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PDK1 promotes breast cancer progression by enhancing the stability and transcriptional activity of HIF-1α

Genes & Diseases 2024年第4期11卷 353-367页

作者： Yu Wei Dian Zhang He Shi Husun Qian Hongling Chen Qian Zeng Fangfang Jin Yan Ye Zuli Ou Minkang Guo Bianqin Guo Tingmei Chen Key laboratory of Clinical laboratory Diagnostics(Ministry of Education) College of Laboratory MedicineChongqing Medical UniversityChongqing 400016China Chongqing Key laboratory of Translational Research for cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing 400030China

Pyruvate dehydrogenase kinase 1(PDK1)phosphorylates the pyruvate dehydroge-nase complex,which inhibits its *** pyruvate dehydrogenase complex inhibits the tricarboxylic acid cycle and the reprogramming of tumor cell metabolism to glycolysis,which plays an important role in tumor *** study aims to elucidate how PDK1 pro-motes breast cancer *** found that PDK1 was highly expressed in breast cancer tissues,and PDK1 knockdown reduced the proliferation,migration,and tumorigenicity of breast cancer cells and inhibited the HIF-1α(hypoxia-inducible factor 1α)*** investigation showed that PDK1 promoted the protein stability of HIF-1αby reducing the level of ubiquitination of HIF-1α.The HIF-1αprotein levels were dependent on PDK1 kinase ***,HIF-1αphosphorylation at serine 451 was detected in wild-type breast cancer cells but not in PDK1 knockout breast cancer *** phosphorylation of HIF-1αat Ser 451 stabilized its protein levels by inhibiting the interaction of HIF-1αwith von Hippel-Lindau and prolyl hydroxylase *** also found that PDK1 enhanced HIF-1αtranscriptional *** summary,PDK1 enhances HIF-1αprotein stability by phosphorylating HIF-1αat Ser451 and promotes HIF-1αtranscriptional activity by enhancing the binding of HIF-1αto ***1 and HIF-1αform a positive feedback loop to promote breast cancer progression.

关键词： Breast cancer HIF-1α PDK1 Protein phosphorylation Transcriptional activity

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Laparoscopic vs open surgery for gastric cancer: Assessing time, recovery, complications, and markers

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World Journal of Gastrointestinal Surgery 2024年第1期16卷 40-48页

作者： Yun-Yao Lu Yun-Xiao Li Meng He Ya-Li Wang Chongqing Key laboratory of Translational Research for cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing 400030China

BACKGROUND Gastric cancer(GC)is one of the most common cancers *** and mortality have increased in recent years,making it an urgent issue to ***-paroscopic radical surgery(LRS)is a crucial method for treating patients with GC;However,its influence on tumor markers is still under *** data of 194 patients treated at Chongqing University cancer Hospital bet-ween January 2018 and January 2019 were retrospectively *** who underwent traditional open surgery and LRS were assigned to the control(n=90)and observation groups(n=104),*** sample t-tests andχ2 tests were used to compare the two groups based on clinical efficacy,changes in tumor marker levels after treatment,clinical data,and the incidence of posto-perative *** investigate the association between tumor marker levels and clinical efficacy in patients with GC,three-year recurrence rates in the two groups were *** Patients in the observation group had a shorter duration of operation,less in-traoperative blood loss,an earlier postoperative eating time,and a shorter hospital stay than those in the control group(P0.05).After treatment,the overall response rate in the control group was significantly lower than that in the observation group(P=0.001).Furthermore,after treatment,the levels of carbohydrate antigen 19-9,cancer antigen 72-4,carcinoembryonic antigen,and cancer antigen 125 decreased *** observation group also exhibited a significantly lower incidence rate of postoperative complications compared to the control group(P0.05).CONCLUSION LRS effectively treats early gastric cancer by reducing intraoperative bleeding,length of hospital stays,and postoperative complications.I

关键词： Laparoscopic radical surgery Gastric cancer Serum tumor markers Prognosis Recurrence Intraoperative bleeding

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The role of proteasomes in tumorigenesis

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Genes & Diseases 2024年第4期11卷 155-169页

作者： Xiangyi Zhou Ruqing Xu Yue Wu Li Zhou Tingxiu Xiang Department of Oncology The First Affliated Hospital of Chongqing Medical UniversityChongqing 400016China Chongqing Key laboratory of Translational Research for cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing 400030China

