Association of matrix metalloproteinase-3 gene polymorphisms with subtypes of ischemic stroke / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To assess the association between matrix metalloproteinase-3 (MM-3) gene polymorphisms and subtypes of ischemic stroke (IS) in northern Han Chinese population.</p><p><b>METHODS</b>A total of 289 patients with acute IS (within 3 days after the onset, including 185 with large artery atherosclerosis (LAA) and 104 for small artery occlusion (SAO)) and 175 matched healthy controls were recruited for this case-control study. Polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) or sequenc-based typing (SBT) was carried out to analyze 3 SNPs of the MMP-3 gene.</p><p><b>RESULTS</b>An incomplete linkage disequilibrium (LD) block was constructed with the 3 SNPs, and the distribution of genotypes of the 3 SNPs differed between the LAA group and controls in a dominant model: Carriers of 5A allele (5A5A+5A6A) of the rs3025058 locus were 1.72 times more susceptible to LAA stroke compared with carriers of 6A6A alleles (P=0.017, OR=1.72, 95% CI: 1.10-2.69), carriers of G alleles (GG+AG) of the rs522616 locus were 0.52 times more susceptible to LAA stroke compared with carriers of AA alleles (P=0.005, OR=0.52, 95% CI: 0.33-0.82), whilst carriers of A allele of the rs679620 locus were 1.55 times more susceptible to LAA stroke compared with carriers of GG alleles (P=0.042, OR=1.55, 95% CI: 1.01-2.37). However, no significant difference has been found between particular genotypes of such SNPs between SAO patients and controls (P> 0.05). Furthermore, 5A-A-A and 6A-A-A haplotypes were significantly more common in LAA group than the controls (P< 0.05), whilst 6A-G-G haplotype has been the opposite (P< 0.01).</p><p><b>CONCLUSION</b>Our study has demonstrated that serum MMP-3 level is significantly increased at acute stage of LAA as well as SAO type strokes. There may be an association of rs3025058, rs522616 and rs679620 of MMP-3 gene with susceptibility to LAA stoke in northern Han Chinese population.</p>

CK19 can be used to predict the early recurrence and prognosis of HBV-related hepatocellular carcinoma patients with low AFP serum concentration after R0 radical hepatectomy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To investigate the expression of CK19 in HBV-related hepatocellular carcinoma (HCC) tissues in patients with low serum AFP concentration and the relationship between them and the recurrence and prognosis of HCC after R0 radical hepatectomy.</p><p><b>METHODS</b>The expressions of CK19 and Ki67 in HCC tissues of 235 cases were examined using tissue microarray and two-step methods of PV-6000 immunohistochemistry. The expression of CK19 mRNA in 20 frozen HCC specimens was examined by RT-PCR. The correlation between gene expressions and tumor recurrence and prognosis was analyzed.</p><p><b>RESULTS</b>Among the 235 HBV-related HCC patients after R0 radical hepatectomy, the median disease-free survival (DFS) was 31.2 months in the patients with serum AFP < 400 µg/L and 13.8 months in the patients with serum AFP ≥ 400 µg/L (P = 0.041), the overall survival (OS) was 84.0 and 58.6 months in the two subgroups (P = 0.125), and the tumor recurrence within one year was in 43 cases (27%) and 37 cases (49.3%), respectively, (P = 0.001). The DFS was 11.6 months in the CK19-positive cases and 27.0 months in the CK19-negative cases (P > 0.05). The OS was significantly lower in the CK19-positive cases than that in the CK19-negative cases (P = 0.023). Both DFS and OS in the CK19-positive cases with AFP < 400 µg/L were significantly lower than those in the CK19-negative cases with AFP < 400 µg/L (both P < 0.05). The CK19 expression was significantly correlated with histological differentiation (P = 0.023), number of tumor foci (P = 0.044), vascular tumor embolism (P = 0.005), regional lymph node metastasis (P = 0.023), and 1-year recurrence (P = 0.006). Among the patients with AFP < 400 µg/L, the 1-year recurrence was 53% in the CK19-positive cases and 23% in the CK19-negative cases (P < 0.001), the median DFS was 11.3 months in CK19-positive cases and 34.0 months in CK19-negative cases (P = 0.010), and the median OS was 19.5 months in the CK19-positive cases, significantly lower than 84.0 months in the CK19-negative cases (P = 0.001). Cox regression analysis showed that CK19-positive expression was an independent factor affecting early HCC recurrence and prognosis.</p><p><b>CONCLUSION</b>In HBV-related HCC patients after radical hepatectomy with AFP < 400 µg/L, positive expression of CK19 indicates a higher proliferation and invasiveness of HCC, and is an important factor of early recurrence and poor prognosis.</p>

