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Concurrent chemoradiotherapy using gemcitabine and nedaplatin in recurrent or locally advanced head and neck squamous cell carcinoma

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World Journal of Clinical Cases 2022年第11期10卷 3414-3425页

作者： Rui-Xue Huo Ying-Ying Jin Yong-Xue Zhuo Xiao-Tong Ji Yu Cui Xiao-Jing Wu Yi-Jia Wang Long Zhang Wen-Hua Zhang Yu-Mei Cai Cheng-Cheng Zheng Rui-Xue Cui Qian-Ye Wang Zhen Sun Feng-Wei Wang Department of Oncology Tianjin Union Medical CenterTianjin 300000China School of medicine Nankai UniversityTianjin 300000China laboratory of oncologic molecular medicine Tianjin Union Medical CenterTianjin 300000China

BACKGROUND Patients with recurrent or locally advanced head and neck squamous cell carcinoma(HNSCC)typically have limited treatment options and poor *** To evaluate the efficacy and safety of two drugs with potent radio-sensitization properties including gemcitabine and nedaplatin as concurrent chemoradiotherapy regimens in treating *** This single-arm prospective study enrolled patients with HNSCC to receive gemcitabine on days 1 and 8 and nedaplatin on days 1 to 3 for 21 *** radiation therapy with a conventional fraction was delivered 5 days per *** response rate(ORR),disease control rate,and toxicity were observed as primary *** survival(OS)and progression free survival were recorded and analyzed as secondary *** A total of 24 patients with HNSCC were *** the median 22.4-mo follow-up,both ORR and disease control rate were 100%.The one-year OS was 75%,and one-year progression-free survival(PFS)was 66.7%(median PFS was 15.1 mo).Recurrent HNSCC patients had a poorer prognosis than the treatment-naïve patients,and patients who achieved complete response had better survival than those in the PR group(all P<0.05).The most common grade 1-4(100%)or grade 3-4 toxicities(75%)were hematological,and the most common grade 3-4 non-hematological toxicity was mucositis in 17(71%)*** Gemcitabine plus nedaplatin with concurrent chemoradiotherapy is a therapeutic option for HNSCC with predictable *** the high adverse event rate,the optimized dose and schedule must be further explored.

关键词： Chemoradiotherapy Gemcitabine Nedaplatin Head and neck cancer Recurrent Locally advanced

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Potentiating CD8^(+) T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling

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Protein & Cell 2021年第4期12卷 240-260页

作者： Juanjuan Yuan Ting Cai Xiaojun Zheng Yangzi Ren Jingwen Qi Xiaofei Lu Huihui Chen Huizhen Lin Zijie Chen Mengnan Liu Shangwen He Qijun Chen Siyang Feng Yingjun Wu Zhenhai Zhang Yanqing Ding Wei Yang Shunde Hospital Southern Medical University(The First People's Hospital of Shunde)Foshan 528308China Guangdong Provincial Key laboratory of molecular oncologic Pathology Department of PathologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Pathology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Provincial Key laboratory of molecular oncologic Pathology Southern Medical UniversityGuangzhou 510515China Center for Precision medicine Guangdong Provincial People's HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510030China

Metabolic regulation has been proven to play a critical role in T cell antitumor ***,cholesterol metabolism as a key component of this regulation remains largely ***,we found that the low-density lipoprotein receptor(LDLR),which has been previously identified as a transporter for cholesterol,plays a pivotal role in regulating CD8+T cell antitumor *** the involvement of cholesterol uptake which is mediated by LDLR in T cell priming and clonal expansion,we also found a non-canonical function of LDLR in CD8+T cells:LDLR interacts with the T-cell receptor(TCR)complex and regulates TCR recycling and signaling,thus facilitating the effector function of cytotoxic T-lymphocytes(CTLs).Furthermore,we found that the tumor microenvironment(TME)downregulates CD8+T cell LDLR level and TCR signaling via tumor cell-derived proprotein convertase subtilisin/kexin type 9(PCSK9)which binds to LDLR and prevents the recycling of LDLR and TCR to the plasma membrane thus inhibits the effector function of ***,genetic deletion or pharmacological inhibition of PCSK9 in tumor cells can enhance the antitumor activity of CD8+T cells by alleviating the suppressive effect on CD8+T cells and consequently inhibit tumor *** previously established as a hypercholesterolemia target,this study highlights PCSK9/LDLR as a potential target for cancer immunotherapy as well.

