Enhanced anticancer activity and endocytic mechanisms by polymeric nanocarriers of n-butylidenephthalide in leukemia cells.

PURPOSE: The purpose of this study was to investigate the antitumor mechanisms of n-butylidenephthalide (BP) and to further examine the delivery efficacy of polycationic liposome containing PEI and polyethylene glycol complex (LPPC)-encapsulated BP in leukemia cells. METHODS: MTS, flow cytometric and TUNEL assays were performed to assess cell viability and apoptosis. BP and BP/LPPC complex delivery efficiency was analyzed by full-wavelength fluorescent scanner and fluorescence microscope. The expressions of cell cycle- and apoptosis-related proteins were conducted by Western blotting. RESULTS: The results showed that BP inhibited leukemia cell growth by inducing cell cycle arrest and cell apoptosis. LPPC-encapsulated BP rapidly induced endocytic pathway activation, resulting in the internalization of BP into leukemia cells, causing cell apoptosis within 1 h. CONCLUSIONS: LPPC encapsulation enhanced the cytotoxic activity of BP and did not influence the effects of BP induction that suggested LPPC-encapsulated BP might be developed as anti-leukemia drugs in future.

TIPE1 suppresses osteosarcoma tumor growth by regulating macrophage infiltration.

BACKGROUND: Osteosarcoma is the most common primary malignancy of the bone, and macrophages play a promotional role during osteosarcoma development and progression. TIPE1 is known to function as a tumor suppressor in diverse cancers by inducing cell arrest and apoptosis. However, the biological function of TIPE1 in osteosarcoma is still unclear. PURPOSE: The purpose of this study was to investigate the expression and function of TIPE1 in osteosarcoma. METHODS: In the present study, TIPE1 expression in osteosarcoma cancer cells was determined by qPCR and western blotting. A subcutaneous tumor model was established to investigate the potential anti-tumor activity of TIPE1 in osteosarcoma. Further, flow cytometry, western blotting, immunofluorescence staining, and ELISA were performed to clarify the underlying mechanism by which TIPE1 regulates growth of osteosarcoma. RESULTS: Our results suggest that TIPE1 is downregulated in osteosarcoma cancer cells, and ectopic expression TIPE1 significantly inhibited osteosarcoma tumor growth in vivo. Furthermore, TIPE1 inhibits the infiltration of macrophages in osteosarcoma tumor by suppressing MCP-1 expression in osteosarcoma cells. Further in vivo study revealed that inhibition of MCP-1/CCR2 axis by Bindarit blocked the inhibitory effect of TIPE1 on osteosarcoma growth. CONCLUSION: Collectively, our results demonstrate the anti-tumor role of TIPE1 in osteosarcoma and reveal a novel therapy target for osteosarcoma.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice.

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Attenuation of atherogenic apo B-48-dependent hyperlipidemia and high density lipoprotein remodeling induced by vitamin C and E combination and their beneficial effect on lethal ischemic heart disease in mice

BACKGROUND AND AIMS: Atherosclerotic cardiovascular disease is highly prevalent and its underlying pathogenesis involves dyslipidemia including pro-atherogenic high density lipoprotein (HDL) remodeling. Vitamins C and E have been proposed as atheroprotective agents for cardiovascular disease management. However, their effects and benefits on high density lipoprotein function and remodeling are unknown. In this study, we evaluated the role of vitamin C and E on non HDL lipoproteins as well as HDL function and remodeling, along with their effects on inflammation/ oxidation biomarkers and atherosclerosis in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. METHODS AND RESULTS: Mice were pre-treated for 5 weeks before and during atherogenic diet feeding with vitamin C and E added to water and diet, respectively. Compared to a control group, combined vitamin C and E administration reduced serum total cholesterol and triglyceride levels by decreasing apo B-48-containing lipoproteins, remodeled HDL particles by reducing phospholipid as well as increasing PON1 and apo D content, and diminished PLTP activity and levels. Vitamin supplementation improved HDL antioxidant function and lowered serum TNF-α levels. Vitamin C and E combination attenuated atherogenesis and increased lifespan in atherogenic diet-fed SR-B1 KO/ApoER61h/h mice. CONCLUSIONS: Vitamin C and E administration showed significant lipid metabolism regulating effects, including HDL remodeling and decreased levels of apoB-containing lipoproteins, in mice. In addition, this vitamin supplementation generated a cardioprotective effect in a murine model of severe and lethal atherosclerotic ischemic heart disease.

