Genetic polymorphisms in CDH1 are associated with endometrial carcinoma susceptibility among Chinese Han women.

The cadherin 1 (CDH1) gene plays critical roles in the epithelial-mesenchymal transition process, potentially offering us a glimpse into the development of endometrial carcinoma (EC). The present study aimed to identify whether genetic variants in CDH1 affect EC susceptibility in Chinese Han women, using a strategy combining haplotype-tagging single nucleotide polymorphisms (htSNPs) association analysis with fine-scale mapping. A total of 9 htSNPs in CDH1 were genotyped among 516 cases and 706 age-matched cancer-free controls. Logistic regression analyses revealed 3 htSNPs (rs17715799, rs6499199 and rs13689) to be associated with increased EC risk and 3 htSNPs (rs12185157, rs10431923 and rs4783689) with decreased EC risk. Furthermore, 14 newly imputed SNPs of CDH1 were identified to be associated with EC risk (P<0.05) using genotype imputation analysis. Notably, multivariate logistic analysis demonstrated that rs13689, rs10431923 and rs10431924 could affect EC susceptibility independently (P≤0.001). Subsequent Generalized Multifactor Dimensionality Reduction analysis revealed several best fitting models for predicting EC risk, including SNP-SNP interactions among rs7100190, rs12185157, rs10431923, rs7186053, rs6499199, rs4783689, rs13689, rs6499197 and rs10431924, and SNP-environment interactions between related SNPs and number of childbirth. Moreover, functional annotations suggest that the majority of these susceptible variants may carry potential biological functions that affect certain gene regulatory elements. In summary, this study suggested that the genetic polymorphisms of CDH1 were indeed associated with EC susceptibility on several levels. If further additional functional studies could verify these findings, these genetic variants may serve as future personalized markers for the early prediction of endometrial cancer in Chinese Han women.

Associations of gene­wide SNPs in SNAI1 and TWIST1 with breast cancer and ovarian cancer susceptibility among Chinese Han women.

Extensive evidence suggests that the genetic etiologies of breast cancer (BC) and ovarian cancer (OC) show a certain degree of similarity. This study aimed to find out whether the single nucleotide polymorphisms (SNPs) of genes SNAI1 and TWIST1 may affect BC and OC susceptibility. A total of 7 tagging­SNPs (tSNPs) were directly genotyped in 1,161 BC cases, 286 OC cases and 1,273 cancer­free controls among Chinese Han women. Twenty­eight variants in these 2 genes were genotyped by 'in silico' genotype imputation. Logistic regression (LR) revealed that tSNPs SNAI1 rs6125849, TWIST1 rs4721746 and TWIST1 rs4721745 were protective genetic variants for BC/OC. Allelic association tests of gene­wide SNPs demonstrated that the minor alleles of SNAI1 rs6125849, TWIST1 rs4721745 and TWIST1 rs11973396 were strongly associated with BC/OC susceptibility. Multivariate LR presented that SNAI1 rs6125849, TWIST1 rs4721745, rs4721746 and rs11973396 affected BC/OC susceptibility independently, and women harboring all four protective genoytpes had the lowest risk. Multifactor dimensionality reduction analysis further showed that SNAI1 rs6125849 and TWIST1 rs4721745 had the strongest synergistic interaction. Functional annotation predicted that the minor alleles of SNAI1 rs6125849 and TWIST1 rs4721745 altered their binding affinities with transcription factors E2F6 and TCF11­MafG respectively. These results indicate that genetic variants in SNAI1 and TWIST1, most probably SNAI1 rs6125849 and TWIST1 rs4721745, may modulate BC and OC susceptibility.

[Expression of Wnt5b in patients with HBV-related hepatocellular carcinoma and its clinical significance].