关键词： LDLR PCSK9 TCR CD8^(+) T cells tumor microenvironment cancer immunotherapy

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Correction to:Potentiating CD8^(+)T cell antitumor activity by inhibiting PCSK9 to promote LDLR-mediated TCR recycling and signaling

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Protein & Cell 2022年第9期13卷 694-700页

作者： Juanjuan Yuan Ting Cai Xiaojun Zheng Yangzi Ren Jingwen Qi Xiaofei Lu Huihui Chen Huizhen Lin Zijie Chen Mengnan Liu Shangwen He Qijun Chen Siyang Feng Yingjun Wu Zhenhai Zhang Yanqing Ding Wei Yang Shunde Hospital Southern Medical University(The First People’s Hospital of Shunde)Foshan 528308China Guangdong Provincial Key laboratory of molecular oncologic Pathology Department of PathologySchool of Basic Medical SciencesSouthern Medical UniversityGuangzhou 510515China Department of Pathology Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Guangdong Provincial Key laboratory of molecular oncologic Pathology Southern Medical UniversityGuangzhou 510515China Center for Precision medicine Guangdong Provincial People’s HospitalSchool of MedicineSouth China University of TechnologyGuangzhou 510030China

Figure *** deficiency hinders the antitumor activity of CD8^(+)T cells.(A)Transcriptional level of genes involved in cholesterol transport in naïve CD8^(+)T cells,CTLs and CD8^(+)TILs(isolated at Day3 or Day7 post CTLs adoptive transfer),(n=4).(B)LDLR expression level on CTLs and CD8^(+)TILs(isolated at Day3 post CTLs adoptive transfer),(n=4).

关键词： LDLR inhibiting cholesterol

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Down-regulated γ-catenin expression is associated with tumor aggressiveness in esophageal cancer

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World Journal of Gastroenterology 2014年第19期20卷 5839-5848页

作者： Wang-Kai Fang Lian-Di Liao Wei Gu Bo Chen Zhi-Yong Wu Jian-Yi Wu Jian Shen Li-Yan Xu En-Min Li Department of Biochemistry and molecular Biology The Key Laboratory of Molecular Biology for High Cancer Incidence Coastal Chaoshan AreaShantou University Medical College Institute of oncologic Pathology Shantou University Medical College Department of Oncology Surgery Affiliated Shantou Hospital of Sun Yat-sen University

AIM: To evaluate the significance of γ-catenin in clinical pathology, cellular function and signaling mechanism in esophageal squamous cell carcinoma (ESCC).

关键词： γ -catenin Esophageal squamous cell carcinoma Independent prognostic factor Cell-cell adhesion Cell migration

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Autoantibodies: Potential clinical applications in early detection of esophageal squamous cell carcinoma and esophagogastric junction adenocarcinoma

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World Journal of Gastroenterology 2019年第34期25卷 5049-5068页

作者： Yi-Wei Xu Yu-Hui Peng Li-Yan Xu Jian-Jun Xie En-Min Li Department of Clinical laboratory medicine Cancer Hospital of Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina The Key laboratory of molecular Biology for High Cancer Incidence Coastal Chaoshan Area Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Institute of oncologic Pathology Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina Department of Biochemistry and molecular Biology Shantou University Medical CollegeShantou 515041Guangdong ProvinceChina

Esophageal squamous cell carcinoma(ESCC)and esophagogastric junction adenocarcinoma(EGJA)are the two main types of gastrointestinal cancers that pose a huge threat to human *** remains one of the most common malignant diseases around the *** contrast to the decreasing prevalence of ESCC,the incidence of EGJA is rising *** detection represents one of the most promising ways to improve the prognosis and reduce the mortality of these *** approaches for early diagnosis mainly depend on invasive and costly ***-invasive biomarkers are in great need to facilitate earlier detection for better clinical management of ***-associated autoantibodies can be detected at an early stage before manifestations of clinical signs of tumorigenesis,making them promising biomarkers for early detection and monitoring of ESCC and *** this review,we summarize recent insights into the iden-tification and validation of tumor-associated autoantibodies for the early detection of ESCC and EGJA and discuss the challenges remaining for clinical validation.

