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Feedback regulation between phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 and transforming growth factor β1 and prognostic value in gastric cancer

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World Journal of Gastroenterology 2020年第1期26卷 21-34页

作者： Qi Shao Zhi-Ming Chen Department of Chemotherapy/Radiotherapy Affiliated Hospital of Nantong University

BACKGROUND Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1(PREX1)was reported to be overexpressed in some cancers and involved in cancer development,but its expression and significance in gastric cancer remain unclear.AIM To evaluate the expression of PREX1 in gastric cancer and its significance in the development of gastric cancer,especially to evaluate the potential mechanism of PREX1 in gastric cancer.METHODS Bioinformatic analysis was performed in order to examine the expression of PREX1 in gastric cancer.The relationship between the survival rate of gastric cancer patients and PREX1 expression was assessed by Kaplan Meier portal.The Gene Set Enrichment Analysis and the correlation between PREX1 and transforming growth factor(TGF)β1 pathway-related mediators were evaluated by cBioPortal for Cancer Genomics.Western blotting and reverse transcriptase polymerase chain reaction assay were used to test the role of TGFβ1 on the expression of PREX1.Western blotting and dual-luciferase reporter system was used to evaluate the effect of PREX1 on the activation of TGFβ1 pathway.Wound healing and Transwell assay were used to assess the effect of PREX1 on the metastasis activity of gastric cancer cells.RESULTS PREX1 was overexpressed in the gastric tumors,and the expression levels were positively associated with the development of gastric cancer.Also,the high expression of PREX1 revealed poor prognosis,especially for those advanced and specific intestinal gastric cancer patients.PREX1 was closely involved in the positive regulation of cell adhesion and positively correlated with TGFβ1-related mediators.Furthermore,TGFβ1 could induce the expression of PREX1 at both the protein and mRNA level.Also,PREX1 could activate the TGFβ1 pathway.The induced PREX1 could increase the migration and invasion activity of gastric cancer cells.CONCLUSION PREX1 is overexpressed in gastric cancer,and the high level of PREX1 predicts poor prognosis.PREX1 is closely associated with TGFβsignaling and promotes the metast

关键词： Phosphatidylinositol-3,4,5-trisphosphate dependent Rac exchange factor 1 Gastric cancer High expression Poor prognosis Metastasis Transforming growth factorβ1 pathway

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Recent progress of chemotherapy and biomarkers for gastroesophageal cancer

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World Journal of Gastrointestinal Oncology 2019年第7期11卷 518-526页

作者： Osamu Maeda Yuichi Ando department of Clinical Oncology and chemotherapy Nagoya University Hospital

Key cytotoxic drugs of chemotherapy for gastroesophageal cancer include fluoropyrimidine, platinum, taxanes and irinotecan. Concurrent chemoradiotherapy is one of the main treatment strategies, especially for esophageal cancer. As molecular target agents, the anti-HER2 antibody trastuzumab for HER2-positive gastric cancer and the anti-angiogenesis agent ramucirumab combined with paclitaxel have been proven to improve the survival of gastric cancer patients. Recently, anti-PD-1 antibodies have become available as second- or later-line chemotherapy. Microsatellite instability is also useful as a biomarker to select patients suitable for immunotherapy. Furthermore, genome-wide analysis has improved our understanding of the biological features and molecular mechanisms of gastroesophageal cancer and will provide optimized treatment selection.

关键词： Gastroesophageal cancer chemotherapy Biomarker HER2

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Rhabdomyolysis and coronavirus disease-2019 in children:A case report and review of the literature

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Pediatric Investigation 2022年第2期6卷 135-139页

作者： Maria Kontou Konstantinos Kakleas Vaso Kimioni Dimitra Georgiadi Vasiliki Spoulou Athanasios Michos First department of Pediatrics Infectious Diseases and Chemotherapy Research LaboratoryMedical School"Aghia Sophia"Children’s HospitalNational and Kapodistrian University of AthensAthensGreece

Introduction:Coronavirus disease-2019(COVID-19)presents with a variety of symptoms,but rhabdomyolysis has rarely been reported in children.Case presentation:We report a 10-year-old girl who presented with fever,myalgia,and limping.The patient was tested positive for severe acute respiratory syndrome coronavirus-2.On admission,creatine kinase(CK)level was 13147 units per liter and the patient was diagnosed with rhabdomyolysis.She was treated with intravenous fluids,which resulted in CK levels decrease.There are currently seven case reports of children with rhabdomyolysis associated with acute COVID-19 infection and two reports with the multisystemic inflammatory syndrome.Conclusion:Children presenting with muscle pain and weakness in the acute phase or following COVID-19 infection,should alert physicians of the possibility of rhabdomyolysis.