Overexpression of catalytic subunit M2 in patients with ovarian cancer / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>The formation and growth of tumors are related to the synthesis of the DNA. The enzyme ribonucleotide reductase (RR) is an enzyme that regulates the total rate of DNA synthesis and thus plays a pivotal role in cell growth. Catalytic subunit M2 (RRM2) is the main unit modulating the ribonucleotide reductase enzymatic activity. This study aimed to investigate the expression of RRM2 mRNA and protein in patients with ovarian cancer and its relevance to diagnosis and clinical outcome of the patients.</p><p><b>METHODS</b>RRM2 mRNA levels and protein expression were detected in 98 ovarian specimens with immunohistochemistry and real-time quantitative polymerase chain reaction (PCR). Expression of the RRM2 protein and correlation of the RRM2 gene expression with clinical pathological features were analyzed. The Kaplan-Meier test was used for evaluating RRM2 expression and time to progression and survival. The Cox proportional model was used to analyze the risk factors in prognosis of patients.</p><p><b>RESULTS</b>Positive RRM2 immunostaining was found in 43 of 62 (69.4%) patients with epithelial ovarian cancer, 10 of 15 (66.7%) patients with borderline neoplasm, 4 of 15 (26.7%) patients with benign growths, and none of the normal group. The RRM2 mRNA levels were significantly over expressed in epithelial ovarian cancer (1.722 ± 0.639) and borderline ovarian neoplasms (1.365 ± 0.615), compared to the normal group (0.678 ± 0.446) and benign group (0.828 ± 0.545). Patients with ovarian caner in clinical FIGO-stages III-IV presented higher RRM2 gene expression than those in clinical FIGO-stages I-II. Furthermore, the survival of patients with low RRM2 mRNA level was significantly better than patients with high levels (P < 0.05). By Cox proportional risk model analysis, the risk of mortality of patients with high level expression of RRM2 mRNA was 2.553 times greater than those with low expression.</p><p><b>CONCLUSION</b>RRM2 expression closely correlates with the development of ovarian tumor and may serve as a novel predictive marker for diagnosis and prognosis of the disease.</p>

Effect of tagalsin on p53 and Bcl-2 expression in hepatoma H(22) tumor-bearing mice / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To explore the effect and mechanism of tagalsin on hepatoma cells.</p><p><b>METHODS</b>The animal models were established by transplanting H(22) mouse hepatoma cells to mouse liver, and ten days later the mice were randomly divided into five groups: blank group, carmofur positive group and tagalsin groups, including low-dose, middle-dose and high-dose groups. Then medicine or oil was given to the mice by gastric gavage in consecutive 5 days with a 2-days interval as a course of treatment, two courses in all. All mice were killed at 24 hours after medication, and the survival period, ascites conditions, aggressive conditions intra- or extra-liver, weight changes, tumor volume and spleen index of the tumor-bearing mice were observed. Pathological changes of the tumors were examined. Apoptotic factors p53 and Bcl-2 protien and mRNA were detected by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR).</p><p><b>RESULTS</b>tagalsin inhibited the hepatoma growth effectively without influencing spleen index to some extent. The tumor inhibition rate of tagalsin low, middle and high dose groups were 17.9%, 63.1% and 71.8%, respectively. Immunohistochemical results showed that the p53 and Bcl-2 protein positive cell counts of the positive control and experimental groups were significantly lower than those of the blank group (P < 0.01). RT-PCR results showed that the p53 mRNA expression was significantly enhanced and Bcl-2 mRNA expression was decreased in the positive control groups and tagalsin treatment groups, especially in the high dose group, compared with those of the blank group (P < 0.05).</p><p><b>CONCLUSIONS</b>tagalsin can inhibit the growth of mouse hepatoma cells significantly. The mechanism of its anti-tumor effect may work via up-regulating the wild type p53 gene expression and down-regulating Bcl-2 gene expression and thus regulating tumor cell apoptosis.</p>

