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Recent advances and remaining challenges in lung cancer therapy

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Chinese Medical Journal 2024年第5期137卷 533-546页

作者： Tasha Barr Shoubao Ma Zhixin Li Jianhua Yu department of Hematology and Hematopoietic cell transplantation City of Hope National Medical CenterLos AngelesCalifornia 91010USA Comprehensive Cancer Center City of HopeLos AngelesCalifornia 91010USA department of Immuno-Oncology Beckman Research InstituteLos AngelesCalifornia 91010USA

Lung cancer remains the most common cause of cancer *** the continued research into new drugs and combination therapies,outcomes in lung cancer have been improved,and clinical benefits have been expanded to a broader patient ***,the overall cure and survival rates for lung cancer patients remain low,especially in metastatic *** the available lung cancer treatment options,such as surgery,radiation therapy,chemotherapy,targeted therapies,and alternative therapies,immunotherapy has shown to be the most *** exponential progress in immuno-oncology research and recent advancements made in the field of immunotherapy will further increase the survival and quality of life for lung cancer *** progress has been made in targeted therapies using tyrosine kinase inhibitors and monoclonal antibody immune checkpoint inhibitors with many US Food And Drug Administration(FDA)-approved drugs targeting the programmed cell death ligand-1 protein(e.g.,durvalumab,atezolizumab),the programmed cell death-1 receptor(e.g.,nivolumab,pembrolizumab),and cytotoxic T-lymphocyte-associated antigen 4(e.g.,tremelimumab,ipilimumab).Cytokines,cancer vaccines,adoptive T cell therapies,and Natural killer cell mono-and combinational therapies are rapidly being studied,yet to date,there are currently none that are FDA-approved for the treatment of lung *** this review,we discuss the current lung cancer therapies with an emphasis on immunotherapy,including the challenges for future research and clinical applications.

关键词： Lung cancer Therapy Immunotherapy Combination therapy Adoptive T cell therapies

TPOL triggers apoptosis with mitochondrial injury through activating a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signaling

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中国病理生理杂志 2024年第8期40卷 1488-1496页

作者： CHENG Zongwei ZENG Boning XING Feiyue department of Immunobiology Institute of Tissue Transplantation and ImmunologyJinan UniversityGuangzhou 510632China

AIM:To explore the influence of ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate(TPOL)on cell apoptosis and its potential ***:HEK293T cells sensitive to TPOL were treated with different concentrations of TPOL with or without exposure to light radiation,before treatment with various inhibitors,N-acetyl-Lcysteine(NAC),pifithrin-αand *** viability was measured by CCK-8 *** V/propidium iodide staining was used to count the number of apoptotic ***-DA staining was used to detect reactive oxygen species(ROS)levels,and JC-1 staining was used to assess mitochondrial membrane potential by flow *** expression of apoptosis-related proteins and cell cycle-regulated molecules was measured by Western ***:TPOL enhanced the apoptosis of HEK293T cells in a dose-dependent manner(Pcellular apoptosis with ROS-mediated mitochondrial membrane damage through the activation of a ROS-dependent p53/p21/p27/Rb/Bax/Cyto C/caspase-mediated signal axis.

关键词： ethyl(2,4,6-trimethylbenzoyl)phenylphosphinate reactive oxygen species mitochondria apoptosis

Homoharringtonine promotes heart allograft acceptance by enhancing regulatory T cells induction in a mouse model

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Chinese Medical Journal 2024年第12期137卷 1453-1464页

作者： Xia Qiu Hedong Zhang Zhouqi Tang Yuxi Fan Wenjia Yuan Chen Feng Chao Chen Pengcheng Cui Yan Cui Zhongquan Qi Tengfang Li Yuexing Zhu Liming Xie Fenghua Peng Tuo Deng Xin Jiang Longkai Peng Helong Dai Medical College Guangxi UniversityNanningGuangxi 530004China department of Kidney transplantation Center of Organ TransplantationThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China National Clinical Research Center for Metabolic Diseases and Department of Metabolism and EndocrinologyThe Second Xiangya Hospital of Central South UniversityChangshaHunan 410011China department of Organ transplantation The Fifth Clinical Medical College of Henan University of Chinese Medicine(Zhengzhou People’s Hospital)ZhengzhouHenan 450000China