关键词： Adolescents Children COVID-19 MIS-C Rhabdomyolysis SARS-CoV-2

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Prognostic value of lactate transporter SLC16A1 and SLC16A3 as oncoimmunological biomarkers associating tumor metabolism and immune evasion in glioma

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Cancer Innovation 2022年第3期1卷 229-239页

作者： Ting Zhu Xiaoqin Ge Shengping Gong Shenchao Guo Qingsong Tao Jianxin Guo Ruishuang Ma department of Radiotherapy and chemotherapy Ningbo First HospitalNingboChina Central Laboratory of the Medical Research Center Ningbo First HospitalNingboChina

Background:Hypoxic microenvironment is immunosuppressive and protu-morigenic,and elevated lactate is an intermediary in the modulation of immune responses.However,as critical lactate transporters,the role of SLC16A1 and SLC16A3 in immune infiltration and evasion of glioma is not fully elucidated.Methods:Gene expression in low‐and high‐grade glioma(LGG and GBM)was evaluated with TCGA database.The TISIDB,TIMER and CIBERSORT databases were utilized for the analysis of the correlation between SLC16A1 or SLC16A3 and immunocyte infiltration as well as immune checkpoints.Results:Compared with normal tissues,a significant increase of both SLC16A1 and SLC16A3 was found in LGG and GBM,and closely related to the poor prognosis only in LGG.Cancer SEA indicated that SLC16A1 was involved in hypoxia while SLC16A3 contributed to metastasis and inflamma-tion in glioma.The SLC16A3 expression was significantly correlated with neutrophil activation by GO analysis.TISCH showed the distribution of SLC16A1 on glioma cells and SLC16A3 on immune cells,which was correlated to tumor‐associated macrophages and neutrophils that are immunosuppressive.SLC16A1 and SLC16A3 were identified to tightly interacted with diverse immune checkpoints(especially PD1,PD‐L1,PD‐L2,Tim‐3)and immunosuppressive factors(TGF‐βand IL‐10)in glioma.Furthermore,SLC16A3 had a positive correlation to activation markers of tumor‐associated neutrophils and chemokines such as CCL2,CCL22,CXCR2,CXCR4 in LGG and CCL7,CCL20 CXCL8 in GBM,which could enhance infiltration of immunosuppressive cells to the tumor microenvironment.Conclusion:In general,our results suggest that SLC16A1 and SLC16A3 act as a bridge between tumor metabolism and immunity by promoting immuno-suppressive cell infiltration,which contributes to immune evasion and a worse prognosis in glioma.Targeting SLC16A1 and SLC16A3 may provide novel therapeutic strategy for immunotherapy in glioma.

关键词： glioma SLC16A1(MCT1) SLC16A3(MCT4) immune checkpoints immune evasion

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Sodium-glucose cotransporter 2 inhibitors in Asian patients with heart failure

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Chinese Medical Journal 2023年第8期136卷 1004-1005页

作者： Shingo Kato Nobuyuki Horita Daisuke Utsunomiya department of Diagnostic Radiology Yokohama City University Graduate School of MedicineKanagawaJapan department of Cardiology Kanagawa Cardiovascular and Respiratory CenterKanagawaJapan chemotherapy Center Yokohama City University HospitalKanagawaJapan

To the Editor:Sodium-glucose cotransporter 2(SGLT-2)inhibitors are recognized as one of the essential drugs for the treatment of heart failure(HF).Recent randomized controlled trials(RCTs)have shown that the SGLT-2 in... 详细信息

关键词： patients drugs mortality

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Prioritizing the efforts:lived experiences of family when taking care of people with cancer

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Frontiers of Nursing 2023年第3期10卷 315-322页

作者： Titan Ligita Merry Andriani Hazwani Hazwani Ersy Aprilya Fransiska Shafira Aulya department of Medical Surgical Nursing School of NursingTanjungpura UniversityPontianakWest Kalimantan 78124Indonesia Department of Chemotherapy Doctor Soedarso General HospitalPontianakWest Kalimantan 78124Indonesia

