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Feng R.,Fujian Medical University | Yang S.,Fujian Medical University | Yang S.,Fujian Key Laboratory of Translational Cancer Medicine
Journal of International Medical Research | Year: 2016

Objective: To investigate the synergistic effects of combining erlotinib and RNA-interference downregulation of focal adhesion kinase (FAK) expression on the proliferation, apoptosis, invasion and migration of the human gastric adenocarcinoma cell line AGS. Methods: Cells were divided into five experimental groups: Group A, nontransfected control; Group B, transfected with empty vector; Group C, transfected with FAK-shRNA; Group D, erlotinib treatment; Group E, combination erlotinib treatment and transfected with FAK-shRNA. FAK protein levels were confirmed via Western blotting. Cell proliferation (CCK-8 assay, apoptosis (flow cytometry), cell invasion (transwell assay) and migration (scratch assay) were evaluated. Results: RNA interference significantly decreased FAK protein levels. Cell proliferation, invasion and migration were significantly lower in Groups C, D and E compared with Group A, and significantly lower in Group E than in Groups C and D. Conclusions: RNA interference effectively silences FAK expression and inhibits malignant cell proliferation and invasion in gastric cancer cells. The effect of FAK inhibition is increased by co-treatment with erlotinib. © 2016, © The Author(s) 2016. Source

Ye Y.B.,Fujian Key Laboratory of Translational Cancer Medicine
Xi bao yu fen zi mian yi xue za zhi = Chinese journal of cellular and molecular immunology | Year: 2011

To reveal the classification of lymphocytes and expression of cytokines infiltrating in HCC, and investigate the significance of changes of immune microenvironment in HCC. 76 tumor and non-tumor tissues of HCC were collected to detect the amount of immune cells in the tissues by FCM and immunohistochemistry (IHC). Th1/Th2 cytokines in tissues were detected by Cytometric bead array (CBA), and TGF-1, VEGF detected by ELISA. There were more CD3(+); T cells, CD4(+); Th cells, Treg cells, and CD45RO(+); memory T cells in tumors than in non-tumor tissues. On the contrary there were less CD8(+); CTLs in tumors. There was negative correlation between Treg and Th or CTL cells. CD69, which is the early activating factor, expressed less on CD3(+); T cells and NK cells in tumors than non-tumor tissues. Whereas HLA-DR, which is the late activating factor, expressed more on CD3(+); T cells in tumors than non-tumor tissues. More IL-10, TGF-1 and VEGF were secreted in tumors than non-tumor tissues. Along with the decrease of effective immune cells and increase of suppressor immune cells and cytokines, the lymphocytes infiltrating in the tumor were immune incompitence, which contributed to the tumorigenesis. Source

Hou P.,Beckman Research Institute | Hou P.,Fujian Medical University | Hou P.,Fujian Key Laboratory of Translational Cancer Medicine | Kuo C.-Y.,Beckman Research Institute | And 5 more authors.
PLoS ONE | Year: 2014

Hypoxia-inducible factor 1 a (HIF-1α), a major mediator of tumor physiology, is activated during tumor progression, and its abundance is correlated with therapeutic resistance in a broad range of solid tumors. The accumulation of HIF-1α is mainly caused by hypoxia or through the mutated succinate dehydrogenase A (SDHA) or fumarate hydratase (FH) expression to inhibit its degradation. However, its activation under normoxic conditions, termed pseudohypoxia, in cells without mutated SDHA or FH is not well documented. Here, we show that dimethyl-2-ketoglutarate (DKG), a cell membrane-permeable precursor of a key metabolic intermediate, α-ketoglutarate (α-KG), known for its ability to rescue glutamine deficiency, transiently stabilized HIF-1α by inhibiting activity of the HIF prolyl hydroxylase domain-containing protein, PHD2. Consequently, prolonged DKGtreatment under normoxia elevated HIF-1α abundance and up-regulated the expression of its downstream target genes, thereby inducing a pseudohypoxic condition. This HIF-1α stabilization phenotype is similar to that from treatment of cells with desferrioxamine (DFO), an iron chelator, or dimethyloxalyglycine (DMOG), an established PHD inhibitor, but was not recapitulated with other α-KG analogues, such as Octyl-2KG, MPTOM001 and MPTOM002. Our study is the first example of an α-KG precursor to increase HIF-1a abundance and activity. We propose that DKG acts as a potent HIF-1α activator, highlighting the potential use of DKG to investigate the contribution of PHD2-HIF-1α pathway to tumor biology. © 2014 Hou et al. Source

