Introduction: The role of some cytokines, such as interleukin (IL) and tumor necrosis factor-α (TNF-α), in serum in community-acquired pneumonia (CAP) has been mentioned. There are few results on changes in serum cytokines in patients with bacterial CAP. This study aimed at the relationship...

Background: Hepatocellular carcinoma (HCC) represents a major health burden with limited curative treatment options. There is a substantial unmet need to develop innovative approaches to impact the progression of advanced HCC. Haprolid is a novel natural component isolated from myxobacteria. Haprolid has been reported as a potent selective cytotoxin against a panel of tumor cells in recent studies including HCC cells. The aims of this study are to evaluate the antitumor effect of haprolid in HCC and to understand its underlying molecular mechanisms. Methods: The efficacy of haprolid was evaluated in human HCC cell lines (Huh-7, Hep3B and HepG2) and xenograft tumors (NMRI-Foxn1^nu mice with injection of Hep3B cells). Cytotoxic activity of haprolid was determined by the WST-1 and crystal violet assay. Wound healing, transwell and tumorsphere assays were performed to investigate migration and invasion of HCC cells. Apoptosis and cell-cycle distribution were measured by flow cytometry. The effects of haprolid on the Rb/E2F and Akt/mTOR pathway were examined by immunoblotting and immunohistochemistry. Results: haprolid treatment significantly inhibited cell proliferation, migration and invasion in vitro. The epithelial–mesenchymal transition (EMT) was impaired by haprolid treatment and the expression level of N-cadherin, vimentin and Snail was downregulated. Moreover, growth of HCC cells in vitro was suppressed by inhibition of G1/S transition, and partially by induction of apoptosis. The drug induced downregulation of cell cycle regulatory proteins cyclin A, cyclin B and CDK2 and induced upregulation of p21 and p27. Further evidence showed that these effects of haprolid were associated with Rb/E2F downregulation and Akt/mTOR inhibition. Finally, in vivo nude mice experiments demonstrated significant inhibition of tumor growth upon haprolid treatment. Conclusion: Our results show that haprolid inhibits the growth of HCC through dual inhibition of Rb/E2F and Akt/mTOR pathways. Therefore, haprolid might be considered as a new and promising candidate for the palliative therapy of HCC.

Immunotherapy, particularly CAR-T therapy has recently emerged as an innovator for cancer treatment. Gamma-irradiated K562 cells is a common and effective method to stimulated CAR-T cells prior to treatment. However, high cost and limited equipment of gamma-irradiation is drawback of this method. This requires the establishment of CAR-T-expanding alternatives, such as X-ray-irradiated K562 cells.

323 Background: Adiponectin is the key adipokine, which plays an important role in health and disease such as obesity, diabetes, and cancer. Adiponectin is reduced in different tumor types, especially in obesity-related cancer, and recent studies showed that Adiponectin had a potential anti-cancer effect. Obesity is a risk factor for various tumor diseases including cholangiocarcinoma (CC), the second most common primary hepatic cancer. The aim of this study is to investigate for the first time the anti-cancer effect of AdipoR agonist in CC cell lines and a CC engineered mouse model. Methods: Human CC cell lines (TFK-1 and SZ-1) and CC engineered mice (Alb-Cre/KRAS^G12D/p53^L/L) were used to investigate the anti-cancer effects of an AdipoR agonist (2-(4-Benzoylphenoxy)-N-[1-(phenylmethyl)-4-piperidinyl]-acetamide). Cell proliferation, migration, invasion, colony formation, apoptosis assay were applied to evaluate the effect of AdipoR agonist in vitro. In addition, important cancer signalling pathways and targets were analysed by Western Blot. Mice (n = 12) were treated with AdipoR or verhicle and tumor burden and survival were monitored. Results: AdipoR agonist suppressed proliferation, migration, invasion, colony formation and apoptosis in CC cells. AdipoR agonist regulated the expression of different proteins such as EMT markers, pAMPK, pSTAT3, and PARP, which have pivotal functions in cholangiocarcinogenesis. AdipoR agonist also prolonged survival time in a CC engineered mouse model. Conclusions: Our data revealed that AdipoR agonist inhibited successfully cell proliferation, migration, invasion, colony formation and apoptosis in vitro, and prolonged mice survival in vivo through regulation of crucial signaling pathways in cholangiocarcinogenesis. These results suggested that AdipoR agonist might become a new potential candidate for CC treatment in the future.