2635 Background: Immune checkpoint inhibitors (ICIs) have shown significant efficacy in metastatic gastric cancer, but some patients may not respond to them because of immune resistance. Recombinant Human Adenovirus Type 5 (H101), the world’s first oncolytic virus antitumor drug in China, can induce cell death, expose tumor antigens, provide adjuvants for anti-tumor immune priming, and potentially increase responsiveness to immunotherapies. Here, we presented the efficacy and safety of H101 combined with immune checkpoint inhibitors (ICIs) in patients with liver metastatic gastric cancer. Methods: In this multi-center, phase II trial (the TROJAN 021 study, ChiCTR1900027922), patients with liver metastatic gastric cancer received 2 cycles of H101 ultrasound guided injections into liver lesions, bi-weekly in combination with anti-PD-1 antibodies and chemotherapy bi-weekly until progression or intolerable toxicity. The primary objective was safety and objective response rate (ORR). Secondary objective included progression-free survival (PFS), overall survival (OS) and disease control rate (DCR). Efficacy assessments were performed every 4 weeks following RECIST v1.1 criteria. PFS and OS were estimated using the Kaplan-Meier method. Results: From September 2020 to September 2022, 21 patients were enrolled. Of them, 18 were males, median age was 66 years (range: 36-71) and ECOG performance status was either 0 (n=15) or 1 (n=6). 10 patients (47.6%) received as first-line therapy, 1 (4.8%) as second-line and 5 (23.8%) as third line and above therapy. The primary endpoint was met with a median PFS of 4.8 months. The median OS was 13.2 months. Objective tumor responses were CR (n=0), PR (n=7), SD (n=12) and PD (n=2). ORR was 33.3% (7/21), and DCR was 90.5% (19/21). Treatment related adverse events (TRAE) occurred in 12 patients (57.1%). The most frequently observed TRAEs were injection site pain (48.1%), fever (57.1%) and fatigue (23.8%). Three patients (14.3%) had grade 3 treatment-related adverse events. There were no grade 4 and 5 treatment-related adverse events. Grades 3 toxicities included neutropenia (2/21, 9.5%) and hypertension (1/21, 4.8%). Conclusions: These promising results show that combination of Recombinant Human Adenovirus Type 5 (H101) and ICIs demonstrated acceptable toxicity and promising antitumor efficacy in patients with liver metastatic gastric cancer. Further validation of the efficacy in a randomized prospective trial is warranted. Clinical trial information: ChiCTR1900027922.

Objective·To analyze the relationship between the expression level of interferon regulatory factor 3 (IRF3) in colorectal cancer and its clinicopathological features and prognosis, and to observe the effects of IRF3 overexpression on the proliferation and invasion ability of colorectal cancer cells and the related protein molecular pathways.MethodsThe Cancer Genome Atlas (TCGA) data were downloaded and used to analyze the correlation between expression levels of IRF3 and the prognosis of patients (including renal cell carcinoma, colorectal cancer, hepatocellular carcinoma, and prostate cancer). Immunohistochemistry was used to detect the differences in the expression levels of IRF3 between cancerous tissue and adjacent normal tissues of 10 patients with colorectal/renal cancer. The C-terminal residue sites of the IRF3 protein were modified to construct HEK-293T cells overexpressing the phosphorylated IRF3-5D (396/398/402/404/405-D). At 12 and 24 h of cell culture, treatment with TANK-binding kinase 1 (TBK1) inhibitor was performed, and Western blotting was used to detect the expression levels of IRF3 and p-IRF3 (Ser386) in the cells. RNA sequencing (RNA-seq) was employed to explore the correlation between high expression of IRF3-5D and the expression levels of tumor-related proteins. Colorectal cancer cells CT26 and COLON26 overexpressing wild-type IRF3 (IRF3-WT) and IRF3-5D were construct, and cell proliferation and migration ability were assessed by using cell counting, scratch assay, and clonogenic assay.Results·Analysis of TCGA data suggested that the expression level of IRF3 protein in cancer tissues was positively correlated with poor prognosis in patients. Immunohistochemical analysis of pathological tissues from patients with cancer showed that the expression level of IRF3 was significantly upregulated in colorectal cancer tissues and renal cancer tissues, with protein expression concentrated in the cell nucleus. After treatment with TBK1 inhibitors for 12 and 24 h in cell culture, the expression of p-IRF3 (Ser386) protein in HEK-293T cells decreased. The results of RNA-seq and Western blotting showed that the expression levels of multiple proteins associated with poor prognosis [such as IRF9, programmed cell death 1-ligand 1 (PD-L1), etc.] were significantly upregulated under conditions of high expression of IRF3-5D. Overexpression of IRF3-5D in colorectal cancer cells could significantly enhance the proliferation and migration capabilities of cancer cells.Conclusion·The expression level of IRF3 in colorectal cancer is positively correlated with poor patient prognosis. High expression of IRF3-5D protein in colorectal cancer cells can promote malignant biological behavior of cancer cells. Additionally, IRF3-5D is dependent on the TBK1-mediated activation of the IRF3 activation pathway and upregulates the expression levels of multiple tumor-related proteins.

