Quinone oxidoreductase 1 is overexpressed in gastric cancer and associated with outcome of adjuvant chemotherapy and survival

BACKGROUND Quinine oxidoreductase 1(NQO1)plays a vital role in protecting normal cells against oxidative damage and electrophilic attack.It is highly expressed in many solid tumors,suggesting a role in cancer development and progression.However,the role of NQO1 in gastric cancer and its effect on cancer development and prognosis have not been fully investigated.AIM To investigate the clinical relevance of NQO1 protein expression in gastric cancer and to explore the potential of NQO1 to serve as a prognostic biomarker and therapeutic target.METHODS In this retrospective study,gastric cancer specimens of 175 patients who were treated between 1995 and 2011 were subjected to immunohistochemistry analyses for NQO1.The correlation of NQO1 expression with gastric cancer prognosis and clinical and pathological parameters was investigated.RESULTS NQO1 protein was overexpressed in 59.43%(104/175)of the analyzed samples.Overexpression of NQO1 was associated with a significantly inferior prognosis.In addition,multivariate analysis suggested that NQO1 overexpression,along with tumor stage and patient age,are prominent prognostic biomarkers for gastric cancer.Moreover,NQO1 overexpression was correlated to a better response to 5-fluorouracil(5-FU)-based adjuvant chemotherapy.CONCLUSION NQO1 overexpression is associated with a significantly poor prognosis and better response to 5-FU in patients with gastric cancer.These findings are relevant for improving therapeutic approaches for gastric cancer patients.

The expression of HIF-1α and VEGF as well as their correlation with angiogenesis in esophageal squamous cell carcinomas

Objective： To investigate the correlations among the expressions of hypoxia-inducible factor-1α （HIF-1α）, vascular endothelial cell growth factor （VEGF） and microvessel density （MVD）, and their relationships to the clinicopathologic characteristics of esophageal squamous cell carcinomas （ESCC）. Methods： The expressions of HIF-1α, VEGF and MVD were detected by immunohistochemical method in 45 cases of ESCC, 30 intraepithelial neoplasia and 35 normal esophageal mucosal epithelia tissues. The correlations among the expressions of HIF-1α, VEGF and MVD, and their relationships to the clinicopathologic features of ESCC were analyzed. Results： The rate of positive expression of HIF-1α and VEGF which were 80% and 84% in ESCC were significantly higher than those in intraepithelial neoplasia and normal esophageal mucosal epithelium tissues （P 〈 0.01） and so did the MVD value which was71.10 ±15.02 in ESCC （P 〈 0.01）. The expression of HIF-1α and VEGF were positively correlated with the depth of tumor invasion, lymph node metastasis and TNM staging of ESCC. The expressions of HIF-1α were positively correlated with the expressions of VEGF and the value of MVD. Conclusion： Overexpression of HIF-1α is found in ESCC. HIF-1α may induce the angiogenesis in ESCC by upregulating the transcription of VEGF gene. It may play an important role in the carcinogenesis and aggression in ESCC, HIF-1α, VEGF and MVD may be a useful marker for evaluating the biological behaviors of ESCC.

Expression and clinical significance of HIF-1α,VEGF and Survivin in esophageal squamous cell carcinoma