OBJECTIVE: To investigate the expression of Wnt5b in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) tissues and its correlation with the clinicopathological parameters. METHODS: Quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemical staining were employed to measure Wnt5b mRNA and protein expressions in two groups of HBV-related HCC patients (100 cases in each) selected from a cohort of 289 cases with HBV-related HCC using simple random sampling method. The correlation of Wnt5b expression with the clinicopathological parameters and the prognosis of HCC patients was analyzed. RESULTS: Wnt5b mRNA expression was significantly higher in HCC tissues than that of adjacent noncancerous tissues in 65.0% (65/100) of the cases, and the positivity rate of Wnt5b protein was significantly higher in HCC tissues than that of adjacent noncancerous tissues (58.0% vs 22.0%, P<0.05). Wnt5b expression was significantly correlated with the tumor size (P<0.05), tumor number (P<0.01, only at the protein level), tumor differentiation (P<0.01, only at the protein level), TNM stage (P<0.05), BCLC stage (P<0.05), metastasis (P<0.05) and recurrence (P<0.01). The patients with up-regulated Wnt5b mRNA and protein had a shorter relapse-free survival (P<0.01). CONCLUSION: s Up-regulated Wnt5b might contribute to the progression of HBV-related HCC and predicts a poor prognosis.

Loss of tumor suppressor miR-126 contributes to the development of hepatitis B virus-related hepatocellular carcinoma metastasis through the upregulation of ADAM9.

Hepatocellular carcinoma is the most common histological type of primary liver cancer, which represents the second leading cause of cancer-related mortality. MiR-126 was reported to be downregulated in hepatocellular carcinoma tissues, compared with its levels in noncancerous tissues. However, baseline miR-126 expression levels in hepatitis B virus-related hepatocellular carcinoma patients who did not undergo pre-operational treatment remains unknown since hepatitis B virus infection and pre-operational transcatheter arterial chemoembolization were shown to upregulate miR-126 expression. Here, we demonstrated that miR-126 is generally downregulated in a homogeneous population of pre-operational treatment-naïve hepatitis B virus-related hepatocellular carcinoma patients (84.0%, 84/100), and its expression is significantly associated with pre-operational alpha-fetoprotein levels ( p < 0.05), microvascular invasion ( p < 0.05), tumor metastasis ( p < 0.05), as well as early recurrence (12 months after surgery; p < 0.01). Furthermore, the results of our study revealed that miR-126 is negatively correlated with ADAM9 expression in hepatitis B virus-related hepatocellular carcinoma patients. Overexpression of miR-126 was shown to attenuate ADAM9 expression in hepatocellular carcinoma cells, which subsequently inhibits cell migration and invasion in vitro. In addition, Cox proportional hazards regression model analysis showed that ADAM9 levels, tumor number, microvascular invasion, and tumor metastasis rate represent independent prognostic factors for shorter recurrence-free survival. In conclusion, we demonstrated that the loss of tumor suppressor miR-126 in hepatitis B virus-related hepatocellular carcinoma cells contributes to the development of metastases through the upregulated expression of its target gene, ADAM9. MiR-126-ADAM9 pathway-based therapeutic targeting may represent a novel approach for the inhibition of hepatitis B virus-related hepatocellular carcinoma metastases.

Study on Dissociation Properties and Spectra of Halon 1301 in External Electric Field.

Halon-1301 (CF3Br) can make Br radicals with UV radiation, which poses a great threat to the ozone layer in the atmosphere. Necessary methods should be taken for the degradation of the exhausts of Halon-1301. In this paper, density functional (DFT) theory at B3LYP/6-311G++(d,p) level are employed for the study of dissociation properties and spectra of Halon-1301 in external electric field, including bond length, total energy, HOMO-LUMO energy gap, infrared spectra and dissociation potential energy surface (PES). The obtained results show that, with gradually increasing the external field from 0 to 0.03 a.u. along the molecular axis Z (C­Br bond direction), the total energy decreases, while the dipole moment decreases at the beginning and then increases. With the climbing of the field, HOMO-LUMO energy gap increases, and C­Br bond length increases while C­F bond length decreases. The variations of vibrational frequency and intensity of molecular IR spectra in external electric field are also investigated. Further studies show that with increasing the external electric field from 0 to 0.03 a.u., the dissociation PES along C­Br bond becomes unbound with disappearing of the barrier for the dissociation. The external electric field of 0.03 a.u. is sufficient to induce the degradation of CF3Br with C­Br bond breaking. Such results provide an important reference for the degradation of Halons via the external electric field.

[Positive circulating tumor cells in the peripheral blood may indicate a poor prognosis in patients with hepatocellular carcinoma].