Objective: Real-world diagnostic and treatment data for pancreatic cancer in China are lacking. As such, the present study investigated the clinical characteristics, diagnosis, and treatment of advanced pancreatic cancer (including locally advanced and metastatic disease) in the Hospital-based Advanced Pancreatic Cancer Cohort in China of the China Pancreas Data Center database. Methods: A total of 5349 Chinese patients with advanced pancreatic cancer were identified from a database. The entire course of real-world pancreatic cancer management was analyzed. Results: The proportion of patients with advanced pancreatic cancer was higher among males than females (62.4% vs 37.6%, respectively). Patients typically had a history of hypertension (30.8%), diabetes (21.6%), and cholangitis (20.2%). Abdominal pain (51.6%), abdominal distension (27.1%), jaundice (20.1%), and weight loss (16.3%) were the main symptoms observed in patients with advanced pancreatic cancer in this cohort. Serum carbohydrate antigen (CA)19-9 is one of the most common tumor markers. In the present study, 2562 patients underwent first-line therapy. The median progression-free survival (PFS) for patients undergoing first-line therapy was 4.1 months. The major options for first-line therapy included gemcitabine (GEM) plus S-1 (GS/X) (23.4%), nab-paclitaxel plus GEM (AG) (18.1%), oxaliplatin, irinotecan, and leucovorin-modulated fluorouracil (FOLFIRINOX; 11.9%), nab-paclitaxel plus S-1 (AS) (8.9%), and GEM combined with oxaliplatin/cisplatin (GEMOX/GP) (7.6%). The AS and GS/X regimens were associated with the highest PFS rates. Conclusion: This is the first study to report multicenter, real-world data regarding advanced pancreatic cancer in China. Results revealed that real-world treatment options differed from guideline recommendations, and PFS was shorter than that in previously reported data. Improving intelligent follow-up systems and standardizing diagnosis and treatment of pancreatic cancer is recommended.

Treatment options are limited for tumors after failure of standard therapies. Utidelone (UTD1), a novel microtubule stabilizer, given via 5 days intermittent infusion, has demonstrated high activity in heavily pretreated metastatic breast cancer, while its efficacy in other cancers was unclear. Peripheral neuropathy is a common and severe adverse event (AE) of UTD1. We performed a prospective, multicenter, single-arm trial (ChiCTR2300074299) to evaluate the efficacy and safety of UTD1 with a changed administration mode in patients with advanced or metastatic solid tumors after failure of standard therapies. UTD1 (150 mg/m2, alone or in combination with other anticancer agents) was administrated via 120 h continuous intravenous infusion every 21 days until disease progression or intolerable toxicity. A total of 50 patients were enrolled and analyzed, including 20 breast cancer patients, 11 gynecological cancer patients, 8 gastrointestinal cancer patients, 6 lung cancer patients, and 5 patients with other solid tumors. The overall median progression-free survival (PFS) was 4 months, the overall objective response rate and disease control rate were 20% and 66%, respectively, and the median overall survival was not reached. Most of the AEs were grade 1 or 2 and were manageable and reversible, the rate of grade >= 3 AEs including peripheral neuropathy was 4%. This study demonstrated a promising anti-tumor activity of UTD1 in patients with advanced or metastatic solid tumors after failure of the standard therapies. Moreover, 120 h continuous intravenous infusion was a more tolerable administration mode than 5 days intermittent infusion, and worthy of further study.

