 A allele carriers were not at a high risk of developing stomach cancer, with regard to the status of alcohol consumption, and even cumulative amount of alcohol consumption≥1.5 (Kg*years) (OR=1.65, 95%CI:0.56-4.82)., Conclusion: ADH2 and ALDH2 polymorphisms and alcohol drinking may not play an important role in the development of stomach cancer in Chinese males.

Ribonucleotide reductase catalyzes the rate limiting step of deoxyribonucleotide formation, a crucially important step in DNA synthesis and repair. The regulatory subunit M1 of ribonucleotide reductase (RRM1) is the necessary part of the RR function and controls substrate specificity and global on/off enzyme activity. Despite recent research progress, the role of RRM1 in lung cancer sensitivity to chemotherapeutics remains to be elucidated. This study was to investigate the relationship between polymorphisms of the RRM1 gene and sensitivity to platinum-based chemotherapy in non-small cell lung cancer (NSCLC). Genomic DNA samples from 214 NSCLC patients treated with platinum-based chemotherapy were used to determine the RRM1 promoter allelotypes. The RR37CC-RR524TT was the most frequent allelotype (38.50%), followed by RR37AC-RR524CT (26.76%) and RR37CC-RR524CT (14.95%). The average response rate for chemotherapy was 44.4%. The response rates to the treatment regimens in the RR37CC-RR524TT, RR37AC-RR524CT and RR37CC-RR524CT allelotypes were 43.9%, 52.6%, and 51.6%, respectively. The response rates to therapy among patients with RRM1 (-)524 allelotypes were significantly different (p=0.046), whereas that among patients with RRM1 (-)37 allelotypes were not significant. Further analysis showed that the response rate in the patients with RR524CT allelotype (52.3%) was the highest, compared with that with RR37CC-RR524TT allelotype (43.9%, p=0.28), or the Others (RR524CC and RR37AC-RR524TT, 30.2%, p=0.02). Our results suggest that the RR524CT allelotype may be associated with an increased sensitivity to platinum-based chemotherapy in NSCLC. Further research on determining RR524CT as a clinical marker for predicting response to platinum-based therapy in NSCLC patients is warranted.

Objective: To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5, 10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk., Methods: A case-control study was conducted with 669 cases and 682 population-based controls in Jiangsu province of China. MTHFR C677T and A1298C genotypes were identified by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) methods. Dietary folate intake was assessed by using an 83-item food frequency questionnaire. Odds ratios (OR) were estimated with an unconditional logistic model., Results: The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37% (202/624), 48.88% (305/624) and 18.75% (117/624) in cases and 37.66% (235/624), 48.24% (301/624) and 14. 10% (88/624) in controls, respectively. The difference in distribution was significant (chi2 = 6.616, P = 0.037), the T/T genotype being associated with an elevated OR for breast cancer (1.62, 95% CI: 1.14 -2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47% (446/624), 27.08% (169/624) and 1.44% (9/624) in cases and 68.11%(425/624), 30.13% (188/624) and 1.76% (11/624)in controls,with no significant differences found (chi2 = 1.716, P= 0.424). Folate intake of cases [(263.00 +/- 137.38) microg/d] was significantly lower than that of controls [(285.12 +/- 149.61) microg/d] (t = -2. 830, P =0.005). Compared with the lowest tertile (< or = 199.08 microg/d) of folate intake, the adjusted OR for breast cancer in the top tertile (> or = 315.11 microg/d) was 0.70 (95% CI: 0.53 -0.92). Among individuals with the MTHFR A1298C A/A genotype,adjusted OR for breast cancer were 0.89 (95% CI: 0.62 - 1.27) and 1.69 (95% CI: 1.20 - 2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (X2trend = 11.372, P = 0.001)., Conclusion: The findings of the present study suggest that MTHFR genetic polymorphisms,and dietary intake of folate may modify susceptibility to breast cancer.

To evaluate the relationship between dietary folate intake and genetic polymorphisms of 5,10-methylenetetrahydrofolate reductase (MTHFR) with reference to breast cancer risk, we conducted a case-control study with 669 cases and 682 population-based controls in the Jiangsu Province of China. MTHFR C677T and A1298C genotypes were identified using PCR-RFLP (restrictrion fragment length polymorphism) methods. Dietary folate intake was assessed using an 83-item food frequency questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model. The frequencies of MTHFR C677T C/C, C/T and T/T genotypes were 32.37, 48.88 and 18.75% in cases and 37.66, 48.24 and 14.10% in controls, respectively. The difference in distribution was significant (chi(2)=6.616, P=0.037), the T/T genotype being associated with an elevated OR (adjusted for age, menopausal status, body mass index (BMI), income, work intensity and status of smoking and drinking) for breast cancer (1.62, 95% confidence interval (95% CI): 1.14-2.30). The frequencies of MTHFR A1298C A/A, A/C and C/C were 71.47, 27.08 and 1.44% in cases and 68.11, 30.13 and 1.76% in controls, respectively, with no significant differences being found (chi(2)=1.716, P=0.424). A significant inverse relationship was observed between folate intake and breast cancer risk. Compared with the lowest tertile of folate intake, the adjusted OR for breast cancer in the top tertile was 0.70 (95% CI: 0.53-0.92). However, no significant interaction was observed between folate intake and the MTHFR C677T polymorphism. Among individuals with the MTHFR A1298C A/A genotype, adjusted ORs for breast cancer were 0.89 (0.62-1.27) and 1.69 (1.20-2.36) for the second to the third tertile of folate intake compared with the highest folate intake group (tread test, P=0.0008). The findings of this study suggest that MTHFR genetic polymorphisms and dietary intake of folate may modify susceptibility to breast cancer.