Protein homeostasis is the basis of normal life activities,and the proteasomefamily plays an extremely important function in this *** proteasome 2os is a concentric circle structure with twoαrings and twoβrings *** proteasome 2os can perform both ATP-dependent and non-ATP-dependent ubiquitination proteasome degradation by binding to various subunits(such as 19S,11S,and 200 PA),which is performed by its active subunitβ1,β2,andβ*** proteasome can degrade misfolded,excess proteins tomaintain *** the same time,it can be utilized by tumors to degrade over-proliferate and unwanted proteins to support their *** can affect the development of tumors from several aspects including tumor signaling pathways such as NF-kB and p53,cell cycle,immune regulation,and drug ***-encoding genes have been found to be overexpressed in a variety of tumors,providing a potential novel target for cancer *** addition,proteasome inhibitors such as bortezomib,carfilzomib,and ixazomib have been put into clinical application as the first-line treatment of multiple *** and more studies have shown that it also has different therapeutic effects in other tumors such as hepatocellular carcinoma,non-small cell lung cancer,glioblastoma,and ***,proteasome inhibitors are not much effective due to their tolerance and singleness in other ***,further studies on their mechanisms of action and drug interactions are needed to investigate their therapeutic potential.

关键词： Bortezomib cancer therapy Immunoproteasome Multiplemyeloma Proteasome 20S Proteasome inhibitor Thymoproteasom

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The two sides of chromosomal instability:drivers and brakes in cancer

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Signal Transduction and Targeted Therapy 2024年第4期9卷 1595-1624页

作者： Rendy Hosea Sharon Hillary Sumera Naqvi Shourong Wu Vivi Kasim Key laboratory of Biorheological Science and Technology Ministry of EducationCollege of BioengineeringChongqing UniversityChongqing 400045China The 111 Project laboratory of Biomechanics and Tissue Repair College of BioengineeringChongqing UniversityChongqing 400044China Chongqing Key laboratory of Translational Research for cancer Metastasis and Individualized treatment Chongqing University Cancer HospitalChongqing UniversityChongqing 400030China

Chromosomal instability(CIN)is a hallmark of cancer and is associated with tumor cell *** triggers a chain reaction in cells leading to chromosomal abnormalities,including deviations from the normal chromosome number or structural changes in *** arises from errors in DNA replication and chromosome segregation during cell division,leading to the formation of cells with abnormal number and/or structure of *** in DNA replication result from abnormal replication licensing as well as replication stress,such as double-strand breaks and stalled replication forks;meanwhile,errors in chromosome segregation stem from defects in chromosome segregation machinery,including centrosome amplification,erroneous microtubule-kinetochore attachments,spindle assembly checkpoint,or defective sister chromatids *** normal cells,CiN is deleterious and is associated with DNA damage,proteotoxic stress,metabolic alteration,cell cycle arrest,and ***,despite these negative consequences,CiN is one of the hallmarks of cancer found in over 90%of solid tumors and in blood ***,CiN could endow tumors with enhanced adaptation capabilities due to increased intratumor heterogeneity,thereby facilitating adaptive resistance to therapies;however,excessive CiN could induce tumor cells death,leading to the"just-right"model for CIN in *** the complex nature of CIN is crucial for understanding the dynamics of tumorigenesis and for developing effective anti-tumor *** review provides an overview of causes and consequences of CIN,as well as the paradox of CIN,a phenomenon that continues to perplex ***,this review explores the potential of CIN-based anti-tumor therapy.

关键词： chromosomal consequences thereby

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Injectable hydrogel-based drug delivery systems for enhancing the efficacy of radiation therapy:A review of recent advances

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Chinese Chemical Letters 2024年第8期35卷 128-137页

作者： Ningyue Xu Jun Wang Lei Liu Changyang Gong Division of Head&Neck Tumor Multimodality treatment Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China Department of Biotherapy Cancer Center and State Key Laboratory of BiotherapyWest China HospitalSichuan UniversityChengdu 610041China

Radiotherapy(RT)is a crucial treatment for cancer;however,its effectiveness is limited by adverse effects on normal tissues,radioresistance,and tumor *** overcome these challenges,hydrogels have been employed for delivery of radiosensitizers and other therapeutic *** review summarizes recent advancements in the application of hydrogel-based local drug delivery systems for improving the therapeutic efficacy of RT in cancer ***,we introduce the classification and properties of ***,we detail hydrogel-based platforms designed to enhance both external beam radiation therapy and *** also discuss hydrogels used in combination therapy involving RT and ***,we highlight the challenges that hydrogels face in *** surveying the latest developments in hydrogel applications for RT,this review aims to provide insights into the development of more effective and targeted cancer therapies.

关键词： Radiotherapy Drug delivery systems Hydrogel Radiation sensitization Combination therapy

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How can we establish animal models of HIV-associated lymphoma?