Gastric cancer is a common cancer of the gastrointestinal tract, highly occurring in East and Southeast Asian. Roughly more than 50% of the population is exposed to Helicobacter pylori (H. pylori) infection worldwide. H. pylori infection is one of the risk factors for gastric cancer and is strongly associated with the development of gastric cancer. The association between H. pylori infection and metastasis of gastric cancer is still inconclusive but has made some progress. For one thing, H. pylori is colonized in the gastric mucosa. The effect of its key virulence factors, VacA and CagA proteins, keeps H. pylori alive in the stomach for a long time and makes it possible for H. pylori to promote the proliferation, epithelial-mesenchymal transition and metastasis of gastric cancer cells. For another, the tumor microenvironment is the site of interaction between host immune system and tumor. By interfering with the effect of tumor cells and immune cells, enhancing the formation of an acidic and hypoxic environment and altering the differentiation of cells in the tumor microenvironment, H. pylori infection can strengthen immune escape and then facilitate the metastasis of gastric cancer. H. pylori infection has become a global public health problem, and its influence on the evolution of gastric cancer cannot be disregarded. The review addresses the correlation between H. pylori infection and gastric cancer metastasis through both key virulence factors and tumor microenvironment. It will provide reference for clinical and basic research in gastric cancer.

KRAS is widely mutated in human cancers, resulting in unchecked tumor proliferation and metastasis, which makes identifying KRAS-targeting therapies a priority. Herein, we observe that mutant KRAS specifically promotes the formation of the ERK2-p53 complex in stomach/colorectal tumor cells. Disruption of this complex by applying MEK1/2 and ERK2 inhibitors elicits strong apoptotic responses in a p53-dependent manner, validated by genome-wide knockout screening. Mechanistically, p53 physically associates with phosphorylated ERK2 through a hydrophobic interaction in the presence of mutant KRAS, which suppresses p53 activation by preventing the recruitment of p300/CBP; trametinib disrupts the ERK2-p53 complex by reducing ERK2 phosphorylation, allowing the acetylation of p53 protein by recruiting p300/CBP; acetylated p53 activates PUMA transcription and thereby kills KRAS-mutant tumors. Our study shows an important role for the ERK2-p53 complex and provides a potential therapeutic strategy for treating KRAS-mutant cancer.

