Degradation of circulating thyroglobulin

Reported half lives of rat Tg were different according to various investigators. In order to elucidate whether the derivatives of rat Tg in the peripheral circulation affect the results of kinetic studies of Tg, the present study was performed to investigate kinetics of rat Tg after separation of 19S Tg from its derivatives using gel-filtration. Radiolabeled Tg was obtained from thyroids of rats injected with 125I 24 hours before death, and subsequently purified by ammonium sulfate precipitation. The plasma samples obtained at varying time intervals after intravenous injection of 125I-rat Tg were fractionated on a Sephacryl S-300 column. As determined by sucrose density gradient, 99% of in vivo radiolabeled Tg was 19S. On gel-filtration, the injected labeled Tg and plasma samples obtained within two hours after injection showed a single peak in an identical area. A second peak in an area corresponding to a molecular weight of 60,000 to 70,000 appeared within six hours, and became as high as the first within 24 hours. In the second peak, 22.8 +/- 3.8% (mean +/- SE) of radioactivity was precipitated by anti-rat Tg antibody, and 14.4 +/- 1.7% (mean +/- SE) of radioactivity of its TCA precipitate was not extracted by n-butanol. Thus, the second peak could affect the results of Tg kinetic studies which utilize TCA precipitation, n-butanol extraction or RIA procedures. The half life of rat Tg in the present study was calculated from the disappearance curves of radioactivity of 19S Tg separated from other radioactive substances.(ABSTRACT TRUNCATED AT 250 WORDS)     

Inhibitory effects of polyphenol-enriched extract from Ziyang tea against human breast cancer MCF-7 cells through reactive oxygen species-dependent mitochondria molecular mechanism

A polyphenol-enriched extract from selenium-enriched Ziyang green tea (ZTP) was selected to evaluate its antitumor effects against human breast cancer MCF-7 cells. In ZTP, (−)-epigallocatechin gallate (28.2%) was identified as the major catechin, followed by (−)-epigallocatechin (5.7%) and (−)-epicatechin gallate (12.6%). ZTP was shown to inhibit MCF-7 cell proliferation (half maximal inhibitory concentration, IC₅₀ = 172.2 μg/mL) by blocking cell-cycle progression at the G0/G1 phase and inducing apoptotic death. Western blotting assay indicated that ZTP induced cell-cycle arrest by upregulation of p53 and reduced the expression of CDK2 in MCF-7 cells. ZTP-caused cell apoptosis was associated with an increase in Bax/Bcl-2 ratio, and activation of caspase-3 and -9. MCF-7 cells treated with ZTP also showed an overproduction of reactive oxygen species, suggesting that reactive oxygen species played an important role in the induction of apoptosis in MCF-7 cells. This is the first report showing that ZTP is a potential novel dietary agent for cancer chemoprevention or chemotherapy.     

CXCL12/CXCR4在小细胞肺癌患者中的表达及临床意义

目的研究小细胞肺癌(small cell lung cancer,SCLC)患者外周血中CXCL12及其受体CXCR4的表达情况,探讨CXCL12/CXCR4与SCLC发生和发展之间的关系。方法采用ELISA、real-time PCR和Westernblot方法,检测CXCL12与CXCR4在30例局限期(Limited stage disease,LD)SCLC患者、32例扩散期(Expensive stage disease,ED)SCLC患者和10例良性肺部肿瘤患者(对照组,Control)中的转录水平和表达水平,分析CXCL12、CXCR4与SCLC患者临床病理等指标之间的关系。结果 CXCL12、CXCR4在SCLC患者组织中均高表达,其中扩散期患者CXCL12、CXCR4表达平略高于局限期患者组。扩散期患者外周血中CXCL12表达高于其在局限期患者中的水平,二者均高于对照组。血清中CXCL12水平与患者的性别和年龄无关(P0.05),而与肿瘤的大小及淋巴结转移明显相关(P0.01)。结论 CXCL12/CXCR4可能直接或间接参与对SCLC发生和发展的调控。     

Impact of chemokine receptor CXCR3 on tumor-infiltrating lymphocyte recruitment associated with favorable prognosis in advanced gastric cancer

