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Tumor inflammation-specific self-amplifying fluorescent molecular probes induce an anti-tumor immune response

Science China Chemistry 2025年第1期 273-287页

作者： Shuguang Yang Lijun Hu Hong Xiao Zecong Xiao Xintao Shuai PCFM Lab of Ministry of Education School of Materials Science and Engineering Sun Yat-sen University department of Ultrasound The Fifth Affiliated Hospital Sun Yat-sen University department of Medical Ultrasound The Third Affiliated Hospital of Sun Yat-sen University Nanomedicine Research center The Third Affiliated Hospital of Sun Yat-sen University

Enhancing the concentration of exogenous molecular drugs within the tumor microenvironment through enzyme-catalyzed polymerization presents a novel strategy for cancer therapy. Nonetheless, the optimization of the catalytic efficiency is often impeded by the inefficient expression of enzymes. Herein, we reported a self-amplifying fluorescent molecular probe, Bis-HTPICG, for photodynamic therapy(PDT) and subsequent PDT-induced immunoreaction. The Bis-HTP-ICG probe possesses a noticeable enzyme-catalyzed polymerization facilitated by myeloperoxidase(MPO), a crucial enzyme secreted by neutrophils at inflammation sites. Upon exposure to laser irradiation, Bis-HTP-ICG showed a high PDT efficacy, inducing an acute inflammatory response that stimulates further recruitment of neutrophils and then elevated MPO secretion. The heightened level of MPO enhances the accumulation of the Bis-HTP-ICG via self-polymerization or binding with intratumoral proteins following MPO enzyme catalysis, instigating a self-amplifying chain reaction cycle involving Bis-HTP-ICG, neutrophils and ***, PDT efficiently incites immunogenic cell death(ICD) in tumor cells, initiating an anti-tumor immune response including dendritic cells(DCs) maturation, T cell proliferation and reprogramming of tumor-associated neutrophils(TANs). This work portrays a promising strategy for self-amplification of fluorescent molecular probes through adjustable enzyme levels,potentially offering a unique avenue to enhance the tumor accumulation of molecular drugs for improved tumor therapy.

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Inhibiting ceramide synthase 5 expression in microglia decreases neuroinflammation after spinal cord injury

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Neural Regeneration Research 2025年第10期20卷 2955-2968页

作者： Wei Zhang Yubao Lu Ruoqi Shen Yingjie Wu Chenrui Liu Xingxing Fang Liangming Zhang Bin Liu Limin Rong department of Spine surgery The Third Affiliated HospitalSun Yat-sen UniversityGuangzhouGuangdong ProvinceChina National Medical Products Administration(NMPA)Key Laboratory for Quality Research and Evaluation of Cell Products GuangzhouGuangdong ProvinceChina Guangdong Provincial center for Quality Control of Minimally Invasive Spine surgery GuangzhouGuangdong ProvinceChina Guangdong Provincial center for Engineering and Technology Research of Minimally Invasive Spine surgery GuangzhouGuangdong ProvinceChina

Microglia,the resident monocyte of the central nervous system,play a crucial role in the response to spinal cord ***,the precise mechanism remains *** investigate the molecular mechanisms by which microglia regulate the neuroinflammatory response to spinal cord injury,we performed single-cell RNA sequencing dataset analysis,focusing on changes in microglial *** found that the MG1 subpopulation emerged in the acute/subacute phase of spinal cord injury and expressed genes related to cell pyroptosis,sphingomyelin metabolism,and neuroinflammation at high ***,we established a mouse model of contusive injury and performed intrathecal injection of siRNA and molecular inhibitors to validate the role of ceramide synthase 5 in the neuroinflammatory responses and pyroptosis after spinal cord ***,we established a PC12-BV2 cell co-culture system and found that ceramide synthase 5 and pyroptosis-associated proteins were highly expressed to induce the apoptosis of neuron *** ceramide synthase 5 expression in a mouse model of spinal cord injury effectively reduced ***,ceramide synthase 5-induced pyroptosis was dependent on activation of the NLRP3 signaling *** ceramide synthase 5 expression in microglia in vivo reduced neuronal apoptosis and promoted recovery of neurological ***2g7 formed a“bridge”between sphingolipid metabolism and ceramide synthase 5-mediated cell death by inhibiting the NLRP3 signaling ***,these findings suggest that inhibiting ceramide synthase 5 expression in microglia after spinal cord injury effectively suppressed microglial pyroptosis mediated by NLRP3,thereby exerting neuroprotective effects.

