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Genes & Diseases 2024年第1期11卷 42-45页

作者： Pingbao Zhang Pu Zhang Jun Gao Xiaosong Li Chengcheng Wei Weihui Liu QingLiu He Yuan Zhang Department of Urology Zhongshan HospitalFudan UniversityShanghai 200032China Department of Urology Surgery Union HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhanHubei 430022China Department of Liver Surgery and Transplantation Liver Cancer InstituteZhongshan HospitalFudan UniversityShanghai 200032China Clinical Molecular Medicine Testing Center The First Affiliated Hospital of Chongqing Medical UniversityChongqing 400016China Department of Urology The Second Affiliated Hospital of Fujian Medical UniversityQuanzhouFujian 362000China Department of Nephrology Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengduSichuan 610072China

Renal cell carcinoma,which consists of three main histological subtypes,namely,clear cell renal cell carcinoma(ccRCC),papillary RCC(pRCC),and chromophobe RCC(chRCC),accounts for most kidney cancer cases.ccRCC accounts for approximately 85%of all RcC cases,1 and it is a malignant tumor with multiple molecular features and a poor prognosis.Studies have shown that ccRCC is one of the most immune and vaso-invasive cancer types.2 Considering that ccRCC is not sensitive to either radiotherapy or chemotherapy,targeted therapies.

关键词： chemotherapy cancer cases

Genomic medicine and cancer clinical trial in Thailand

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Cancer Biology & Medicine 2024年第1期21卷 10-15页

作者： Lucksamon Thamlikitkul Napa Parinyanitikul Virote Sriuranpong Division of Medical Oncology Department of MedicineFaculty of Medicine Siriraj HospitalMahidol UniversityBangkok 10700Thailand Division of Medical Oncology Department of MedicineFaculty of MedicineChulalongkorn University&The King Chulalongkorn Memorial HospitalBangkok 10330Thailand

Introduction Cancer treatment has been revolutionized with the advent of targeted therapy and immunotherapy.In the past,when cancer treatment modalities were restricted,conventional chemotherapy was the only option for systemic disease.Because chemotherapy empirically affects all dividing cells,the targets are virtually non-specific.In this regard,toxic effects on normal tissue are essentially inevitable.

关键词： chemotherapy cancer Cancer

Deciphering resistancemechanisms and novel strategies to overcome drug resistance in ovarian cancer:a comprehensive review

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Oncology Research 2024年第5期32卷 831-847页

作者： EFFAT ALEMZADEH LEILA ALLAHQOLI AFROOZ MAZIDIMORADI ESMAT ALEMZADEH FAHIMEH GHASEMI HAMID SALEHINIYA IBRAHIM ALKATOUT Infectious Diseases Research Center Birjand University of Medical SciencesBirjandIran Department of Midwifery Ministry of Health and Medical EducationTehranIran Student Research Committee Shiraz University of Medical SciencesShirazIran Department of Biotechnology Faculty of MedicineBirjand University of Medical SciencesBirjandIran Cellular and Molecular Research Center Birjand University of Medical SciencesBirjandIran Social Determinants of Health Research Center Birjand University of Medical SciencesBirjandIran Kiel School of Gynaecological Endoscopy Campus KielUniversity Hospitals Schleswig-HolsteinKielGermany

Ovarian cancer is among the most lethal gynecological cancers,primarily due to the lack of specific symptoms leading to an advanced-stage diagnosis and resistance to chemotherapy.Drug resistance(DR)poses the most significant challenge in treating patients with existing drugs.The Food and Drug Administration(FDA)has recently approved three new therapeutic drugs,including two poly(ADP-ribose)polymerase(PARP)inhibitors(olaparib and niraparib)and one vascular endothelial growth factor(VEGF)inhibitor(bevacizumab)for maintenance therapy.However,resistance to these new drugs has emerged.Therefore,understanding the mechanisms of DR and exploring new approaches to overcome them is crucial for effective management.In this review,we summarize the major molecular mechanisms of DR and discuss novel strategies to combat DR.

