Immunotherapy combined with targeted therapy have become recommended regimens for advanced HCC. Considering that patients are strictly screened in clinical trials, while the efficacy and safety in the real-world are affected by various factors, real-world data of anti-PD-1 antibody combined with targeted therapy is urgently needed.

161 Background: A real-world study to observe the efficacy and safety of apatinib treatment in clinical practice, and explored patients (pts) who could benefit from apatinib. Methods: This is an open-label, prospective, observational study, pts (age ≥ 18 yrs) with pathologically or histologically diagnosed GC who were given apatinib treatment met the inclusion criteria. Results: From September 1, 2017 to September 1, 2018. 954 pts were enrolled. 679 pts received palliative treatment were included in the analysis. 499 (73.6%) were males. The age of the pts was (63.1 ± 10.8) yrs. Pts with ECOG PS 0/1 accounted for 78.1%. Pts received first-line treatment, second-line treatment, third-line treatment or above , respectively were 42.2%, 30.5%, 27.3%. 509 (75.1%) pts were treated with apatinib at dose of 500 mg. There were 375 pts available for efficiency evaluation. Among them, 1 achieved CR, 35 achieved PR, 198 had SD, and 57 had PD, resulting in an ORR of 11.9% and a DCR of 77.4%. The mPFS is 4.2 m (95% CI: 3.5-4.8), OS data was still in follow-up. This study showed its efficacy for pts with monotherapy compared with combined chemotherapy (3.3 m vs. 5.0 m, P = 0.003). The mPFS for patients with hypertension were longer than without hypertension (7.1m vs. 3.7m, P = 0.038). And pts also had longer mPFS with good ECOG PS (0-1) compared to those with poor ECOG PS (2-4) (4.7 m vs. 2.9 m, P = 0.003). The incidence of AEs was 402 (88.2%) and the grade 3/4 treatment-related AEs was 14.7%. The most common treatment-related AEs were debilitation (31.2%), hand-foot syndrome (27.5%), hypertension (25.3%), anorexia (11.5%), diarrhea (10.3%), albumin decreased (38.5%), uric acid elevated (31.6%), and total bilirubin increased (29.1%). Conclusions: In the real world, apatinib is confirmed to be effective and safe for GC pts. Factors associated with better prognosis were apatinib combined chemotherapy, ECOG PS 0/1 and occurrence of hypertension. Further analysis is needed to identify pts who benefit from apatinib treatment. Preliminary results of the study were released in ESMO 2018 Congress (683P). Clinical trial information: NCT 03333967.

Background: Apatinib, a small molecule VEGFR TKI, has been approved in the treatment of advanced or metastatic gastric cancer (GC) in China. We performed a real world study to observe the current status, efficacy and safety of apatinib treatment in clinical practice, and preliminarily define patients (pts) who could benefit from apatinib. Methods: From September 2017, pts (age ≥18 yrs) with pathologically or histologically diagnosed GC who were given apatinib treatment met the inclusion criteria. The target sample size is 1000. Results: As of April 2018, 651 pts from 37 centers were eligible. There are 491 (75.4%) males and 160 (24.6%) females. The median age was 62.5 yrs. The majority pts were at stage IV (399, 61.3%), had prior surgery (370, 56.8%) and chemotherapy (341, 52.4%). Pts with ECOG PS 0–2 were 520 (79.9%), and ECOG PS 1 was most common (403, 61.9%). Metastases were detected in 370 (56.8%) pts, which mainly were hepatic and pulmonary metastases. Pts received apatinib monotherapy or in combination with chemotherapy. The dose of apatinib in most pts (70.0%) was 500 mg qd. Apatinib was used in perioperative treatment for 269 (41.3%) pts. 382 (58.7%) pts with unresectable locally advanced, recurrent, or metastatic disease received apatinib as different lines of systemic therapy; among whom, 284 pts were evaluable for response, and 113 pts obtained complete clinical efficacy and safety assessment. 12 achieved partial response, 79 had stable disease and 22 got progressive disease. Thus, the objective response rate (ORR) and disease control rate (DCR) were 10.6% and 80.5%. 78.8% pts reported adverse events (AEs). The incidence of grade 3-4 AEs was 22.1%. Main apatinib-related AEs were hypertension (20.3%), and hand-foot syndrome (26.5%). There were tendencies showed that prognostic factors related with higher ORR were lines of apatinib (≤2, 11.3%; >2, 9.5%) and duration of medication (< 90 days, 7.1%; 90-120 days, 6.7%; >120 days, 11.9%). Conclusions: In the real world, GC pts receiving apatinib therapy are mainly elderly men, stage IV, and ECOG PS 1. Apatinib is confirmed to be effective and safe for GC pts. Further analysis is needed to identify pts who obtain benefits from apatinib treatment. Clinical trial identification: NCT03333967. Legal entity responsible for the study: The First Affiliated Hospital of Anhui Medical University. Funding: Has not received any funding. Disclosure: All authors have declared no conflicts of interest.

