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951.
Miao Ding Yi Fei Jianmin Zhu Ji Ma Guoqing Zhu Ni Zhen Jiabei Zhu Siwei Mao Fenyong Sun Feng Wang Qiuhui Pan 《Cancer science》2022,113(7):2258
IL‐27 is an anti‐inflammatory cytokine that triggers enhanced antitumor immunity, particularly cytotoxic T lymphocyte responses. In the present study, we sought to develop IL‐27 into a therapeutic adjutant for adoptive T cell therapy using our well‐established models. We have found that IL‐27 directly improved the survival status and cytotoxicity of adoptive OT‐1 CD8+ T cells in vitro and in vivo. Meanwhile, IL‐27 treatment programs memory T cell differentiation in CD8+ T cells, characterized by upregulation of genes associated with T cell memory differentiation (T‐bet, Eomes, Blimp1, and Ly6C). Additionally, we engineered the adoptive OT‐1 CD8+ T cells to deliver IL‐27. In mice, the established tumors treated with OT‐1 CD8+ T‐IL‐27 were completely rejected, which demonstrated that IL‐27 delivered via tumor antigen–specific T cells enhances adoptive T cells’ cancer immunity. To our knowledge, this is the first application of CD8+ T cells as a vehicle to deliver IL‐27 to treat tumors. Thus, this study demonstrates IL‐27 is a feasible approach for enhancing CD8+ T cells’ antitumor immunity and can be used as a therapeutic adjutant for T cell adoptive transfer to treat cancer. 相似文献
952.
Weiwei Weng Meng Zhang Shujuan Ni Cong Tan Midie Xu Xin Wang Hui Sun Lei Wang Dan Huang Weiqi Sheng 《Journal of gastrointestinal oncology.》2022,13(3):1035
BackgroundAlpha-fetoprotein-producing gastric cancer (AFPGC) is a subtype of gastric cancer (GC) with more aggressive biological behavior. As a highly specific tight junction component exclusively present in gastric mucosa and gastric adenocarcinomas, claudin-18.2 (CLDN18.2) has become an emerging target in GC. In this study, we aimed to provide insight into AFPGC and investigate the expression and the clinical implications of CLDN18.2 in AFPGC.MethodsWe retrospectively collected 98 cases of AFPGC and reviewed their clinical, morphological, and immunohistochemical features. Another 356 patients with stage-matched conventional GC (cGC) were enrolled as a control group. We further surveyed CLDN18.2 expression by immunohistochemistry (IHC) in 51 AFPGC tissues and explained its association with the clinicopathological parameters of AFPGC.ResultsOur results showed that AFPGC was a unique GC type with elevated serum alpha-fetoprotein (AFP), which was a predictor of a worse prognosis. AFPGC showed typical morphological features and positive staining of at least 1 hepatocytic or enteroblastic marker. The expression rate of CLDN18.2 was low, with a positivity rate of 21.6%, which was much lower than that observed in cGC tissues (38.5%). A significant correlation was found between CLDN18.2 expression and the differentiation of AFPGC. CLDN18.2 expression was negatively correlated with the serum AFP level of AFPGC. We also found that AFPGC with a hepatoid type (HPT) component showed a significantly lower CLDN18.2 expression than those without.ConclusionsThis study demonstrated that CLDN18.2 was significantly decreased in AFPGC and was negatively correlated with the patient’s preoperative serum AFP level. The negative correlation between AFP and CLDN18.2 could be explained by retro-differentiation of AFPGC. Special treatment strategies might be needed for this unique tumor type. 相似文献
953.
Jian Zhai Jianwei Liu Zhigang Fu Shilei Bai Xiaowei Li Zengqiang Qu Yanfu Sun Ruiliang Ge Feng Xue 《Journal of gastrointestinal oncology.》2022,13(3):1278
BackgroundThere is lack of studies on sequential regorafenib after sorafenib and lenvatinib treatment failure in patients with unresectable hepatocellular carcinoma (HCC). This study was to explore the safety and prognosis of sequential regorafenib after sorafenib and lenvatinib failure in HCC patients.MethodsThis study was a retrospective, real-world study that included 50 HCC patients who received sequential regrafinib after sorafenib and lenvatinib failure. The safety and prognosis of two groups were compared.ResultsThe incidence of all grade and III/IV adverse events were 68% and 24%. According to Response Evaluation Criteria in Solid Tumours (RECIST) 1.1 and modified (m) RECIST standards, the objective response rates (ORRs) after receiving regorafenib were 14.0% and 22.0%, respectively. The disease control rates (DCRs) were 62.0% and 60.0%, respectively. Based on different first-line targeted drugs, 50 patients were divided into sorafenib (n=22) and lenvatinib group (n=28). There was no differences between two groups except age and bilirubin. And there was no differences in other treatments before or after regorafenib. The baseline between two groups was basically same and had good comparability. There was no difference in incidence of all grade and III/IV adverse events, ORR and DCR between two groups (P>0.05). On long-term prognosis, total overall survival (TOS) in sorafenib and lenvatinib group were 23.0 (95% CI: 15.1–30.9) vs. 29.7 (95% CI: 21.4–38.1) months. The difference was statistically significant (P=0.041). Besides, regorafenib overall survival (ROS) in sorafenib and lenvatinib group were 11.7 (95% CI: 7.1–16.3) vs. 15.9 (95% CI: 8.3–23.5) months. The difference was statistically significant ( P=0.045). The regorafenib progression-free survival (RPFS) was 5.6 (95% CI: 1.9–9.2) vs. 8.0 (95% CI: 5.1–10.9) months in sorafenib and lenvatinib group, respectively, and difference was not statistically significant (P=0.380).ConclusionsRegorafenib is an effective drug for second-line treatment of HCC, with fewer severe adverse events, ORR and DCR was 14–22% and 62–60%, respectively. Both TOS and ROS in lenvatinib group were better than those in sorafenib group. For HCC patients whose first-line targeted drug is lenvatinib, it is safe and effective to accept regorafenib after disease progresses. 相似文献
954.