Genetic Polymorphism of GSTP1: Prediction of Clinical Outcome to Oxaliplatin/5-FU-based Chemotherapy in Advanced Gastric Cancer

The aim of this study was to evaluate the predictive value of the polymorphism Glutathione S-transferase P1 (GSTP1) Ile(105)Val on oxaliplatin/5-FU-based chemotherapy in advanced gastric cancer. Patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. GSTP1 Ile(105)Val polymorphism was detected by TaqMan-MGB probe allelic discrimination method. Response to treatment was assessed by disease controlled rate. Time to progression, overall survival and toxicities were recorded. Final patient outcomes were as follows: the allele frequencies of GSTP1 were (105)Ile/(105)Ile 52%, (105)Ile/(105)Val 41% and (105)Val/(105)Val 7%. For patients with (105)Ile/(105)Ile and those with at least one (105)Val allele, disease control rate was 39% and 71% (P=0.026), respectively; median time to progression was 4.0 and 7.0 months (P=0.002); median overall survival time was 7.0 and 9.5 months (P=0.002). Neurological toxicity was more frequently occurred in patients with two (105)Ile alleles (P=0.005). In conclusion, patients with at least one (105)Val allele have better prognosis and response to oxaliplatin/5-FU-based regimen as first-line treatment for patients with advanced gastric cancer.

Association between genetic polymorphisms of ERCC1, XRCC1, GSTP1 and survival of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based chemotherapy / 中华肿瘤杂志

<p><b>OBJECTIVE</b>To evaluate the association between the polymorphisms of excision repair cross complementation group 1 (ERCC1), X-ray repair cross complementing 1 (XRCC1), glutathione S-transferase Pi 1 (GSTP1) and the survival of advanced gastric cancer patients treated with oxaliplatin-based combination chemotherapy.</p><p><b>METHODS</b>Eighty five patients with advanced gastric cancer accepted oxaliplatin/5-FU-based chemotherapy as first-line chemotherapy were investigated. Peripheral venous blood was taken before chemotherapy. DNA was extracted from peripheral venous blood. The genetic polymorphisms were detected by real-time PCR assay. The association between time to progression, overall survival and the polymorphisms was analyzed.</p><p><b>RESULTS</b>The median time to progression of the 85 cases was 5.3 months, and the median overall survival was 8.0 months. ERCC1-118 C/C, XRCC1-399 G/G and GSTP1-105 A/G + G/G were favorable genotypes and the number of the favorable genotypes was associated with survival of the patients. The median overall survival was 12.5 months, 10.0 months, 6.5 months and 4.5 months for patients with 3 favorable genotypes, 2 favorable genotypes, 1 favorable genotype and none favorable genotype, respectively, with a significant difference (χ(2) = 35.54, P < 0.01).</p><p><b>CONCLUSION</b>Genetic polymorphisms of ERCC1-118, XRCC1-399 and GSTP1-105 are associated with TTP and OS of advanced gastric cancer patients treated with oxaliplatin/5-Fu-based combination chemotherapy as the first-line chemotherapy.</p>

Proliferative inhibition and apoptotic induction effects of crocin on human leukemia HL-60 cells and their mechanisms / 中国实验血液学杂志

This study was to investigate the proliferative inhibition and apoptosis of human leukemia HL-60 cells induced by crocin and their possible mechanisms. The cell viability was tested by cell counting. The morphology of HL-60 cells was observed by fluorescence microscopy. The MTT assay was used to evaluate the inhibitory effect of crocin on the growth of HL-60 cells. Flow cytometry was used to measure the cell cycle. RT-PCR was used to detect bcl-2 and bax expression. The results indicated that the growth of HL-60 cells was inhibited remarkably in the dose and time dependent way. When the crocin concentration was higher than 5 mg/ml, the percentage of apoptotic HL-60 cells was not increased, on the contrary this percentage decreased, the cells manifested necrosis. Flow cytometry profiles revealed that cells were blocked in G₀/G₁ phase, the cell proliferation was inhibited obviously at 5 mg/ml. RT-PCR detection revealed that the expression of bcl-2 was down-regulated strikingly and bax was up-regulated. It is concluded that the crocin can inhibit the proliferation of HL-60 cells effectively, and block cells in G₀/G₁ phase. The mechanisms by which crocin induced apoptosis in HL-60 cells may be related to the inhibition of bcl-2 and activation of bax.