关键词： chemotherapy Drug resistance mechanisms Ovarian cancer PARP inhibitors VEGF inhibitor

Recent clinical trials and optical control as a potential strategy to develop microtubule-targeting drugs in colorectal cancer management

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World Journal of Gastroenterology 2024年第13期30卷 1780-1790页

作者： Katsuhiro Kita Allen Burdowski Department of Biology St.Francis CollegeBrooklynNY 11201United States

Colorectal cancer(CRC)has remained the second and the third leading cause of cancer-related death worldwide and in the United States,respectively.Although significant improvement in overall survival has been achieved,death in adult populations under the age of 55 appears to have increased in the past decades.Although new classes of therapeutic strategies such as immunotherapy have emerged,their application is very limited in CRC so far.Microtubule(MT)inhibitors such as taxanes,are not generally successful in CRC.There may be some way to make MT inhibitors work effectively in CRC.One potential advantage that we can take to treat CRC may be the combination of optical techniques coupled to an endoscope or other fiber optics-based devices.A combination of optical devices and photo-activatable drugs may allow us to locally target advanced CRC cells with highly potent MT-targeting drugs.In this Editorial review,we would like to discuss the potential of optogenetic approaches in CRC management.

关键词： Colorectal cancer chemotherapy Microtubule Combretastatin Photopharmacology

Cell fate regulation governed by p53: Friends or reversible foes in cancer therapy

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Cancer Communications 2024年第3期44卷 297-360页

作者： Bin Song Ping Yang Shuyu Zhang Laboratory of Radiation Medicine West China Second University HospitalSichuan UniversityChengduSichuanP.R.China The Second Affiliated Hospital of Chengdu Medical College China National Nuclear Corporation 416 HospitalChengduSichuanP.R.China Laboratory of Radiation Medicine NHC Key Laboratory of Nuclear Technology Medical TransformationWest China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengduSichuanP.R.China

Cancer is a leading cause of death worldwide.Targeted therapies aimed at key oncogenic driver mutations in combination with chemotherapy and radiother-apy as well as immunotherapy have benefited cancer patients considerably.Tumor protein p53(TP53),a crucial tumor suppressor gene encoding p53,reg-ulates numerous downstream genes and cellular phenotypes in response to various stressors.The affected genes are involved in diverse processes,includ-ing cell cycle arrest,DNA repair,cellular senescence,metabolic homeostasis,apoptosis,and autophagy.However,accumulating recent studies have contin-ued to reveal novel and unexpected functions of p53 in governing the fate of tumors,for example,functions in ferroptosis,immunity,the tumor microenvi-ronment and microbiome metabolism.Among the possibilities,the evolutionary plasticity of p53 is the most controversial,partially due to the dizzying array of biological functions that have been attributed to different regulatory mechanisms of p53 signaling.Nearly 40 years after its discovery,this key tumor suppressor remains somewhat enigmatic.The intricate and diverse functions of p53 in reg-ulating cell fate during cancer treatment are only the tip of the iceberg with respect to its equally complicated structural biology,which has been painstak-ingly revealed.Additionally,TP53 mutation is one of the most significant genetic alterations in cancer,contributing to rapid cancer cell growth and tumor pro-gression.Here,we summarized recent advances that implicate altered p53 in modulating the response to various cancer therapies,including chemotherapy,radiotherapy,and immunotherapy.Furthermore,we also discussed potential strategies for targeting p53 as a therapeutic option for cancer.

