Successful immunotherapy with PD-1 Iinhibitor for advanced pancreatic cancer: report of two cases and review of literature.

Pancreatic cancer is a highly malignant tumor, and most patients are diagnosed at an advanced stage. Unfortunately, due to the immunosuppressive tumor microenvironment of pancreatic cancer, the benefits of immunotherapy for patients with advanced pancreatic cancer are still unclear. Here, we present two cases of advanced pancreatic cancer being controlled by immunotherapy, with pathological diagnoses of ductal adenocarcinoma and acinar cell carcinoma, respectively. Next-generation sequencing (NGS) of both patients is high tumor mutation burden (tumor mutation burden-High) and microsatellite stable. The patient with pancreatic ductal adenocarcinoma was diagnosed as a locally advanced disease (stage III). She received irreversible electroporation, used the programmed death receptor-1 (PD-1) inhibitor (pembrolizumab) combined with chemotherapy (S-1), and then used only the PD-1 inhibitor as a maintenance treatment. As a result, the patient's lesion was significantly reduced, with a partial response time of up to 31 months. The patient with acinar cell carcinoma was diagnosed as a metastatic disease (stage IV), next-generation sequencing revealed mutations in SMAD4 and KMT2D, and two chemotherapy regimens were used unsuccessfully. Then, the combination of chemotherapy with PD-1 (tislelizumab) and vascular endothelial growth factor/vascular endothelial growth factor receptor (anlotinib) inhibitors were used, and the lesions of the patient were significantly reduced, and the progression-free survival after immunotherapy was 19 months. In advanced pancreatic cancer, a prognosis of this magnitude is rare. Our cases reveal the potential of immunotherapy as a cornerstone treatment in the management of advanced pancreatic cancer.

Molecular mechanisms of HCG18 in the sorafenib resistance of hepatocellular carcinoma.

Sorafenib has been approved for advance hepatocellular carcinoma (HCC), however, drug resistance often occurred. Therefore, it is of great significance to clarify the underlying mechanisms of sorafenib resistance and to find out the effective strategies to overcome sorafenib resistance. The expression of HCG18 was detected by qPCR, MTT, colony formation, flow cytometry and TUNEL assay were used to explore the function of HCG18 on sorafenib resistance in HCC. RNA pull-down, RNA immunoprecipitation, immunofluorescence labeling, luciferase reporter assay, western blot and qPCR were used to investigate the mechanism of HCG18 regulating sorafenib resistance in HCC. Our results showed that HCG18 was significantly increased in HCC, which resulted in shorter 5-year survival for patients with HCC. Sorafenib can induce the expression of HCG18, suggesting HCG18 might be involved in sorafenib resistance in HCC. Further analysis showed that knockdown of HCG18 can reduce viability and increase apoptosis of HCC cells. Mechanistically, HCG18 can bind to USP15, further regulated the protein stability of p65, TAB2 and TAB3, and nuclear location of p65, which finally modulated the NF-κB signaling. Our findings showed that HCG18 played an important role in sorafenib resistance in HCC. And knockdown of HCG18 can promote the sensitivity of HCC cells to sorafenib, inferring that targeting HCG18 might be an effective strategy to overcome sorafenib resistance in HCC.

A radiomics nomogram prediction for survival of patients with "driver gene-negative" lung adenocarcinomas (LUAD).

BACKGROUND: To study the role of computed tomography (CT)-derived radiomics features and clinical characteristics on the prognosis of "driver gene-negative" lung adenocarcinoma (LUAD) and to explore the potential molecular biological which may be helpful for patients' individual postoperative care. METHODS: A total of 180 patients with stage I-III "driver gene-negative" LUAD in the First Affiliated Hospital of Sun Yat-Sen University from September 2003 to June 2015 were retrospectively collected. The Least Absolute Shrinkage and Selection Operator (LASSO) Cox regression model was used to screen radiomics features and calculated the Rad-score. The prediction performance of the nomogram model based on radiomics features and clinical characteristics was validated and then assessed with respect to calibration. Gene set enrichment analysis (GSEA) was used to explore the relevant biological pathways. RESULTS: The radiomics and the clinicopathological characteristics were combined to construct a nomogram resulted in better performance for the estimation of OS (C-index: 0.815; 95% confidence interval [CI]: 0.756-0.874) than the clinicopathological nomogram (C-index: 0.765; 95% CI: 0.692-0.837). Decision curve analysis demonstrated that in terms of clinical usefulness, the radiomics nomogram outperformed the traditional staging system and the clinicopathological nomogram. The clinical prognostic risk score of each patient was calculated based on the radiomics nomogram and divided by X-tile into high-risk (> 65.28) and low-risk (≤ 65.28) groups. GSEA results showed that the low-risk score group was directly related to amino acid metabolism, and the high-risk score group was related to immune and metabolism pathways. CONCLUSIONS: The radiomics nomogram was promising to predict the prognosis of patients with "driver gene-negative" LUAD. The metabolism and immune-related pathways may provide new treatment orientation for this genetically unique subset of patients, which may serve as a potential tool to guide individual postoperative care for those patients.

A simple monoselective C-H oxygenation approach for the synthesis of ursane triterpenoids.

Herein, we presented a simple approach for C-H oxidation in the C23 or/and C24 of ursane triterpenoids without any protection of a Δ12,13 double bond. As a result, from commercial ursolic acid (UA), six naturally occurring ursane triterpenoids were synthesized in overall yields of 3.4% to 36.8%, which implied the importance of this approach for the derivation of natural products and their application in biological activity.

Icotinib and pemetrexed in treatment of lung adenocarcinoma and the effects on prognostic survival rate of patients.

Efficacy comparison of icotinib and pemetrexed in the treatment of lung adenocarcinoma and the effects on the prognostic survival rate of patients were investigated. A retrospective analysis was performed in 132 lung adenocarcinoma patients who were treated in the Affiliated Hospital of Weifang Medical University from July 2010 to July 2015. Among them, 69 patients were treated with icotinib (icotinib group), and 63 patients were treated with pemetrexed (pemetrexed group). In the icotinib group, 125 mg icotinib was orally administered continuously, 3 times a day, until progressive disease or intolerable adverse reactions occurred. In the pemetrexed group, 500 mg/m2 pemetrexed was intravenously dripped for a total of 4 cycles, 21 days for 1 cycle, until progressive disease or intolerable adverse reactions occurred. The efficacy, toxic and side effects, and survival rate of the two groups were evaluated. There was a statistically significant difference in toxic and side effects between the two groups of drugs after the treatment of lung adenocarcinoma (P<0.05). The median survival time of patients was 16 months in the icotinib group and 10 months in the pemetrexed group, with a statistically significant difference (P<0.05). The 1-year survival rate was higher in the icotinib group than that in the pemetrexed group (P<0.05). There was no difference in 2- and 3-year survival rates between the two groups (P>0.05). In conclusion, the clinical efficacy of icotinib is similar to that of pemetrexed in the treatment of lung adenocarcinoma, but icotinib has less adverse reactions, with better improvement in disease control.