ABSTRACT
Platinum-based chemotherapy resistance is a key factor of poor prognosis and recurrence in hepatocellular carcinoma (HCC). Herein, RNAseq analysis revealed that elevated tubulin folding cofactor E (TBCE) expression is associated with platinum-based chemotherapy resistance. High expression of TBCE contributes to worse prognoses and earlier recurrence among liver cancer patients. Mechanistically, TBCE silencing significantly affects cytoskeleton rearrangement, which in turn increases cisplatin-induced cycle arrest and apoptosis. To develop these findings into potential therapeutic drugs, endosomal pH-responsive nanoparticles (NPs) were developed to simultaneously encapsulate TBCE siRNA and cisplatin (DDP) to reverse this phenomena. NPs (siTBCE + DDP) concurrently silenced TBCE expression, increased cell sensitivity to platinum treatment, and subsequently resulted in superior anti-tumor effects both in vitro and in vivo in orthotopic and patient-derived xenograft (PDX) models. Taken together, NP-mediated delivery and the co-treatment of siTBCE + DDP proved to be effective in reversing chemotherapy resistance of DDP in multiple tumor models.
ABSTRACT
Objective To investigate the expression levels of serum miR-210and miR-375in patients with non-small cell lung cancer (NSCLC).Methods A total of 25NSCLC patients (NSCLC group) and 14healthy volunteers (control group) were enrolled in this study.The relative expression levels of 9miRNAs (miR-182, miR-126, miR-31, miR-21, miR-221, miR-200b, miR-183, miR-210and miR-375) in 6 NSCLC patients and 6healthy volunteers were measured by RT-qPCR.The dysregulated miRNAs will be selected as candidate miR-NAs.The diagnostic value were evaluated by ROC curve.Results Compared with control group, 2 (miR-210and miR-375) out of 9miRNAs were up-regulated in NSCLC group, and the differences were statistically significant (P＜0.05), while the other 7miRNAs were not consistent with the reported literatures.Therefore, miR-210and miR-375were selected as candidate miRNAs.We found that the relative expression level of miR-210in the lung adenocarcinoma group was significantly different from control group (P＜0.05), while there was no significant difference between the squamous cell carcinoma group and the control group (P＞0.05).There was no significantly statistical difference in the relative expression level of miR-375between lung squamous cell carcinoma group, lung adenocarcinoma group and the control group (P＞0.05).The AUC of serum miR-210of lung adenocarcinoma group was 0.737 5 (95％CI:0.498 3-0.976 7, P=0.091 4) with a medium diagnostic value.Conclusion MiR-210is highly expressed in the serum of patients with lung adenocarcinoma, suggesting that miR-210may be a novel tumor marker for the diagnosis of lung adenocarcinoma.The value of miR-375in the diagnosis of lung cancer still needs to be further explored.
ABSTRACT
Objective A state quo survey of laboratory animal resource in Guangdong province is performed to provide reference data for government management decision-making and market assessment of laboratory animals. Methods We used questionnaires focusing on the laboratory animal facilities with authorization by Guangdong Province Government, which mainly included the production and use of laboratory animals,the qualification of employees and the facilities space. Results The total production and use of laboratory animals(except for the eggs)had been increasing in the last four years. 1.57 million laboratory animals were produced and 0.754 million laboratory animals were used in 2016. There were 2352 employees,roughly the same as in 2015. The facilities space for breeding was 121008 m2,and for animal experiment was 73470 m2,which were rising in the past three years. Conclusions In order to reinforce the industry development of laboratory animals in Guangdong province,some suggestions were given in our study,such as facilitating the application of superiority resource including non-human primate and aquatic laboratory animals,supporting the standardization production of several scarce mice and rats, improving relevant employees' overall level and constructing laboratory animal facilities sharing platform.