Background Early detection of hepatocellular carcinoma (HCC) is important in order to improve patient prognosis and survival rate. Methylation sequencing combined with neural networks to identify cell-free DNA (cfDNA) carrying aberrant methylation offers an appealing and non-invasive approach for HCC detection. However, some limitations exist in traditional methylation detection technologies and models, which may impede their performance in the read-level detection of HCC. Methods We developed a low DNA damage and high-fidelity methylation detection method called No End-repair Enzymatic Methyl-seq (NEEM-seq). We further developed a read-level neural detection model called DeepTrace that can better identify HCC-derived sequencing reads through a pre-trained and fine-tuned neural network. After pre-training on 11 million reads from NEEM-seq, DeepTrace was fine-tuned using 1.2 million HCC-derived reads from tumor tissue DNA after noise reduction, and 2.7 million non-tumor reads from non-tumor cfDNA. We validated the model using data from 130 individuals with cfDNA whole-genome NEEM-seq at around 1.6X depth. Results NEEM-seq overcomes the drawbacks of traditional enzymatic methylation sequencing methods by avoiding the introduction of unmethylation errors in cfDNA. DeepTrace outperformed other models in identifying HCC-derived reads and detecting HCC individuals. Based on the whole-genome NEEM-seq data of cfDNA, our model showed high accuracy of 96.2%, sensitivity of 93.6%, and specificity of 98.5% in the validation cohort consisting of 62 HCC patients, 48 liver disease patients, and 20 healthy individuals. In the early stage of HCC (BCLC 0/A and TNM I), the sensitivity of DeepTrace was 89.6 and 89.5% respectively, outperforming Alpha Fetoprotein (AFP) which showed much lower sensitivity in both BCLC 0/A (50.5%) and TNM I (44.7%). Conclusions By combining high-fidelity methylation data from NEEM-seq with the DeepTrace model, our method has great potential for HCC early detection with high sensitivity and specificity, making it potentially suitable for clinical applications. DeepTrace: https://github.com/Bamrock/DeepTrace

Cervical cancer is the fourth most common female malignancy for both incidence and mortality worldwide and is one of the major threats to women's health. The role of long non‑coding RNAs (lncRNAs) in cervical cancer remains largely unknown. In the present study, the differentially expressed lncRNAs in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) tissues were retrieved form The Cancer Genome Atlas (TCGA) and were analyzed. The expression analysis of related genes was performed with GEPIA. The proliferation and migratory and invasive abilities of MIR205HG knockdown CESC cells were analyzed using Cell Counting Kit‑8 and transwell assays. The expression of Ki‑67 and p16 was detected by immunofluorescence. A total of 203 differentially expressed lncRNAs were identified. The results demonstrated that MIR205HG was overexpressed in CESC tissues. Furthermore, the genes related to MIR205HG were enriched in cancer‑related pathways. MIR205HG knockdown significantly decreased the proliferation and migratory and invasive abilities of CESC cells. In addition, silencing of MIR205HG significantly decreased the expression of p16 in C‑33 A cells. The expression of fibroblast growth factor receptor 3, thymidine phosphorylase and GTPase HRas was downregulated in MIR205HG knockdown CESC cells. These findings revealed some potential lncRNA candidates for cervical cancer research and suggested that MIR205HG may have a pro‑tumor role in CESC.

Pancreatic cancer is one of the leading causes of cancer-related mortality in both developed and developing countries. The incidence of pancreatic cancer in China accounts for about a quater of the global incidence, and the epidemiological characteristics and therapeutic strategies differ due to social, economic, cultural, environmental, and public health factors. Non-domestic guidelines do not reflect the clinicopathologic characteristics and treatment patterns of Chinese patients. Thus, in 2018, the Chinese Society of Clinical Oncology (CSCO) organized a panel of senior experts from all sub-specialties within the field of pancreatic oncology to compile the Chinese guidelines for the diagnosis and treatment of pancreatic cancer. The guidelines were made based on both the Western and Eastern clinical evidence and updated every one or two years. The experts made consensus judgments and classified evidence-based recommendations into various grades according to the regional differences, the accessibility of diagnostic and treatment resources, and health economic indexes in China. Here we present the latest version of the guidelines, which covers the diagnosis, treatment, and follow-up of pancreatic cancer. The guidelines might standardize the diagnosis and treatment of pancreatic cancer in China and will encourage oncologists to design and conduct more clinical trials about pancreatic cancer.

Radiation-induced lung injury (RILI) is a common complication after radiotherapy for lung cancer and alternative thoracic malignant tumors, while ferroptosis is a regulated cell death triggered by iron-dependent membrane lipid peroxidation. In this article, the relationship between RILI and ferroptosis was investigated from oxidative damage induced by reactive oxygen species, antioxidant network and iron homeostasis regulated by nuclear factor erythroid 2-related factor 2(Nrf2) as well as transforming growth factor involved in the inflammatory response, aiming to mitigate or inhibit the occurrence of RILI through regulating ferroptosis, thereby improving clinical prognosis of patients undergoing radiotherapy.