OBJECTIVE: To assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC). METHODS: A total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrol(TM) CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed. RESULTS: s CTCs were detected in 64.5% (191/296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05). CONCLUSION: Positive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.

Genetic Polymorphisms of TGFB1, TGFBR1, SNAI1 and TWIST1 Are Associated with Endometrial Cancer Susceptibility in Chinese Han Women.

Endometrial cancer (EC) is a complex disease involving multiple gene-gene and gene-environment interactions. TGF-ß signaling plays pivotal roles in EC development. This study aimed to investigate whether the genetic polymorphisms of TGF-ß signaling related genes TGFB1, TGFBR1, SNAI1 and TWIST1 contribute to EC susceptibility. Using the TaqMan Genotyping Assay, 19 tagging-SNPs of these four genes were genotyped in 516 EC cases and 707 controls among Chinese Han women. Logistic regression (LR) showed that the genetic variants of TGFB1 rs1800469, TGFBR1 rs6478974 and rs10733710, TWIST1 rs4721745 were associated with decreased EC risk, and these four loci showed a dose-dependent effect (Ptrend < 0.0001). Classification and regression tree (CART) demonstrated that women carrying both the genotypes of TGFBR1 rs6478974 TT and rs10512263 TC/CC had the highest risk of EC (aOR = 7.86, 95% CI = 3.42-18.07, P<0.0001). Multifactor dimensionality reduction (MDR) revealed that TGFB1 rs1800469 plus TGFBR1 rs6478974 was the best interactional model to detect EC risk. LR, CART and MDR all revealed that TGFBR1 rs6478974 was the most important protective locus for EC. In haplotype association study, TGFBR1 haplotype CACGA carrier showed the lowest EC risk among women with longer menarche-first full term pregnancy intervals (˃11 years) and BMI˂24 (aOR = 0.39, 95% CI = 0.17-0.90, P = 0.0275). These results suggest that polymorphisms in TGFB1, TGFBR1, SNAI1 and TWIST1 may modulate EC susceptibility, both separately and corporately.

MicroRNA-30 inhibits antiapoptotic factor Mcl-1 in mouse and human hematopoietic cells after radiation exposure.

We previously reported that microRNA-30 (miR-30) expression was initiated by radiation-induced proinflammatory factor IL-1ß and NFkB activation in mouse and human hematopoietic cells. However, the downstream effectors of miR-30 and its specific role in radiation-induced cell death are not well understood. In the present study, we evaluated effects of radiation on miR-30 expression and activation of intrinsic apoptotic pathway Bcl-2 family factors in in vivo mouse and in vitro human hematopoietic cells. CD2F1 mice and human CD34+ cells were exposed to different doses of gamma-radiation. In addition to survival studies, mouse blood, bone marrow (BM) and spleen cells and human CD34+ cells were collected at 4 h, and 1, 3 and 4 days after irradiation to determine apoptotic and stress response signals. Our results showed that mouse serum miR-30, DNA damage marker γ-H2AX in BM, and Bim, Bax and Bak expression, cytochrome c release, and caspase-3 and -7 activation in BM and/or spleen cells were upregulated in a radiation dose-dependent manner. Antiapoptotic factor Mcl-1 was significantly downregulated, whereas Bcl-2 was less changed or unaltered in the irradiated mouse cells and human CD34+ cells. Furthermore, a putative miR-30 binding site was found in the 3' UTR of Mcl-1 mRNA. miR-30 directly inhibits the expression of Mcl-1 through binding to its target sequence, which was demonstrated by a luciferase reporter assay, and the finding that Mcl-1 was uninhibited by irradiation in miR-30 knockdown CD34+ cells. Bcl-2 expression was not affected by miR-30. Our data suggest miR-30 plays a key role in radiation-induced apoptosis through directly targeting Mcl-1in hematopoietic cells.

Involvement of bone marrow in lymphoma: pathological investigation in a single-center from northern China.