The title complex, [Ni(2)Cl(4)(C(22)H(17)N(3))(2)], was synthesized solvothermally. The molecule is a centrosymmetric dimer with the unique Ni(II) centre in a distorted octahedral N(3)Cl(3) coordination environment. The chloride bridges are highly asymmetric. In the 4'-p-tolyl-2,2':6',2''-terpyridine ligand, the p-tolyl group is perfectly coplanar with the attached pyridine ring, and this differs from the situation found in previously reported compounds; however, there are no pi-pi interactions between the ligands. The terminal Cl atom forms four intermolecular C-H...Cl hydrogen bonds with one methyl and three methine groups. The methyl group also forms intermolecular C-H...pi interactions with a pyridine ring. These nonclassical hydrogen bonds extend the molecule into a three-dimensional network.

Objective: To evaluate the impact of alcohol dehydrogenase-2 (ADH2) and aldehyde dehydrogenase-2 (ALDH2) polymorphisms on the susceptibility of esophageal cancer., Methods: A case-control study including 221 cases of esophageal cancer and 191 controls was carried out in Taixing city of Jiangsu province. ADH2 and ALDH2 genotypes were tested by PCR and denaturing high performance liquid chromatography (DHPLC)., Results: (1) Compared with ALDH2 G/G carriers, ALDH2 A/A (OR = 5.69, 95% CI: 2.51-12.18) and ALDH2 G/A (OR = 1.70, 95% CI: 1.08-2.68) carriers showed a significantly elevated risk of developing esophageal cancer, especially among alcohol drinkers with ALDH2 A/A (OR = 8.63, 95% CI: 2.07-35.95). (2) Statistical relation was not found between ADH2 genotypes and the risk of esophageal cancer, with regard to the status of alcohol consumption. (3) Whether subjects with whatever ADH2 genotype, ALDH2 G/A or A/A carriers was found to have significantly increased the risk of developing esophageal cancer, with ALDH2 A/A carriers appeared having higher esophageal cancer risk than those ALDH2 G/A carriers. (4)Compared those non-drinkers with both ALDH2 G/G and ADH2 A/A, drinkers with ALDH2 G/A or A/A and ADH2 G/A or G/G genotypes showed a significantly elevated risk of developing esophageal cancer (OR = 8.36, 95% CI: 2.98-23.46)., Conclusion: These results revealed that it was not ADH2 but ALDH2 polymorphisms and drinking alcohol had a significant interaction with the development of esophageal cancer, suggesting that in order to help lowering the risk of esophageal cancer, individuals who are carrying ALDH2 A/A or G/A genotypes should be encouraged to reduce their consumption of alcohols.

Objective: To establish a method for SNP genotyping of multi-genes by allele-specific oligonucleotide probe ligation mediated by a thermostable ligase, and to explore the genetic polymorphisms of drug-metabolizing enzymes in breast cancer patients and their association with chemotherapeutic responses., Methods: 10 SNP loci of enzyme genes related to chemotherapeutic drugs such as taxanes, anthracyclines and cyclophosphamide were selected, and were genotyped for blood samples from 126 breast cancer patients by the established method. Their correlations with therapeutic responses were retrospectively evaluated., Results: The lower detection limit of genomic DNA by this developed method was 6.25 ng. The fluorescent peak locations of ligation products on ABI PRISM 377 DNA sequencer were accurate and consistent with prospective sizes in bases (Bias range 0.08 - 0.69 bp, x(-) = 0.31 bp, s = 0.18 bp). Same genotyping results were obtained for repeat tests of 8 random samples, which were further confirmed by sequencing analysis. The 10 SNP loci were polymorphic of different frequency in the breast cancer patients. The combinations with GSTP1 genotypes and GSTM1 genotypes were related to anthracycline-based chemotherapy efficacy (P = 0.037), and the low GSTs activity group (GSTP1 variant allele + GSTM1 null) showed the best effects (85.7%). GSTM1 genotypes and their combinations with GSTP1 and/or CYP3A5*3 genotypes were related to taxane-based therapy efficacy (P < 0.05 for all), and both the low GSTs activity group and the drug slow-metabolising group (low GSTs activity group + CYP3A5*3 wild allele) showed better effects (100%)., Conclusion: The established method is reliable and applicable in multiplex SNPs genotyping of multi-genes. SNPs combination may have a better clinical application value for prediction of chemotherapeutic responses.