结直肠癌(colorectal cancer,CRC)是世界范围内五大恶性肿瘤之一,其发病率位居恶性肿瘤第三,死亡率位居第二,严重威胁着人类的生命健康.流行病学研究显示,经济发达国家的CRC发病率显著高于不发达国家,城市的CRC发病率高于农村.处于不同地理环境的人群的CRC发病特点间差异提示,饮食因素给CRC发病率及患者预后带来了较显著的影响.有证据表明,以高脂饮食为代表的西方饮食结构与CRC的发生发展密切相关,且探索高脂饮食在CRC进程中的相关作用机制对预防CRC的发生、改善患者预后十分重要.该文就近年来国内外关于高脂饮食与CRC发生发展的相关作用机制进行概述,并提出对应的预防策略,从精准医学的层面为膳食结构相关研究和CRC的预防、诊断及治疗提供理论参考.

AbstractBackgroundRadiation pneumonitis (RP) is a common side effect in lung cancer patients who received radiotherapy. Our previous study found genetic variations in DNA repair gene NEIL1 may be a predictor of RP in patients with esophageal cancer. So, we hypothesis genetic variations in NEIL1 gene could affect the risk of RP in lung cancer patients following radiotherapy.MethodsGenetic variations rs4462560 G>C and rs7402844 C>G in NEIL1 gene were genotyped in 174 lung cancer patients received radio(chemo)therapy. Luciferase assay, real‐time PCR and Western blot were used to access the effect of the variants on NEIL1 in HELF and HEF cell lines which were transfected with plasmids containing rs4462560 G>C and rs7402844 C>G.ResultsPatients with rs4462560 CC genotype had a lower risk of RP grade ≥2 than GG genotype. Compared with the CC genotype, rs7402844 GG genotype was associated with an increased RP grade ≥2 risk. What is more, rs4462560 G decreased the relative luciferase activity of NEIL1 gene promoter compared with the negative control in vitro, while rs4462560 C can increase the relative luciferase activity. The mRNA and protein level of the NEIL1 gene in rs4462560 G were lower than rs4462560 C.ConclusionsGenetic variants of NEIL1 are associated with RP risk through regulation of NEIL1 expression and serve as independent biomarkers for prediction of RP in patients treated with thoracic radiotherapy.

目的 检测微小RNA-103(miR-103)、嗅觉介导素4(OLFM4)信使核糖核酸(mRNA)在前列腺癌(PCa)组织中的表达及其对PCa的影响.方法 选取2013年6月—2015年9月上海交通大学医学院附属新华医院肿瘤科和泌尿外科手术切除PCa患者120例为PCa组,另选取良性前列腺增生患者50例为对照组,采用实时荧光定量PCR方法检测PCa组织和增生组织miR-103和OLFM4 mRNA的表达情况,并对两者与PCa临床病理参数的关系进行分析;采用Kaplan-Meier进行生存曲线分析;Logistic回归分析影响PCa患者预后的因素.结果 PCa组miR-103和OLFM4 mRNA的表达水平均显著低于对照组(t/P=50.899/0.000、71.029/0.000);PCa患者癌组织中miR-103和OLFM4 mRNA的表达水平与年龄无关(P>0.05),与前列腺特异性抗原(PSA)水平、临床分期、有无病灶转移、Gleason评分有关(miR-103:χ2/P=13.337/0.000、12.841/0.002、8.929/0.003、4.201/0.040;OLFM4 mRNA:16.348/0.000、17.306/0.000、4.802/0.028、10.035/0.002);miR-103 mRNA高表达组的生存率显著高于miR-103 mRNA低表达组(χ2/P=13.744/0.000),OLFM4 mRNA高表达组的生存率显著高于OLFM4 mRNA低表达组(χ2/P=10.382/0.001);多因素Logistic分析发现,PSA高水平、临床高分期、病灶转移、Gleason高评分、miR-103 mRNA低表达和OLFM4 mRNA低表达均是影响预后生存的独立危险因素[OR(95％CI)=1.423(1.092～1.854)、1.811(1.404～2.337)、1.601(1.224～2.094)、1.825(1.398～2.382)、2.228(1.720～2.886)、1.961(1.490～2.580)].结论 PCa组织中miR-103和OLFM4 mRNA表达与临床特征及预后密切相关,可作为患者早期检测和预后生存监测指标.

