Jiangsu Key Laboratory of Molecular and Translational Cancer Research

Nanjing, China

Jiangsu Key Laboratory of Molecular and Translational Cancer Research

Nanjing, China

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Yin L.,Nanjing Medical University | Yin L.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | Wu J.,Nanjing Medical University | Wu J.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | And 16 more authors.
BioMed Research International | Year: 2014

This study aims to evaluate the radiosensitization effect of nedaplatin on nasopharyngeal carcinoma (NPC) cell lines with different Epstein-Barr virus (EBV) status. Human NPC cell lines CNE-2 (EBV-negative) and C666 (EBV-positive) were treated with 0-100 g/mL nedaplatin, and inhibitory effects on cell viability and IC50 were calculated by MTS assay. We assessed changes in radiosensitivity of cells by MTS and colony formation assays, and detected the apoptosis index and changes in cell cycle by flow cytometry. MTS assay showed that nedaplatin caused significant cytotoxicity in CNE-2 and C666 cells in a time- and dose-dependent manner. After 24 h, nedaplatin inhibited growth of CNE-2 and C666 cells with IC50 values of 34.32 and 63.69 g/mL, respectively. Compared with radiation alone, nedaplatin enhanced the radiation effect on both cell lines. Nedaplatin markedly increased apoptosis and cell cycle arrest in G2/M phase. Nedaplatin radiosensitized human NPC cells CNE-2 and C666, with a significantly greater effect on the former. The mechanisms of radiosensitization include induction of apoptosis and enhancement of cell cycle arrest in G2/M phase. © 2014 Li Yin et al.


Yang X.,Nanjing Medical University | Yang X.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | Hu J.-W.,Nanjing Medical University | Hu J.-W.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | And 12 more authors.
PLoS ONE | Year: 2014

Background and Objective: Evidence has shown that matrix metalloproteinases-3 (MMP3) is important for cancer progression. Recent studies about the association between the -1171(5A.6A) polymorphism in MMP3 promoter region and cancer risk have yielded conflicting results. Methodology/Principal Findings: We performed a meta-analysis of 41 studies including 11112 cases and 11091 controls to determine whether the -1171(5A>6A) polymorphism of MMP3 was associated with cancer risk. We assessed the strength of association and performed sub-group analyses by cancer types, ethnicity, smoking status, genotyping method, source of controls and sample size. The pooled results revealed that no significant association of the -1171(5A>6A) polymorphism with overall cancer risk in any of four models. Further sub-group analysis revealed that individuals with the 6A allele had lower risk of gastrointestinal cancer in two models: heterozygote comparison (6A/5A vs. 5A/5A: OR = 0.74, 95%CI: 0.60-0.91; I2 = 1.9%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR = 0.77, 95%CI: 0.64-0.94; I2 = 29.0%). Additionally, the associations were significant in Asian populations for three models: homozygote comparison (6A/6A vs. 5A/5A, OR = 0.68, 95%CI: 0.52-0.90; I2 = 26.7%), heterozygote comparison (6A/5A vs. 5A/5A: OR = 0.75, 95%CI: 0.58-0.98; I2 = 0.0%), and dominant model (6A/6A+6A/5A vs. 5A/5A: OR = 0.69, 95%CI: 0.54-0.88; I2 = 0.5%). It was noteworthy that we had a contrary finding in non-smokers: the variant 6A/6A homozygote might statistically increase cancer risk compared with 6A/5A+5A/5A genotype (OR = 1.92, 95%CI: 1.25-2.96; I2 = 72.7%). Conclusion: This meta-analysis suggests that the -1171(5A>6A) polymorphism in MMP3 promoter region is not associated with overall cancer risk, but it may contribute to decreased cancer risk in Asian population when compared with Caucasian population and significantly reduce the risk of gastrointestinal cancer. © 2014 Yang et al.


Gu J.,Nanjing Medical University | Gu J.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | Yin L.,Nanjing Medical University | Yin L.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | And 13 more authors.
Biochemistry Research International | Year: 2016

Nasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disappointing. Hence, a potent systemic therapy is needed for this cancer. Epidermal growth factor receptor (EGFR) represents a promising new therapeutic target in cancer. We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. In this study, we selected HNE1 and CNE2 cells, which have been proved to possess different EGFR expression levels, to validate our conjecture. The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. Our results showed that cisplatin-induced apoptosis was significantly enhanced by cetuximab in the high EGFR-expressing HNE1 cells but not in CNE2 cells. Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. Thus, the regimen may be applied in personalized NPC treatments. © 2016 Jiajia Gu et al.