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Animal Models and Experimental Medicine 2024年第4期7卷 484-496页

作者： Qing Xiao Liuyue Zhai Xiaomei Zhang Yi Liu Jun Li Xiaoqing Xie Guofa Xu Sanxiu He Huihui Fu Yifeng Tang Fujie Zhang Yao Liu Chongqing Key laboratory of Translational Research for cancer Metastasis and Individualized treatment Department of Hematology-OncologyChongqing University Cancer HospitalChongqingChina Beijing Ditan Hospital Capital Medical UniversityBeijingChina

Human immunodeficiency virus(HIV)infection is strongly associated with a height-ened incidence of *** mirror the natural course of human HIV infection,animal models have been *** models serve as valuable tools to inves-tigate disease pathobiology,assess antiretroviral and immunomodulatory drugs,ex-plore viral reservoirs,and develop eradication ***,there are currently no validated in vivo models of HIV-associated lymphoma(HAL),hampering progress in this crucial domain,and scant attention has been given to developing animal models dedicated to studying HAL,despite their pivotal role in advancing *** re-view provides a comprehensive overview of the existing animal models of HAL,which may enhance our understanding of the underlying pathogenesis and approaches for malignancies linked to HIV infection.

关键词： animal model HIV-associated lymphoma(HAL) human immunodeficiency virus(HIV) immunodeficient mice primate model

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Expression of cyclin-dependent kinase 9 is positively correlated with the autophagy level in colon cancer

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World Journal of Gastrointestinal Oncology 2024年第2期16卷 314-330页

作者： Lei Zheng Jia Lu Da-Lu Kong Department of Colorectal cancer Surgery National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China Department of Infection Management National Clinical Research Center for CancerKey Laboratory of Cancer Immunology and Biotherapy of TianjinTianjin Key Laboratory of Digestive CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerTianjin Medical University Cancer Institute and HospitalTianjin 300060China

BACKGROUND Cyclin-dependent kinase 9(CDK9)expression and autophagy in colorectal cancer(CRC)tissues has not been widely ***9,a key regulator of transcription,may influence the occurrence and progression of *** expression of auto-phagy-related genes BECN1 and drug resistance factor ABCG2 may also play a role in *** normal physiological conditions,autophagy can inhibit tumorigenesis,but once a tumor forms,autophagy may promote tumor ***,understanding the relationship between autophagy and cancer,partic-ularly how autophagy promotes tumor growth after its formation,is a key motivation for this *** To investigate the relationship between CDK9 expression and autophagy in CRC,assess differences in autophagy between left and right colon cancer,and analyze the associations of autophagy-related genes with clinical features and *** We collected tumor tissues and paracarcinoma tissues from colon cancer patients with liver metastasis to observe the level of autophagy in tissues with high levels of CDK9 and low levels of *** also collected primary tissue from left and right colon cancer patients with liver metastasis to compare the autophagy levels and the expression of BECN1 and ABCG2 in the tumor and paracarcinoma *** The incidence of autophagy and the expression of BECN1 and ABCG2 were different in left and right colon cancer,and autophagy might be involved in the occurrence of chemotherapy *** analysis of the rela-tionship between the expression of autophagy-related genes CDK9,ABCG2,and BECN1 and the clinical features and prognosis of colorectal cancer showed that the high expression of CDK9 indicated a poor prognosis in colorectal *** This study laid the foundation for further research on the combination of CDK9 inhibitors and autophagy inhibitors in the treatment of patients with CRC.

关键词： Autophagy Tumorigenesis Tumor tissue Paracarcinoma tissue Expression Left/right colon cancer

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Addressing chemoresistance with a lipid gemcitabine nanotherapeutic strategy for effective treatment of pancreatic cancer

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Nano Research 2024年第9期17卷 8377-8388页

作者： Jiawei Hong Shiyun Xian Shusen Zheng Hangxiang Wang Donghai Jiang The First Affiliated Hospital NHC Key Laboratory of Combined Multi-Organ TransplantationCollaborative Innovation Center for Diagnosis and Treatment of Infectious DiseasesState Key Laboratory for Diagnosis and Treatment of Infectious DiseasesSchool of MedicineZhejiang UniversityHangzhou 310003China Jinan Microecological Biomedicine Shandong laboratory Jinan 250117China

Resistance to gemcitabine in pancreatic cancer poses a significant clinical *** investigation is warranted to assess whether nano-formulation strategy can be employed to enhance the sensitivity of resistant strains to gemcitabine *** this study,using gemcitabine-resistant pancreatic cancer cell lines,we examined the therapeutic potential of a gemcitabine nanodelivery platform and assessed the ability to overcome drug resistance against resistant *** of human equilibrative nucleoside transporter 1(hENT1)led to reduced cellular uptake of gemcitabine,resulting in chemoresistance in pancreatic *** nanoparticles circumvented the entry blockade caused by hENT1 silencing through *** entry via clathrin-mediated endocytosis increased intracellular gemcitabine accumulation in gemcitabine-resistant pancreatic cancer ***,gemcitabine nanoparticles are preferential in vivo delivery to tumor tissues,likely due to the enhanced permeability and retention *** comparison to free gemcitabine,gemcitabine nanoparticles demonstrate a more pronounced cytotoxic effect on gemcitabine-resistant pancreatic cancer cells,with favorable *** study improved the efficacy of gemcitabine through nanotechnology,providing a novel strategy to address gemcitabine-resistant pancreatic cancer.

