Osteosarcoma is the most common primary sarcoma of the bone. Lung osteosarcoma metastases at diagnosis have a significantly poor prognosis, even when surgery plus chemotherapy are performed. Our goal was to analyze clinical and sarcoma characteristics that could help identify factors related to an increased rate of lung metastasis and to identify different modes of treatment and its correlation with survival. The Surveillance, Epidemiology, and End Results (SEER) database was used to identify all osteosarcoma patients diagnosed from 2010 to 2015. Patient characteristics such as age, sex, ethnicity, marital status, tumor location, histologic grade, surgery, chemotherapy, radiation therapy, SEER cause-specific death classification, survival, and lung metastasis were collected. These factors were analyzed using Univariate and multivariate regression models in survival analyses. A total of 1057 osteosarcoma patients diagnosed from 2010 to 2015 were included, of which 176 were patients with lung metastasis. Substantial disparities in the rate of lung metastasis existed when osteosarcoma patients were stratified according to tumor location (P = 0.0002) and tumor size (P < .001). Using a Multivariate Cox regression model, being older than 30 years (vs. younger than 30, HR = 2.171, 95% CI = 1.623-2.905, P < .0001), having a tumor >5-10 cm (vs. 10 cm (vs. <5 cm, HR = 3.610, 95% CI = 2.066-6.310, P < .0001) were related to an increased HR for all-cause death. The HR decreased in patients with surgery (vs. no surgery, HR = 0.189, 95% CI = 0.138-0.260, P < 0.0001) and osteosarcoma. As for osteosarcoma patients with lung metastases, Multivariate Cox regressions revealed that an increased HR was associated with being older than 30 years (vs. younger than 30 years, HR = 2.142, 95% CI = 1.273-3.605, P = .0041) and married (vs. no marriage, HR = 2.418, 95% CI = 1.400-4.176, P= .0015), while a decreased HR was related to having had surgery (vs. no surgery, HR = 0.282, 95% CI = 0.171-0.464, P < .0001) and chemotherapy (vs. no chemotherapy, HR = 0.107, 95% CI = 0.050-0.229, P < .0001). Advanced age (older than 30 years) and large tumors were related to a higher risk of lung metastases in osteosarcoma patients. Therefore, patients who were diagnosed at advanced age or had large tumors should receive comprehensive chest CT scans. Surgery and chemotherapy can significantly improve the survival of metastatic patients, while radiotherapy did not improve survival in these patients.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Xiaoyi Huang1,*, Xiaosong Zhi2,*, Yisha Gao1, Na Ta1, Hui Jiang1 and Jianming Zheng1 1 Department of Pathology, Changhai Hospital, Second Military Medical University, Shanghai, China 2 Department of Cell Biology, Second Military Medical University, Shanghai, China * These authors have contributed equally to this work Correspondence to: Jianming Zheng, email: // <![CDATA[ mail("jmzheng1962","smmu.edu",23,"") // ]]> Hui Jiang, email: // <![CDATA[ mail("jianghuismmu","163",0,"") // ]]> Keywords: pancreatic cancer; lncRNA; pathogen; mechanism; clinical Received: March 23, 2016 Accepted: June 17, 2016 Published: July 12, 2016

Pancreatic cancer is a devastating disease with poor prognosis. The association between vitamin A, retinol and carotenoid intake and the risk of pancreatic cancer occurrence remains controversial, and therefore it is necessary to make a meta-analysis to clarify the association between vitamin A, retinol and carotenoid intake and pancreatic cancer risk. In the present study, PubMed and EMBASE databases were used to identify qualified studies. The association between dietary vitamin A, retinol and carotenoids was estimated by pooled odds ratios (ORs) and corresponding 95% confidence intervals (CIs). It was found that there was an inverse correlation between vitamin A, beta-carotene and lycopene intake and the risk of pancreatic cancer (for vitamin A, pooled OR = 0.85, 95%CI = 0.74–0.97, P = 0.015; for beta-carotene, pooled OR = 0.78, 95%CI = 0.66–0.92, P = 0.003; for lycopene, pooled OR = 0.84, 95%CI = 0.73–0.97, P = 0.020), which was more prominent in case-control study subgroup. In conclusion, dietary vitamin A, beta-carotene and lycopene might inversely correlate with pancreatic cancer.