Mao Q.,Nanjing Medical University | Mao Q.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | Qiu M.,Nanjing Medical University | Qiu M.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | And 14 more authors.
OncoTargets and Therapy | Year: 2015

The association between polymorphic CAG repeats in the androgen receptor gene in women and breast cancer susceptibility has been studied extensively. However, the conclusions regarding this relationship remain conflicting. The purpose of this meta-analysis was to identify whether androgen receptor CAG repeat lengths were related to breast cancer susceptibility. The MEDLINE, PubMed, and EMBASE databases were searched through to December 2014 to identify eligible studies. Data and study quality were rigorously assessed by two investigators according to the Newcastle-Ottawa Quality Assessment Scale. The publication bias was assessed by the Begg’s test. Seventeen eligible studies were included in this meta-analysis. The overall analysis suggested no association between CAG polymorphisms and breast cancer risk (odds ratio [OR] 1.031, 95% confidence interval [CI] 0.855-1.245). However, in the subgroup analysis, we observed that long CAG repeats significantly increased the risk of breast cancer in the Caucasian population (OR 1.447, 95% CI 1.089-1.992). Additionally, the risk was significantly increased in Caucasian women carrying two alleles with CAG repeats ≥ 22 units compared with those with two shorter alleles (OR 1.315, 95% CI 1.014-1.707). These findings suggest that long CAG repeats increase the risk of breast cancer in Caucasian women. However, larger scale case-control studies are needed to validate our results. © 2015 Mao et al.


Bian C.,Nanjing Medical University | Bian C.,Nanjing Jiangbei Peoples Hospital | Li Z.,Jiangsu Key Laboratory of Molecular and Translational Cancer Research | Xu Y.,Nanjing Medical University | And 3 more authors.
World Journal of Surgical Oncology | Year: 2015

Background: Whole-exome sequencing has shown that lung adenocarcinoma (LAC) can be driven by mutant genes, including TP53, P16, and Smad4. The aim of this study was to clarify protein alterations of P53, P16, and Smad4 and to explore their correlations between the protein alterations and clinical outcome. Methods: We investigated associations among P53 mutant (P53Mut) expression, and P16 and Smad4 loss-of-expression, with clinical outcome in 120 LAC patients who underwent curative resection, using immunohistochemical (IHC) methods. Results: Of the 120 patients, 76 (63.3%) expressed P53Mut protein, whereas 54 (45.0%) loss of P16 expressed and 75 (62.5%) loss of Smad4 expressed. P53Mut expression was associated with tumor size (P = 0.041) and pathological stage (P = 0.025). Loss of P16 expression was associated with lymph node metastasis (P = 0.001) and pathological stage (P < 0.001). Loss of Smad4 expression was associated with tumor size (P = 0.033), lymph node metastasis (P = 0.014), pathological stage (P = 0.017), and tumor differentiation (P = 0.022). Kaplan-Meier survival analysis showed that tumor size (P = 0.031), lymph node metastasis (P < 0.001), pathological stage (P < 0.001), P53Mut protein expression (P = 0.038), and loss of p16 or Smad4 expression (P < 0.001) were significantly associated with shorter overall survival(OS), whereas multivariate analysis indicated that lymph node metastasis (P = 0.014) and loss of p16 or Smad4 expression (P < 0.001) were independent prognostic factors. Analysis of protein combinations showed patients with more alterations had poorer survival (P < 0.001). Spearman correlation analysis showed that loss of Smad4 expression inversely correlated with expression of P53Mut (r = -0.196, P = 0.032) and positively with lost P16 expression (r =0.182, P = 0.047). Conclusions: The findings indicate that IHC status of P53Mut, P16, and Smad4 may predict patient outcomes in LAC. © Bian et al.; licensee BioMed Central.