AIM:To investigate the significance of endothelial progenitor cells (EPCs) in predicting severe acute pancreatitis (SAP). METHODS:We recruited 71 patients with acute pancreatitis (AP) and excluded 11 of them; finally, cases of mild acute pancreatitis (MAP) (n = 30) and SAP (n = 30), and healthy volunteers (n = 20) were internalized to investigate levels of EPCs, C-reactive protein (CRP), tumor necrosis factor-alpha (TNF-α), fibrinogen (FIB) and white blood cells (WBC) in peripheral blood. RESULTS:The levels of TNF-α, WBC, FIB and CRP were higher both in SAP and MAP cases than in healthy volunteers (P < 0.05, all). Interestingly, the level of EPCs was higher in SAP than MAP (1.63% ± 1.47% vs 6.61% ± 4.28%, P < 0.01), but there was no significant difference between the MAP cases and healthy volunteers (1.63% ± 1.47% vs 0.55% ± 0.54%, P > 0.05). Receiver operating characteristics curve (ROC) showed that EPCs, TNF-α, CRP and FIB were significantly associated with SAP, especially EPCs and CRP were optimal predictive markers of SAP. When the cut-off point for EPCs and CRP were 2.26% and 5.94 mg/dL, the sensitivities were 90.0% and 73.3%, and the specificities were 83.3% and 96.7%. Although, CRP had the highest specificity, and EPCs had the highest sensitivity and highest area under the curve value (0.93). CONCLUSION:Data suggest that EPCs may be a new biological marker in predicting SAP.

Histone H3 lysine-9 (H3K9) methylation is essential for retinoblastoma protein (RB)-mediated heterochromatin formation, epigenetic silencing of S-phase genes and permanent cell cycle arrest or cellular senescence. Besides as an H3K4 demethylase, lysine-specific demethylase-1 (LSD1) has been shown to promote H3K9 demethylation. However, it is unexplored whether LSD1 has a causal role in regulating cell cycle entry and senescence. Here we demonstrate that genetic depletion or pharmacological inhibition of LSD1 triggers G1 arrest and cellular senescence. Genome-wide chromatin immunoprecipitation-sequencing analysis reveals that LSD1 binding sites overlap significantly with those bound by the S-phase gene transcription factor E2F1. Gene ontology analysis demonstrates that a large portion of E2F1 and LSD1 cotargeted genes are involved in cell cycle and proliferation. Further analyses show that depletion of LSD1 increases the level of H3K9me2 and thereby represses expression of the LSD1-E2F1 cotarget genes, but has no effects on H3K4me2 level in those loci. In contrast, knockdown of the H3K4me2 reader PHF8 decreases the H3K4me2 level at the LSD1-E2F1 cotargeted loci, but this effect is rescued by codepletion of LSD1. Furthermore, the enzymatic activity of LSD1 is essential for H3K9me2 demethylation at cell cycle gene loci. Notably, cotreatment of chemotherapeutic agent camptothecin enhanced LSD1 inhibitor-induced senescence and growth inhibition of cancer cells in vitro and in mice. Our data reveal LSD1 as a molecular rheostat selectively regulating H3K9 demethylation at cell cycle gene loci, thereby representing a key player in oncogenesis and a viable target for cancer therapy.

It is accepted that endothelial progenitor cells (EPCs) are recruited into tumor sites and take part in the neovascularization of tumors. However, few articles have discussed the specific distribution of EPCs in vivo in tissues of gastric cancer patients. For this reason, the present study sought to elucidate EPC distribution in vivo in tissues of patients with gastric cancer. Fresh tumor tissues were collected from 26 newly diagnosed patients with histologically confirmed gastric cancer (mean age, 51 years; range, 21-81 years; 7 females, 19 males). All patients were treated surgically with curative intent. One portion of the fresh tissues was prepared for flow cytometric analysis and another was immediately snap frozen in liquid nitrogen and stored at -80°C for later use in quantitative polymerase chain reaction. The analysis was based on two groups of tissues, namely the cancer group and cancer-adjacent group. The presence of CD34/CD133 double-positive cells was determined in cancer-adjacent and cancer tissues by flow cytometry. The analysis revealed that the total number of EPCs in cancer tissue was slightly greater than the number in the cancer-adjacent tissue, but not to the point of statistical significance. The number of EPCs in cancer-adjacent and cancer tissues of patients with early-stage gastric cancer was higher than the EPC count in late-stage gastric cancer patients, and significant differences were identified in the number of EPCs in cancer tissue between patients of different tumor stages. Levels of cluster of differentiation (CD)34, CD133 and vascular endothelial growth factor receptor 2 were not significantly different in cancer-adjacent tissue compared with cancer tissue. These results suggest that cancer-adjacent and cancer tissue of gastric cancer patients may be used as a reference index in the clinical and pathological staging of tumors.