Diagnostic value of the dual-luciferase report assay for predicting response to glucocorticoid in children with acute lymphoblastic leukemia.

OBJECTIVE: Resistance to glucocorticoid (GC) is a significant clinical problem in some cases of acute lymphoblastic leukemia (ALL). Current methods of assessing GC resistance are time consuming and have limited reproducibility; in this study, we sought to define a new method of evaluating GC sensitivity and resistance in vitro. METHODS: Based on the mechanisms of GC resistance, we hypothesized that the dual-luciferase report (DLR) assay could reflect the transcription effects of GC downstream of the GC-glucocorticoid receptor signaling pathway, thereby allowing the evaluation of reactions to GC. Sixty-two patients with differential GC response were included in this study. The prednisone induction test was used to divide the children with ALL into two groups: GC sensitive (GCS) and GC resistant (GCR). DLR assay was later conducted on those patients to evaluate its value for diagnosis of the GC reactivity. Receiver operating characteristic curves were used to identify the optimal assay cutoff for identifying response to GC. RESULTS: Using the DLR assay analysis, we found that GCR subjects showed significantly lower reporter/control ratios for luciferase, as compared with GCS subjects. The optimal cutoff value for GC response was 0.67, with sensitivity of 77.1% and specificity of 93.3%. The DLR assay results were consistent with prednisone induction test results. Further, the DLR assay was simpler, more sensitive, and less time-consuming than the prednisone induction test. CONCLUSIONS: Our study showed that the DLR assay is relatively fast, simple, and sensitive. Accordingly, it could be useful for detecting GC response in children with ALL.

A large-scale analysis study on the clinical and viral characteristics of hepatitis B infection with concurrence of hepatitis B surface or E antigens and their corresponding antibodies.

Concurrent detection of hepatitis B surface antigen (HBsAg) and anti-HBs antibody or hepatitis B surface E antigen (HBeAg) and anti-HBe antibody in patients with chronic hepatitis B (CHB) infection is well established. However, the clinical implications of these proteins remain largely unknown. In this study, demographic, clinical, and laboratory data from 124,865 patients with chronic CHB infection were analyzed. Viral genotypes were determined by nested polymerase chain reaction. A chemiluminescent assay was applied to measure HBsAg, HBsAb, HBeAg, HBeAb, and HBcAb in sera. Among 124,865 patients with CHB infection, 324 (0.3%) were concurrently positive for HBsAg and anti-HBs, and 206 (0.2%) were concurrently positive for HBeAg and anti-HBe. The HBeAg+/anti-HBe+ group was composed of younger patients (P < 0.05). Subgenotype B2 was prevalent in HBV patients concurrently positive for HBeAg and anti-HBe, while HBV patients positive for both HBsAg and anti-HBs exhibited the C2 subgenotype. Among 530 concurrent patients, 126 (39%) HBsAg+/anti-HBs+ patients were in the low-replication phase, and 62 (19%) were in the reactivation phase; 87 (42%) HBeAg+/anti-HBe+, and 19 (6%) HBsAg+/anti-HBs+ patients were in the immune clearance phase. In this large-scale analysis, the clinical and viral characteristics of HBV infections with concurrent HBs Ag/antibody or HBe Ag/antibody presentations have been examined, and the results may contribute to the diagnosis and treatment of CHB patients.

Expression of M3 acetylcholine receptor in asthmatic mice and bronchial airway remodeling prediction.