OBJECTIVES: This study aimed to evaluate key features of bone marrow trephine biopsy (BMT) involvement of lymphoma in Northern China. METHODS: 950 cases were assessed for the occurrence of bone marrow involvement and architectural features including volume percentage, involvement pattern (diffuse, nodular, focal, para trabecular, or interstitial), and presence/absence of background changes (granuloma, stromal fibrosis or necrosis). Correlations with bone marrow aspirate (BMA) and flow cytometry (FCM) findings were made in a subset of paired cases (359 BMA and 364 FCM). RESULTS: 153 (16.1%) cases involved BMT. The most frequent type was mantle cell lymphoma (28/153, 18.3%). Architectural features were similar to previous studies except that diffuse large B-cell lymphoma (DLBCL) preferred focal pattern (16/22 cases, 72.7%) most of all. BMA and BMT agreed in 84.1% of cases (302 of 359: 277 both negative, 25 both positive), while FCM and BMT agreed in 80.8% of cases (294 of 364: 242 both negative, 52 both positive). Both varied widely among different subgroups. CONCLUSIONS: Occurrence of BMT involvement by lymphoma in Northern China is relatively low. The volume percentage, distribution patterns and background changes may be useful pointers towards a particular lymphoma type in Chinese. FCM is more sensitive and reliable than BMA in China.

Application of Combined Two-Dimensional and Three-Dimensional Transvaginal Contrast Enhanced Ultrasound in the Diagnosis of Endometrial Carcinoma.

Objective. The goal of this study was to explore the clinical value of combining two-dimensional (2D) and three-dimensional (3D) transvaginal contrast-enhanced ultrasounds (CEUS) in diagnosis of endometrial carcinoma (EC). Methods. In this prospective diagnostic study, transvaginal 2D and 3D CEUS were performed on 68 patients with suspected EC, and the results of the obtained 2D-CEUS and 3D-CEUS images were compared with the gold standard for statistical analysis. Results. 2D-CEUS benign endometrial lesions showed the normal uterine perfusion phase while EC cases showed early arrival and early washout of the contrast agent and nonuniform enhancement. The 3D-CEUS images differed in central blood vessel manifestation, blood vessel shape, and vascular pattern between benign and malignant endometrial lesions (P < 0.05). Sensitivity, specificity, positive predictive value, negative predictive value, and accuracy of transvaginal 2D-CEUS and 2D-CEUS combined with 3D-CEUS for diagnosis of benign and malignant endometrial lesions were 76.9%, 73.8%, 64.5%, 83.8%, and 75.0% and 84.6%, 83.3%, 75.9%, 89.7%, and 83.8%, respectively. Conclusion. 3D-CEUS is a useful supplement to 2D-CEUS and can clearly reveal the angioarchitecture spatial relationships between vessels and depth of myometrial invasion in EC. The combined use of 2D and 3D-CEUS can offer direct, accurate, and comprehensive diagnosis of early EC.

Delta-tocotrienol suppresses radiation-induced microRNA-30 and protects mice and human CD34+ cells from radiation injury.

We reported that microRNA-30c (miR-30c) plays a key role in radiation-induced human cell damage through an apoptotic pathway. Herein we further evaluated radiation-induced miR-30 expression and mechanisms of delta-tocotrienol (DT3), a radiation countermeasure candidate, for regulating miR-30 in a mouse model and human hematopoietic CD34+ cells. CD2F1 mice were exposed to 0 (control) or 7-12.5 Gy total-body gamma-radiation, and CD34+ cells were irradiated with 0, 2 or 4 Gy of radiation. Single doses of DT3 (75 mg/kg, subcutaneous injection for mice or 2 µM for CD34+ cell culture) were administrated 24 h before irradiation and animal survival was monitored for 30 days. Mouse bone marrow (BM), jejunum, kidney, liver and serum as well as CD34+ cells were collected at 1, 4, 8, 24, 48 or 72 h after irradiation to determine apoptotic markers, pro-inflammatory cytokines interleukin (IL)-1ß and IL-6, miR-30, and stress response protein expression. Our results showed that radiation-induced IL-1ß release and cell damage are pathological states that lead to an early expression and secretion of miR-30b and miR-30c in mouse tissues and serum and in human CD34+ cells. DT3 suppressed IL-1ß and miR-30 expression, protected against radiation-induced apoptosis in mouse and human cells, and increased survival of irradiated mice. Furthermore, an anti-IL-1ß antibody downregulated radiation-induced NFκBp65 phosphorylation, inhibited miR-30 expression and protected CD34+ cells from radiation exposure. Knockdown of NFκBp65 by small interfering RNA (siRNA) significantly suppressed radiation-induced miR-30 expression in CD34+ cells. Our data suggest that DT3 protects human and mouse cells from radiation damage may through suppression of IL-1ß-induced NFκB/miR-30 signaling.