For decades, tumor-bearing murine models established using tumor cell lines have been the most commonly used models to study human cancers. Even though there are several studies reported that implant sites caused disparities in tumor behaviors, few of them illuminated the positional effect on immunotherapy. Herein, we describe surgical techniques for a novel orthotopic implantation of syngeneic pancreatic ductal adenocarcinoma (PDAC) tissue slices. This method has a high success modeling rate and stable growth kinetics, which makes it useful for testing novel therapeutics. Pathological examination indicated that the orthotopic tumor displayed poor vascularization, desmoplastic stromal reaction, and a highly immunosuppressive tumor microenvironment. This unique microenvironment resulted in limited response to PD1/CTLA4 blockade therapy and anti-MUC1 (αMUC1) CAR-T transfer treatment. To reverse the suppressive tumor microenvironment, we developed gene modified T-cells bearing a chimeric receptor in which activating receptor NKG2D fused to intracellular domains of 4-1BB and CD3ζ (NKG2D CAR). The NKG2D CAR-T cells target myeloid-derived suppressor cells (MDSCs), which overexpress Rae1 (NKG2D ligands) within the TME. Results indicated that NKG2D CAR-T cells eliminated MDSCs and improved antitumor activity of subsequently infused CAR-T cells. Moreover, we generated a bicistronic CAR-T, including αMUC1 CAR and NKG2D CAR separated by a P2A element. Treatment with the dual targeted bicistronic CAR-T cells also resulted in prolonged survival of orthotopic model mice. In summary, this study describes construction of a novel orthotopic PDAC model through implantation of tissue slices and discusses resistance to immunotherapy from the perspective of a PDAC microenvironment. Based on the obtained results, it is evident that elimination MDSCs by NKG2D CAR could rescue the impaired CAR-T cell activity.

Obesity is a risk factor of cancer. Several genes have been found to play an important role in aetiology of obesity and tumourigenesis. Recently, some studies suggested that rs9939609 polymorphism might be significantly associated with cancer risk, while the results of some other studies were controversial. Databases with time limitation from January 1984 to April 2015 were searched. The pooled odds ratio (OR) with 95% confidence interval was calculated to assess the associations, and subgroup meta-analyses were performed according to the type of cancer and ethnicity of the study populations. Overall, the significant association between rs9939609 polymorphism and cancer risk was found in homozygote model and recessive model. As to subgroup classified by cancer type, there was significant association in endometrial cancer and pancreatic cancer, while no statistical significance was detected in other kind of cancers. Besides, in the subgroup analysis of ethnicity, our results indicated that rs9939609 polymorphism was significantly associated with cancer risk in Asians. The rs9939609 polymorphism may be involved the susceptibility of endometrial cancer and pancreatic cancer, especially in Asian populations. Thus, rs9939609 may be a potential biomarker in early diagnosis or gene therapy target of endometrial cancer and pancreatic cancer.

Background/Aims: MicroRNAs (miRNAs) are a group of non-coding RNAs that play diverse roles in pancreatic carcinogenesis. In pancreatic ductal adenocarcinoma (PDAC), NF-kB is constitutively activated in most patients and is linked to a mutation in KRAS via IkB kinase complex 1 (IKK1, also known as IKKa). We investigated the link between PDAC aggressiveness and miR-1290. Methods: We used miRCURY^TM LNA Array and in situ hybridization to investigate candidate miRNAs and validated the findings with PCR. The malignant behavior of cell lines was assessed with Cell Counting Kit-8, colony formation, and Transwell assays. A dual-luciferase reporter assay was used to evaluate the interaction between miR-1290 and IKK1. Protein expression was observed by western blotting. Results: In this study, 36 miRNAs were dysregulated in high-grade pancreatic intraepithelial neoplasia (PanIN) and PDAC tissues compared with low-grade PanIN tissues. The area under the curve values of miR-1290 and miR-31-5p were 0.829 and 0.848, respectively (95% confidence interval, 0.722–0.936 and 0.749–0.948, both P < 0.001). There was a significant correlation between miR-1290 and histological differentiation (P = 0.029), pT stage (P = 0.006), and lymph node metastasis (P = 0.001). In addition, the in vitro work showed that miR-1290 promoted PDAC cell proliferation, invasion, and migration. Western blotting and the dual-luciferase reporter assay showed that miR-1290 promoted cancer aggressiveness by directly targeting IKK1. The synergist effect of miR-1290 on the proliferation and metastasis of PDAC cells was attenuated and enhanced by IKK1 overexpression and knockdown, respectively. Consistent with the in vitro results, a subcutaneous tumor mouse model showed that miR-1290 functioned as a potent promoter of PDAC in vivo. Conclusion: MiR-1290 may act as an oncogene by directly targeting the 3’-untranslated region of IKK1, and the miR-1290/IKK1 pathway may prove to be a novel diagnostic and therapeutic target for PDAC.