This study aimed to investigate the role of M3 acetylcholine receptor (M3-AChR) expression in airway remodeling. Additionally, we aimed to evaluate the effects of ipratropium bromide solution inhaled in an early phase of asthma on airway remodeling in ovalbumin (OVA)-sensitized and challenged mice. Thirty BALB/c mice were divided into three groups, namely, control group (saline sensitized/challenged mice), asthma group (OVA sensitized/challenged mice), and treatment group (OVA sensitized/challenged mice treated by ipratropium bromide). Pathological changes were detected by histological staining in the bronchopulmonary tissue of mice. WAt/Pbm (the airway wall area /basement membrane perimeter) ratio of the asthma group (25.37 ± 4.25) increased significantly (P < 0.05) when compared with that of the control (12.89 ± 1.71) and treatment group (15.82 ± 2.91). WAm/Pbm (smooth muscle wall area / basement membrane perimeter) ratio of the asthma group (7.58 ± 2.16) increased significantly (P < 0.05) when compared with that of the control (2.55 ± 0.72) and treatment group (3.36 ± 1.69). M3-AChR concentration increased in the treatment group (29.24 ± 3.59) and was significantly different (P < 0.05) from that of the control group (25.50 ± 1.83). During asthma treatment, SAMA can alleviate airway remodeling in murine model by lessening the thickness of bronchial walls and inhibiting the proliferation of smooth muscle cells. There were no obvious changes in M3-AChR density in the murine model of asthma characterized by airway remodeling. However, ipratropium bromide may up-regulate the expression of M3-AChR in bronchial walls of asthmatic murine model.

Prognostic significance of microRNA-10b overexpression in breast cancer: a meta-analysis.

Many microRNAs (miRNAs) exhibit altered expression levels in cancers, and they may be considered as valuable prognostic biomarkers for cancers. Here we aimed to summarize the recent advances in miR-10b involvement in human breast cancer and analyze the predicting role of miR-10b for survival. We searched, Embase, and Wanfang databases to identify studies on the prognostic role of miR-10b expression in breast cancer. A total of 770 patients from 7 eligible studies were included in the analysis. Pooled risk ratios (RRs) with 95% confidence interval (95%CI) were calculated to estimate the effect. Our results showed that high miR-10b expression in patients with breast cancer was significantly associated with poor disease-free survival (DFS) (RR = 1.53; 95%CI = 1.06-2.21; P = 0.02). However, no significant association between miR-10b and overall survival was found in overall studies. Subgroup analysis indicated that high expression of miR-10b was significantly correlated with DFS in Asia (RR = 2.94; 95%CI = 1.71-5.05). The present meta-analysis demonstrated that high expression of miR-10b might predict poor survival in patients with breast cancer. Larger clinical studies are required to further evaluate the role of miR-10b in clinical practice.

Identification of disturbed pathways in heart failure based on Gibbs sampling and pathway enrichment analysis.

We identified disturbed pathways in heart failure (HF) based on Gibbs sampling combined with pathway enrichment analysis. A total of 396 Markov chains (MCs) (gene count >5) were obtained. After Gibbs sampling, six differentially expressed molecular functions (DEMFs) (possibility ≥0.8) were obtained. As statistical analysis was performed on the number of individual differentially expressed genes (DEGs), we found that there were 137 DEGs with frequency of occurrence ≥2 in the DEMFs. Pathway enrichment analysis showed that these 137 DEGs were enriched in eight significant pathways under the condition of P < 0.001. The five most significant pathways were: the calcium signaling pathway (P = 9.08E-19), arrhythmogenic right ventricular cardiomyopathy (P = 5.66E-13), cardiac muscle contraction (P = 8.04E-13), hypertrophic cardiomyopathy (P = 2.55E-12), and dilated cardiomyopathy (P = 7.30E-12). In conclusion, this novel method for identifying significant pathways in HF based on Gibbs sampling combined with pathway enrichment analysis was suitable. We predict that several altered pathways (such as the calcium signaling pathway and dilated cardiomyopathy) may play important roles in HF and are potentially novel predictive and prognostic markers for HF.