Association of genetic polymorphisms in AURKA, BRCA1, CCNE1 and CDK2 with the risk of endometrial carcinoma and clinicopathological parameters among Chinese Han women.

OBJECTIVE: Centrosome aberrations and cell-cycle deregulations have important implications for the development of endometrial carcinoma. AURKA, BRCA1, CCNE1 and CDK2 genes play pivotal roles in centrosome duplication and cell-cycle regulation. This study aimed to investigate whether genetic polymorphisms in these four genes may contribute to endometrial carcinoma susceptibility and progression in Chinese Han women. STUDY DESIGN: A total of twenty-two single nucleotide polymorphisms (SNPs) were selected according to the public HapMap database (HapMap Data Release #27; Chinese Beijing population), and genotyped using TaqMan Realtime PCR method in 530 endometrial adenocarcinoma cases and 825 age-matched controls from Chinese Han women. Then, haplotype blocks were reconstructed according to our genotyping data. RESULTS: For AURKA, the rs911162 was associated with increased risk of endometrial carcinoma [in co-dominant model: adjusted odds ratio (aOR) = 4.92, 95% CI = 1.24-19.55, P = 0.0235]. The haplotype GA (rs6064391 + rs911162) in block 1 of AURKA was also associated with increased risk of endometrial carcinoma (aOR = 1.25, 95% CI = 1.07-2.06, P = 0.0189). For BRCA1, the minor allele homozygotes of rs8067269 could decrease the risk of endometrial carcinoma (in co-dominant models: aOR = 0.52, 95% CI = 0.34-0.80, P = 0.0032), so was the haplotype CTCAG (rs8176323 + rs8176199 + rs3737559 + rs8067269 + rs2070833) (aOR = 0.69, 95% CI = 0.50-0.95, P = 0.0234). Moreover, we found several associations between genetic variations in CCNE1, BRCA1 and AURKA and clinicopathological parameters. CONCLUSIONS: This study indicates that genetic polymorphisms of AURKA, BRCA1 and CCNE1 may contribute to endometrial carcinoma susceptibility or progression in Chinese Han women.

Circulating interleukin-18 as a biomarker of total-body radiation exposure in mice, minipigs, and nonhuman primates (NHP).

We aim to develop a rapid, easy-to-use, inexpensive and accurate radiation dose-assessment assay that tests easily obtained samples (e.g., blood) to triage and track radiological casualties, and to evaluate the radioprotective and therapeutic effects of radiation countermeasures. In the present study, we evaluated the interleukin (IL)-1 family of cytokines, IL-1ß, IL-18 and IL-33, as well as their secondary cytokines' expression and secretion in CD2F1 mouse bone marrow (BM), spleen, thymus and serum in response to γ-radiation from sublethal to lethal doses (5, 7, 8, 9, 10, or 12 Gy) at different time points using the enzyme-linked immune sorbent assay (ELISA), immunoblotting, and cytokine antibody array. Our data identified increases of IL-1ß, IL-18, and/or IL-33 in mouse thymus, spleen and BM cells after total-body irradiation (TBI). However, levels of these cytokines varied in different tissues. Interestingly, IL-18 but not IL-1ß or IL-33 increased significantly (2.5-24 fold) and stably in mouse serum from day 1 after TBI up to 13 days in a radiation dose-dependent manner. We further confirmed our finding in total-body γ-irradiated nonhuman primates (NHPs) and minipigs, and demonstrated that radiation significantly enhanced IL-18 in serum from NHPs 2-4 days post-irradiation and in minipig plasma 1-3 days post-irradiation. Finally, we compared circulating IL-18 with the well known hematological radiation biomarkers lymphocyte and neutrophil counts in blood of mouse, minipigs and NHPs and demonstrated close correlations between these biomarkers in response to radiation. Our results suggest that the elevated levels of circulating IL-18 after radiation proportionally reflect radiation dose and severity of radiation injury and may be used both as a potential biomarker for triage and also to track casualties after radiological accidents as well as for therapeutic radiation exposure.