Poly[(mu(4)-pyrazine-2,5-dicarboxylato)cadmium(II)], [Cd(C(6)H(2)N(2)O(4))](n) or [Cd(pzdc)](n) (pzdc is the pyrazine-2,5-dicarboxylate dianion), has been synthesized hydrothermally. The asymmetric unit consists of a Cd(II) atom and two independent halves of pzdc ligands that can be expanded via inversion through the centres of the ligands so that each ligand binds to four Cd(II) atoms with the same binding mode using six donor atoms. The Cd(II) centre is in a distorted octahedral coordination geometry with four O- and two N-atom donors from four pzdc ligands. The infinite linkage of the metal atoms and ligands forms a three-dimensional framework with a rectangular channel which is so narrow that there is no measurable void space in the overall structure. This coordination polymer represents the first example of (4,4,4)-connected three-nodal framework.

To evaluate the relationship between body size, physical activity and risk of breast cancer, we conducted a case-control study with 669 cases and 682 population-based controls in Jiangsu Province of China. A structured questionnaire was used to elicit detailed information. All subjects completed an in-person interview. The body mass index (BMI) was calculated based on weights and heights. Unconditional logistic regression analysis was performed to calculate odds ratios (ORs) and 95% confidence intervals (CIs) as measures of risk for breast cancer. Current height, weight and weight at around age 20 years were significantly positively correlated with risk of breast cancer. Obese women (current BMI > or = 25 kg/m2) were at significantly increased risk for developing breast cancer (adjusted OR= 1.35, 95%CI: 1.01-1.81), but, between BMI at around age 20 years and risk of breast cancer showed an inverse association (P for trend = 0.001). Women who had middle physical force work were at significantly lowered OR (0.62, 95%CI: 0.41-0.93) compared with women of headwork. Using women who standing or ambulation per day less than one hour as the reference, women who standing or ambulation more than one hour had a decreased risk of breast cancer. Using women who slept less than 5 hours per day as the reference, the women who slept 5-8 hours were at significantly decreased risk of breast cancer. Women who had habit of recreational physical activity were at significantly decreased risk (adjusted OR= 0.68, 95%CI: 0.53-0.88), with an inverse association between the exercise times per week and risk of breast cancer (P for trend = 0.025). These findings support that breast cancer risk is associated with body size, and that moderate occupational and recreational physical activity has protective effects on breast cancer.

The title compound, [MnCl(2)(C(12)H(8)N(2)O(2))(2)], displays a novel supramolecular chain formed by intermolecular O-H...Cl hydrogen bonds and aromatic stacking. The molecule has crystallographically imposed twofold symmetry with the Mn(II) atom on the twofold axis. In the 1,10-phenanthroline-5,6-diol ligand, each H atom of the two hydroxy groups is oriented towards the other hydroxy O atom. Both hydroxy groups form intermolecular O-H...Cl hydrogen bonds with a single Cl atom of an adjacent molecule. These hydrogen bonds connect the molecules via operation of the molecular twofold axis and the centre of inversion of the crystal lattice, forming a doubly-bridged one-dimensional structure with Mn atoms as the nodes. Strong aromatic pi-stacking between two antiparallel neighbouring 1,10-phenanthroline-5,6-diol ligands also helps to stabilize the chain.

Objectives: To study the relation between genetic polymorphisms of methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the susceptibility of colorectal cancer., Methods: We conducted a case-control study with 315 cases of colorectal cancer and 371 population-based controls in Jiangsu province, China. The epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR C677T and A1298C genotypes were detected by the PCR-RFLP method., Results: (1) When men and women were assessed together, the frequencies of the MTHFR C677T and A1298 genotypes or their alleles were not significantly different between controls and colon cancer or rectal cancer cases. No significant relation was observed between MTHFR C677T or A1298C polymorphisms and colon or rectal cancer susceptibility. (2) Among males, individuals who had MTHFR C677T T/T genotype were at a significantly higher risk of developing colon cancer (age-, residence-, smoking-, alcohol drinking-, tea consumption-adjusted OR=2.15, 95%CI: 1.07-4.33) compared with those who had C677T C allele. Individuals who had C677T T/T and A1298C A/A genotypes were at an increased risk of developing colon cancer (adjusted OR=2.64, 95%CI: 1.20-5.81) compared with those with C677T C allele and A1298C A/A genotypes among males. On the contrary, individuals who had C677T T/T and A1298C A/A genotypes were at an decreased risk of developing rectal cancer (adjusted OR=0.47, 95%CI: 0.22-1.03)., Conclusions: These results in the present study suggested that polymorphisms of the MTHFR C677T could influence susceptibility to colon or rectal cancer and that there was a coordinated effect between MTHFR A1298C A/A and C677T T/T genotypes among males.