Background:Homoharringtonine(HHT)is an effective anti-inflammatory,anti-viral,and anti-tumor protein synthesis inhibitor that has been applied ***,we explored the therapeutic effects of HHT in a mouse heart transplant ***:Healthy C57BL/6 mice were used to observe the toxicity of HHT in the liver,kidney,and hematology.A mouse heart transplantation model was constructed,and the potential mechanism of HHT prolonging allograft survival was evaluated using Kaplan-Meier analysis,immunostaining,and bulk RNA sequencing *** HHT-T cell crosstalk was modeled ex vivo to further verify the molecular mechanism of HHT-induced regulatory T cells(Tregs)***:HHT inhibited the activation and proliferation of T cells and promoted their apoptosis ex *** of 0.5 mg/kg HHT for 10 days significantly prolonged the mean graft survival time of the allografts from 7 days to 48 days(Pcells in the spleen(Pcell receptor(TCR)signaling pathway-related genes(CD4,H2-Eb1,TRAT1,and CD74)and upregulated the expression of IL-10 and transforming growth factor(TGF)-βpathway-related genes and Treg signature genes(CTLA4,Foxp3,CD74,and ICOS).HHT increased CD4^(+)Foxp3^(+)cells and Foxp3 expression ex vivo,and it enhanced the inhibitory function of inducible ***:HHT promotes Treg cell differentiation and enhances Treg suppressive function by attenuating the TCR signaling pathway and upregulating the expression of Treg signature genes and IL-10 levels,thereby promoting mouse heart allograft *** findings may have therapeutic implications for organ tr

关键词： Heart transplantation Homoharringtonine Immunosuppressive agents T-lymphocytes,Regulatory Graft acceptance

Hippo(YAP)-autophagy axis protects against hepatic ischemia-reperfusion injury through JNK signaling

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Chinese Medical Journal 2024年第6期137卷 657-668页

作者： Shuguang Zhu Xiaowen Wang Haoqi Chen Wenfeng Zhu Xuejiao Li Ruiwen Cui Xiaomeng Yi Xiaolong Chen Hua Li Genshu Wang department of Hepatic Surgery Liver TransplantationThe Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Hepatology lab The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of General Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Organ transplantation The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Renal transplantation Guangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China department of Surgical Intensive Care Unit The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhouGuangdong 510630China department of Hepatic Surgery Liver TransplantationGuangdong Provincial Hospital of Chinese MedicineGuangzhouGuangdong 510630China

Background:Hepatic ischemia-reperfusion injury(HIRI)remains a common complication during liver transplantation(LT)in *** a key downstream effector of the Hippo pathway,Yes-associated protein(YAP)has been reported to be involved in various physiological and pathological ***,it remains elusive whether and how YAP may control autophagy activation during ***:Human liver tissues from patients who had undergone LT were obtained to evaluate the correlation between YAP and autophagy *** an in vitro hepatocyte cell line and in vivo liver-specific YAP knockdown mice were used to establish the hepatic ischemia-reperfusion models to determine the role of YAP in the activation of autophagy and the mechanism of ***:Autophagy was activated in the post-perfusion liver grafts during LT in patients,and the expression of YAP positively correlated with the autophagic level of ***-specific knockdown of YAP inhibited hepatocytes autophagy upon hypoxia-reoxygenation and HIRI(P<0.05).YAP deficiency aggravated HIRI by promoting the apoptosis of hepatocytes both in the in vitro and in vivo models(P<0.05).Attenuated HIRI by overexpression of YAP was diminished after the inhibition of autophagy with *** addition,inhibiting autophagy activation by YAP knockdown exacerbated mitochondrial damage through increasing reactive oxygen species(P<0.05).Moreover,the regulation of autophagy by YAP during HIRI was mediated by AP1(c-Jun)N-terminal kinase(JNK)signaling through binding to the transcriptional enhanced associate domain(TEAD).Conclusions:YAP protects against HIRI by inducing autophagy via JNK signaling that suppresses the apoptosis of *** Hippo(YAP)-JNK-autophagy axis may provide a novel strategy for the prevention and treatment of HIRI.

关键词： YAP-signaling proteins Autophagy c-Jun N-terminal kinase Ischemia-reperfusion injury Liver transplantation

Pericytes protect rats and mice from sepsis-induced injuries by maintaining vascular reactivity and barrier function:implication of miRNAs and microvesicles

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Military Medical Research 2024年第1期11卷 1-18页

作者： Zi-Sen Zhang Yi-Yan Liu Shuang-Shuang He Dai-Qin Bao Hong-Chen Wang Jie Zhang Xiao-Yong Peng Jia-Tao Zang Yu Zhu Yue Wu Qing-Hui Li Tao Li Liang-Ming Liu State Key Laboratory of Trauma Burns and Combined InjuryDepartment of Shock and TransfusionResearch Institute of SurgeryDaping HospitalArmy Medical UniversityChongqing 400042China