Overexpression of forkhead box protein M1 (FOXM1) plays a critical role in colorectal cancer.

BACKGROUND: The forkhead box M1 (FOXM1), an important regulator of cell differentiation and proliferation, is overexpressed in a number of aggressive human carcinomas. However, the clinical significance of FOXM1 signaling in human colorectal cancer (CRC) pathogenesis remains unknown. The aim of this study was to evaluate the role of FOXM1 in CRC tumorigenesis. METHODS: We investigated FOXM1 expression in 103 cases of primary CRC and matched normal tissue specimens and explored the underlying mechanisms of altered FOXM1 expression and the impact of this altered expression on CRC proliferation and metastasis using in vitro models of CRC. RESULTS: The results showed that high expression of FOXM1 staining was 85.44% (88/103) in 103 cases of CRC and 20.39% (21/103) in 103 cases of adjacent non-cancerous tissue samples; the difference of FOXM1 expression between two groups was statistically significant (P < 0.001). Silencing of FOXM1 inhibited the proliferation of CRC cells, and the invasion and migration of CRC cells were distinctly suppressed. Furthermore, FOXM1 knockdown led to substantial reductions in VEGF-A levels in CRC cell lines. CONCLUSIONS: Our data suggest that the pathogenesis of CRC maybe mediated by FOXM1, and FOXM1 could represent selective targets for the molecularly targeted treatments of CRC.

Clinical significance of plasma fibrinogen and D-dimer in predicting the chemotherapy efficacy and prognosis for small cell lung cancer patients.

PURPOSE: Elevated plasma fibrinogen and D-dimer levels indicate activation of hemostasis and fibrinolysis, and this activation is required for tumor angiogenesis, metastasis, and invasion. Previous studies demonstrated that the plasma fibrinogen and D-dimer levels correlate with patient's prognosis in several solid tumors. The aim of this study is to examine the relationship between plasma fibrinogen and D-dimer levels before and during chemotherapy and treatment response and survival in patients with small cell lung cancer (SCLC). METHODS: Plasma fibrinogen and D-dimer levels before and during chemotherapy were prospectively measured in 74 SCLC patients who received first-line therapy. The results were analyzed for correlation between fibrinogen and D-dimer levels and treatment response, as well as progressive-free survival (PFS) and overall survival (OS). RESULTS: The levels of fibrinogen and D-dimer in SCLC patients before (C0) and after two cycles (C2) of chemotherapy were significantly higher than those in controls. Fibrinogen and D-dimer levels decreased during chemotherapy, and changes in fibrinogen and D-dimer levels between at C0 and at C2 were associated with treatment response. No matter which disease stage, patients with fibrinogen or D-dimer positivities at C0 and C2 time points had worse PFS and OS than those with fibrinogen or D-dimer negativities. Multivariate analyses revealed that fibrinogen and D-dimer positivities after two chemotherapy cycles were independently unfavorable factors for PFS and OS. CONCLUSION: Fibrinogen and D-dimer levels after two cycles of chemotherapy are predictors for response on chemotherapy and prognosis in SCLC patients.

Effect of sphingosine-1-phosphate and myoblast transplantation on rat acute myocardial infarction.

In this study, we investigated the effects of sphingosine-1-phosphate (S1P) combined with myoblast transplantation on the treatment of acute myocardial infarction and provided a foundation for its clinical application. A rat model of acute myocardial infarction was established by ligating the anterior descending branch of the coronary artery. Serum-free media, myoblasts, myoblasts with S1P liposomes, or myoblasts with liposomes were then injected into the infarcted area. Apoptosis of the transplanted cells was assessed after 24 and 48 h, and changes in heart function and myocardial infarction area were assessed after 4 weeks. After transplantation of S1P into myoblasts, myocardial function was improved compared to that in the other groups. Specifically, the apoptosis of transplanted cells and the area of myocardial infarction decreased significantly (P < 0.01), while cardiac function significantly improved (P < 0.01). The efficacy of S1P and myoblast transplantation on acute myocardial infarction was significantly better than that in the control group (i.e., injection of myoblasts and liposomes) and the serum-free medium group, demonstrating the feasibility of joint S1P and myoblast transplantation for treating myocardial infarction.