关键词： ceramide synthase 5 gasdermin D microglia neuroinflammation NLRP3 nuclear factor kappa B Pla2g7 pyroptosis sphingomyelin metabolism spinal cord injury

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Prognostic value of the neutrophil-to-lymphocyte ratio for hepatocellular carcinoma patients with portal/hepatic vein tumor thrombosis

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World Journal of Gastroenterology 2017年第17期23卷 3122-3132页

作者： Shao-Hua Li Qiao-Xuan Wang Zhong-Yuan Yang Wu Jiang Cong Li Peng sun Wei Wei Ming Shi Rong-Ping Guo State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineCancer Center of Sun Yat-Sen University department of Hepatobiliary surgery Cancer Center of Sun Yat-Sen University department of Radiation Oncology Cancer Center of Sun Yat-Sen University department of Head and Neck surgery Cancer Center of Sun Yat-Sen University department of colorectal surgery Cancer Center of Sun Yat-Sen University department of Anesthesia Cancer Center of Sun YatSen University

AIM To investigate whether the preoperative neutrophil-tolymphocyte ratio(NLR) could predict the prognosis of hepatocellular carcinoma(HCC) patients with portal/hepatic vein tumor thrombosis(PVTT/HVTT) after *** The study population included 81 HCC patients who underwent hepatectomy and were diagnosed with PVTT/HVTT based on pathological examination. The demographics, laboratory analyses, and histopathology data were *** Overall survival(OS) and disease-free survival(DFS) were determined in the patients with a high(> 2.9) and low(≤ 2.9) NLR. The median OS and DFS duration in the high NLR group were significantly shorter than those in the low NLR group(OS: 6.2 mo vs 15.7 mo, respectively, P = 0.007; DFS: 2.2 mo vs 3.7 mo, respectively, P = 0.039). An NLR > 2.9 was identified as an independent predictor of a poor prognosis of OS(P = 0.034, HR = 1.866; 95%CI: 1.048-3.322) in uni-and multivariate analyses. Moreover, there was a significantly positive correlation between the NLR and the Child-Pugh score(r = 0.276, P = 0.015) and the maximum diameter of the tumor(r = 0.435, P 2.9 indicates poorer OS and DFS.

关键词： Hepatocellular carcinoma Portal/hepatic vein tumor thrombosis Neutrophil-to-lymphocyte ratio Prognosis

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Concurrent chemoradiotherapy combined with enteral nutrition support:a radical treatment strategy for esophageal squamous cell carcinoma patients with malignant istulae

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Chinese Journal of cancer 2017年第1期36卷 26-33页

作者： Li Ma Guang-Yu Luo Yu-Feng Ren Bo Qiu Hong Yang Chun-Xia Xie Song-Ran Liu Shi-Liang Liu Zhao-Lin Chen Qun Li Jian-Hua Fu Meng-Zhong Liu Yong-Hong Hu Wen-Feng Ye Hui Liu sun yat-sen university cancer center State Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer Medicine Guangdong Esophageal cancer Research Institute department of Radiation Oncology Sun Yat-sen University Cancer Center department of Endoscopy Sun Yat-sen University Cancer Center department of Radiation Oncology The First Affiliated Hospital of Sun Yat-sen University department of Thoracic surgery Sun Yat-sen University Cancer Center department of Clinical Nutrition Sun Yat-sen University Cancer Center

Background: Concurrent chemoradiotherapy(CCRT) significantly increases the survival rate of esophageal squa?mous cell carcinoma(ESCC) patients with malignant fistulae. Recent clinical evidence has shown the benefits of enteral nutrition for malnourished cancer patients. In this study, we aimed to validate that, with the support of enteral nutrition, ESCC patients who develop malignant fistulae might be able to complete CCRT and achieve long?term ***: We reviewed the medical records of 652 patients with ESCC who received definitive CCRT at sun yat?sen university cancer center between January 2010 and December 2012. Treatment outcome and toxicity were ret?rospectively evaluated in 40 ESCC patients with malignant fistulae. All the 40 patients were treated with CCRT and evaluated by clinical nutritionists using nutrition risk screening(NRS) before, during, and after treatment. Twenty?two patients received a nasogastric tube, and 18 underwent percutaneous endoscopic gastrostomy feeding. The median energy intake was 2166 kcal/day. Treatment response was evaluated at 3 months after the completion of ***: With a median follow?up of 18 months(range, 3–39 months), patients' 1?year overall survival(OS) rate was 62.5%, and the estimated OS time was 25.5 months. Univariate analysis showed that the NRS score(P n NRS score(P se to treatment(P < 0.001) were sig= 0.003), increase i= 0.024), fistula closure(P = 0.011), and responnifi?cantly associated with OS. Multivariate analysis showed that tumor response(P = 0.044) and increase in NRS score(P = 0.044) were independent predictors of OS. Grade 3 vomiting was observed in 8 patients(20.0%), grade 3 neutro?penia was observed in 11 patients(27.5%), and grade 3 cough was observed in 13 patients(32.5%); 2 patients(5.0%) died of massive bleeding during ***: CCRT combined with enteral nutrition support is effective for ESCC patients with malignant fistulae. Patients have an increased potential to be