[Risk factors for the failure of the InSure method in very preterm infants with respiratory distress syndrome].

OBJECTIVE: To study the risk factors for the failure of the InSure method in very preterm infants with respiratory distress syndrome (RDS). METHODS: Seventy-one very preterm infants with RDS treated with InSure method were enrolled. These infants were categorized into two groups: InSure success (42 cases) and InSure failure (29 cases). The differences in basic information were compared between the two groups, and logistic regression analysis was used to identify the risk factors for InSure failure. RESULTS: The failure rate of the InSure method was 41%. The failure group were much lower in the birth weight, the antenatal steroids utilization rate and the vaginal delivery rate than the success group (P<0.05). The incidence of patent ductus arteriosus in the failure group was significantly higher than in the success group (P<0.05). PaO2, PaO2/FiO2 and PaO2/PAO2 in the failure group were significantly lower than in the success group (P<0.05). PaCO2 in the failure group was much higher than in the success group (P<0.05). Further logistic regression analysis showed that birth weight <1 150 g (OR=22.240 95%CI=2.124-232.901), PaCO2>54 mm Hg(OR=9.360, 95%CI=1.958-44.741, and PaO2/FiO2 <195 (OR=6.570, 95%CI=1.027-42.003), were the independmend risk factors for InSure failure. Furthermore, the duration of oxygen therapy, the total time of hospitalization and the incidence of BPD in the failure group were much longer and higher than in the success group (P<0.05). CONCLUSIONS: Low birth weight, elevated PaCO2 and low PaO2/PiO2 ratio are the risk factors for the failure of the InSure method in very preterm infants.

Evaluation of the prognostic value of the metastatic lymph node ratio for gastric cancer.

BACKGROUND: The aim of this study was to investigate the prognostic value of metastatic lymph node (LN) ratio (LNR) compared with pathologic node (pN) category. METHODS: Three hundred ninety-nine patients with gastric cancer with R0 resection were reviewed. LNR, pN, and the number of retrieved LNs were evaluated in node-positive groups with ≥15 or <15 LNs resected and a node-negative group, respectively, by univariate and multivariate analyses. Associations of pN and LNR with the number of retrieved LNs were determined using Spearman's rank correlation test. RESULTS: LNR and pN were correlated with overall survival. For the node-positive group with ≥15 LNs retrieved, pN and LNR were independent prognostic factors, with the hazard ratio higher for LNR; neither was correlated with the number of retrieved LNs. For the group with <15 LNs retrieved, LNR but not pN was an independent prognostic factor, with LNR uncorrelated with the number of LNs retrieved. For the node-negative group, the number of LNs retrieved retained an independent prognostic factor. CONCLUSIONS: LNR is an independent prognostic factor in node-positive patients with gastric cancer with R0 resection, and it is uninfluenced by the number of LNs retrieved. It may be superior to pN.

Delta-tocotrienol protects mice from radiation-induced gastrointestinal injury.

We recently demonstrated that natural delta-tocotrienol (DT3) significantly enhanced survival in total-body irradiated (TBI) mice, and protected mouse bone marrow cells from radiation-induced damage through Erk activation-associated mTOR survival pathways. Here, we further evaluated the effects and mechanisms of DT3 on survival of radiation-induced mouse acute gastrointestinal syndrome. DT3 (75-100 mg/kg) or vehicle was administered as a single subcutaneous injection to CD2F1 mice 24 h before 10-12 Gy (60)Co total-body irradiation at a dose rate of 0.6 Gy/min and survival was monitored. In a separate group of mice, jejunum sections were stained with hematoxylin and eosin and the surviving crypts in irradiated mice were counted. Apoptosis in intestinal epithelial cells was measured by terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling (TUNEL) staining and bacterial translocation from gut to heart, spleen and liver in irradiated mice were evaluated. DT3 (75 mg/kg) significantly enhanced survival in mice that received 10, 10.5, 11 or 12 Gy TBI. Administration of DT3 protected intestinal tissue, decreased apoptotic cells in jejunum and inhibited gut bacterial translocation in irradiated mice. Furthermore, DT3 significantly inhibited radiation-induced production of pro-inflammatory factors interleukin-1ß and -6 and suppressed expression of protein tyrosine kinase 6 (PTK6), a stress-induced kinase that promotes apoptosis in mouse intestinal cells. Our data demonstrate that administration of DT3 protected mice from radiation-induced gastrointestinal system damage.