ABSTRACT
Objective:With the development of modern skull base minimally invasive technology mature and neural radio surgery techniques,it is necessary to re-examine the therapeutic strategy for the treat-ment of petroclival meningiomas.To sum up the operative experience and methods in microsurgical resec-tion of petroclival meningiomas by the combining trans-subtemporal and suboccipital retrosigmoid keyhole approach.To explore the minimally invasive operation approach of petroclival meningiomas,to raise the removal degree and to improve the postoperative result using this approach.Methods:The clinical data of the consecutive 21 patients with the petroclival meningiomas were reviewed retrospectively.The meth-od,degree of tumor resection,techniques of the combining keyhole approach,Karnofsky performance score (KPS)before and after operation were also analyzed.The neuronavigation guided operation was performed in 9 cases,and 12 cases were operated in the neuroelectrophysiological monitoring.Results:Total excision of the tumor resection (Simpson,Ⅰ -Ⅱlevels)was conducted in 18 cases (85.7%,18 /21),and 3 patients underwent close resection (Simpson Ⅲ level,14.3%,3 /21).Postoperative three-dimensional CT showed good lock bone flap restoration;Postoperative pathology confirmed meningioma. Postoperative cranial nerve dysfunction or new original nerve dysfunction were aggravated in 5 cases (23.8%),including transient trochlear nerve (3 cases),abducent nerve (1 case),and the motor branch of trigeminal nerve paralysis (1 case).Abducent nerve paralysis (1 case)appeared,with hearing impairment.After the 3-month follow-up,11 cases had the same KPS aspreoperation,7 cases improved,and 3 cases not improved.The KPS score was 77.14 ±23.12 on average,and there was no statistically significant difference compared with that before operation (P >0.05 ).The postoperative follow-up for half a year showed fluent speaking and writing in 19 cases (KPS 70 or higher),and general recovery in 2 cases (KPS <70).The postoperative follow-up for 3 -29 months showed no tumor recur-rence or progress.Conclusion:The combining trans-subtemporal and suboccipital retrosigmoid keyhole approach is simple,safe,and minimally invasive,and an ideal operation approach of petroclival menin-gioma.To master the operation skills and the intraoperative matters needing attention in the operation,is favorable to improve the resection rate and curative effect.
ABSTRACT
miRNAs are a class of small endogenous RNAs that degrade target mRNAs or repress their translation process. Several miRNAs in glioma are up?regulated, while some others down?regulated. Some miRNAs promote tumorigenesis; some others, however, play a similar function of tumor suppressor genes. Therefore, studies on the expression profiles of miRNAs in glioma may afford auxiliary basis for early clinical diagnosis and novel srtategies for therapy of glioma. This paper will review on researches about the expression levels of miRNAs and their targets in glioma.
ABSTRACT
Aim To investigate the effect of DHA on NGF-induced neuronal differentiation of PC12 cells and explore the possible mechanism via regulating BMP pathway. Methods PC12 cells were treated with 100μg·L-1 NGF and 100 μg·L-1 NGF + 10 μmol· L-1 DHA for 3, 6 and 9 days respectively. The length and number of neurite were detected by immunofluores-cenc. DHA content was analyzed by gas chromatogra-phy in all groups. The protein expression of BMP4, BMP7 , BMPR-II and p-Smad 1/5/8 was determined by Western blot. Results The length of total primary neurite in NGF+DHA groups was obviously increased, longer than that in NGF group; DHA content in 10μmol · L-1 DHA group was higher than that in the control group;NGF+DHA groups also unregulated the protein expression of BMP4 , BMP7 , BMPR-II and p-Smad 1/5/8 . Conclusion DHA promotes NGF-in-duced neuronal differentiation in PC12 cells, which may be associated with the upregulation of BMP path-way protein.
ABSTRACT
Objective To study the initial application of 3.0T high field intensity intraoperative magnetic resonance(iMR)for cranial tumors.Methods Forty-three patients with cranial tumors including 23 glioma cases,12 pituitary tumor cases,3 brain stem cavernous hemangioma cases,2 meningioma cases,2metastatic tumor cases,1 neurilemmoma case,received operation examined with GE Signa HDX 3.0T iMR system.The operation process and influence of iMR were reviewed.Results In 43 patients,average iMR examination was 1.3(1-3)times.In 16 patients the first iMR examination revealed tumor remnants,and in 13 of them continued surgical interventions and complete resection.The rate of complete resection was increased from 63％(27/43)to 93％(40/43).No complications related to iMR occurred.Conclusion 3.0T high field intensity iMR can provide accurate positioning and real-time navigation for the surgery,increase the rate of complete resection,improve the accuracy and safety of cranial tumor resection,and decrease complications.