关键词： Esophageal squamous cell carcinoma Malignant istula Radiotherapy Concurrent chemotherapy Enteral nutrition support

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Tumor-derived apoptotic extracellular vesicle-mediated intercellular communication promotes metastasis and stemness of lung adenocarcinoma

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Bioactive Materials 2024年第6期36卷 238-255页

作者： Xiaotian He Yiyang Ma Yingsheng Wen Rusi Zhang Dechang Zhao Gongming Wang Weidong Wang Zirui Huang Guangran Guo Xuewen Zhang Huayue Lin Lanjun Zhang State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineGuangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhouChina department of Thoracic surgery Sun Yat-sen University Cancer CenterSun Yat-sen UniversityGuangzhouChina department of Breast surgery Sun Yat-sen University Cancer CenterSun Yat-sen UniversityGuangzhouChina department of Anesthesiology Sun Yat-sen University Cancer CenterSun Yat-sen UniversityGuangzhouChina Guangdong Provincial Key Laboratory of Malignant Tumor Epigenetics and Gene Regulation Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina Breast Tumor center Sun Yat-sen Memorial HospitalSun Yat-sen UniversityGuangzhouChina

Apoptosis has long been recognized as a significant mechanism for inhibiting tumor formation,and a plethora of stimuli can induce apoptosis during the progression and treatment of ***,tumor-derived apoptotic extracellular vesicles(apoEVs)are inevitably phagocytosed by live tumor cells,promoting tumor *** the mechanism by which apoEVs regulate tumor cells is imperative for enhancing our knowledge of tumor metastasis and ***,we conducted a series of in vivo and in vitro experiments,and we report that tumor-derived apoEVs promoted lung adenocarcinoma(LUAD)metastasis,self-renewal and ***,we demonstrated that apoEVs facilitated tumor metastasis and stemness by initiating the epithelial-mesenchymal transition program and upregulating the transcription of the stem cell factor *** addition,we found that ALDH1A1,which was transported by apoEVs,activated the NF-κB signaling pathway by increasing aldehyde dehydrogenase enzyme activity in recipient tumor ***,targeting apoEVs-ALDH1A1 significantly abrogated these ***,our findings elucidate a novel mechanism of apoEV-dependent intercellular communication between apoptotic tumor cells and live tumor cells that promotes the formation of cancer stem cell-like populations,and these findings reveal that apoEVs-ALDH1A1 may be a potential therapeutic target and biomarker for LUAD metastasis and recurrence.

关键词： Lung adenocarcinoma Apoptotic extracellular vesicles Stemness Proteomics SOX2

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A nomogram to predict prognosis for gastric cancer with peritoneal dissemination

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Chinese Journal of cancer Research 2018年第4期30卷 449-459页

作者： Shi Chen Xijie Chen Runcong Nie Liying Ou Yang Aihong Liu Yuanfang Li Zhiwei Zhou Yingbo Chen Junsheng Peng Guangdong Provincial Key Laboratory of colorectal and Pelvic Floor Diseases the Sixth Affiliated Hospital of Sun Yat-sen University department of Gastrointestinal surgery the Sixth Affiliated Hospital of Sun Yat-sen University department of Gastropancreatic surgery Sun Yat-sen University Cancer Center department of Intensive Care Sun Yat-sen University Cancer Center

Objective： To identify independent prognostic factors to be included in a nomogram to predict the prognosis ofgastric cancer patients with peritoneal ***： This is a retrospective study on 684 patients with a histological diagnosis of gastric cancer withperitoneal dissemination from the sun yat-sen university cancer center as the development set, and 62 gastriccancer patients from the Sixth Affiliated Hospital of sun yat-sen university as the validation group. Chi-square testand Cox regression analysis were used to compare the clinicopathological variables and the prognosis of gastriccancer patients with peritoneal dissemination. The Harrell＇s concordance index （C-index） and calibration curvewere determined for comparisons of predictive ability of the ***： Univariate and multivariate analyses showed that serum carcinoembryonic antigen （CEA） level（P=0.032）, ascites grading （P=0.008）, presence of extraperitoneal metastasis （P〈0.001）, seeding status （P=0.016） andperformance status （P=0.009） were independent prognostic factors for gastric cancer patients with peritonealdissemination in the development set. The nomogram model was constructed using these five factors. Internalvalidation showed that the C-index of the model was 0.641. For the external validation, the C-index of this modelwas ***： We developed and validated a nomogram to predict the prognosis for gastric cancer patients withperitoneal dissemination. This nomogram may play an important clinical role in guiding palliative therapy for thesetypes of patients, although it may need more data for optimization.