Objective： To evaluate the expression and correlation of hypoxia inducible factor la （HIF-la） and vascular endothelial growth factor （VEGF） and Survivin proteins in biopsy specimens of esophageal squamous cell carcinoma （ESCC）, and then determine whether the levels of expression of these proteins could predict the clinical effectiveness of radiotherapy in individual cancers. Methods： The expressions of HIF-IQ, VEGF and Survivin were shown by S-P immunohistochemical staining method in biopsy specimens of ESCC, which were obtained endoscopically from 50 patients before radiotherapy, and 10 cases of normal esophageal tissue. Results： The positive expression rates of H IF-IQ, VEGF and Survivin were 68%, 74% and 72% in ESCC respectively. However, the three tumor markers had negative expressions in normal esophageal tissue. The positive rate of HIF-IQ was positively correlated with VEGF and Survivin proteins. The positive rates of HIF-IQ and Survivin were closely related to the clinical stage, radiotherapy effectiveness and survival, otherwise, the expression of HIF-IQ was closely related to distant metastasis; both of them were no correlation with the differentiation degree of tumor. The effective rates of radiotherapy and mean survival periods of those cases with positive and negative expressions of HIF-IQ were 8.8%, 10 months and 81.25%, 25 months, respectively. The one, two, and three years survival rates of patients with positive and negative expressions of HIF-IQ were 38.2%, 5.9%, 2.9%, and 81.3%, 54.2%, 15.8%, respectively （P = 0.001）. Patients with HIF-IQ positive expression obviously survived less than those with negative expression and the difference was significant. The expression of VEGF was only related to the distant metastasis. Conclusion： Over expressions of HIF-IQ, VEGF and Survivin were found in ESCC. The positive rate of HIF-IQ was positively correlated with VEGF and Survivin proteins. The expression of HIF-IQ may serve as an important parameter in evaluating response for radiotherapy and prognosis of ESCC. It may play an important role by up-regulating the transcription of VEGF and Survivin genes.

Biomechanical evaluation of lumbosacral reconstruction after subtotal sacrectomy: A three-dimensional finite element analysis

Objective： The aim of this study was to investigate the biomechanical property of lumbosacral reconstruction after subtotal sacrectomy. Methods： Three three-dimensional finite element models of lumbosacral region were established： （1） An intact model （INT）; （2） A defective model （DEF） on which subtotal sacrectomy was performed cephalad to the $1 foramina; （3） A reconstructed model （REC）. These models were validated by compared with literature. Upright posture was stimulated under a compression load of 925N. A finite element analysis was performed to account for the displacement and stress on the models. The REC model was calculated twice, with the material property of reconstruction instrument set as titanium and stainless steel, respectively. Results： The displacements of anchor point on the L3 vertebrae in INT, DEF and REC model were 6.63 mm, 10.62 mm, 4.29 mm （titanium） and 3.86 mm （stainless steel）, respectively. The stress distribution of the instrument in REC model showed excessively concentration on caudal spinal rod, which may cause rod failure between spine and ilia. The maximum von Mise stress of stainless steel instrument was higher than that of titanium instruments （992 MPa vs 655 MPa）, and the value of stress of anchor point around sacroiliac joint in REC model were 26.4 MPa with titanium instruments and 23.9 MPa with stainless steel instruments. Conclusion： Lumbosacral reconstruction can significantly increase the stiffness of spino-pelvis of the patient who underwent subtotal sacrectomy. However, the rod between L5 and ilia is the weakest region of all the instruments. It is suggested that the bending of rod should be conducted carefully and smoothly to avoid significant stress concentration so as to reduce the risk of rod failure. And stainless steel instrument has higher maximum stress and significantly greater stress shielding effect than titanium instrument, which means stainless steel instruments are of higher risk of rod failure and less favorable for lumboiliac arthrodesis than titanium instruments.

MicroRNA-142-3p is frequently upregulated in colorectal cancer and may be involved in the regulation of cell proliferation

MicroRNAs are small single-stranded RNA molecules consisting of approximately 22 nucleotides (nt), and have post-transcriptional regulatory functions. By gene chip screening, we previously showed that miR-142-3p was significantly upregulated in colorectal cancer tissue and was associated with clinicopathological features, compared with matched non-tumor tissue. In this study, we confirmed significant upregulation of miR-142-3p in 60 colorectal cancer samples and three colorectal cancer cell lines by quantitative real-time PCR (qRT-PCR). Using software and network resources, we predicted TCF7 as a target of miR-142-3p, which we confirmed with dual-luciferase assays. By RT-PCR and Western blot analysis, we found miR-142-3p negatively regulates TCF7 expression post-transcriptionally. CCK8 assays and growth curves indicated that overexpression of miR-142-3p in SW480 colorectal cancer cells potently inhibited cell proliferation in vitro. The expression of TCF7 mRNA and protein was upregulated in both colorectal cancer tissues and colorectal cancer cell lines, closely correlating with its function as an oncogene in promoting tumor cell proliferation and inhibiting apoptosis. With TCF7 as a direct target, our results suggested that miR-142-3p may be involved in the regulation of cell proliferation in colorectal cancer.