Aim: To investigate associations between the Rsa I polymorphism of CYP2E1 and risk of colorectal cancer., Methods: A case-control study was conducted with 315 colorectal cancer cases (105 colon, 210 rectal) and 439 population-based controls in Jiangsu Province of China. Genomic DNA samples were assayed for restriction fragment length polymorphisms in CYP2E1 by PCR amplification followed by digestion with Rsa I. Information on smoking and alcohol drinking was collected using a questionnaire. Odds ratios (ORs) were estimated with an unconditional logistic model., Results: The proportional distribution of the CYP2E1 Rsa I c1/c1, c1/c2 and c2/c2 genotypes were 61.4%, 35.6% and 3.0% in controls, 60.6%, 33.7% and 5.8% in colon cancer cases, and 58.4%, 34.0% and 7.7% in rectal cancer cases, respectively. A significant difference was noted between controls and rectal cancer cases (P = 0.029), the c2/c2 genotype being associated with elevated OR (adjusted age, sex and status of the smoking and alcohol drinking) for rectal cancer (1.64, 95% CI, 1.12-2.41, vs c1 allele carriers), but not for colon cancer. In interaction analysis between the CYP2E1 Rsa I genotype and smoking and drinking habits, we found a significant cooperative action between the c2/c2 genotype and alcohol drinking in the sex-, age-adjusted ORs for both colon (4.74, 95% CI, 1.10-20.40) and rectal (5.75, 95% CI, 1.65-20.05) cancers. Among non-smokers, the CYP2E1 Rsa I c2/c2 genotype was also associated with elevated ORs in the two sites (1.95, 95% CI, 0.99-3.86 and 2.30, 95% CI, 1.32-3.99)., Conclusion: The results of the present study suggest that the CYP2E1 c2/c2 genotype increases susceptibility to rectal cancer and the gene-environmental interactions between the CYP2E1 polymorphism and smoking or alcohol drinking exist for colorectal neoplasia in general.

Polymorphism which is either in the thymidylate synthase (TS)enhancer region (TSER) of the 5-primer untranslation region (5' UTR) or in the 3-primer untranslation region (3' UTR) has been reported to be associated with the alterations in TS mRNA and protein levels. The TSER is characteristic of the presence of variable double (2R) and triple (3R) number tandem repeats (VNTRs). In addition to VNTRs, single nucleotide polymorphism (SNPs) in 3R, as well as the polymorphism of the fragment length(FLP) in the TS 3'-UTR which is characteristic of the presence or absence of a 6 bp- nucleotide fragment, has recently been reported to be associated with the response to 5-fuorouracil (5-FU)-based chemo-therapy. The aim of the present study was to develop a specifc denaturing high-performance liquid chromatography (DHPLC) method for the rapid and simultaneous detection of these variations in clinical samples. Multi-PCR primers were designed to amplify the two regions simultaneously, The 8.6 min DHPLC gradient was optimized to include the analysis of multiplexed TSER/3' UTR chromatogram peaks, allowing for the simultaneous detection of 28 bp VNTRs and 6 bp FLP under nondenaturing conditions (50). The optimal melting temperature was determined experimentally for the detection of SNP in the TSER VNTRs. Finally, the DHPLC analysis was verified in parallel with PCR-RFLP and sequencing. The optimized DHPLC method resolved 100% of the known TS variations, discriminated between homozygous and heterozy-gous genotypes. This developed DHPLC method could permit the rapid, sensitive, and accurate identification of the TS genotypes (VNTRs, SNPs, and FLP).

Purpose: To demonstrate the application of Disability Adjusted Life Year (DALY) as an aid in health outcome measures to evaluate the epilepsy disease burden in rural China and to provide Chinese data to achieve a better understanding of disease burden due to epilepsy., Methods: The DALY is the sum of the number of years of survival with disability (Years Lived with Disability, YLD) and the number of years lost because of premature mortality (Years of Life Lost, YLL). We calculated the YLD based on the prevalence survey of epilepsy among 66,393 people sampled in Heilongjiang, Henan, Jiangsu, Ningxia, Shanghai, and Shanxi provinces in 2000. The epilepsy mortality data from Chinese literature provided the YLL due to epilepsy. We applied sensitivity analysis to evaluate the influence of uncertainty on the epilepsy mortality value and disability weight in the study., Results: In 2000, epilepsy caused 1.83 and 2.48 DALY lost per 1,000 population in Henan and Ningxia province, which had the lowest and the highest DALY lost among the six study areas. Overall, epilepsy caused 1.41 YLLs and 0.67 YLDs per 1,000 population; thus the DALYs lost because of epilepsy was 2.08 per 1,000 population, representing the epilepsy disease burden in rural China., Conclusions: The DALY measure, which includes the extent of disability from epilepsy, provides a useful tool for the epilepsy disease burden assessment. The disease burden of epilepsy in China is considered higher than previous estimations.