Effect of Rhizoma paridis total saponins on apoptosis of colorectal cancer cells and imbalance of the JAK/STAT3 molecular pathway induced by IL-6 suppression.

We observed the influence of different concentrations of Rhizoma paridis total saponins (RPTS) on the apoptosis of colorectal cancer cells and explored the internal mechanism involved. We determined whether RPTS influences the interleukin-6 (IL-6)/Janus kinase (JAK)-signal transducer and activator of transcription-3 (STAT3) apoptosis molecular pathway and looked for colon cancer-related signal transduction pathways or targets inducing apoptosis. We also cultured SW480 colorectal cancer cells using different concentrations of RPTS (10, 20, 40, and 80 µg/ mL), and observed the effect of RPTS on SW480 cell morphology under a fluorescence inverted microscope. We detected serum IL-6 using the polymerase chain reaction and the expression of JAK-STAT3 protein by western blot. After treating SW480 with RPTS and Hoechst 33258 dyeing, we found that the typical apoptosis morphology had changed. Secretion of IL-6 in the serum decreased significantly (P < 0.05), and STAT3 levels were reduced. RPTS can significantly promote apoptosis in SW480 colorectal cancer cells. The mechanism may be that it suppresses the secretion of IL-6 and inhibits the IL-6/JAK-STAT3 protein signaling pathway.

Aberrant expression of UCA1 in gastric cancer and its clinical significance.

Long noncoding RNAs (lncRNAs) have been shown to regulate tumor biology and might be used for cancer diagnosis, prognosis and potential therapeutic targets. Although up-regulation of lncRNA UCA1 (urothelial carcinoma-associated 1) in several cancers has been found, its role in gastric cancer remains elusive. The aim of this study was to detect the expression of lncRNA UCA1 in gastric cancer and its clinical association. The expression of UCA1 was detected in 112 pairs of tumorous and adjacent normal tissues from patients with gastric cancer, as well as in four gastric cancer cell lines and a human normal gastric epithelium cell line using RT-qPCR. Results showed that UCA1 expression was remarkably increased in gastric cancer tissues and cell lines compared with that in the normal control. Clinicopathologic analysis revealed that high UCA1 expression correlated with worse differentiation, tumor size, invasion depth and TNM stage in gastric cancer. Kaplan-Meier analysis showed that increased UCA1 expression contributed to poor overall survival (p = 0.017) and disease-free survival (p = 0.024) of patients. A multivariate survival analysis also indicated that UCA1 could be an independent prognostic marker. The levels of UCA1 in gastric juice from gastric patients were significantly higher than those from normal subjects (p = 0.016). Moreover, validation analysis showed that UCA1 levels were robust in differentiating gastric cancer patients from control subjects [area under the curve (AUC) = 0.721; 95 % confidence interval (CI) = 0.655-0.788, p < 0.01]. These results suggested that UCA1 might serve as a promising biomarker for early detection and prognosis prediction of gastric cancer.

Prognostic and predictive value of plasma D-dimer in advanced non-small cell lung cancer patients undergoing first-line chemotherapy.