关键词： cancer chemotherapy drug targeting immunotherapy p53 tumor suppressor

Verteporfin fluorescence in antineoplastic-treated pancreatic cancer cells found concentrated in mitochondria

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 968-978页

作者： Ying-Qiao Zhang Qing-Hao Liu Lu Liu Peng-Yu Guo Run-Ze Wang Zhi-Chang Ba Department of Radiology Harbin Medical University Cancer HospitalHarbin 150010Heilongjiang ProvinceChina Department of Digestive Internal Medicine Harbin Medical University Cancer HospitalHarbin 150010Heilongjiang ProvinceChina

BACKGROUND Traditional treatments for pancreatic cancer(PC)are inadequate.Photodynamic therapy(PDT)is non-invasive,and proven safe to kill cancer cells,including PC.However,the mitochondrial concentration of the photosensitizer,such as verteporfin,is key.AIM To investigate the distribution of fluorescence of verteporfin in PC cells treated with antitumor drugs,post-PDT.METHODS Workable survival rates of PC cells(AsPC-1,BxPC-3)were determined with chemotherapy[doxorubicin(DOX)and gemcitabine(GEM)]and non-chemotherapy[sirolimus(SRL)and cetuximab(CTX)]drugs in vitro,with or without verteporfin,as measured via MTT,flow cytometry,and laser confocal microscopy.Reduced cell proliferation was associated with GEM that was more enduring compared with DOX.Confocal laser microscopy allowed observation of GEM-and verteporfin-treated PC cells co-stained with 4’,6-diamidino-2-phenylindole and MitoTracker Green to differentiate living and dead cells and subcellular localization of verteporfin,respectively.RESULTS Cell survival significantly dropped upon exposure to either chemotherapy drug,but not to SRL or CTX.Both cell lines responded similarly to GEM.The intensity of fluorescence was associated with the concentration of verteporfin.Additional experiments using GEM showed that survival rates of the PC cells treated with 10μmol/L verteporfin(but not less)were significantly lower relative to nil verte-porfin.Living and dead stained cells treated with GEM were distinguishable.After GEM treatment,verteporfin was observed primarily in the mitochondria.CONCLUSION Verteporfin was observed in living cells.In GEM-treated human PC cells,verteporfin was particularly prevalent in the mitochondria.This study supports further study of PDT for the treatment of PC after neoadjuvant chemotherapy.

关键词： Photodynamic therapy Pancreatic cancer Verteporfin Mitochondria chemotherapy Gemcitabine

Dynamic shielding of bacterial outer membrane vesicles for safe and efficient chemo-immunotherapy against tumors

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Nano Research 2024年第2期17卷 836-847页

作者： Shuping Li Xin Li Jiaqi Meng Weier Bao Shuang Wang Peng Ye Xiao-Dong Gao Wei Wei Key Laboratory of Carbohydrate Chemistry and Biotechnology Ministry of Education School of BiotechnologyJiangnan UniversityWuxi 214122China State Key Laboratory of Biochemical Engineering Institute of Process EngineeringChinese Academy of SciencesBeijing 100190China School of Chemical Engineering University of Chinese Academy of SciencesBeijing 100049China

Bacterial outer membrane vesicles(OMVs)are potent immunostimulants of regulating the tumor microenvironment(TME)for immunotherapy,and can be used to deliver drugs.However,the severe systemic inflammatory response triggered by OMVs upon intravenous(i.v.)injection has limited their application.Here,we developed a safe and effective strategy by conjugating doxorubicin-loaded serum albumin(SA-DOX,AD)onto the surface of OMVs using a matrix metalloproteinase(MMP)-cleavable peptide linker(cL).This approach enabled the dynamic shielding of OMVs to reduce the systemic side effects while simultaneously enhancing the anti-tumor effects through chemo-immunotherapy.Specifically,the resulting OMV-cL-AD formulation exhibited significantly enhanced accumulation at the tumor site after i.***.administration,facilitated by the SA decoration on the OMVs surface.Subsequently,the shield on the OMV-cL-AD was cleaved by the over-expressed MMP in the TME,leading to the release of both OMVs and AD.This process provided OMV-induced immunotherapy and DOX-induced chemotherapy,resulting in synergistic tumor inhibition.In conclusion,our work demonstrated the potential of OMV-cL-AD as an effective immunochemotherapy strategy that can prolong the survival time of mice without inducing side effects.