Objective: To investigate the diagnosis,treatment and requirement of epilepsy patients in some urban communities in China, and to provide the evidence of searching for effective treatment and management on epilepsy under the China's context., Methods: A face-to-face survey were conducted in 3 urban communities in Shanghai, Beijing and Changsha, respectively. The questions in the questionniare were general information, hospital visit, treatment, the level and way of getting on the knowledge of epilepsy, as well as the current obstacles and needs., Results: Most of the patients selected the regular hospitals (90.8%) and the departments (92.3%) for their epielspy diagnosis and treatment. They used AEDs modo dictu (77.4%), and had controlled the seizures quite well (82.6%). A small part of patients still could not deeply understand the basic knowledge on epilepsy (13.5%). They ignored to follow up the drug concentration (45.8%) in blood and the blood biocheminstry indicators (43.9%). Some patients went to private clinics (12.9%) and used lay people remedies (7.7%). Longtime waiting (36.8%), inconvenient traffic (23.2%), and high expenses (22.6%) were the main problems influencing the timely treatment. The main obstacles of the patients were employment (47.2%), marriage (29.9%), psychological conditions (44.4%) and interpersonal relationship (29.9%). The main requirements were the effectiveness (87.0%) and cheap AEDs (40.9%) as well as the convenience of hospital visit (37.0%)., Conclusion: It is very important to emphasize knowledge and publicity/education on epilepsy as well as the psychological treatment according to the requirements of patients.

Objective: To evaluate the efficacy of phenobarbital in treatment of patients with convulsive forms of epilepsy in rural areas and to develop a suitable relevant model for rural China., Methods: A demonstration protocol was conducted in the rural areas of 8 counties from 6 provinces and municipality in China, Heilongjiang, Ningxia, Henan, Jiangsu, Shanxi, and Shanghai from December 2001 to June 2004. Epidemiological investigation of the prevalence and treatment gap of epilepsy was carried out. Patients with convulsive forms of epilepsy thus screened underwent treatment of phenobarbital. Physicians of township hospitals received short-term training to be in charge of the treatment and regular follow-up of the patients., Results: A total of 2455 patients with generalized tonic-clonic seizures in these 6 rural areas were screened and entered the treatment group. 347 patients (26.2%) had been seizure-free during the period of these 2 years, 415 patients (31.3%) had their seizure frequencies decreased by > 75% as compared with those during the period of 6 months before treatment, and the conditions of 26.1% of the patients did not change or even became worse. About 26.1% of the patients had mild side effects, 3.7% had moderate side effects, and only 0.3% had severe side effects when the dosage of phenobarbital in the first 3 months was increased. 597 patients (24.3%) withdrew from the treatment group because of various reasons., Conclusion: This protocol was suitable to the rural areas of China. The trained physicians are capable of fulfilling the task to treat the patients with epilepsy. Phenobarbital is an effective drug for most patients with convulsive seizures and has no severe side effect.

The manganese-oxo "cubane" core complex Mn(4)O(4)L(1)(6) (1, L(1) = Ph(2)PO(2-)), a partial model of the photosynthetic water oxidation site, was shown previously to undergo photodissociation in the gas phase by releasing one phosphinate anion, an O(2) molecule, and the intact butterfly core cation (Mn(4)O(2)L(1)(5+)). Herein, we investigate the photochemistry and electronic structure of a series of manganese-oxo cubane complexes: [Mn(4)O(4)L(2)(6)] (2), 1(+)(ClO(4-)), 2(+)(ClO(4-)), and Mn(4)O(3)(OH)L(1)(6) (1H). We report the atomic structure of [Mn(4)O(4)L(2)(6)](ClO(4)), 2(+)(ClO(4-)) [L(2) = (4-MeOPh)(2)PO(2-)]. UV photoexcitation of a charge-transfer band dissociates one phosphinate, two core oxygen atoms, and the Mn(4)O(2)L(5)(+) butterfly as the dominant (or exclusive) photoreaction of all cubane derivatives in the gas phase, with relative yields: 1H >> 2 > 1 > 2(+) > 1(+). The photodissociation yield increases upon (1) reducing the core oxidation state by hydrogenation of a corner oxo (1H), (2) increasing the electron donation from the phosphinate ligand (L(2)), and (3) reducing the net charge from +1 to 0. The experimental Mn-O bond lengths and Mn-O bond strengths and the calculated ligand binding energy explain these trends in terms of weaker binding of phosphinate L(2) versus L(1) by 14.7 kcal/mol and stronger Mn-(mu(3)-O)(core) bonds in the oxidized complexes 2(+) and 1(+) versus 2 and 1. The calculated electronic structure accounts for these trends in terms of the binding energy and antibonding Mn-O(core) and Mn-O'(ligand) character of the degenerate highest occupied molecular orbital (HOMO), including (1) energetic destabilization of the HOMO of 2 relative to 1 by 0.75 eV and (2) depopulation of the antibonding HOMO and increased ionic binding in 1(+) and 2(+) versus 1 and 2.