关键词： Gastric cancer prognosis peritoneal dissemination nomogram

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CD30 expression in extranodal natural killer/T-cell lymphoma,nasal type among 622 cases of mature T-cell and natural killer-cell lymphoma at a single institution in South China

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Chinese Journal of cancer 2017年第6期36卷 258-266页

作者： Yanfen Feng Huilan Rao Yiyan Lei Yuhua Huang Fang Wang Yu Zhang Shaoyan Xi Qiuliang Wu Jianyong Shao State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer MedicineSun Yat-sen University Cancer Center department of Pathology Sun Yat-sen University Cancer Center department of Thoracic surgery The First Affiliated Hospital of Sun Yat-sen University department of Molecular Diagnostics Sun Yat-sen University Cancer Center

Background:Mature T-cell and natural killer(NK)-cell lymphomas compose a heterogeneous group of non-Hodgkin lymphomas,and extranodal NK/T-cell lymphoma,nasal type(ENKTL) is an aggressive subtype with sporadic CD30 ***,the significance of CD30 expression in ENKTL is *** aimed to classify a large cohort of patients with mature T-cell and NK-cell lymphomas according to the 2016 World Health Organization(WHO) classification guidelines and to study the association between CD30 expression and prognosis of patients with ***:We selected consecutive patients with mature T-cell and NK-cell lymphomas who attended our institution between September 1,2009 and August 31,*** classified the lymphomas according to the 2016 revision of the WHO classification of lymphoid neoplasms,analyzed the associations between CD30 expression and clinicopathologic features of ENKTL patients,and evaluated the prognostic implications of CD30 ***:We identified 622 consecutive patients with mature T-cell and NK-cell lymphomas,including 317(51.0%)patients with *** addition,CD30 expression was detected in 43(47.3%) of a subset of 91 patients with *** clinicopathologic features were associated with CD30 expression,and CD30 positivity showed no prognostic significance in patients with ***:ENKTL is the most common type of mature T-cell and NK-cell lymphoma diagnosed at our ***30 is frequently expressed in ENKTL and represents a therapeutic target;however,it may not be a prognostic marker.

关键词： NK细胞淋巴瘤 T细胞中国南方地区成熟机构世界卫生组织鼻

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Prognostic value of preoperative mean corpuscular volume in esophageal squamous cell carcinoma

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World Journal of Gastroenterology 2013年第18期19卷 2811-2817页

作者： Yu-Zhen Zheng Shu-Qin Dai Wei Li Xun Cao Yong Li Lan-Jun Zhang Jian-Hua Fu JunYe Wang department of Thoracic Oncology Cancer Center Sun Yat-Sen University department of Clinical Laboratory Sun Yat-Sen University Cancer Center department of Anesthesia Sun Yat-Sen University Cancer Center Intensive Care Unit Sun Yat-Sen University Cancer Center department of Pathology Sun Yat-Sen University Cancer Center

AIM: To evaluate whether preoperative mean corpuscular volume (MCV) is a prognostic indicator in patients with resectable esophageal squamous cell carcinoma (ESCC). METHODS: A total of 298 consecutive, prospectively enrolled patients with histologically diagnosed ESCC who underwent surgery with curative intent from 2001 to 2011 were retrospectively evaluated. Patients were excluded if they had previous malignant disease, distant metastasis at the time of primary treatment, a history of neoadjuvant treatment, had undergone nonradical resection, or had died of a non-tumor-associated cause. Survival status was verified in September 2011. Pathological staging was performed based on the 2010 American Joint Committee on cancer criteria. Preoperative MCV was obtained from blood counts performed routinely within 7 d prior to surgery. Receiver operating characteristic (ROC) curve analysis was used to determine a cutoff for preoperative MCV. RESULTS: The 298 patients consisted of 230 males and 68 females, with a median follow-up of 30.1 mo. ROC analysis showed an optimal cutoff for preoperative MCV of 95.6 fl. Fifty-nine patients (19.8%) had high (> 95.6 fl) and 239 (80.2%) had low (≤ 95.6 fl) preoperative MCV. Preoperative MCV was significantly associated with gender (P=0.003), body mass index (P=0.017), and preoperative red blood cell count (P<0.001). The predicted 1-, 3and 5-year overall survival (OS) rates were 72%, 60% and 52%, respectively. Median OS was significantly longer in patients with low than with high preoperative MCV (27.5 mo vs 19.4 mo, P<0.001). Multivariate analysis showed that advanced pT (P=0.018) and pN (P<0.001) stages, upper thoracic location (P=0.010), lower preoperative albumin concentration (P=0.002), and high preoperative MCV (P=0.001) were negative prognostic factors in patients with ESCC. Preoperative MCV also stratified OS in patients with T3, N1-N3, G2-G3 and stage Ⅲ tumors. CONCLUSION: Preoperative MCV is a prognostic factor in patients with E