Diagnosis and management of acquired thrombotic thrombocy- topenic purpura in southeast China： a single center experience of 60 cases

Acquired thrombotic thrombocytopenic purpura （TTP） is a rare life-threatening thrombotic microangiopathy. This study aimed to provide a profile of the diagnosis and management of patients with acquired TTP collected in 10 years in a single center in southeast China. A total of 60 patients diagnosed with acute acquired TTP from March 2005 to August 2015 were enrolled. Among the 60 patients, 52 patients presented with their first episodes, and eight patients had two or more episodes. The median age at presentation was 49 （range, 17 to 78） years with a female predominance （male：female ratio, 1：1.60）. ADAMTS 13 activity were analyzed in 43 patients, among whom 33 （76.7%） patients had a baseline level of 〈 5%. Mortality was 30%. Plasma exchange （PEX） was performed in 62 of 69 （89.9%） episodes. Corticosteroids were administered in 54 of 69 （78.3%） episodes. Other immunosuppressants （e.g., vincristine, cyclosporine, and cyclosporin） were used in 7 of 69 （10.1%） episodes. Rituximab was documented in 4 patients with refractory/relapsed TTP for 5 episodes, showing encouraging results. In conclusion, the diagnosis of TTP depended on a comprehensive analysis of clinical data. Plasma ADAMTS13 activity assay helped confirm a diagnosis. PEX was the mainstay of the therapy, and rituximab can be used in relapsed/refractory disease.

Tuning the Stability of the Polyplex Nanovesicles of Oligonucleotides via a Zinc(Ⅱ)-Coordinative Strategy

Oligonucleotide therapeutics have great potential to target the currently undruggable genes and to generate entirely new therapeutic paradigms in multiple types of disease,thus having attracted much attention in recent years.However,their applications are greatly hindered by a lack of safe and efficient oligonucleotide-delivery vectors.Polyplex nanovesicles formed from oligonucleotides and the cationic block have shown exceptional features for the delivery of therapeutic oligonucleotides and other biopharmaceuticals.Nevertheless,these polyplex nanovesicles are deeply fraught with difficulty in tolerating physiological ionic strength.Inspired by the high binding ability between the dipicolylamine(DPA)/zinc(Ⅱ)complex and the phosphodiester moieties of oligonucleotides,herein,we designed a coordinative cationic block to solve the intrinsic stability dilemma.Moreover,we found the stability of the resulted polyplex nanovesicles could be easily tuned by the content of coordinated zinc ions.In vitro cellular studies implied that the prepared zinc(Ⅱ)-coordinative polyplex nanovesicles preferred to retain in the lysosomes upon internalization,making them ideal delivery candidates for the lysosome-targeting oligonucleotide therapeutics.

PIWI-interacting RNAs: Mitochondria-based biogenesis and functions in cancer

PIWI-interacting RNA(piRNAs),once thought to be mainly functioning in germlines,are now known to play an essential role in somatic and cancerous tissues.Ping-pong cycle initi-ation and mitochondria-based phased production constitute the core of the piRNA biogenesis and these two processes are well conserved in mammals,including humans.By being involved in DNA methylation,histone marker deposition,mRNA degradation,and protein modification,piRNAs also contribute to carcinogenesis partly due to oncogenic stress-induced piRNA dysre-gulation.Also,piRNAs play important roles in cancer stemness,drug resistance,and tumor immunology.Results from liquid biopsy analysis of piRNA can be used in both cancer diagnoses and cancer prognoses.A combination of targeting piRNA with other therapeutic strategies could be groundbreaking cancer treatment.