ABSTRACT
Objective To study the cell immunity and eytokines responses to avian influenza A H5N1 virus infections in a BALB/c model to better understand the pathogenesis of H5N1 avian influenza disease. Methods Two hundred and twenty BALB/c mice of the infected group were inoculated with 0.1 ml (10-4.875 TCID50) of A/Goose/Guangdong/NH/2003 ( H5N1 ) virus intra-nasally. Fifty control mice received noninfectious allantoic fluid and another fifty control mice received normal sodium. Blood and spleen samples were collected from the live mice every 24 h during the 14 d post-infection. The changes of CD3 + T cells , CD4 + T cells, CD8 + T cells for cell immunity in blood circulation and spleen were detected by flow cytometry. And the cytokines and antibody responses in blood circulation were detected by ELISA. Necropsy was performed on mice that died during the experiment and those euthanized at end of study. Results Avian influenza A( H5N1) virus infections can make damages to the cell immune system transiently. The CD3 + T cells, CD4 + T cells, CDS + T cells declined at 24 days post infection in blood circulation and declined at 5-8 days in spleen, then recovered to the normal level gradually. The eytokines responses to the infections can be detected: the level of IFN-γ,TNF-α declined, IL-4, IL-18, IL-10 increased, and IL-2 changed little. The antibody increased rapidly from day 7 post infection until the end of the study (day 14 post infection). Conclusion Collectively, avian influenza A(H5N1) virus can cause cell immunity deficiency and an imbalance in the level of eytokines, which may contribute to the unusual severity of disease caused by the H5N1 avian influenza virus.
ABSTRACT
Objective To test our hypothesis that sensitivity to avian influenza A(H5N1)virus varies among mouse strain backgrounds, we compared the pathogenicity of H5N1 viral infection in 5 mouse strains. Methods Onehundred-fifty mice from 2 inbred strains(BALB/c and C57BL/6), and 3 outbred stocks(ICR, NIH Swiss, and KM Swiss)were used. Thirty mice of each strain were subjected to an infected group(20 mice), in which mice were inoculated with 0. 1 mL(104.875 TCID50)of A/Goose/Guangdong/NH/2003(H5N1)virus intra-nasally; ten control mice received noninfectious allantoic fluid. Clinical signs were assessed daily for 14 days post-infection. Necropsy was performed on mice that died during the experiment and those euthanized at end of study. Tissue samples were collected for viral isolation and pathological analysis. Results H5N1 virus infection can cause respiratory illness in all 5 strains with severe or minor acute respiratory distress symptoms, but with different mortality rates: 70% in BALB/c; 50% in ICR; 40% in NIH Swiss; 25% in C57BL/6; and 10% in KM Swiss mice. Necrotizing interstitial pneumonia was found in all cases of death. The virus was isolated from the lungs of all infected dead mice. Conclusion A/Goose/Guangdong/NH/2003 (H5N1)virus can infect all mouse strains used in this study, and can cause clinical symptoms and pathological changes similar to those found in humans infected with HSN1 viruses. However, the pathogenicity of H5N1 viral infection varies significantly between the different mouse strains. Thus, in future study of H5N1 virus infections the mouse strain most relevant to their particular research purpose should be selected as animal model.
ABSTRACT
Aim To observe the change of amyloid, acetylcholine transferase and glial fibrillary acidic protein expression in Macaca Rhesus hippocampal after infused the Aβ_(1-42) and thiorphan and explore the possibility of the establishment of Macaca Rhsus AD model in brain.Method The Rhesus monkeys were anesthetized (im), the skull was exposed by a midline scalp incision, and oriented craniotomy was performed on left side by dental drill.First, neprilysin in cerebral cortex and basal nucleus was consumed by infusion thiorphan. Then cerebral cortex and basal nucleus were slowly infused with fibrilla Aβ_(1-42). Finally, the cannula for thiorphan infusion was implanted into the basal nucleus.Miniosmotic pump (Alzet MODEL 2ML4,) was subcutaneously fixed by bio gel 454 on the calvaria (Loctite Co. Ltd,USA) according to the manufacturer's instructions.After 50 days' survival, animals were deep anesthetized with ketamine and sacrificed. The pathological changes were observed by HE staining and immunostaining in monkey brains.Result Neuronal loss and a proliferation of microglia were detected in hippocampal formation by HE staining.Immuno-staining showed Aβ_(1-42),ChAT and GFAP positive cells density were 0.59±0.05,0.21±0.04 and 0.19±0.04 separately.Compared with control group, the density in experimental groups showed distinct difference in statistic analysis (P<0.01).Conclusion The same pathological change was detected in the thioaphan and Aβ_(1-42) infusion in Macaca Rhesus hippocampal formation as what was found in AD patients.