Shanghai Institute of Nutrition and Health, Shanghai Institutes for Biological Sciences, University 8 of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China. 9 Department of Radiation Oncology, The Cancer Hospital of University of Chinese Academy of 10 Sciences (Zhejiang Cancer Hospital), Hangzhou 310022, P.R. China. 11 Department of Oncology, Xinhua Hospital, School of Medicine, Shanghai Jiao Tong University, 12 Shanghai 200092, P.R. China. 13 School of Pharmaceutical Science & Yunnan Key Laboratory of Pharmacology for Natural 14 Products, Kunming Medical University, Kunming 650500, P.R. China. 15

目的:研究E1B-55kDa基因缺陷型溶瘤腺病毒H101对结肠癌HCT-116细胞及其小鼠皮下移植瘤生长的影响,并探讨可能的作用机制.方法:使用不同效价的缺陷型溶瘤腺病毒H101作用于结肠癌HCT-116、SW480和RKO细胞24、48和72 h后,采用CCK-8法检测细胞的存活率.随后,用效价为1.0×107 vp/mL的缺陷型溶瘤腺病毒H101处理HCT-116细胞72 h后,在光学显微镜下观察细胞形态学变化,同时采用蛋白质印迹法检测HCT-116细胞中腺病毒衣壳蛋白Hexon的表达情况,以及FCM法检测对细胞周期的影响.采用不同效价(1.0×106和2.5×106 vp/mL)的缺陷型溶瘤腺病毒H101处理HCT-116细胞48 h后,通过细胞集落形成实验检测缺陷型溶瘤腺病毒H101对HCT-116细胞集落形成能力的影响,以及Transwell小室实验检测对HCT-116细胞的迁移和侵袭能力的影响.用HCT-116细胞构建裸小鼠皮下移植瘤模型,瘤内注射缺陷型溶瘤腺病毒H101,观察腺病毒对小鼠移植瘤生长的影响,并采用免疫组织化学法检测Ki-67和血管内皮生长因子(vascular endothelial growth factor,VEGF)在移植瘤中的表达情况.结果:与对照组相比,缺陷型溶瘤腺病毒H101明显抑制HCT-116细胞的生长活力(P<0.05),且这种抑制作用呈一定的浓度和时间依赖性;而SW480和RKO细胞,仅在缺陷型溶瘤腺病毒H101效价高(1.0×107 vp/mL)和作用时间长(72 h)时,对细胞的增殖具有抑制作用(P均<0.05).缺陷型溶瘤腺病毒H101(1.0×107 vp/mL)处理HCT-116细胞72 h后,HCT-116细胞失去正常形态,悬浮细胞数目增多,并出现细胞破裂导致膜内容物流出;HCT-116细胞的集落形成能力明显降低(P<0.001);缺陷型溶瘤腺病毒H101感染后可上调HCT-116细胞中腺病毒衣壳蛋白Hexon的表达水平(P<0.001),证明缺陷型溶瘤腺病毒H101可在HCT-116细胞中有效表达.缺陷型溶瘤腺病毒H101抑制HCT-116细胞的迁移和侵袭(P均<0.01),并将HCT-116细胞阻滞在S期(P<0.01).缺陷型溶瘤腺病毒H101能明显抑制裸小鼠皮下移植瘤的生长,移植瘤的体积和质量明显减小(P均<0.001),抑瘤率为92.28％.HE染色结果显示,与对照组相比,缺陷型溶瘤腺病毒H101治疗组移植瘤组织中细胞坏死范围更大.免疫组织化学法检测结果提示,缺陷型溶瘤腺病毒H101治疗组移植瘤中表达Ki-67和VEGF的细胞数均明显减少(P均<0.001),表明缺陷型溶瘤腺病毒H101具有显著的抑制肿瘤细胞增殖和抗肿瘤血管生成的作用.结论:E1B-55kDa缺陷型溶瘤腺病毒H101对结肠癌HCT-116细胞具有显著的体外和体内抗肿瘤作用,是一个潜在的抗肿瘤药物.

