Wen X.,Guangzhou University |
Huang A.,Sun Yat Sen University |
Hu J.,Sun Yat Sen University |
Zhong Z.,Sun Yat Sen University |
And 5 more authors.
Neuroscience | Year: 2015
Oxidative stress (OS) mediated the pathogenesis of Alzheimer's disease (AD). Astaxanthin (ATX) has been reported to exert antioxidant activities as well as neuroprotective effects in vivo and in vitro. But it is still unknown whether the Akt/glycogen synthase kinase-3β (GSK-3β) signaling mediated the neuroprotective effect of ATX in HT22 cells. Flow cytometric analysis was used to evaluate reactive oxygen species (ROS) generation. Caspase and PARP activity was measured. The expressions of heme oxygenase-1 (HO-1), nuclear factor-E2-related factor 2 (Nrf2), Bcl-2, Bax, apoptosis-inducing factor (AIF), cytochrome-c (Cyto-c), p-Akt and p-GSK-3β were evaluated to elucidate the underlying mechanism. Our results showed that ATX significantly attenuated glutamate-induced cell viability loss and lactate dehydrogenase (LDH) release, decreased the expression of caspase-3/8/9 activity and cleaved PARP, and suppressed the intracellular accumulation of ROS in HT22 cells after exposure to glutamate. ATX also increased the mitochondrial expression of AIF, Cyto-c as well as Bax while decreased Bcl-2. Moreover, ATX also induced the HO-1 expression in a dose and time-dependent manner, increased the antioxidant-responsive element (ARE) activity and nuclear Nrf2 expression. Furthermore, treatment with ATX restored the p-Akt and p-GSK-3β (Ser9) as well as HO-1 expression reduced by glutamate. This protective effect was partially blocked by the inhibitors lithium chloride treatment in HT22, indicating the involvement of Akt/GSK-3β inactivation during the neuroprotective effect of ATX. Our results provide the first evidence that ATX can protect glutamate-induced cytotoxicity in HT22 via attenuating caspase activation and mitochondrial dysfunction and modulating the Akt/GSK-3β signaling, indicating ATX may be useful for the treatment of neurodegenerative disorders such as AD. © 2015 IBRO. Source
Zhang R.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
Shi X.-D.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
Zeng H.,Sun Yat Sen University |
Cai Z.-X.,Sun Yat Sen University |
And 4 more authors.
Experimental and Therapeutic Medicine | Year: 2015
Autoimmune pancreatitis (AIP) is a rare type of chronic pancreatitis that is often misdiagnosed as pancreatic cancer (PaC). This study was undertaken to investigate the clinicopathological characteristics of AIP, in order to improve the diagnosis and treatment of the disease. Among the 271 patients with PaC who underwent pancreatoduodenectomy between January 2003 and December 2012 at the Sun Yat-Sen Memorial Hospital, chronic pancreatitis was identified and tissue samples obtained from 16 patients. The clinicopathological and imaging characteristics of 16 of the patients with chronic pancreatitis were analyzed retrospectively. The expression of immunoglobulin G4 (IgG4) in the pancreas tissue was detected by immunohistochemistry. Immunohistochemistry showed that IgG4 was highly expressed in 12 out of the 16 patients, and those 12 patients were diagnosed with AIP. Among those 12 patients, 6 presented with emaciation and 7 with jaundice and abdominal pain, respectively. Among the 16 included patients, 12 had an elevated level of serum γ-glutamyltransferase and 9 had an elevated level of serum carbohydrate antigen 19-9. The imaging features were as follows: Pancreatic enlargement in 11 patients (particularly pancreatic head enlargement), pancreatic miniature in 1, ‘sausage-like’ pancreatic changes in 4 and ‘halo’ sign pancreatic changes in 5. Massive plasma cell infiltration (11/12) and parenchymal fibrosis (8/12) were observed in the pancreatic tissues through pathology. These results suggest that combining imaging with IgG4 expression for the purpose of diagnosis can enhance the preoperative diagnostic value and reduce the rate of AIP misdiagnosis. © 2015, Spandidos Publications. All rights reserved. Source
Ding L.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
Ding L.,Sun Yat Sen University |
Li Q.-J.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
You K.-Y.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
And 4 more authors.