PURPOSE: Previous studies have demonstrated that plasma D-dimer, a degradation product of cross-linked fibrin, correlated with tumor stage and prognosis in cancer patients. The aim of this study is to examine whether plasma D-dimer levels before and during chemotherapy predict tumor response and survival in advanced NSCLC patients undergoing first line chemotherapy. METHODS: Plasma D-dimer levels before (B0), and after one (B1) and two (B2) cycles of chemotherapy in 82 patients with advanced NSCLC were measured and correlated with treatment response, clinical features, progression-free survival (PFS) and overall survival. RESULTS: A significant correlation was identified between changes in D-dimer levels before and after two chemotherapy cycles and treatment response. In addition, there were significant correlations between D-dimer positivity at B0, B1 and B2 time points and tumor stage, number of metastatic sites and treatment response. Patients with positivity of D-dimer at B0, B1 and B2 had significantly shorter PFS compared with those with negativity. Notably, positivity of D-dimer at B1 and B2 time points was an independent predictive factor for unfavorable PFS. CONCLUSIONS: The positivity of D-dimer before and during chemotherapy is a predictor of treatment response and worse PFS in patients with advanced NSCLC. D-dimer levels provide prognostic information in addition to that of imaging studies.

Segregation analysis of microsatellite (SSR) markers in sugarcane polyploids.

No information is available on segregation analysis of DNA markers involving both pollen and self-progeny. Therefore, we used capillary electrophoresis- and fluorescence-based DNA fingerprinting together with single pollen collection and polymerase chain reaction (PCR) to investigate simple sequence repeat (SSR) marker segregation among 964 single pollens and 288 self-progenies (S1) of sugarcane cultivar LCP 85-384. Twenty SSR DNA fragments (alleles) were amplified by five polymorphic SSR markers. Only one non-parental SSR allele was observed in 2392 PCRs. SSR allele inheritance was in accordance with Mendelian laws of segregation and independent assortment. Highly significant correlation coefficients were found between frequencies of observed and expected genotypes in pollen and S1 populations. Within the S1 population, the most frequent genotype of each SSR marker was the parental genotype of the same marker. The number of genotypes was higher in pollen than S1 population. PIC values of the five SSR markers were greater in pollen than S1 populations. Eleven of 20 SSR alleles (55%) were segregated in accordance with Mendelian segregation ratios expected from pollen and S1 populations of a 2n = 10x polyploid. Six of 20 SSR alleles were segregated in a 3:1 (presence:absence) ratio and were simplex markers. Four and one alleles were segregated in 77:4 and 143:1 ratios and considered duplex and triplex markers, respectively. Segregation ratios of remaining alleles were unexplainable. The results provide information about selection of crossing parents, estimation of seedling population optimal size, and promotion of efficient selection, which may be valuable for sugarcane breeders.

Association between MTHFR gene polymorphisms (C677T, A1298C) and genetic susceptibility to prostate cancer: a meta-analysis.

Genetic polymorphisms (C677T and A1298C) in methylenetetrahydrofolate reductase (MTHFR) were shown to be related to prostate cancer risk in previous studies; however, the results are controversial. We performed a meta-analysis of previous studies and quantitatively estimated these associations. Pubmed, Embase, and Cochrane Library Database were searched for published case-control studies evaluating the association between C677T (or A1298C) and prostate cancer risk. Pooled associations were presented as odds ratios (ORs) along with their 95% confidence intervals. Twenty-one case control studies were identified for meta-analysis that included 21,581 participants. No significant associations were found between the MTHFR polymorphisms C677T or A1298C and prostate cancer risk in our meta-analysis. However, in subgroup analyses, the C677T CT polymorphism was associated with increased prostate cancer risk in East Asians (CT vs CC+TT: OR = 1.324, P = 0.03). The A1298C CC polymorphism in MTHFR was also linked to slightly reduced prostate cancer risk in European residents (CC vs AC+AA: OR = 0.751, P = 0.004; CC vs AA: OR = 0.768, P = 0.011), whereas it was associated with a significantly increased prostate cancer risk in Asian residents (CC vs AA: OR = 1.862, P = 0.006). The C677T CT polymorphism of MTHFR may be a risk factor for prostate cancer in East Asians. The association between the MTHFR A1298C CC genotype and prostate cancer risk may vary within different populations. Large-scale well-designed studies are required to confirm these associations.

Association of the IFNAR1-17470 and IL-10-592 cytokine variants with susceptibility to chronic hepatitis B viral infections in a Chinese population.

