Inflammatory CXCL12-CXCR4/CXCR7 axis mediates G-protein signaling pathway to influence the invasion and migration of nasopharyngeal carcinoma cells.

This study explored whether the migration, invasion, and apoptosis of nasopharyngeal carcinoma (NPC) cells were affected by the CXCR4/CXCR7-CXCL12 axis and if this mechanism was related to G-protein signaling pathway. A total of 72 NPC patients admitted in our hospital between April 2013 and February 2015 were incorporated in this study. Immunohistochemistry was performed to compare the expression levels of CXCR4, CXCR7, and CXCL12 between NPC tissues and adjacent normal tissues. Then, the correlation analysis was implemented to assess the association among CXCR4, CXCR7, and CXCL12 expressions. Jellyfish glow protein experiment was carried out after the cultivation of CNE-2Z cell lines in order to observe the intracellular calcium mobilization resulted from G-protein activation contributed by CXCR4/CXCR7-CXCL12 axis. The impact of CXCR4/CXCR7-CXCL12 axis on the migration and invasion of NPC cells was explored using transwell experiments. Finally, the anti-apoptosis effects of CXCR4/CXCR7-CXCL12 axis on NPC cells were investigated by the splicing of poly ADP-ribose polymerase (PARP). Compared to NPC patients with low-grade (stage I-II) tumor node metastasis (TNM) and those without lymph node metastasis, the expression of CXCR4, CXCR7, and CXCL12 were significantly higher in NPC patients with high-grade (stage III-IV) TNM and those with lymph node metastasis (P < 0.05). Moreover, there was significant positive correlation between the expression level of CXCL12 and CXCR7 (r s = 0.484, P < 0.001) as well as the expression level of CXCL12 and CXCR4 (r s = 0.414, P < 0.001). As suggested by cellular experiments using CNE-2Z, the calcium mobilization degree induced by CXCR4-CXCL12 axis in activating G proteins seemed to be slightly more effective than that induced by CXCR4/CXCR7-CXCL12 axis, while the CXCR7-CXCL12 axis could hardly activate calcium mobilization. Furthermore, the transwell experiment showed that CXCR4/CXCR7-CXCL12 axis could exacerbate the migration and invasion of NPC cells (P < 0.05). The transwell experiment also suggested that the CXCR4/CXCR7-CXCL12 axis was associated with the expression of matrix metallo proteinase 9 (MMP9) which is a substance in the downstream of G-protein pathways (P < 0.05). Results from PARP shear zone also indicated that the CXCR4/CXCR7-CXCL12 axis could suppress NPC cell apoptosis (P < 0.05). The expressional levels of CXCR4, CXCR7, and CXCL12 significantly varied with clinical stages and status of lymph node metastasis of NPC patients. This revealed potential indicators which can be used for NPC prognosis. Additionally, the CXCR4/CXCR7-CXCL12 axis may regulate the expression of downstream proteins (e.g., MMP-9) through the activation of G-protein signaling pathways. These conclusions may provide key evidence for NPC aetiology which can be further investigated to develop novel molecular targets for NPC treatments.

Retinoblastoma-binding protein 2 induces epithelial-mesenchymal transition in esophageal squamous cancer cells.

OBJECTIVES: To investigate the effect of retinoblastoma-binding protein 2 (RBP2) on epithelial-mesenchymal transition (EMT) in esophageal squamous cancer cells and to compare the effect of RBP2 in lung squamous cancer cells and esophageal squamous cancer cells. RESULTS: When transfected with RBP2 siRNA, the migrated cells were 36.3 ± 6.03 by transwell migration assay, compared to 107 ± 6.7 cells in the control group. The mRNA level of epithelial cadherin (E-cadherin) was 1.54 ± 0.14 times higher than in the control group, and that of neural cadherin (N-cadherin) fell to 0.76 ± 0.03 times. The relative luciferase activity of E-cadherin promoter rose to 3.84 ± 0.23 times. Correspondingly, the expression of E-cadherin protein increased and that of N-cadherin protein decreased. When SK-MES-1 cells were transfected with RBP2 siRNA, their relative mRNA level of E-cadherin was 8.6 ± 0.37 times as high as that in control group, which was higher than that in Eca-109 cells. The E-cadherin protein was also greater in SK-MES-1 cells. CONCLUSION: RBP2 could induce EMT in esophageal cancer cells and exert a greater effect on the expression of E-cadherin in lung squamous cells than in esophageal squamous cells.

Anti-Hsp20 antibody concentrations inversely correlated with tumor progression in ovarian cancer.

PURPOSE: To investigate the serum concentrations of anti-heat shock protein 20 (anti-Hsp20) antibodies in women with ovarian cancer at different clinical stages, and the relationship between these concentrations and tumor progression. MATERIALS AND METHODS: Blood samples were obtained from 72 patients undergoing surgery for ovarian cancer, 21 women with ovarian carcinoid, and 42 healthy women. Anti-Hsp20 antibody concentrations were determined by enzyme-linked immunosorbent assay. RESULTS: Mean anti-Hsp20 antibody concentrations were significantly lower in patients with ovarian cancer than in the control group. The anti-Hsp20 antibody concentrations were negatively correlated with ovarian cancer malignancy. CONCLUSIONS: The present findings suggest that anti-Hsp20 antibodies may play a protective role against ovarian cancer progression, and that anti-Hsp20 antibodies may be a new index for the early diagnosis and treatment of ovarian cancer.

Expression of heat shock protein 20 inversely correlated with tumor progression in patients with ovarian cancer.