关键词： Preoperative markers Mean corpuscular volume Prognosis Resectable Esophageal neoplasms

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Clinicopathologic and prognostic relevance of ARID1A protein loss in colorectal cancer

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World Journal of Gastroenterology 2014年第48期20卷 18404-18412页

作者： Xiao-Li Wei De-Shen Wang Shao-Yan Xi Wen-Jing Wu Dong-Liang Chen Zhao-Lei Zeng Rui-Yu Wang Ya-Xin Huang Ying Jin Feng Wang Miao-Zhen Qiu Hui-Yan Luo Dong-Sheng Zhang Rui-Hua Xu department of Medical Oncology Sun Yat-Sen University Cancer Center State Key Laboratory of Oncology in South China Collaborative Innovation Center for Cancer Medicine department of Pathology Sun Yat-Sen University Cancer Center department of Breast surgery Sun Yat-Sen Memorial Hospital Sun Yat-Sen University Zhongshan School of Medicine Sun Yat-Sen University

AIM: To explore the association between AT-rich interactive domain 1A (ARID1A) protein loss by immunohistochemistry and both clinicopathologic characteristics and prognosis in patients with colorectal cancer.

关键词： AT-rich interactive domain 1A Switching defective/sucrose non-fermenting complexes colorectal cancer Clinicopathologic characteristics Prognosis

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Mast Cells in Adjacent Normal Colon Mucosa rather than Those in Invasive Margin are Related to Progression of Colon cancer

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Chinese Journal of cancer Research 2011年第4期23卷 276-282页

作者： Qing Xia Ya Ding Xiao-jun Wu Rui-qing Peng Qiang Zhou Jing Zeng Jing-hui Hou Xing Zhang Yi-xin Zeng Xiao-shi Zhang Ying-bo Chen State Key Laboratory of Oncology in South China Cancer Center Sun Yat-sen University Guangzhou 510060 China department of Medical Oncology Cancer Center Sun Yat-sen University Guangzhou 510060 China Biotherapy center Cancer Center Sun Yat-sen University Guangzhou 510060 China department of colorectal Oncology Cancer Center Sun Yat-sen University Guangzhou 510060 China department of Medical Oncology the First People Hospital of Yueyang Yueyang 414000 China department of Pathology Cancer Center Sun Yat-sen University Guangzhou 510060 China department of Gastric and Pancreatic Oncology Cancer Center Sun Yat-sen University Guangzhou 510060 China

Objective: Mast cells (MC) reside in the mucosa of the digestive tract as the first line against bacteria and toxins. Clinical evidence has implied that the infiltration of mast cells in colorectal cancers is related to malignant phenotypes and a poor prognosis. This study compared the role of mast cells in adjacent normal colon mucosa and in the invasive margin during the progression of colon cancer. Methods: Specimens were obtained from 39 patients with colon adenomas and 155 patients with colon cancers treated at the sun yat-sen university cancer center between January 1999 and July 2004. The density of mast cells was scored by an immunohistochemical assay. The pattern of mast cell distribution and its relationship with clinicopathologic parameters and 5-year survival were analyzed. Results: The majority of mast cells were located in the adjacent normal colon mucosa, followed by the invasive margin and least in the cancer stroma. Mast cell count in adjacent normal colon mucosa (MCCadjacent) was associated with pathologic classification, distant metastases and hepatic metastases, although it was not a prognostic factor. In contrast, mast cell count in the invasive margin (MCCinvasive) was associated with neither the clinicopathlogic parameters nor overall survival. Conclusion: Mast cells in the adjacent normal colon mucosa were related to the progression of colon cancer, suggesting that mast cells might modulate tumor progression via a long-distance mechanism.

关键词： Mast cell Colon cancer Mucosa Invasive margin Prognosis

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