An association between the sequence variants of cytokine genes and various clinical outcomes in subjects infected with the hepatitis B virus (HBV) has been demonstrated. However, the results are inconsistent and inconclusive. Further studies in other populations and the evaluation of a greater number of individuals may contribute to a better understanding of the influence of the cytokine genetic variants on the evolution of HBV infections. This study was performed to explore the relationships between the sequence variants of TNF-A-308, IFNAR1-17470, and IL-10-592 and the susceptibility to chronic hepatitis B (CHB) in a Chinese population. A total of 160 patients with CHB and 124 individuals who had spontaneously recovered (SR) from hepatitis B were enrolled in the present study. The variants at TNF-A-308, IFNAR1-17470, and IL-10-592 were determined by PCR-restriction fragment length polymorphism analysis and were confirmed by bidirectional DNA sequencing. Significant differences were found between the CHB and the SR groups in the frequency and distribution of the genotypes of both IFNAR1-17470 and IL-10-592 genes. In comparison with the CHB patients with the IFNAR1-17470 G/G variant, the odds ratio (OR) of the CHB patients with the IFNAR1-17470 C/C variant developing chronic hepatitis was 2.06 (95%CI = 1.03-4.14). In addition, the OR of the patients with CHB having the IL-10-592 C/C variant developing chronic hepatitis was 2.77 (95%CI = 1.13-4.57) when compared with that of the patients with the IL-10-592 A/A variant. In conclusion, sequence variants of both the IFNAR1-17470 and IL-10-592 genes were correlated with susceptibility to CHB.

Influence of the human MIF promoter polymorphism on hepatocellular carcinoma prognosis.

Hepatocellular carcinoma (HCC) is one of the most common worldwide malignancies. A relative complete diagnosis system for primary carcinoma of liver has already been established, but the surgical prognosis for HCC, which depends mainly on postoperative pathological classification and data of recurrence and metastasis, lacks valid experimental indicators. Macrophage migration inhibition factor (MIF) is related to many cancers; hence, the polymorphism of MIF genes may be associated with the surgical prognosis of HCC. The purpose of this study was to investigate the relationship between polymorphisms of MIF gene promoter 794CATT (MIF-794CATT) microsatellite repeats and HCC surgical prognosis and evaluate the contribution of polymorphism to the prognosis of hepatectomy. Sequencing was used to identify the MIF-794CATT of 241 patients who had been submitted to HCC surgery. These patients were classified into 2 groups: one with MIF-794CATT high-repetitive-sequence genotypes (7/x+8/x) and one with low-repetitive-sequence genotypes (5/5+5/6+6/6). Five indictors were analyzed: average survival times were compared using the t-test, and tumor-node-metastasis staging, recurrence and metastasis, differentiation grade, and survival rate were compared using the chi-square test. The (7/x+8/x) CATT group had 139 patients and the (5/5+5/6+6/6) CATT group had 102. Significant differences were found in the 5 factors (P = 0.000, 0.008, 0.002, 0.000, and 0.003, respectively). Patients with MIF-794CATT5-8 low-repetitive-sequence genotypes had better prognosis than those with high-repetitive-sequence genotypes. The polymorphism detection of MIF-794CATT microsatellite repeats is valuable for HCC surgical prognosis.

Gamma Knife radiosurgery as a primary treatment option for solitary brain metastases from ovarian carcinoma.

We present three patients with brain metastasis cases from ovarian carcinoma (BMOC) treated at William Beaumont Hospital with a median follwow-up of 77 months and a mean survival after brain involvement of 23.66 months (range 5-44). Clinical and physical aspects are presented. Between December 2006 and August 2008, three cases of BMOC were treated using Gamma Knife (GK) radiosurgery. All patients had FIGO Stage III primary disease at initial diagnosis. Treatment sequences and features are described. GK achieves excellent local control of BMOC. Other parameters could be considered as biologically effective.