To investigate the relationship between polymorphism in the 3'-untranslated region (3'-UTR) of the thymidylate synthase (TS) gene and sensitivity of gastric cancer to 5-fluorouracil (5-FU)-based chemotherapy, 106 cases of advanced gastric cancer were analyzed. All patients were treated with 5-FU-based chemotherapy; DNA from peripheral blood leukocytes was obtained before therapy. TS 3'-UTR genotypes were detected by PCR-RFLP. Polymorphism in the TS 3'-UTR can be classified into three groups according to the presence or absence of a 6 bp nucleotide fragment: the -6/-6 bp, -6/+6 bp and +6/+6 bp groups. The response rate of the -6/-6 bp and -6/+6 bp groups was found to be significantly higher than the +6/+6 bp group. These results show that the presence of the TS 3'-UTR 6 bp nucleotide fragment can be correlated with the sensitivity of gastric cancer to 5-FU-based chemotherapy, and that the TS 3'-UTR polymorphism profile can be used to guide the choice of 5-FU-based chemotherapy in advanced gastric cancer.

A binuclear complex [(phen)Cu(mu-bipp)Cu(phen)](ClO(4))(4), where phen=1,10-phenanthroline and bipp=2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline, has been synthesized and its interaction with calf-thymus DNA in the buffer containing 5mM Tris and 50mM NaCl has been studied by means of electronic absorption titration, luminescence titration and viscometric measurements. The absorbance of the complex in the range of 320-400 nm, which is mainly based on bipp showed no obvious change upon addition of DNA, while the peak at 270 nm, which is determined by both phen and bipp decreased by up to 18%. The emission band of the complex around 360 nm decreased remarkably in presence of DNA. The emission quenching of this complex by [Fe(CN)(6)](4-) was depressed greatly when bound to DNA. The relative viscosity of DNA was increased by this complex more significantly than a bipp directed intercalating reagent. These results suggest that this complex binds to calf thymus DNA by intercalation of the two phenanthrolinecopper terminals. The apparent intrinsic binding constant of the complexes with DNA was 1.6 x 10(4)M(-1) as determined by UV-visible titration.

Objective: To investigate the relationship between polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T or A1298C and the response to fluoropyrimidine (5-FU)-based chemotherapy in advanced stomach cancer (SC)., Methods: 75 cases with advanced SC were analyzed. All patients were treated with 5-FU-based chemotherapy and DNA of peripheral blood leukocytes was obtained before therapy. MTHFR genotypes were detected by PCR-RFLP method., Results: (1) Of all the cases, the frequencies of MTHFR C677T C/C, C/T and T/T genotype were 32.0%, 44.0% and 24.0%, while the frequencies of MTHFR A1298C A/A, A/C and C/C genotype were 69.3%, 29.3% and 1.3%, respectively. The overal response rate to 5-FU-based chemotherapy was 29.3%. (2) The response rate to therapy among MTHFR C677T T/T genotype patients (83.3%) was significantly higher than the C677T C/T genotype (15.2%, chi(2) = 22.27, P = 0.000) or the C677T C/C genotype (8.3%, chi(2) = 23.44, P = 0.000). As compared with patients with C677T C allele, patients with C677T T/T genotype had a 7.64-fold sensitivity to 5-FU-based chemotherapy (adjusted for sex, age, prior adjuvant therapy and chemotherapy program, 95% CI: 3.14 - 18.62). The response rate to therapy among patients with MTHFR A1298C A/A genotype (36.5%) was significantly higher than patients with A1298C C allele (13.0%, chi(2) = 4.19, P = 0.041, adjusted OR = 3.75, 95% CI: 0.94 - 14.87). The response rate to therapy among patients with MTHFR C677T T/T and A1298C A/A genotypes (86.7%) was significantly higher than other groups of C677T and A1298C genotypes (15.0%, Fisher exact: P = 0.000, adjusted OR = 6.57, 95% CI: 2.8 - 15.6). (3) The incidence rates of nausea/vomiting in MTHFR C677T T/T, C/T or A1298C A/A genotypes were significantly higher than other genotypes, but the incidence rates of other treatment-related adverse reaction in MTHFR C677T or A1298C genotypes were not significantly different., Conclusion: These results in the present study suggested that the polymorphisms of MTHFR were associated with clinical response to 5-FU-based chemotherapy, suggesting that MTHFR genotypes could identify advanced SC patients that would be responsive to 5-FU-based chemotherapy.