Lin G.,Fujian Medical University | Zheng X.-W.,Fujian Medical University | Li C.,Fujian Medical University | Chen Q.,Fujian Key Laboratory of Translational Cancer Medicine | And 3 more authors.
Digestive Diseases and Sciences | Year: 2012

Background: Evidence shows a strong relationship between KRAS mutations and the NF-κB signaling pathway. In colorectal cancer, however, the study of this subject has been very limited and results are inconsistent. Aims: To examine the relationship between KRAS mutations and NF-κB activation and their effect on chemotherapy response and survival of colorectal cancer patients. Materials and Methods: NF-κB activation was analyzed by immunohistochemistry in 167 primary colorectal cancer specimens in which the KRAS mutation status was confirmed. Clinical and pathologic data were extracted from the medical records and reviewed. Results: Of 167 tumors screened, 63 (37.7 %) had NF-κB activation, 59 (35.3 %) had KRAS mutations, and 30 (18.0 %) had both NF-κB activation and KRAS mutations. The frequency of NF-κB activation in tumors with KRAS mutations was significantly higher than in tumors with wild type KRAS; 50.8 versus 30.6 %, P = 0.012. Patients with both KRAS mutations and NF-κB activation had a lower objective response to first-line chemotherapy than patients with other tumors, 23.8 versus 49.4 % (P = 0.035). Compared to patients with both KRAS mutations and NF-κB activation, overall survival of patients in other groups was significantly higher; median overall survival was 28.4 months (95 % CI 21.0-35.8) versus 46.3 months (95 % CI 39.4-53.2), hazard ratio 0.259 (95 % CI 0.125-0.538), P = 0.005. Conclusions: NF-κB activation was associated with KRAS mutation, and both KRAS mutation and NF-κB activation were indicative of high tolerance of chemotherapy and poor prognosis for colorectal cancer patients. Tumors with KRAS mutations and NF-κB activation may be a unique subtype of colorectal cancer. © 2012 Springer Science+Business Media, LLC. Source

Zhong D.T.,Fujian Medical University | Zhong D.T.,Fujian Key Laboratory of Translational Cancer Medicine | Shi C.M.,Fujian Medical University | Shi C.M.,Fujian Key Laboratory of Translational Cancer Medicine | And 5 more authors.
Journal of Cancer Research and Clinical Oncology | Year: 2012

Objective To evaluate through retrospective analysis the efficacy and toxicity of combination chemotherapy with etoposide, vincristine, doxorubin and dexamethasone (EVAD) as second-line therapy in patients with advanced AIDS-related Kaposi's sarcoma (AIDS-KS) after failure of first-line chemotherapy. Methods Eighty-eight patients with poor-risk AIDS-KS were treated intravenously with combination chemotherapy with EVAD; etoposide at a dose of 100 mg/m 2 on three consecutive days, vincristine 1.4 mg/m 2 with a maximum single dosage of 2.0 mg on day one, doxorubicin 30 mg/m 2 on day one and dexamethasone 40 mg on three consecutive days, with a three week cycle. All eligible patients had relapsed or progressed after prior two to six cycles of combination chemotherapy with doxorubicin, bleomycin and vincristine (ABV) or bleomycin and vincristine (BV). Results Assessment of the response of all the patients was made. The overall objective response rate was 59.1% (95% CI 48.83-69.37%), with five complete responses and 47 partial responses. Twenty-six cases of stable disease and 10 of progressive disease were observed in the remaining patients. The median follow-up period was 27 months (range 8-52 months). The median time to progression was 6.80 months (95% CI 2.04-11.56 months), and the median overall survival was 14.24 months (95% CI 10.26- 18.22 months). Leucopenia was seen in 92.0% of patients, of which 20 patients had grade 3 and 12 had grade 4. Conclusions Combination chemotherapy with EVAD oVers a new, active and safe therapeutic approach for the treatment of advanced AIDS-related KS. © Springer-Verlag 2011. Source

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