Medicine (United States) | Year: 2016
Apatinib is a novel tyrosine kinase inhibitor targeting vascular endothelial growth factor receptor-2, which has been proved to be effective and safe in treating heavily pretreated patients with gastric cancer. The aim of the study was to explore the use of apatinib in treatment of nonsmall cell lung cancer and its side effects. We report 2 patients presented with advanced nonsmall-cell lung cancer, who received apatinib after failure in the first-or third-line chemotherapy. They are treated with apatinib in daily dose of 850mg, 28 days per cycle. Favorable oncologic outcomes were achieved in the 2 cases after the treatment of apatinib. Patient I's progression-free-survival has increased to 4.6 months after palliative therapy of apatinib, whereas Patient II nearly 6 months. The common side effects of apatinib were hypertension and hand-foot syndrome; however, the toxicity of apatinib was controllable and tolerable. Apatinib may be an option for advanced nonsmall cell lung cancer after failure of chemotherapy or other targeted therapy. But that still warrants further investigation in the prospective study. © 2016 Wolters Kluwer Health, Inc. All rights reserved. Source
Zhao Y.-N.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
Zhao Y.-N.,Sun Yat Sen University |
Chen G.-S.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
Chen G.-S.,Sun Yat Sen University |
And 2 more authors.
Experimental Hematology and Oncology | Year: 2014
MicroRNAs (miRNAs) have been demonstrated to play critical roles in many physiological and pathophysiological processes. The presence of altered miRNA profiles in human body fluids has been reported for a number of diseases including gynecological malignancies. In this review, we summarized the current progresses of circulating miRNAs associated with malignancies in gynecology, with an emphasizing on the circulating miRNAs as diagnostic and prognostic biomarkers in ovarian cancer, endometrial carcinoma and cervical cancer. © 2014 Zhao et al. Source
Chen C.,Sun Yat sen Memorial Hospital |
Chen C.,Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation |
Cai Q.,Sun Yat Sen University |
He W.,Sun Yat sen Memorial Hospital |
And 12 more authors.
International Journal of Cancer | Year: 2016
The L-plastin gene is involved in the invasion and metastasis of prostate cancer. However, the molecular mechanisms underlying L-plastin transcription are unclear. We hypothesize that the occurrence of polymorphic genetic variations in the L-plastin promoter might affect an individual's susceptibility to prostate cancer. In this study, we identified a single nucleotide polymorphism (SNP) at position -1,687 in the L-plastin promoter by genotype sequencing. The SNP -1,687 showed different transcriptional activity in the luciferase assay in vitro. The TRANSFAC software was applied to predict the multiple cis-elements, and luciferase assay was used to further identify the L-plastin regulatory region. We performed EMSAs, supershift assays and ChIP-qPCR demonstrated that the transcriptional suppressor NKX3.1 binds to the SNP site of the L-plastin promoter. SNP -1,687 (T/T) led to an increase in the affinity of NKX3.1 for L-plastin promoter, resulted in lower levels of L-plastin RNA and protein expression. Furthermore, we collected and sequenced samples from 640 individuals (372 prostate cancer patients and 268 healthy controls) from 2000 to 2013. The results showed that SNP -1,687 (T/T) occurred more frequently in the healthy individuals than that in the prostate cancer patients compared to SNP -1,687 (C/C). Similarly, SNP -1,687 (T/T) genotype occurred more frequently compared to SNP -1,687 (C/C) genotype in the patients with low and moderately differentiated tumors. In conclusion, SNP -1,687, located in the NKX3.1 binding site within the L-plastin promoter, might reduce the expression of L-plastin and potentially decrease the tumorigenesis and progression of prostate cancer. This SNP could be a potential prognostic factor for prostate cancer. What's new? A single base pair change in a gene's promoter region can influence cancer progression, according to new results. The L-plastin gene is important for prostate cancer invasion and metastasis, and these authors sequenced the promoter region looking for variable regions. They identified a SNP at position-1687; then they showed that a transcriptional suppressor binds this site. One of the variant sequences helps that suppressor bind more strongly, and that variant showed up more often in healthy individuals and low recurrence risk in those with cancer. Thus, this L-plastin promoter SNP could be a useful indicator for prostate cancer prognosis. © 2015 UICC. Source