关键词： Esophageal squamous cell carcinoma Esophagogastric junction adenocarcinoma Biomarker Autoantibody Diagnosis

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RIOK1 synergizes with TRIP13 by regulating the E2F-Rb signaling pathway to promote the proliferation of esophageal cancer cells

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Genes & Diseases 2024年第3期11卷 55-58页

作者： Chengyu Li Deyuan Pan Wan Lin Danxia Deng Yingxin Zhou Hui Zhao Feng Pan Liyan Xu Enmin Li Lin Long The Key laboratory of molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041China Guangdong Provincial Key laboratory of Infectious Diseases and molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041China Clinical Research Center Shantou Central HospitalShantouGuangdong 515041China

Esophageal cancer is one of the leading causes of cancer death in the world,with approximately half of the new cases occurring in China every year.^(1)Esophageal squamous cell carcinoma(ESCC)is the main subtype,accounting for more than 90%,and the five-year survival rate is less than 10%.Using large-scale genome analysis,many driver mutations and key pathways associated with ESCC have been ***,these genomic signatures have not improved the clinical management of EscC patients,or established effective targeted therapy.^(2)Esophageal cancer still lacks representative molecular markers.

关键词： cancer esophageal Esophageal

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Multisystem inflammatory syndrome in pediatric COVID-19 patients:a meta-analysis

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World Journal of Pediatrics 2021年第2期17卷 141-151页

作者： Eman A.Toraih Mohammad H.Hussein Rami M.Elshazli Adam Kline Ruhul Munshi Nasrin Sultana Sharven Taghavi Mary Killackey Juan Duchesne Manal S.Fawzy Emad Kandil Department of Surgery Tulane UniversitySchool of MedicineNew OrleansLAUSA Genetics Unit Department of Histology and Cell BiologyFaculty of MedicineSuez Canal UniversityIsmailiaEgypt Department of Biochemistry and molecular Genetics Faculty of Physical TherapyHorus University-EgyptNew Damietta 34517Egypt Tulane University School of MedicineNew OrleansLAUSA Division of Endocrine and oncologic Surgery Department of SurgerySchool of MedicineTulane UniversityNew OrleansLA 70112USA Department of medicine Larkin Community HospitalFlorida.MiamiUSA Trauma/Acute Care and Critical Care Department of SurgeryTulane UniversitySchool of MedicineNew OrleansLAUSA Department of Medical Biochemistry and molecular Biology Faculty of MedicineSuez Canal UniversityIsmailiaEgypt Department of Biochemistry College of MedicineNorthern Border UniversityArarKingdom of Saudi Arabia

Background We aimed to systematically review the clinical and laboratory features of patients with the multisystem inflam-matory syndrome in pediatrics diagnosed during the COVID-19 *** sources A literature search in Web of Science,PubMed,Scopus,and Science Direct was made up to June 29,*** Analysis of 15 articles(318 COVID-19 patients)revealed that although many patients presented with the typical multisystem inflammatory syndrome in pediatrics,Kawasaki-like features as fever(82.4%),polymorphous maculopapular exanthema(63.7%),oral mucosal changes(58.1%),conjunctival injections(56.0%),edematous extremities(40.7%),and cervical lymphadenopathy(28.5%),atypical gastrointestinal(79.4%)and neurocognitive symptoms(31.8%)were also *** had elevated serum lactic acid dehydrogenase,D-dimer,C-reactive protein,procalcitonin,interleukin-6,troponin I levels,and *** 77.0%developed hypotension,and 68.1%went into shock,while 41.1%had acute kidney *** care was needed in 73.7%of cases;13.2%were intubated,and 37.9%required mechanical *** immunoglobulins and steroids were given in 87.7%and 56.9%of the patients,respectively,and anticoagulants were utilized in 67.0%.Pediatric patients were discharged after a hospital stay of 6.77 days on average(95%CI 4.93-8.6).Conclusions Recognizing the typical and atypical presentation of the multisystem inflammatory syndrome in pediatric COVID-19 patients has important implications in identifying children at *** cardiac and renal decompensation and early interventions in patients with multisystem inflammatory syndrome is critical to prevent further morbidity.