OBJECTIVE: To investigate a possible correlation between expression levels of heat shock protein 20 (HSP20) and tumor progression in patients with ovarian cancer. MATERIALS AND METHODS: The study included 34 patients with ovarian cancer who were to undergo surgery, seven patients with ovarian carcinoid tumors, and five patients with normal ovaries as a control group. Ovarian tissues were obtained from patients by surgical resection and then analyzed by western blot. RESULTS: Expression levels of HSP20 were inversely correlated with the grade of malignancy. CONCLUSION: The present findings suggest that HSP20 may play a protective role against the progression of ovarian cancer. Thus, HSP20 may represent a new target for the prediction and treatment of ovarian cancer.

The value of mesothelin in the diagnosis and follow-up of surgically treated ovarian cancer.

OBJECTIVE: To assess the value of serum mesothelin concentration for diagnosis of ovarian cancer and for monitoring the therapeutic effect of surgical treatment. MATERIALS AND METHODS: The study consisted of 42 patients with ovarian cancer undergoing surgery, 48 with benign ovarian tumors, and 49 healthy controls. Blood was drawn pre-operatively and one month post-operatively to test serum mesothelin levels. RESULTS: Mesothelin values were higher in the ovarian cancer group compared to controls and higher preoperatively vs post-operatively in the ovarian cancer group. For the diagnosis of ovarian cancer, the positive predictive value of serum mesothelin was 80.5%, the negative predictive value was 81.6%, sensitivity was 78.6%, and specificity was 83.3%. CONCLUSION: Serum mesothelin is increased in ovarian cancer, has high-specificity, and can be used in the pre-operative diagnostic evaluation for ovarian cancer.

Extended-field intensity-modulated radiotherapy and concurrent cisplatin-based chemotherapy for postoperative cervical cancer with common iliac or para-aortic lymph node metastases: a retrospective review in a single institution.

OBJECTIVE: Retrospectively, to assess the toxicity of delivering postoperative extended-field intensity-modulated radiotherapy (EF-IMRT) and concurrent cisplatin chemotherapy for patients with cervical cancer with a pathologically confirmed positive common iliac node and/or a para-aortic node. METHODS: Each patient received postoperative EF-IMRT and concurrent cisplatin chemotherapy. The clinical target volume included regional lymph node regions (obturator; common, internal, and external iliac nodal regions; presacral region; and para-aortic regions) and the upper 2.0 cm of the vagina and paravaginal soft tissue lateral to the vagina. The acute and late toxicity were scored using the Common Terminology Criteria for Adverse Events (CTCAE) and the Radiation Therapy Oncology Group late radiation morbidity scoring criteria, respectively. RESULTS: Fifty-eight patients were treated with postoperative EF-IMRT and concurrent cisplatin chemotherapy. The median follow-up was 34 months. Eighteen patients (31%) had recurrence. The region of recurrence was in-field in 2 patients (3.4%) and out-field in 16 patients (27.6%). Acute grade 3 or higher gastrointestinal, genitourinary, and hematologic toxicity occurred in 2, 1, and 11 patients, respectively. Three patients (5.1%) had late grade 3 toxicities. Thirteen patients experienced ovarian transposition; of these, 10 patients (77%) maintained ovarian function. Forty-one patients (71%) were alive at the last follow-up. CONCLUSIONS: Concurrent cisplatin chemotherapy with postoperative EF-IMRT was safe and well tolerated. The acute and late toxicities are acceptable. The locoregional control rates are hopeful, although distant metastases continue to be the primary mode of failure. Postoperative EF-IMRT provides an opportunity to preserve endocrine function for patients with ovarian transposition.

Association between the telomerase reverse transcriptase (TERT) rs2736098 polymorphism and cancer risk: evidence from a case-control study of non-small-cell lung cancer and a meta-analysis.

BACKGROUND: A common genetic variant, telomerase reverse transcriptase (TERT) rs2736098, was recently reported to be associated with lung cancer risk in Caucasians. In addition, many studies have investigated the role of this polymorphism in the etiology of cancer of various organs. Nevertheless, the results of related case-control studies remain inconsistent. METHODS: We hypothesized that the genetic risk variant identified in Caucasians may potentially influence the susceptibility to lung cancer in the Chinese population. To test this hypothesis, a case-control study including 539 non-small-cell lung cancer (NSCLC) cases and 627 cancer-free controls was conducted. Furthermore, to investigate the association between rs2736098 and cancer risk, a meta-analysis based on previously published studies and our case-control study was also performed. RESULTS: Multivariate logistic regression demonstrated that individuals carrying the A allele or the AA genotype exhibited a significantly elevated risk of NSCLC compared with those carrying the G allele or GG genotype (A vs. G: OR = 1.21, 95% CI = 1.02-1.43, P = 0.028; AA vs. GG: OR = 1.48, 95% CI = 1.05-2.09, P = 0.025). Additionally, this association was stronger among adenocarcinoma cases (AA vs. GG: OR = 1.67, 95% CI = 1.12-2.50, P = 0.013; A vs. G: OR = 1.28, 95% CI = 1.05-1.57, P = 0.016). In the meta-analysis, a borderline significant association between the rs2736098 polymorphism and overall cancer risk was observed (AA vs. GG: OR = 1.25, 95% CI = 1.07-1.46; AA vs. AG+GG: OR = 1.22, 95% CI = 1.06-1.41; additive model: OR = 1.10, 95% CI = 1.02-1.18), and further stratifications demonstrated a moderately increased risk for lung and bladder cancer, Asian ethnicity and hospital-based studies. CONCLUSIONS: Our results suggest that the rs2736098 polymorphism may contribute to the risk of lung cancer, especially adenocarcinoma, in the Chinese population. In addition, the current meta-analysis indicates that this genetic variant is only weakly associated with overall cancer risk. However, the rs2736098 polymorphism may affect individual susceptibility to lung and bladder cancer. Further studies are needed to validate our findings.