Background Vascular hyporeactivity and leakage are key pathophysiologic features that produce multi-organ damage upon *** hypothesized that pericytes,a group of pluripotent cells that maintain vascular integrity and tension,are protective against sepsis via regulating vascular reactivity and *** We conducted a series of in vivo experiments using wild-type(WT),platelet-derived growth factor receptor-β(PDGFR-β)-Cre+mT/mG transgenic mice and Tie2-Cre+Cx43^(flox/flox)mice to examine the relative contribution of pericytes in sepsis,either induced by cecal ligation and puncture(CLP)or lipopolysaccharide(LPS)*** a separate set of experiments with Sprague-Dawley(SD)rats,pericytes were depleted using CP-673451,a selective PDGFR-βinhibitor,at a dosage of 40 mg/(kg·d)for 7 consecutive *** pericytes,vascular endothelial cells(VECs)and vascular smooth muscle cells(VSMCs)were used for mechanistic *** effects of pericytes and pericyte-derived microvesicles(PCMVs)and candidate miRNAs on vascular reactivity and barrier function were also *** CLP and LPS induced severe injury/loss of pericytes,vascular hyporeactivity and leakage(Ptransplantation with exogenous pericytes protected vascular reactivity and barrier function via microvessel colonization(P<0.05).Cx43 knockout in either pericytes or VECs reduced pericyte colonization in microvessels(P<0.05).Additionally,PCMVs transferred miR-145 and miR-132 to VSMCs and VECs,respectively,exerting a protective effect on vascular reactivity and barrier function after sepsis(P<0.05).miR-145 primarily improved the contractile response of VSMCs by activating the sphingosine kinase 2(Sphk2)/sphingosine-1-phosphate receptor(S1PR)1/phosphorylation of myosin light chain 20 pathway,whereas miR-132 effectively improved the barrier function of VECs by activating the Sphk2/S1PR2/zonula occludens-1 and vascular endothelial-cadherin *** Pericytes are protective a

关键词： Pericyte Vascular reactivity Vascular permeability Cx43 Microvesicle

Depletion of anti-CD47mAb in plasma by genetically modified cells for pre-transfusion testing

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Genes & Diseases 2024年第5期11卷 102-104页

作者： Fei Wang Wenting Wang Xiaoshuang Wu Zhixin Liu Yafen Wang Rong Zhang Shunli Gu Qunxing An Yaozhen Chen Xingbin Hu department of transfusion Medicine Xijing HospitalFourth Military Medical UniversityXi’anShaanxi 710032China Xi’an Medical University Xi’anShaanxi 710021China

Allogeneic red blood cell(RBC)transfusion is commonly performed in medical practice because of its efficacy and low-risk ***,pre-transfusion tests are susceptible to monoclonal antibody(mAb)interference.1 Currently,mAb therapies are being developed to treat many diseases,such as ***,certain mAbs,such as anti-CD38mAb and anti-CD47mAb,can bind to RBC membranes;this binding interferes with pre-transfusion tests.2 CD47 has gained considerable attention in recent years because of its potential as a therapeutic target for hematologic malignancies and solid tumors.3 The binding of anti-CD47mAb to RBCs may lead to false-positive results in pan-agglutination tests and cause delays and risks in establishing compatible RBCs for transfusion.

关键词： CD47 transfusion diseases

Thrombotic microangiopathy after kidney transplantation: Expanding etiologic and pathogenetic spectra

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World Journal of transplantation 2024年第1期14卷 84-95页

作者： Muhammed Mubarak Amber Raza Rahma Rashid Fnu Sapna Shaheera Shakeel department of Histopathology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan department of Nephrology Sindh Institute of Urology and TransplantationKarachi 74200SindhPakistan department of Pathology Montefiore Medical CenterThe University Hospital for Albert Einstein School of MedicineBronxNY 10461United States

Thrombotic microangiopathy(TMA)is an uncommon but serious complication that not only affects native kidneys but also transplanted *** review is specifically focused on post-transplant TMA(PT-TMA)involving kidney transplant *** reported prevalence in the latter population varies from 0.8%to 14%with adverse impacts on both graft and patient *** has many causes and associations,and the list of etiologic agents and associations is growing *** pathogenesis is equally varied and a variety of pathogenetic pathways lead to the development of microvascular injury as the final common ***-TMA is categorized in many ways in order to facilitate its ***,more than one causes are contributory in PT-TMA and it is often difficult to pinpoint one particular cause in an individual ***,the hallmark lesions are endothelial cell injury and intravascular thrombi affecting the *** diagnosis and classification of PT-TMA are imperative for optimal outcomes but are challenging for both clinicians and *** Banff classification has addressed this issue and has developed minimum diagnostic criteria for pathologic diagnosis of PT-TMA in the first *** of the condition is also challenging and still largely *** varies from simple maneuvers,such as plasmapheresis,drug withdrawal or modification,or dose reduction,to lifelong complement blockade,which is very expensive.A thorough understanding of the condition is imperative for an early diagnosis and quick treatment when the treatment is potentially *** review aims to increase the awareness of relevant stakeholders regarding this important,potentially treatable but under-recognized cause of kidney allograft dysfunction.