关键词： COVID-19 Kawasaki-like syndrome Multisystem inflammatory syndrome in pediatrics SARS-CoV-2

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P300/CBP-associated factor(PCAF)-mediated acetylation of Fascin at lysine 471 inhibits its actin-bundling activity and tumor metastasis in esophageal cancer

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Cancer Communications 2021年第12期41卷 1398-1416页

作者： Yin-Wei Cheng Fa-Min Zeng Da-Jia Li Shao-Hong Wang Jian-Zhong He Zhen-Chang Guo Ping-Juan Nie Zhi-Yong Wu Wen-Qi Shi Bing Wen Xiu-E Xu Lian-Di Liao Zhi-Mao Li Jian-Yi Wu Jun Zhan Hong-Quan Zhang Zhi-Jie Chang Kai Zhang Li-Yan Xu En-Min Li The Key laboratory of molecular Biology for High Cancer Incidence Coastal Chaoshan Area Department of Biochemistry and Molecular BiologyShantou University Medical CollegeShantouGuangdong 515041P.R.China Institute of Basic Medical Science Cancer Research CenterShantou University Medical CollegeShantouGuangdong 515041P.R.China Shantou Central Hospital Affiliated Shantou Hospital of Sun Yat-sen UniversityShantouGuangdong 515041P.R.China Guangdong Provincial Key laboratory of Infectious Diseases and molecular Immunopathology Institute of Oncologic PathologyShantou University Medical CollegeShantouGuangdong 515041P.R.China Tianjin Key laboratory of Medical Epigenetics Department of Biochemistry and Molecular BiologySchool of Basic Medical SciencesTianjin Medical UniversityTianjin 300070P.R.China State Key laboratory of Natural and Biomimetic Drugs Peking University Health Science CenterBeijing 100191P.R.China School of medicine Tsinghua UniversityBeijing 100084P.R.China

Background:Fascin is crucial for cancer cell filopodium formation and tumor metastasis,and is functionally regulated by post-translational ***,whether and how Fascin is regulated by acetylation remains *** study explored the regulation of Fascin acetylation and its corresponding roles in filopodium formation and tumor ***:Immunoprecipitation and glutathione-S-transferase pull-down assays were performed to examine the interaction between Fascin and acetyltransferase P300/CBP-associated factor(PCAF),and immunofluorescence was used to investigate their *** in vitro acetylation assay was performed to identify Fascin acetylation sites by using mass spectrometry.A specific antibody against acetylated Fascin was generated and used to detect the PCAF-mediated Fascin acetylation in esophageal squamous cell carcinoma(ESCC)cells using Western blotting by overexpressing and knocking down PCAF *** in vitro cell migration assay was performed,and a xenograft model was established to study in vivo tumor ***-cell imaging and fluorescence recovery after photobleaching were used to evaluate the function and dynamics of acetylated Fascin in filopodium *** clinical significance of acetylated Fascin and PCAF in ESCC was evaluated using ***:Fascin directly interacted and colocalized with PCAF in the cytoplasm and was acetylated at lysine 471(K471)by *** the specific antiAcK471-Fascin antibody,Fascin was found to be acetylated in ESCC cells,and the acetylation level was consequently increased after PCAF overexpression and decreased after PCAF ***,Fascin-K471 acetylation markedly suppressed in vitro ESCC cell migration and in vivo tumor metastasis,whereas Fascin-K471 deacetylation exhibited a potent oncogenic ***,Fascin-K471 acetylation reduced filopodial length and density,and lifespan of ESCC cells,while its deacetylation produced the opp

关键词： acetylation actin-bundling esophageal cancer fascin filopodium formation P300/CBPassociated factor(PCAF) tumor metastasis

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Heat shock protein 90 promotes RNA helicase DDX5 accumulation and exacerbates hepatocellular carcinoma by inhibiting autophagy

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Cancer Biology & medicine 2021年第3期18卷 693-704页

作者： Ting Zhang Xinrui Yang Wanping Xu Jing Wang Dawei Wu Zhixian Hong Shengxian Yuan Zhen Zeng Xiaodong Jia Shanshan Lu Rifaat Safadi Sen Han Zhihong Yang Leonard M.Neckers Suthat Liangpunsakul Weiping Zhou Yinying Lu Department of the Fifth Medical Center General Hospital of PLABeijing 100039China Division of Gastroenterology and Hepatology Department of MedicineIndiana University School of MedicineIndianapolis 46202USA Urologic oncologic Branch Center for Cancer ResearchNational Cancer InstituteBethesda 20814USA State Key laboratory of Toxicology and Medical Countermeasures Beijing Institute of Pharmacology and ToxicologyBeijing 100039China The Third Department of Hepatic Surgery Eastern Hepatobiliary Surgery HospitalShanghai 200438China Hadassah Medical Organization Hadassah Hebrew University Medical CenterJerusalem 9112001Israel Department of Biochemistry and molecular Biology Indiana University School of MedicineIndianapolis 46202USA Center for Synthetic and Systems Biology(CSSB) Tsinghua UniversityBeijing 100085China