Objective:Cancer has one of the highest disease mortality rates.Families are very important in the treatment of people with cancer.By using a phenomenological design,this study aimed to explore the experience of families in caring for a person with cancer and to identify the needs of these families.Methods:First,eight interviews were under taken with family members selected through a purposive sampling method.Then,another three interviews were conducted for data validation.The collected data were analyzed using the framework method of analysis.Results:The core theme,“Prioritizing the efforts:Being aware of the best we could do for our family,”reflected family’s experiences of caring for a person with cancer and was underpinned by five themes:“Decisions to make,”“Keeping up the good support,”“Acknowledging the others’contributions,”“Assisting my family to alleviate the disease,”and“Adapting to the current situation.”Conclusions:The results suggest that building mutual trust and communication between family and healthcare professionals is vital in decision-making for people with cancer.Family may also work with the person in fulfilling their needs,without disregarding the needs of the family.When suppor ting the needs of people with diabetes,the family requires appropriate information,and thus,healthcare professionals wisely select which information can help the family make a decision regarding the treatment.After administering the treatment and providing information for people with cancer and their family,asking for feedback is required for evaluation.

关键词： cancer decision-making family needs phenomenology priority treatment

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Immune response to SARS-CoV-2 in children: A review of the current knowledge

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Pediatric Investigation 2021年第3期5卷 217-228页

作者： Filippos Filippatos Elizabeth-Barbara Tatsi Athanasios Michos First department of Pediatrics Infectious Diseases and Chemotherapy Research LaboratoryMedical SchoolNational and Kapodistrian University of Athens“Aghia Sophia”Children’s HospitalAthensGreece

Host immune responses to severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),especially in children,are still under investigation.Children with coronavirus disease 2019(COVID-19)constitute a significant study group of immune responses as they rarely present with severe clinical manifestations,require hospitalization,or develop complications such as multisystem inflammatory syndrome in children(MIS-C)associated with SARS-CoV-2 infection.The deciphering of children’s immune responses during COVID-19 infection will provide information about the protective mechanisms,while new potential targets for future therapies are likely to be revealed.Despite the limited immunological studies in children with COVID-19,this review compares data between adults and children in terms of innate and adaptive immunity to SARS-CoV-2,discusses the possible reasons why children are mostly asymptomatic,and highlights unanswered or unclear immunological issues.Current evidence suggests that the activity of innate immunity seems to be crucial to the early phases of SARS-CoV-2 infection and adaptive memory immunity is vital to prevent reinfection.

关键词： SARS-CoV-2 COVID-19 Immunity Multisystem inflammatory syndrome Children

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chemotherapy with or without gefitinib in patients with advanced non-small-cell lung cancer： a meta-analysis of 6844 patients

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Chinese Medical Journal 2013年第17期126卷 3348-3355页

作者： ZHOU Hang ZENG Chao WANG Li-yang XIE Hua ZHOU Jin DIAO Peng YAO Wen-xiu ZHAO Xin WEI Yang Department of Chemotherapy Sichuan Cancer Hospital Chengdu Sichuan 610041 China department of Gastroenterology Third People's Hospital of Chengdu Chengdu Sichuan 610031 China

Background Gefitinib is widely used in patients with advanced non-small-cell lung cancer （NSCLC）, in whom chemotherapy had failed. Previous trials reported inconsistent findings regarding the efficacy of gefitinib on overall survival （OS） and progression free survival （PFS）. This study was to evaluate the effects of chemotherapy plus gefitinib versus chemotherapy alone on survival of patients with NSCLC. Methods We systematically searched Medline, EmBase, the Cochrane Central Register of Controlled Trials, reference lists of articles, and proceedings of major meetings for relevant literature. Randomized controlled trials （RCTs） comparing chemotherapy with and without gefitinib in the treatment of patients with advanced NSCLC were included in our analysis. The primary endpoints were OS and PFS. Results Of 182 relevant studies, 12 were included in the final analysis, which consisted of 6844 patients with NSCLC. Overall, we noted that gefitinib therapy had an 8% improvement in the OS as compared to the gefitinib-free therapy, but this difference was not statistically significant （HR, 0.92; 95% CI： 0.85-1.00; P=0.051）. Furthermore, gefitinib therapy had significantly longer PFS compared to gefitinib-free therapy （HR, 0.72; 95% CI 0.60-0.87, P=0.001）. Patients receiving gefitinib therapy also had a more frequent objective response rate （ORR） than the control arm （OR, 2.51; 95% CI, 1.67- 3.78, P 〈0.001）. Rashes, diarrhea, dry skin, pruritus, paronychia, and abnormal hepatic function were more frequent in the gefitinib therapy group. Conclusions Treatment with gefitinib had a clear effect on PFS and ORR, and it might contribute considerably to the OS. Furthermore, there was some evidence of benefit for gefitinib therapy among patients with adenocarcinoma.