关键词： Thrombotic microangiopathy Microvascular injury Anemia Thrombocytopenia Kidney allograft failure

Combined hepatocellular cholangiocarcinoma: A clinicopathological update

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World Journal of Hepatology 2024年第5期16卷 766-775页

作者： Mukul Vij Fadl H Veerankutty Ashwin Rammohan Mohamed Rela department of Pathology Institute of Liver Disease and TransplantationChennai 600044India Comprehensive Liver Care Institute VPS LakeshoreCochin 682040India Institute of Liver Disease and transplantation Dr.Rela Institute and Medical CentreChennai 600044India

Combined hepatocellular-cholangiocarcinoma(cHCC-CCA)is a rare primary liver cancer associated with an appalling *** diagnosis and manage-ment of this entity have been challenging to physicians,radiologists,surgeons,pathologists,and oncologists *** diagnostic and prognostic value of biomarkers such as the immunohistochemical expression of nestin,a progenitor cell marker,have been explored *** a better understanding of biology and the clinical course of cHCC-CCA,newer treatment modalities like immune checkpoint inhibitors are being tried to improve the survival of patients with this rare *** this review,we give an account of the recent developments in the pathology,diagnostic approach,and management of cHCC-CCA.

关键词： Combined hepatocellular-cholangiocarcinoma Immunotherapy Nestin Hepatocellular carcinoma Cholangiocarcinoma Liver cancer Biomarker Immune checkpoint inhibitors Pathology Genomic landscape

Comprehensive analysis of the role of ubiquitin-specific peptidases in colorectal cancer:A systematic review

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World Journal of Gastrointestinal Oncology 2024年第1期16卷 197-213页

作者： Eman Al-Balushi Amina Al Marzouqi Shima Tavoosi Amir Hossein Baghsheikhi Arash Sadri Leyla Sharifi Aliabadi Mohammad-Mahdi Salarabedi Syed Azizur Rahman Nabeel Al-Yateem Alireza Mosavi Jarrahi Aram Halimi Mohammad Ahmadvand Wael M Abdel-Rahman College of Health Sciences University of SharjahSharjah 27272United Arab Emirates department of Biology Faculty of SciencesUniversity of IsfahanIsfahan 81746-73441Iran department of Biology Science and Research BranchIslamic Azad UniversityTehran 11365/4435Iran Students’Scientific Research Center Tehran University of Medical SciencesTehran ***Iran cell Therapy and Hematopoietic Stem cell transplantation Research Center Research Institute for OncologyHematologyand Cell TherapyTehran University of Medical SciencesTehran ***Iran Student Research Committee School of MedicineShahid Beheshti University of Medical SciencesTehran ***Iran department of Nursing University of SharjahSharjah 27272United Arab Emirates Cancer Research Centre Shahid Beheshti University of Medical SciencesTehran ***Iran department of Medical Laboratory Sciences University of SharjahSharjah 27272United Arab Emirates

BACKGROUND Colorectal cancer(CRC)is the third most frequent and the second most fatal *** search for more effective drugs to treat this disease is ongoing.A better understanding of the mechanisms of CRC development and progression may reveal new therapeutic ***-specific peptidases(USPs),the largest group of the deubiquitinase protein family,have long been implicated in various *** have been numerous studies on the role of USPs in CRC;however,a comprehensive view of this role is *** To provide a systematic review of the studies investigating the roles and functions of USPs in *** We systematically queried the MEDLINE(via PubMed),Scopus,and Web of Science *** Our study highlights the pivotal role of various USPs in several processes implicated in CRC:Regulation of the cell cycle,apoptosis,cancer stemness,epithelial–mesenchymal transition,metastasis,DNA repair,and drug *** findings of this study suggest that USPs have great potential as drug targets and noninvasive biomarkers in *** dysregulation of USPs in CRC contributes to drug resistance through multiple *** Targeting specific USPs involved in drug resistance pathways could provide a novel therapeutic strategy for overcoming resistance to current treatment regimens in CRC.

关键词： Ubiquitin-specific peptidases Colorectal cancer Deubiquitinase protein family Drug target discovery Biomarker discovery