目的:研究视野半侧缺损的原发性开角型青光眼(POAG)视盘旁和黄斑区血管密度的改变及其与视网膜神经纤维层(RNFL)厚度及视野指标的关系。方法:横断面研究。收集2015年10月至2018年10月于复旦大学附属眼耳鼻喉科医院眼科应用Humphery视野计30-2程序检测为视野半侧缺损的POAG患者(POAG组)28例(2... 相似文献
955.
BackgroundLINC00941 has been proved to be related to various tumors, but its relationship with laryngocarcinoma remains vague.MethodsLINC00941 expression in laryngocarcinoma tumor and laryngocarcinoma cells was determined by real time‐quantitative polymerase chain reaction (RT‐qPCR). Besides, the five‐year survival of laryngocarcinoma patients with different LINC00941 expression was analyzed with Kaplan–Meier survival analysis, and the clinical characteristics of laryngocarcinoma patients were also recorded. After transfection, cell viability, cell proliferation, apoptosis, cell cycle, migration, and invasion were detected by cell counting kit‐8 (CCK‐8), colony formation, flow cytometry, cell scratch, and Transwell assays, respectively. Glycolysis was assessed by the colorimetric method. Expressions of proliferation‐associated proteins, migration‐associated proteins, glycolysis‐associated proteins, and phosphatidylinositol 3‐kinase (PI3K)/AKT/mammalian target of rapamycin (mTOR) signal pathway‐associated proteins were detected by Western blot.ResultsIn laryngocarcinoma tumor tissues and cells, LINC00941 was highly expressed. High expression of LINC00941 decreased the 5‐year survival of laryngocarcinoma patients, and it was positively related to lymph node metastasis and clinical stages. LINC00941 overexpression decreased apoptosis but promoted cell viability, proliferation, cell‐cycle progression, migration, and invasion, and glucose consumption and lactate production in laryngocarcinoma cells. Moreover, LINC00941 overexpression elevated expressions of Ki‐67, PCNA, MMP2, N‐Cadherin, HK2, PFKFB4, and PKM, activated the PI3K/AKT/mTOR signal pathway but reduced E‐Cadherin expression, while LINC00941 silencing had the opposite effects. PKM overexpression reversed the effects of LINC00941 silencing on cellular and glycolytic phenotypes.ConclusionLINC00941 promoted in vitro progression and glycolysis of laryngocarcinoma cells by upregulating PKM via activating the PI3K/AKT/mTOR signaling pathway. 相似文献
956.
957.
Xu Hu Yan Xiao Jianan Sun Bao Ji Shanshan Luo Bo Wu Chao Zheng Peng Wang Fanxing Xu Keguang Cheng Huiming Hua Dahong Li 《药学学报(英文版)》2021,11(5):1148-1157
As one of the most lethal diseases, pancreatic cancer shows a dismal overall prognosis and high resistance to most treatment modalities. Furthermore, pancreatic cancer escapes early detection during the curable period because early symptoms rarely emerge and specific markers for this disease have not been found. Although combinations of new drugs, multimodal therapies, and adjuvants prolong survival, most patients still relapse after surgery and eventually die. Consequently, the search for more effective treatments for pancreatic cancer is highly relevant and justified. As a newly re-discovered mediator of gasotransmission, hydrogen sulfide (H2S) undertakes essential functions, encompassing various signaling complexes that occupy key processes in human biology. Accumulating evidence indicates that H2S exhibits bimodal modulation of cancer development. Thus, endogenous or low levels of exogenous H2S are thought to promote cancer, whereas high doses of exogenous H2S suppress tumor proliferation. Similarly, inhibition of endogenous H2S production also suppresses tumor proliferation. Accordingly, H2S biosynthesis inhibitors and H2S supplementation (H2S donors) are two distinct strategies for the treatment of cancer. Unfortunately, modulation of endogenous H2S on pancreatic cancer has not been studied so far. However, H2S donors and their derivatives have been extensively studied as potential therapeutic agents for pancreatic cancer therapy by inhibiting cell proliferation, inducing apoptosis, arresting cell cycle, and suppressing invasion and migration through exploiting multiple signaling pathways. As far as we know, there is no review of the effects of H2S donors on pancreatic cancer. Based on these concerns, the therapeutic effects of some H2S donors and NO–H2S dual donors on pancreatic cancer were summarized in this paper. Exogenous H2S donors may be promising compounds for pancreatic cancer treatment.KEY WORDS: Pancreatic cancer, Hydrogen sulfide donor, Sulfur-containing compound, Cell proliferation, Antitumor effect, Signaling pathway 相似文献
958.