[Relationship between the expressions of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma and clinicopathological parameters].

OBJECTIVE: To explore the expressions of indoleamine 2, 3-dioxygenase (IDO) in hepatocellular carcinoma and analyze its relationship with clinicopathological parameters. METHODS: Quantitative real-time polymerase chain reaction (PCR), fluorogenic quantitative PCR, immunohistochemical and immunofluorescence were used to detect the expression of indoleamine 2, 3-dioxygenase in hepatocellular carcinoma. RESULTS: The IDO mRNA expression in cancerous tissues increased markedly than that in the corresponding non-cancerous tissues (2(-ΔΔCT) = 1.71, P = 0.001) . The immunohistochemical and immunofluorescence results showed that IDO protein was expressed in cytoplasm of hepatocellular carcinoma and tumor-surrounding tissues. But there was no expression in normal liver tissues from benign hepatic lesions and corresponding non-cancerous tissues. An over-expression of IDO protein was detected in 43 patients (48.3%) , a low expression in 25 (28.1%) and no expression in 21 (23.6%). Relationship between IDO expression and clinicopathological parameters: an over-expression of IDO in HCC was associated with recurrence, survival time, metastasis and TNM stage (P < 0.05), but not associated with patient's cirrhosis, AFP level, histological differentiation type, Barcelona clinic liver cancer stage, gender, age, HbsAg positivity, number of tumors and tumor size (P > 0.05). CONCLUSION: An over-expression of IDO in HCC patients may affect patient prognosis.

[Diagnostic value of microtubule-associated protein-2 in small cell lung carcinoma: an analysis of 240 biopsy cases].

OBJECTIVE: To investigate the diagnostic value of microtubule-associated protein-2 (MAP-2) in biopsy of small cell lung carcinoma (SCLC). METHODS: Immunohistochemical technique was applied to detect the expression of synaptophysin (Syn), chromogranin A (CgA), CD56, MAP-2 and TTF-1 in 240 cases of SCLC from 2008 to 2011 in this hospital. RESULTS: The positive rate of MAP-2 expression in SCLC was 95.8% (230/240), which was much higher than that of Syn (57.1%, 137/240), CgA (38.8%, 93/240) and CD56 (89.2%, 214/240). The sensitivity and accuracy of MAP-2 (99.1%, 95.4%) expression were also higher than those of Syn (58.3%, 42.5%), CgA (39.9%, 42.5%) and CD56 (91.5%, 87.9%). CONCLUSIONS: MAP-2 is a new neuroendocrine marker with higher sensitivity and accuracy, and thus recommended to be added to the immunohistochemical panel for the diagnosis of SCLC.

Genistein nanoparticles protect mouse hematopoietic system and prevent proinflammatory factors after gamma irradiation.

Previous studies demonstrated that genistein protects mice from radiation-induced bone marrow failure. To overcome genistein's extremely low water solubility, a nanoparticle suspension of genistein has been formulated for more rapid dissolution. In the current study, we evaluated the radioprotective effects of a nanoparticle formulation of genistein on survival and hematopoietic recovery in mice exposed to total-body gamma irradiation. A single intramuscular injection of a saline-based genistein nanosuspension (150 mg/kg) administered to CD2F1 mice 24 h before 9.25 Gy (60)Co radiation exposure resulted in a 30-day survival rate of 95% compared to 25% in vehicle-treated animals. In mice irradiated at 7 Gy, the genistein nanosuspension increased mouse bone marrow cellularity from approximately 2.9% (vehicle treated) to 28.3% on day 7 postirradiation. Flow cytometry analysis demonstrated decreased radiation-induced hematopoietic stem and progenitor cell (HSPC, Lineage(-)/cKit(+)) death from 77.0% (vehicle) to 43.9% (genistein nanosuspension) with a significant recovery of clonogenicity 7 days after irradiation. The genistein nanosuspension also attenuated the radiation-induced elevation of proinflammatory factors interleukin 1 beta (IL-1ß), IL-6 and cyclooxygenase-2 (COX-2) in mouse bone marrow and spleen, which may contribute to protecting HSPCs.