关键词： outer membrane vesicles doxorubicin tumor microenvironment immunotherapy chemotherapy

Primary pancreatic peripheral T-cell lymphoma:A case report

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1668-1675页

作者： Yan-Liang Bai Li-Jie Wang Hui Luo Ya-Bin Cui Jin-Hui Xu Hui-Jie Nan Pei-Yao Yang Jun-Wei Niu Ming-Yue Shi Department of Hematology Zhengzhou University People's Hospital and Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina Department of Hematology Henan University People's Hospital and Henan Provincial People's HospitalZhengzhou 450003Henan ProvinceChina Department of Radiation Oncology The Affiliated Cancer Hospital of Zhengzhou UniversityZhengzhou 450008Henan ProvinceChina

BACKGROUND Primary pancreatic lymphoma(PPL)is an exceedingly rare tumor with limited mention in scientific literature.The clinical manifestations of PPL are often nonspecific,making it challenging to distinguish this disease from other panc-reatic-related diseases.chemotherapy remains the primary treatment for these individuals.CASE SUMMARY In this case study,we present the clinical details of a 62-year-old woman who initially presented with vomiting,abdominal pain,and dorsal pain.On further evaluation through positron emission tomography-computed tomography,the patient was considered to have a pancreatic head mass.However,subsequent endoscopic ultrasonography-guided fine needle aspiration(EUS-FNA)revealed that the patient had pancreatic peripheral T-cell lymphoma,not otherwise specified(PTCL-NOS).There was a substantial decrease in the size of the pancreatic mass after the patient underwent a cycle of chemotherapy comprised of brentuximab vedotin,decitabine,and oxaliplatin(brentuximab vedotin and Gemox).The patient had significant improvement in radiological findings at the end of the first cycle.CONCLUSION Primary pancreatic PTCL-NOS is a malignant and heterogeneous lymphoma,in which the clinical manifestations are often nonspecific.It is difficult to diagnose,and the prognosis is poor.Imaging can only be used for auxiliary diagnosis of other diseases.With the help of immunostaining,EUS-FNA could be used to aid in the diagnosis of PPL.After a clear diagnosis,chemotherapy is still the first-line treatment for such patients,and surgical resection is not recommended.A large number of recent studies have shown that the CD30 antibody drug has potential as a therapy for several types of lymphoma.However,identifying new CD30-targeted therapies for different types of lymphoma is urgently needed.In the future,further research on antitumor therapy should be carried out to improve the survival prognosis of such patients.

关键词： Pancreatic cancer Lymphoma chemotherapy Primary pancreatic lymphoma Case report

Microbiota enterotoxigenic Bacteroides fragilis-secreted BFT-1 promotes breast cancer cell stemness and chemoresistance through its functional receptor NOD1

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Protein & Cell 2024年第6期15卷 419-440页

作者： Wei Ma Lu Zhang Weilong Chen Zhaoxia Chang Juchuanli Tu Yuanyuan Qin Yuwen Yao Mengxue Dong Jiajun Ding Siqin Li Fengkai Li Qiaodan Deng Yifei Yang Tingting Feng Fanrong Zhang Xiying Shao Xueyan He Lixing Zhang Guohong Hu Quentin Liu Yi-Zhou Jiang Shu Zhu Zhi Xiao Dan Su Tong Liu Suling Liu Fudan University Shanghai Cancer Center & Institutes of Biomedical Sciences State Key Laboratory of Genetic EngineeringCancer InstitutesDepartment of OncologyKey Laboratory of Breast Cancer in ShanghaiThe Shanghai Key Laboratory of Medical EpigeneticsShanghai Key Laboratory of Radiation OncologyThe International Co-laboratory of Medical Epigenetics and MetabolismMinistry of Science and TechnologyShanghai Medical CollegeFudan UniversityShanghai 200032China Intelligent Pathology Institute and Department of Pathology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230071China Department of Thyroid Breast and Vascular SurgeryXijing HospitalFourth Military Medical UniversityXi’an 710032China Institute of Immunology CAS Key Laboratory of Innate Immunity and Chronic DiseaseSchool of Basic Medical SciencesDivision of Life Science and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Pathology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast Surgery The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Department of Breast Medical Oncology The Cancer Hospital of the University of Chinese Academy of Sciences (Zhejiang Cancer Hospital)Institute of Basic Medicine and Cancer (IBMC)Chinese Academy of SciencesHangzhou 310022China Shanghai Institute of Nutrition and Health University of Chinese Academy of SciencesChinese Academy of SciencesShanghai 200031China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China Department of Breast Surgery Xiangya HospitalChangsha 410008China Department of Breast Surgery Tumor Hospital of Harbin Medic