Jing Ma Adrien Guillot Zhihong Yang Bryan Mackowiak Seonghwan Hwang Ogyi Park Brandon J. Peiffer Ali Reza Ahmadi Luma Melo Praveen Kusumanchi Nazmul Huda Romil Saxena Yong He Yukun Guan Dechun Feng Pau Sancho-Bru Mengwei Zang Andrew MacGregor Cameron Ramon Bataller Frank Tacke Zhaoli Sun Suthat Liangpunsakul Bin Gao 《The Journal of clinical investigation》2022,132(14)
Intrahepatic neutrophil infiltration has been implicated in severe alcoholic hepatitis (SAH) pathogenesis; however, the mechanism underlying neutrophil-induced injury in SAH remains obscure. This translational study aims to describe the patterns of intrahepatic neutrophil infiltration and its involvement in SAH pathogenesis. Immunohistochemistry analyses of explanted livers identified two SAH phenotypes despite a similar clinical presentation, one with high intrahepatic neutrophils (Neuhi), but low levels of CD8+ T cells, and vice versa. RNA-Seq analyses demonstrated that neutrophil cytosolic factor 1 (NCF1), a key factor in controlling neutrophilic ROS production, was upregulated and correlated with hepatic inflammation and disease progression. To study specifically the mechanisms related to Neuhi in AH patients and liver injury, we used the mouse model of chronic-plus-binge ethanol feeding and found that myeloid-specific deletion of the Ncf1 gene abolished ethanol-induced hepatic inflammation and steatosis. RNA-Seq analysis and the data from experimental models revealed that neutrophilic NCF1-dependent ROS promoted alcoholic hepatitis (AH) by inhibiting AMP-activated protein kinase (a key regulator of lipid metabolism) and microRNA-223 (a key antiinflammatory and antifibrotic microRNA). In conclusion, two distinct histopathological phenotypes based on liver immune phenotyping are observed in SAH patients, suggesting a separate mechanism driving liver injury and/or failure in these patients. 相似文献
959.
Jianian Hu Ye Tan Xuemei Li Youlin Zhu Guoqiang Luo Jian Zhang Ruizhi Zhang Yi Sun Qiang Shen Lianmeng Zhang 《Materials》2022,15(14)
With the need of developing new materials, exploring new phenomenon, and discovering new mechanisms under extreme conditions, the response of materials to high-pressure compression attract more attention. However, the high-pressure state deviating from the Hugoniot line is difficult to realize by conventional experiments. Gas gun launching graded materials could reach the state. In our work, the corresponding Al-Cu composites and graded materials are prepared by tape casting and hot-pressing sintering. The microstructure and the acoustic impedance of the corresponding Al-Cu composites are analyzed to explain the impact behavior of Al-Cu graded materials. Computed tomographic testing and three-dimension surface profilometry machine results demonstrated well-graded structure and parallelism of the graded material. Al-Cu GMs with good parallelism are used to impact the Al-LiF target at 2.3 km/s using a two-stage light-gas gun, with an initial shock impact of 20.6 GPa and ramping until 27.2 GPa, deviating from the Hugoniot line. 相似文献
960.
Kiki S. N. Liu Julie Y. Chen Kai-Sing Sun Joyce P. Y. Tsang Patrick Ip Cindy L. K. Lam 《Nutrients》2022,14(14)
To tackle unhealthy eating among adolescents, it is crucial to understand the dietary knowledge, attitudes, and practices (KAP) on which adolescent eating habits are based. This qualitative study identifies the gaps in KAP by exploring what Chinese adolescents know, perceive, and practice regarding healthy eating to better inform targeted interventions for this important health problem. Parent–adolescent dyads were purposively sampled based on, for example, the dietary intake, age, and gender of the adolescent and household income, and each completed a 30 to 60 min interview. Twelve themes were synthesized: knowledge: (1) dietary recommendations, (2) health outcomes of healthy eating, (3) nutrition content in food, and (4) access to healthy meals; attitudes: (5) outcome expectation for healthy eating, (6) food preferences, and (7) self-efficacy regarding adopting healthy eating; and practices: (8) going grocery shopping for healthy food, (9) eating home-prepared meals. (10) eating out in restaurants or consuming takeaway food, (11) fruit and vegetable consumption, and (12) snacking, perceived unhealthy eating to be low risk, made unhealthy choices regarding snacking and eating out, and had insufficient fruit and vegetable intake. Programs should emphasize the positive short-term health outcomes of healthy eating and empower adolescents to acquire food preparation skills to sustain healthy eating habits. 相似文献