PubMed | Nanjing Medical University, Xuzhou Medical College and Jiangsu Key Laboratory of Molecular and Translational Cancer Research
Type: | Journal: Biochemistry research international | Year: 2016

Nasopharyngeal carcinoma (NPC) is a common malignant cancer in South China. Cisplatin is a classical chemotherapeutic employed for NPC treatment. Despite the use of cisplatin-based concurrent chemoradiotherapy, distant failure still confuses clinicians and the outcome of metastatic NPC remains disappointing. Hence, a potent systemic therapy is needed for this cancer. Epidermal growth factor receptor (EGFR) represents a promising new therapeutic target in cancer. We predicted that combining the conventional cytotoxic drug cisplatin with the novel molecular-targeted agent cetuximab demonstrates a strong antitumor effect on NPC cells. In this study, we selected HNE1 and CNE2 cells, which have been proved to possess different EGFR expression levels, to validate our conjecture. The two-drug regimen showed a significant synergistic effect in HNE1 cells but an additive effect in CNE2 cells. Our results showed that cisplatin-induced apoptosis was significantly enhanced by cetuximab in the high EGFR-expressing HNE1 cells but not in CNE2 cells. Further molecular mechanism study indicated that the EGFR/AKT pathway may play an important role in cell apoptosis via the mitochondrial-mediated intrinsic pathway and lead to the different antitumor effects of this two-drug regimen between HNE1 and CNE2 cells. Thus, the regimen may be applied in personalized NPC treatments.


PubMed | Nanjing Medical University and Jiangsu Key Laboratory of Molecular and Translational Cancer Research
Type: | Journal: OncoTargets and therapy | Year: 2015

The association between polymorphic CAG repeats in the androgen receptor gene in women and breast cancer susceptibility has been studied extensively. However, the conclusions regarding this relationship remain conflicting. The purpose of this meta-analysis was to identify whether androgen receptor CAG repeat lengths were related to breast cancer susceptibility. The MEDLINE, PubMed, and EMBASE databases were searched through to December 2014 to identify eligible studies. Data and study quality were rigorously assessed by two investigators according to the Newcastle-Ottawa Quality Assessment Scale. The publication bias was assessed by the Beggs test. Seventeen eligible studies were included in this meta-analysis. The overall analysis suggested no association between CAG polymorphisms and breast cancer risk (odds ratio [OR] 1.031, 95% confidence interval [CI] 0.855-1.245). However, in the subgroup analysis, we observed that long CAG repeats significantly increased the risk of breast cancer in the Caucasian population (OR 1.447, 95% CI 1.089-1.992). Additionally, the risk was significantly increased in Caucasian women carrying two alleles with CAG repeats 22 units compared with those with two shorter alleles (OR 1.315, 95% CI 1.014-1.707). These findings suggest that long CAG repeats increase the risk of breast cancer in Caucasian women. However, larger scale case-control studies are needed to validate our results.


PubMed | Nanjing Medical University and Jiangsu Key Laboratory of Molecular and Translational Cancer Research
Type: | Journal: World journal of surgical oncology | Year: 2015

Whole-exome sequencing has shown that lung adenocarcinoma (LAC) can be driven by mutant genes, including TP53, P16, and Smad4. The aim of this study was to clarify protein alterations of P53, P16, and Smad4 and to explore their correlations between the protein alterations and clinical outcome.We investigated associations among P53 mutant (P53(Mut)) expression, and P16 and Smad4 loss-of-expression, with clinical outcome in 120 LAC patients who underwent curative resection, using immunohistochemical (IHC) methods.Of the 120 patients, 76 (63.3%) expressed P53(Mut) protein, whereas 54 (45.0%) loss of P16 expressed and 75 (62.5%) loss of Smad4 expressed. P53(Mut) expression was associated with tumor size (P = 0.041) and pathological stage (P = 0.025). Loss of P16 expression was associated with lymph node metastasis (P = 0.001) and pathological stage (P < 0.001). Loss of Smad4 expression was associated with tumor size (P = 0.033), lymph node metastasis (P = 0.014), pathological stage (P = 0.017), and tumor differentiation (P = 0.022). Kaplan-Meier survival analysis showed that tumor size (P = 0.031), lymph node metastasis (P < 0.001), pathological stage (P < 0.001), P53(Mut) protein expression (P = 0.038), and loss of p16 or Smad4 expression (P < 0.001) were significantly associated with shorter overall survival(OS), whereas multivariate analysis indicated that lymph node metastasis (P = 0.014) and loss of p16 or Smad4 expression (P < 0.001) were independent prognostic factors. Analysis of protein combinations showed patients with more alterations had poorer survival (P < 0.001). Spearman correlation analysis showed that loss of Smad4 expression inversely correlated with expression of P53(Mut) (r = (-)0.196, P = 0.032) and positively with lost P16 expression (r =0.182, P = 0.047).The findings indicate that IHC status of P53(Mut), P16, and Smad4 may predict patient outcomes in LAC.

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