Background Anti-apoptotic protein Bcl-2 plays a substantial role in the carcinogenesis, whereas the regulation for Bcl-2 in gastric carcinoma (GC) is poorly understood. Specifically, a role of microRNA (miR)-383 in the control of Bcl-2 has not been shown in GC and thus addressed in the current study. Methods We investigated the levels of miR-383 and Bcl-2 in 50 GC specimens, and compared them with patients' clinical characteristics. Bioinformatics analyses and luciferase-reporter assay were applied for analyzing the relationship between Bcl-2 and miR-383. An CCK assay was used to determine the survival of Fluorouracil-treated GC cells, and apoptosis of GC cells was assessed by flow cytometric FITC Annexin V apoptosis detection assay and expression of apoptosis-associated proteins. Results The levels of miR-383 were lower while the levels of Bcl-2 levels were higher in GC specimens, compared to tissue from the adjacent non-tumor region. Low miR-383 and high Bcl-2 seemed to be associated with high malignancy and metastasis. In GC specimens, the levels of Bcl-2 and miR-383 inversely correlated. The overall survival of miR-383-low cases was poorer. Mechanistically, miR-383 targeted the 3 '-UTR of Bcl-2 mRNA to inhibit its protein translation. Overexpression of miR-383 downregulated Bcl-2, resulting in reduced survival of Fluorouracil-treated GC cells. Similar conclusion was drawn through analysis of published database. Conclusion MiR-383 reduces survival of Fluorouracil-treated GC cells through downregulating of Bcl-2.

Abstract Gastric cancer is one of the most common and deadly cancer types. Currently, four subtypes have been identified with unique molecular alterations: Epstein–Barr virus (EBV)‐positive, microsatellite instability (MSI), chromosomal instability (CIN), and genomic stable (GS) tumors. Notably, many gastric tumors are associated with the bacterium Helicobacter pylori but the genomic landscape of this subgroup of tumors remains largely unknown. Targeted sequencing covering 425 genes was performed retrospectively on 1703 gastric tumor tissues and matched normal blood samples. Nonsynonymous mutations, copy‐number variation (CNV), and MSI status were called from human DNA reads; nonhuman DNA reads were mapped to NCBI microbial reference genome using Kraken and significant species were identified. Overall, 37 (2.76%) from a total of 1703 samples were EBV‐positive, 200 (11.74%) samples were H. pylori‐positive, and 10 samples were positive for both. Among the rest, 59 (3.46%) samples were MSI, 380 (22.31%) were CIN, and 1017 (59.72%) were GS. Most of the 200 H. pylori‐positive samples tend to be genome stable (85.5%, p < 0.001) and microsatellite stable (95%, p = 0.04). Compared to 1017 GS tumors, mutations in AKT3, EPAS1, MLH1, and BKT and amplifications of NFE2L2, TERC, MCL1, and TOP1 were significantly enriched in H. pylori‐positive tumors. And compared to EBV‐positive tumors, mutations in PIK3CA, ARID1A, and PTEN were significantly depleted in H. pylori‐positive subtype while TP53 mutations were enriched. This study characterized the unique genomic landscape of H. pylori‐positive gastric tumors using targeted panel sequencing. The successful identification of DNA reads from infectious agents in tumor samples indicates that deep sequencing is a promising way to uncover characteristics of microbial environment in tumors.