Chemokine receptor CXCR3 has been proved to play an important role in tumorigenesis and tumor progression in many malignancies, but its precise efficacy on gastric cancer (GC) has not been evaluated yet. The present study was aimed to explore the correlation of chemokine receptor CXCR3 with tumor-infiltrating lymphocytes (TILs) and prognosis in advanced gastric cancer (GC). Expression of CXCR3 and CD4+, CD8+ TILs was conducted in 192 advanced GC specimens and 48 corresponding paracancerous tissues by immunohistochemical (IHC) analysis. CXCR3 expression in GC tissues was significantly higher than that in paracancerous tissues (P<0.001) and CD8+, CD4+ TILs infiltration increased with high CXCR3 expression (P=0.032 and P<0.001, respectively). Our study showed significantly lower CXCR3 expression in patients with greater tumor invasion depth and lymph node metastasis compared with patients with lesser tumor invasion depth and without lymph node metastasis (P=0.002 and P=0.001, respectively). Univariate analysis indicated that patients with high CXCR3 expression and high CD8+ TILs infiltration had longer overall survival (OS) (log-rank test, P<0.001 and P=0.002, respectively). Univariate and multivariate analyses indicated that CXCR3 expression was an independent prognostic factor for OS (P=0.002). The present study suggested that CXCR3 expression was upregulated in advanced GC and was associated with increased CD4+, CD8+ TILs infiltration and improved OS. Therefore, CXCR3 overexpression is implicated as a favorable prognostic biomarker in human advanced GC.     

B7-H6 expression correlates with cancer progression and patient’s survival in human ovarian cancer

B7-H6, a newly identified B7 family member molecule, binds to its receptor on NK cells, NKp30, and then triggers the anti-tumor NK cell cytotoxicity and leads to the cytokine secretion. As of now, numerous studies have demonstrated that the higher B7-H6 expression could be found in certain human cancers and have important clinical significance. In our present study, we carried out the tissue microarray and the immunohistochemistry assay to investigate the clinical significance of B7-H6 expression in human ovarian cancer. Our results showed that the positive B7-H6 staining was predominantly observed on the membrane and in the cytoplasm of the ovarian cancer cells. In order to further investigate the correlation between clinical parameters and the B7-H6 protein levels in the ovarian tissues, we categorized all the 110 patients into two major subgroups according to the intensity of B7-H6 immunohistochemical staining, i.e., the lower B7-H6 expression group, 34 cases (0 ≤ H-score < 100), and the higher B7-H6 expression group, 76 cases (H-score ≥ 100), and we found that B7-H6 expression in the ovarian cancer tissues is significantly correlated with distant metastasis status (P = 0.028) and FIGO stage (P = 0.031), whereas it is not correlated with patient’s age, tumor size, tumor location, pathological stage or nodal metastasis. The survival analysis demonstrated that the overall survival rate of the subgroup with lower B7-H6 expression is significantly better than that of the subgroup with higher B7-H6 expression (P = 0.0456, Hazard Ratio: 1.707, 95% CI, 1.010-2.885). Thus, our present data revealed that higher B7-H6 expression in ovarian cancer tissues was positively correlated with tumor metastasis and cancer progression, and supports the notion that B7-H6 expression is involved in the progression of human ovarian cancer, the detailed mechanism merits further investigation.     

Comparing triage algorithms using HPV DNA genotyping,HPV E7 mRNA detection and cytology in high-risk HPV DNA-positive women

BackgroundHigh-risk human papillomavirus (hrHPV) DNA positive women require triage testing to identify those with high-grade cervical intraepithelial neoplasia or cancer (≥CIN2).ObjectiveComparing three triage algorithms (1) E7 mRNA testing following HPV16/18/31/33/45/52/58 genotyping (E7 mRNA test), (2) HPV16/18 DNA genotyping and (3) cytology, for ≥CIN2 detection in hrHPV DNA-positive women.Study designhrHPV DNA-positive women aged 18–63 years visiting gynecology outpatient clinics were included in a prospective observational cohort study. From these women a cervical scrape and colposcopy-directed biopsies were obtained. Cervical scrapes were evaluated by cytology, HPV DNA genotyping by bead-based multiplex genotyping of GP5+6+-PCR-products, and presence of HPV16/18/31/33/45/52/58 E7 mRNA using nucleic acid sequence-based amplification (NASBA) in DNA positive women for respective HPV types. Sensitivities and specificities for ≥CIN2 were compared between E7 mRNA test and HPV16/18 DNA genotyping in the total group (n = 348), and E7 mRNA test and cytology in a subgroup of women referred for non-cervix-related gynecological complaints (n = 133).ResultsSensitivity for ≥CIN2 of the E7 mRNA test was slightly higher than that of HPV16/18 DNA genotyping (66.9% versus 60.9%; ratio 1.10, 95% CI: 1.0002–1.21), at similar specificity (54.8% versus 52.3%; ratio 1.05, 95% CI: 0.93–1.18). Neither sensitivity nor specificity of the E7 mRNA test differed significantly from that of cytology (sensitivity: 68.8% versus 75.0%; ratio 0.92, 95% CI: 0.72–1.17; specificity: 59.4% versus 65.3%; ratio 0.91, 95% CI: 0.75–1.10).ConclusionFor detection of ≥CIN2 in hrHPV DNA-positive women, an algorithm including E7 mRNA testing following HPV16/18/31/33/45/52/58 DNA genotyping performs similar to HPV16/18 DNA genotyping or cytology.