关键词： pancreatic cancer gemcitabine resistance gemcitabine nanoparticle human equilibrative nucleoside transporter 1

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Comparative analysis of two digestive tract reconstruction methods in total laparoscopic radical total gastrectomy

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 1109-1120页

作者： Tian-Xiang Dong Dong Wang Qun Zhao Zhi-Dong Zhang Xue-Feng Zhao Bi-Bo Tan Yu Liu Qing-Wei Liu Pei-Gang Yang Ping-An Ding Tao Zheng Yong Li Zi-Jing Liu Third Department of Surgery of the Fourth Hospital of Hebei Medical University Hebei Key Laboratory of Precision Diagnosis and Comprehensive Treatment of Gastric CancerShijiazhuang 050011Hebei ProvinceChina

BACKGROUND The incidence of gastric cancer has significantly increased in recent *** resection is the main treatment,but the method of digestive tract reconstruction after gastric cancer surgery remains *** the current study,we sought to explore a reasonable method of digestive tract reconstruction and improve the quality of life and nutritional status of patients after *** this end,we statistically analyzed the clinical results of patients with gastric cancer who underwent jejunal interposition double-tract reconstruction(DTR)and esophageal jejunum Roux-en-Y reconstruction(RY).AIM To explore the application effect of DTR in total laparoscopic radical total gastrectomy(TLTG)and evaluate its safety and *** We collected the relevant data of 77 patients who underwent TLTG at the Fourth Hospital of Hebei Medical University from October 2021 to January *** them,35 cases were treated with DTR,and the remaining 42 cases were treated with traditional *** 1:1 propensity score matching,the cases were grouped into 31 cases per group,with evenly distributed *** clinical characteristics and short-and long-term clinical outcomes of the two groups were statistically *** The two groups showed no significant differences in basic data,intraoperative blood loss,number of lymph node dissections,first defecation time after operation,postoperative hospital stay,postoperative complications,and laboratory examination results on the 1st,3rd,and 5th days after *** operation time of the DTR group was longer than that of the RY group[(307.58±65.14)min vs(272.45±62.09)min,P=0.016],but the first intake of liquid food in the DTR group was shorter than that in the RY group[(4.45±1.18)d vs(6.0±5.18)d,P=0.028].The incidence of reflux heartburn(Visick grade)and postoperative gallbladder disease in the DTR group was lower than that in the RY group(P=0.033 and P=0.038).Although there was no significant difference in bod

关键词： Gastric cancer Jejunal interposition double-tract reconstruction Roux-en-Y reconstruction Laparoscope

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Ordered mesoporous materials for water pollution treatment: Adsorption and catalysis

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Green Energy & Environment 2024年第8期9卷 1239-1256页

作者： Peng Zhang Mingming He Wei Teng Fukuan Li Xinyuan Qiu Kexun Li Hao Wang College of Environmental Science and Engineering MOE Key Laboratory of Pollution Processes and Environmental CriteriaTianjin Key Laboratory of Environmental Remediation and Pollution TreatmentTianjin Key Laboratory of Environmental Technology for Complex Trans-Media PollutionNankai University Department of Chemistry and State Key laboratory Marine Pollution Hong Kong Institute for Advanced Study City University of Hong Kong State Key laboratory for Pollution treatment College of Environmental Science and EngineeringShanghai Institute of Pollution Treatment and Ecological SecurityTongji University State Key laboratory of Simulation and Regulation of Water Cycles in River Basins China Institute of Water Resources and Hydropower Research

To meet the growing emission of water contaminants,the development of new materials that enhance the efficiency of the water treatment system is *** mesoporous materials provide opportunities in environmental processing applications due to their exceptionally high surface areas,large pore sizes,and enough pore *** properties might enhance the performance of materials concerning adsorption/catalysis capability,durability,and *** this review,we enumerate the ordered mesoporous materials as adsorbents/catalysts and their modifications in water pollution treatment from the past decade,including heavy metals (Hg2+,Pb2+,Cd2+,Cr6+,etc.),toxic anions （nitrate,phosphate,fluoride,etc.）,and organic contaminants （organic dyes,antibiotics,etc.）.These contributions demonstrate a deep understanding of the synergistic effect between the incorporated framework and homogeneous active ***,the challenges and perspectives of the future developments of ordered mesoporous materials in wastewater treatment are *** work provides a theoretical basis and complete summary for the application of ordered mesoporous materials in the removal of contaminants from aqueous solutions.

关键词： Water pollution treatment Ordered mesoporous materials Toxic contaminants Adsorption Catalysis

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