A new member of the Mn-oxo cubane core complex family [Mn2III,2IV4O4L6] (1), where L = (p-MeOPh)2PO2-, has been synthesized and characterized. Compound 1 possesses structurally inequivalent MnIII and MnIV with clear valence electron localization in the crystal phase, quite unlike the structurally equivalent sites, tetrahedral core symmetry, and delocalized valence of its analogue where L = Ph2PO2-. Compound 1 exhibits appreciable positive shifts (0.1-0.3 V) of both the oxidation and reduction electrochemical potentials, attributable to the remote electron donating p-MeO groups. Reduction of 1 by methanol yields a novel core complex [MnIII4O2(OMe)2(MeOH)[(p-MeOPh)2PO2]6] (2). Each MnIII of 2 is tetragonally distorted due to the Jahn-Teller effect with elongated Mn-O bonds that are directed at the two micro3-MeO bridges and neither of the two micro3-oxos. These electronically driven distortions provide a structural rationale for the greater basicity of the former sites and explain why 2 of the 4 corner oxos are preferentially reduced to water molecules., (Copyright 2004 American Chemical Society)

Background & Objective: Methylenetrahydrofolate reductase (MTHFR) C677T polymorphism modifies enzyme activity and thus effects the level of 5, 10-methylenetetrahydrofolate (5,10-MTHR), which correlates with the tumor response to 5-fluorouracil (5-FU). This study was to evaluate the effect of MTHFR C677T polymorphism on chemosensitivity and toxicity to 5-FU in patients with gastric carcinoma., Methods: A total of 75 patients with histologically confirmed advanced gastric carcinoma were included. All patients received 5-fluoropyrimidine-based chemotherapy. Two milliliters of peripheral blood was extracted from each patient before treatment. PCR-RFLP was used to determine the genotypes of MTHFR, including wild-type homozygotes (C/C), heterozygotes (C/T), and mutant homozygotes (T/T)., Results: C/C genotype presented in 24 patients (24/75, 32.0%), C/T genotype presented in 33 patients (33/75, 44.0%), and T/T genotype presented in 18 patients (18/75, 24.0%). Total response rate of chemotherapy was 29.3%, among which 22 with partial response, 29 with no change, and 24 with progressive disease. Response rate in patients with T/T genotype (20/24, 83.3%) was significantly greater than either that in patients with C/C genotype (2/24, 8.3%) (Chi2=24.01, P< 0.001), or that in patients with C/T genotype (5/33, 15.2%) (Chi2=22.7, P< 0.001). There was no difference of response rate between C/C and C/T genotypes (Chi2=0.6, P=0.439). Multiple variances logistic regression analysis (adjusted for gender, age, chemotherapy regimens, and adjuvant chemotherapy factors) showed that the probability of chemotherapy work on patients with combination of C/C and C/T genotypes was 0.017-fold to that in patients with T/T genotype (95% CI ranging from 0.003 to 0.102, P< 0.001); incidence of treatment-related side effects, vomiting and nausea, was significantly greater in latter patients than in former patients (Chi2=12.264, P=0.002)., Conclusions: MTHFR C677T polymorphism can predict the effects and toxicity of 5-fluoropyrimidine-based chemotherapy in advanced gastric carcinoma.

The surface-enhanced Raman spectra of glycine, valine and lysine adsorbed on silver colloidal particles and the Raman spectrum of lysine in aqueous solution were obtained. The adsorption was accompanied by the appearance of the 238 cm(-1) band corresponding to the oscillation of the molecule-metal chemical bond and indicating chemisorption of the amino acid. In the surface-enhanced Raman spectra of three amino acids, the peak bands at 900-930 cm(-1), near 1100 cm(-1) and near 1400 cm(-1), corresponding to the carbon-carbon bond, carboxyl and amino group vibrations, respectively, were markedly increased on the silver colloidal particles. It means that the Raman spectra of polar groups such as COO-, N2 and C-COO- were strongly enhanced via the carboxyl group. There was no influence under the low pH condition in the experimental system used.

Objective: To investigate the relationship between polymorphisms of methylenetetra-hydrofolate reductase gene 1298A-->C (MTHFR 1298A-->C) and its susceptibility of esophageal cancer (EC)., Methods: We conducted a case-control study with 141 cases of EC and 228 population-based controls in Huaian city of Jiangsu province, China. Epidemiological data were collected, and DNA of peripheral blood leukocytes was obtained from all of the subjects. MTHFR genotypes were identified by polymerase chain reaction., Results: (1) The frequency of MTHFR 1298AA, AC and CC genotype were 63.8%, 34.0% and 2.1% in EC and 71.9%, 28.1% and 0.0% in controls, respectively (chi(2)(MH) = 6.69, P = 0.035). The frequency of the MTHFR 1298C allele was 0.19 for EC and 0.14 for controls. (2) Individuals having MTHFR 1298C allele and smoking habit were at a significantly higher risk of developing EC (adjusted OR = 3.48, 95% CI: 1.57 - 7.71) compared with those who having AA genotype but no smoking habit. Individuals having MTHFR 1298C allele and habit of frequent alcohol drinking were at an increased risk of developing EC (adjusted OR = 2.91, 95% CI: 1.20 - 7.08) compared with those with AA genotype and low consumption of alcohol. Individuals having MTHFR 1298C allele but no habit of tea drinking had a 3.52-fold (95% CI: 1.64 - 7.54) increased risk of developing EC compared with tea drinkers with AA genotype. As compared with subjects having AA genotype, low consumption of alcohol, no smoking habit but having habit of drinking tea, the individuals having 1298C allele, habits of frequent alcohol drinking, smoking but no habit of tea drinking had a 12.64-folds (95% CI: 1.39 - 114.65) increased risk of developing EC., Conclusion: Results in the present study suggested that there was a coordinated effect between MTHFR 1298 genotypes and habits of smoking, alcohol drinking and tea consumption in the development of EC.