关键词： non-small-cell-lung cancer gefitinib meta-analysis

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LIM domain only 1:an oncogenic transcription cofactor contributing to the tumorigenesis of multiple cancer types

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Chinese Medical Journal 2021年第9期134卷 1017-1030页

作者： Guo-Fa Zhao Li-Qin Du Lei Zhang You-Chao Jia department of Medical Oncology Hebei Key Laboratory of Cancer Radiotherapy and ChemotherapyAffiliated Hospital of Hebei UniversityBaodingHebei 071000China department of Chemistry and Biochemistry Texas State UniversitySan MarcosTX 78666USA

The LIM domain only 1(LMO1)gene belongs to the LMO family of genes that encodes a group of transcriptional cofactors.This group of transcriptional cofactors regulates gene transcription by acting as a key"connector"or"scaffold"in transcription complexes.All LMOs,including LMO1,are important players in the process of tumorigenesis.Unique biological features of LMO1 distinct from other LMO members,such as its tissue-specific expression patterns,interacting proteins,and transcriptional targets,have been increasingly recognized.Studies indicated that LMO1 plays a critical oncogenic role in various types of cancers,including T-cell acute lymphoblastic leukemia,neuroblastoma,gastric cancer,lung cancer,and prostate cancer.The molecular mechanisms underlying such functions of LMO1 have also been investigated,but they are currently far from being fully elucidated.Here,we focus on reviewing the current findings on the role of LMO1 in tumorigenesis,the mechanisms of its oncogenic action,and the mechanisms that drive its aberrant activation in cancers.We also briefly review its roles in the development process and non-cancer diseases.Finally,we discuss the remaining questions and future investigations required for promoting the translation of laboratory findings to clinical applications,including cancer diagnosis and treatment.

关键词： LIM domain only 1 Cancer Single-nucleotide polymorphisms T-cell acute lymphoblastic leukemia Neuroblastoma

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The Protective Effect of Ascorbic Acid and Thiamine Supplementation against Damage Caused by Lead in the Testes of Mice

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Journal of Huazhong University of Science and Technology(Medical Sciences) 2009年第1期29卷 68-72页

作者：陕光唐甜张孝斌 department of Urology Renmin Hospital of Wuhan University department of Cancer Radio-chemotherapy Zhongnan Hospital and Cancer Research Center Wuhan University

Lead is a ubiquitous environmental and industrial pollutant that may have toxic effects on the male. Vitamins may protect against toxic effects of lead in the liver and reproductive system, which is confirmed by our initial research. The aim of this study was to further investigate the protective effects of vitamins （ascorbic acid combined with thiamine） on lead acetate （Pb）-induced reproductive toxicities in mice and study the possible mechanisms underlying these effects. Forty-five male mice were randomly divided into 3 groups, 15 mice in each and received daily intragastric administration with control, Pb （20 mg/kg）, and Pb＋vitamins （ascorbic acid of 420 mg/kg＋thiamine of 30 mg/kg） for 6 weeks, respectively. The Pb-treated animals showed significant decreases in the epididymal sperm count and motility compared to the control group, while the Pb＋vitamins group had significant increases for these variables. Moreover, an increasing apoptosis of germinal cells induced by Pb was reduced by vitamin treatment. Pb induced the activation of Caspase-3, Fas/Fas-L and Bcl-2 with elevated levels, and the adaptor protein primarily regulated signaling through Fas and required for Fas-induced apoptosis. In conclusion, ascorbic acid combined with thiamine exhibited protective effect on reproductive system by inhibiting Pb-induced excessive cell apoptosis.

关键词： lead ascorbic acid thiamine reproductive toxicity apoptosis

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