Background Matrix metalloproteinase-9 (MMP-9) is an important member of the matrix metalloproteinase family and is considered to be involved in the invasion and metastasis of cancer cells. This study analyzed the expression of MMP-9 in colon cancer patients and the relationship between this expression and clinicopathological features and survival. Methods We immunohistochemically investigated 68 specimens of colon cancer tissues and corresponding distal normal mucosa tissues using MMP-9 antibody. Then, the correlation between MMP-9 expression and clinicopathological features and its prognostic relevance were determined. Results The expression rate of MMP-9 in colon cancer tissues was significantly higher than that in distal normal mucosa (69.1% versus 2.9%, P < 0.001). Significant correlations were only found between high levels of MMP-9 expression and metastasis of lymph nodes and Dukes’ stage. Overexpression of MMP-9 was associated with shorter survival times in univariate analysis. Multivariate analysis confirmed that MMP-9 expression was an independent prognostic factor. Conclusions MMP-9 is correlated with the metastasis of lymph nodes, and its elevated expression may be an adverse prognostic indicator for the patients of colon cancer.

Context: There are few reports of endothelial progenitor cells (EPCs) in peripheral blood have been found in patients with gastric cancer.Objective: We quantified EPCs in the peripheral blood of patients with gastric cancer, with the expectation that this approach might lead to a new marker for the diagnosis of gastric cancer.Methods: We enumerated CD34+/CD133+ EPCs in the peripheral blood of 145 subjects by use of flow cytometry.Results and conclusion: The quantity of peripheral blood EPCs in patients with gastric cancer are correlated with patient's age. In addition, the number of peripheral blood EPCs in patients with gastric cancer increased with tumor node metastasis stage and histological differentiation of the cancers, and with the operative status of the patients.

OBJECTIVE To construct a recombinant adenovirus (pAdxsi-GFP-HIF) encoding human hypoxia inducible factor 1 α gene (HIF-1 α) and to express it in endothelial cells. METHODS HIF-1 α gene was obtained from human lung cancer cell line A549, which was cultured in hypoxia condition, by RT-PCR. The HIF-1 α gene was subcloned into shuttle vector p Shuttle-CMV-EGFP at KpnI and BamHI sites. After identified with restriction enzymes, plasmid p Shuttle-GFP-HIF was linearized by digestion with restriction endonuclease I-CeuI and I-SceI, and subsequently cotransformed into E.coli DH5a with adenoviral backbone plasmid pAdxsi to make homologous recombination. After linearized by PacI, the homologous recombinant adenovirus plasmid was transfected into 293 cells to package and amplify. The recombinant adenovirus was infected with human umbilical vein endothelial cells (ECV304), and the expression level of HIF-1 α protein was evaluated by ELISA. RESULTS The recombinant adenovirus vector containing HIF-1 α gene (pAdxsi-GFP-HIF) was successfully constructed and amplified with titer of 3.38 X 10(10) pfu/mL. The green fluorescence protein was detected under fluorescent microscope in ECV304 at 24h after transfection and with a stronger degree after 48h. The concentration of HIF-1 protein was (48.93 ±3.86)ng/mL in supernatant at 48 h after transfection. CONCLUSION A recombinant adenovirus vector pAdxsi-GFP-HIF, encoding human hypoxia inducible factor 1 α gene, has been constructed in vitro and expressed successfully in ECV304 cells.

目的 研究内皮祖细胞(EPCs)、C反应蛋白(CRP)、肿瘤坏死因子-α(TNF-α)、纤维蛋白原(FIB)及白细胞(WBC)五项指标在急性胰腺炎(AP)患者及健康志愿者外周血中的分布水平.分析五项指标在重症型急性胰腺炎(SAP)、轻症型急性胰腺炎(MAP)患者外周血中的水平是否存在某种相关性.方法 采集60例AP患者(分为MAP组和SAP组)及20例健康志愿者(对照组)的外周血.采用流式细胞术、ELISA、免疫比浊法等实验方法,检测了各组外周血中EPCs、CRP、TNF-α、FIB及WBC五项指标的水平,采用Spearman′s 相关分析对这五项指标间的相互关系作出评估.结果 TNF-α、WBC、FIB及CRP水平在对照组、MAP及SAP组中,依次升高,具有统计学差异(P＜0.05).SAP组的EPCs水平明显高于MAP组(P＜0.01),而在MAP组与对照组间EPCs的水平没有统计学差异(P＞0.05);MAP组及SAP组外周血中,EPCs、TNF-α、WBC、FIB及CRP水平之间呈正相关.结论 在五项指标中,EPCs和CRP在AP早期预测SAP最具有价值.EPCs可能成为一种新的、具有潜力的生物学指标预测SAP.