Thymidylate synthetase (TS) and methylenetetrahydrofolate reductase (MTHFR) are major enzymes in the metabolism of folates, involved in DNA 'breaks', instability and hypomethylation. To investigate the possible relations between the TS 3'-UTR and MTHFR C677T polymorphisms and environmental factors impacting on risk of esophageal and stomach cancers, we conducted a case-control study in a high incidence region of China for these cancers. We recruited 138 esophageal and 155 stomach cancer cases, and 223 controls. The TS 3' -UTR and MTHFR C677T genotypes were detected by RFLP assay, using PCR products. The frequency of the -6 bp homozygous TS 3' -UTR genotype was 37.7 % in controls, higher than in Caucasians, although the present distribution was not in Hardy-Weinberg equilibrium. Ever-smoking with the -6 bp/-6 bp TS genotype elevated the ORs (2.61, 1.24-5.49; 3.54, 1.60-7.82) for cases of esophageal and stomach cancers, respectively, when compared with never-smoking with the +6 bp/+6 bp and +6 bp/-6 bp genotypes. No combination between the TS and MTHFR genotypes gave increased ORs. The present results suggest that TS polymorphism may modify the risk of esophageal and stomach cancer with smoking, pointing to the necessity for further investigations with information on folate and methionine intake with a larger population.

A novel binuclear complex [(bpy)2Ru(mu-bipp)Ru(bpy)2](ClO4)4, where bpy=2,2'-bipyridine and bipp=2,9-bis(2-imidazo[4,5-f][1,10]phenanthroline)-1,10-phenanthroline has been synthesized. Photophysical results reveal that this complex interacts with calf-thymus DNA with intrinsic binding constant 2.6 x 10(5) M(-1) in the buffer containing 5 mM Tris and 50 mM NaCl. The fact that the intraligand transition of bipp around 370 nm decreased by up to 50% in the presence of DNA, much more pronounced than the metal to ligand charge transfer band around 445 nm indicates the bridging ligand bipp is also the intercalating ligand into DNA base pairs. The emission band around at 601 nm increased by 1.4-fold, and red shifted 14 nm when DNA was added to saturation. The emission quenching of this complex by K4[Fe(CN)6] was depressed greatly when DNA was present. Viscometric measurements also proved the intercalative binding mode.

Objective: To evaluate interactions between lifestyle, methylanetetrahydrofolate reductase gene (MTHFR) and polymorphisms in the 3'-untranslated region (3'-UTR) of the thymidylate synthase gene (TS) with reference to development of stomach cancer (SC)., Methods: We conducted a case-control study with 107 cases of SC and 200 population-based controls in Huaian city of Jiangsu province, China. TS genotypes were identified by polymerase chain reaction., Results: (1) The frequencies of TS genotypes (+6 bp/+6 bp, +6 bp/-6 bp and -6 bp/-6 bp) among the cases were 5.6%, 47.7% and 46.7% and among the controls were 9.0%, 54.0% and 37.0%, respectively. Individuals identified as -6 bp/-6 bp genotype had a slightly higher risk for SC than those individuals with +6 bp alleles (the crude OR = 1.49, 95% CI: 0.90 - 2.47; adjusted OR = 1.36, 95% CI: 1.00 - 1.78, P = 0.047). (2) Individuals having TS -6 bp/-6 bp genotype and having smoking habit were at a significantly higher risk of developing SC (adjusted OR = 2.79, 95% CI: 1.51 - 5.18) compared with those who had +6 bp alleles with no smoking habit. Individuals having TS -6 bp/-6 bp genotype and habit of frequent alcohol drinking were at an increased risk of developing SC (adjusted OR = 1.76, 95% CI: 1.07 - 2.90) compared with those with +6 bp alleles and low consumption of alcohol. As compared with individuals with +6 bp alleles and who had habit of tea drinking, individuals who had TS -6 bp/-6 bp genotype and but without habit of tea drinking had an increased risk of developing SC (adjusted OR = 2.34, 95% CI: 1.43 - 3.82). (3) Individuals with TS -6 bp/-6 bp genotype and with MTHFR T alleles had an increased risk of developing SC (adjusted OR = 2.67, 95% CI: 1.07 - 6.70) compared with those with +6 bp alleles and with MTHRF C/C genotype., Conclusion: Results in the present study suggested that there was a combined effect between lifestyle, MTHFR C/T or T/T genotype and TS -6 bp/-6 bp genotype in the development of SC.