Objective:Hepatocellular carcinoma(HCC),the main type of liver cancer,has a high morbidity and mortality,and a poor *** helicase DDX5,which acts as a transcriptional co-regulator,is overexpressed in most malignant tumors and promotes cancer cell *** shock protein 90(HSP90)is an important molecular chaperone in the conformational maturation and stabilization of numerous proteins involved in cell growth or ***:DDX5 m RNA and protein expression in surgically resected HCC tissues from 24 Asian patients were detected by quantitative real-time PCR and Western blot,*** interaction of DDX5-HSP90 was determined by molecular docking,immunoprecipitation,and laser scanning confocal *** autophagy signal was detected by Western *** cell functions and signaling pathways of DDX5 were determined in 2 HCC cell *** different murine HCC xenograft models were used to determine the function of DDX5 and the therapeutic effect of an HSP90 ***:HSP90 interacted directly with DDX5 and inhibited DDX5 protein degradation in the AMPK/ULK1-regulated autophagy *** subsequent accumulation of DDX5 protein induced the malignant phenotype of HCC by activating theβ-catenin signaling *** silencing of DDX5 or treatment with HSP90 inhibitor both blocked in vivo tumor growth in a murine HCC xenograft *** levels of HSP90 and DDX5 protein were associated with poor ***:HSP90 interacted with DDX5 protein and subsequently protected DDX5 protein from AMPK/ULK1-regulated autophagic ***5 and HSP90 are therefore potential therapeutic targets for HCC.

关键词： Hepatocellular carcinoma heat shock protein 90 RNA helicase DDX5 autophagy β-catenin pathway

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Gut mucosal microbiota profiles linked to colorectal cancer recurrence

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World Journal of Gastroenterology 2022年第18期28卷 1946-1964页

作者： Rui-Xue Huo Yi-Jia Wang Shao-Bin Hou Wei Wang Chun-Ze Zhang Xue-Hua Wan Department of Oncology Tianjin Union Medical CenterNankai UniversityTianjin 300121China laboratory of oncologic molecular medicine Tianjin Union Medical CenterNankai UniversityTianjin 300121China Advanced Studies in Genomics Proteomics and BioinformaticsUniversity of Hawaii at ManoaHonoluluHI 96822United States TEDA Institute of Biological Sciences and Biotechnology Nankai UniversityTianjin 300457China Department of Colorectal Surgery Tianjin Union Medical CenterNankai UniversityTianjin 300121China Tianjin Institute of Coloproctology Tianjin 300121China

BACKGROUND Emerging evidence links gut microbiota to various human diseases including colorectal cancer(CRC)initiation and ***,gut microbiota profiles associated with CRC recurrence and patient prognosis are not completely understood yet,especially in a Chinese *** To investigate the relationship between gut mucosal microbiota profiles and CRC recurrence and patient *** We obtained the composition and structure of gut microbiota collected from 75 patients diagnosed with CRC and 26 healthy *** patients were followed up by regular examination to determine whether tumors ***-paired samples from on-tumor,adjacent-tumor and off-tumor sites of patients diagnosed with/without CRC recurrence were analyzed to assess spatial-specific patterns of gut mucosal microbiota by 16S ribosomal RNA ***,we carried out bioinformatic analyses,Kaplan-Meier survival analyses and Cox regression analyses to determine the relationship between gut mucosal microbiota profiles and CRC recurrence and patient *** We observed spatial-specific patterns of gut mucosal microbiota profiles linked to CRC recurrence and patient prognosis.A total of 17 bacterial genera/families were identified as potential biomarkers for CRC recurrence and patient prognosis,including Anaerotruncus,Bacteroidales,Coriobacteriaceae,Dialister,Eubacterium,Fusobacterium,Filifactor,Gemella,Haemophilus,Mogibacteriazeae,Pyramidobacter,Parvimonas,Porphyromonadaceae,Slackia,Schwartzia,TG5 and *** Our work suggests that intestinal microbiota can serve as biomarkers to predict the risk of CRC recurrence and patient death.

关键词： Gut microbiota Colorectal cancer Prognosis Colorectal cancer recurrence Biomarker 16S rRNA sequencing analysis

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