Tumor-resident microbiota in breast cancer promotes cancer initiation and malignant progression.However,targeting microbiota to improve the effects of breast cancer therapy has not been investigated in detail.Here,we evaluated the microbiota composition of breast tumors and found that enterotoxigenic Bacteroides fragilis(ETBF)was highly enriched in the tumors of patients who did not respond to taxane-based neoadjuvant chemotherapy.ETBF,albeit at low biomass,secreted the toxic protein BFT-1 to promote breast cancer cell stemness and chemoresistance.Mechanistic studies showed that BFT-1 directly bound to NOD1 and stabilized NOD1 protein.NOD1 was highly expressed on ALDH+breast cancer stem cells(BCSCs)and cooperated with GAK to phosphorylate NUMB and promote its lysosomal degradation,thereby activating the NOTCH1-HEY1 signaling pathway to increase BCSCs.NOD1 inhibition and ETBF clearance increase the chemosensitivity of breast cancer by impairing BCSCs.

关键词： NOD1 breast chemotherapy

MMAE-loaded PLGA nanomedicine with improved biosafety to achieve efficient antitumor treatment

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Journal of Innovative Optical Health Sciences 2024年第2期17卷 79-93页

作者： Changqiang Xie Yan Wang Zhenzhen Cai Jianghai Du Zhengyu Chen Junjie Wang Xingzhou Peng State Key Laboratory of Digital Medical Engineering School of Biomedical Engineering Hainan University Haikou 570228P.R.China Key Laboratory of Biomedical Engineering of Hainan Province One Health Institute Hainan University Haikou 570228P.R.China Key Laboratory of Hainan Trauma and Disaster Rescue The First Affiliated Hospital of Hainan Medical University Hainan Medical University Haikou 571199P.R.China Engineering Research Center for Hainan Bio.Smart Materials and Bio-Medical Devices Key Laboratory of Emergency and Trauma Ministry of EducationKey Laboratory of Hainan Functional Materials and Molecular ImagingCollege of Emergency and Trauma Hainan Medical UniversityHaikou 571199P.R.China

Monomethyl auristatin E(MMAE)is a derivative of the marine peptide Dolastatin 10,which has therapeutic effects against various cancers according to its antimitotic activity in multiple clinical trials.The antibody drug conjugate(ADC)of MMAE is currently used in clinical practice.However,the safety issues of MMAE-based ADC,such as high drug toxicity and poor bioavailability,still exist when using it for anticancer therapy.A sustained release of drug delivery approach should be used to reduce toxicity and achieve sufficient anticancer effects.Herein,PLGA-b-PEG 2000 with excellent biocompatibility and slow degradation ability was adopted to construct MMAE-loaded nanoparticles for safe and effective chemotherapy.The sustained release effect and the immunogenic cell death(ICD)effect of PLGA-MMAE nanoparticles were assessed by in vitro experiments.The PLGA-MMAE nanoparticles effectively accumulated in the tumor through the enhanced permeability and retention(EPR)effect,inducing cell apoptosis and causing a certain degree of immune response.The sustained drug release of PLGA-MMAE improved the bioavailability and effectively reduced the toxicity and development of the tumor compared to the effect of free MMAE or ADC.Overall,this study provides a safe and effective chemotherapeutic approach,as well as a simple and effective synthetic process for MMAE-based nanoparticles,improving their therapeutic efficacy and safety.

关键词： Monomethyl auristatin E poly(lactic-co-glycolic acid)nanoparticles sustained release chemotherapy immunogenic cell death