溶瘤病毒是一类能选择性地感染并杀死肿瘤细胞而不损伤正常细胞的天然或重组病毒[1].与传统免疫治疗相比,溶瘤病毒治疗具有靶向性好、不良反应小、杀伤肿瘤途径多、不易产生耐药性等优势.多项临床研究[2-3]显示,溶瘤病毒可为不同类型、不同进展阶段,甚至转移性和无法治愈的肿瘤患者带来临床获益.更重要的是,其与化疗、放疗、免疫治疗等联合应用时,具有协同增效的作用,可使原先对免疫检查点抑制剂等免疫治疗药物反应欠佳的瘤种变得敏感[2,4]. 自2005年国家药品监督管理局批准第一个溶瘤腺病毒药物H101(重组人5型腺病毒,安柯瑞?) 联合化疗用于治疗晚期鼻咽癌患者以来[5],溶瘤病毒的研究数量不断增加,截至目前,全球在ClinicalTrials上注册的溶瘤病毒相关临床研究已超过100项.2015年美国食品药品管理局(Food and Drug Administration,FDA)和欧洲药品管理局相继批准Ⅰ型单纯疱疹病毒(herpes simplex virus type 1,HSV-1)T-VEC(talimogene laherparepvec,Imlygic?)[3]治疗晚期黑色素瘤,进一步促进了溶瘤病毒疗法的发展和成熟.目前,溶瘤病毒正在成为癌症免疫治疗的重要手段之一.

Fulminant hepatic failure (FHF) is a potentially fatal liver disease that is associated with intrahepatic infiltration of inflammatory cells. As the receptor of polyunsaturated long chain fatty acids, GPR120 can regulate cell differentiation, proliferation, metabolism, and immune response. However, whether GPR120 is involved in FHF remains unknown. Using Propionibacterium acnes (P. acnes)-primed, LPS-induced FHF in mice, we found that interference with GPR120 activity using pharmacological agonist attenuated the severity of the liver injury and mortality of FHF in mice, while a lack of GPR120 exacerbated the disease. GPR120 activation potently alleviated FHF and led to decreased T helper (Th) 1 cell response and expansion of regulatory T cells (Tregs). Interestingly, GPR120 agonist didn't directly target T cells, but dramatically induced a distinct population of CD11c+MHC IIlowCD80lowCD86low regulatory DCs in the livers of FHF mice. GPR120 was found to restrict HIF-1α-dependent glycolysis. The augmented HIF-1α stabilization caused by GPR120 antagonism or deletion could be attenuated by the inhibition of ERK or by the activation of AMPK. Through the analysis of the clinical FHF, we further confirmed the activation of GPR120 was negatively associated with the severity in patients. Our findings indicated that GPR120 activation has therapeutic potential in FHF. Strategies to target GPR120 using agonists or free fatty acids (FFAs) may represent a novel approach to FHF treatment.

宫颈上皮内瘤样病变(cervical intraepithelial neoplasia,CIN)属于宫颈癌前病变,虽然CIN进展成宫颈癌时间一般较长,但其发病率增多及发病年龄变小,对女性身心健康造成严重影响.随着宫颈癌筛查技术的进步和分子生物学技术的发展,高级别的宫颈癌上皮内瘤样变的早期检查确认并进行阻断已成为筛查的目标.p16被认为是发现最早的抑癌基因,在鉴别低级别与高级别宫颈鳞状上皮内病变中有重要作用.Ki-67为常见肿瘤标志物,在多种肿瘤中表达.p16/Ki-67双染为新型宫颈病变筛查或诊断方法,即同一细胞内检测到p16、Ki-67共表达,则提示细胞周期失调,考虑为宫颈上皮内高级别瘤样病变.国内近年有研究报道p16和Ki-67在CIN中的作用,未见到相关的综述报道.本文对宫颈上皮内瘤样病变与p16/Ki-67共表达的相关性作一综述,为临床宫颈病变鉴别、诊断提供参考.