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整合素α6靶向自组装促凋亡纳米多肽对中枢神经系统急性淋巴细胞白血病的靶向治疗

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Engineering 2024年第4期35卷 226-240页

作者： Jia-Cong Ye Wan-Qiong Li Mei-Ling Chen Qian-Kun Shi Hua Wang Xin-Ling Li Ying-He Li Jie Yang Qiao-Li Wang Fang Hu Yan-Feng Gao Shu-Wen Liu Mu-Sheng Zeng Guo-Kai Feng Guangdong Provincial key laboratory of New Drug Screening&NMPA key laboratory of Drug Metabolism Research and Evaluation School of Pharmaceutical SciencesSouthern Medical UniversityGuangzhou 510515China state key laboratory of oncology in South China&Guangdong key laboratory of Nasopharyngeal Carcinoma Diagnosis and Therapy Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou 510060China School of Pharmaceutical Sciences(Shenzhen) Shenzhen Campus of Sun Yat-sen UniversityShenzhen 518107China Guangdong Provincial key laboratory of Construction and Detection in Tissue Engineering Biomaterials Research CenterSchool of Biomedical EngineeringSouthern Medical UniversityGuangzhou 510515China state key laboratory of Organ Failure Research Guangdong Provincial Institute of NephrologySouthern Medical UniversityGuangzhou 510515China

There is currently no effective targeted therapeutic strategy for the treatment of central nervous system acute lymphoblastic leukemia(CNS-ALL).Integrinα6 is considered a potential target for CNS-ALL diagnosis and therapy because of its role in promoting CNS-ALL disease *** targeted peptide D(RWYD)(abbreviated RD),with nanomolar affinity to integrinα6 was identified by peptide scanning techniques such as alanine scanning,truncation,and ***,we developed a therapeutic nanoparticle based on the integrinα6-targeted peptide for treating *** self-assembled proapoptotic nanopeptide_(D)(RWYD)-_(D)(KLAKLAK)_(2)-G_(D)(FFY)(abbreviated RD-KLA-Gffy)contains the integrinα6-targeted peptide RD,the well-known proapoptotic peptide_(D)(KLAKLAK)_(2)(abbreviated KLA),and the self-assembling tetrapeptide GD(FFY)(abbreviated Gffy).The functional mechanism of RD-KLA-Gffy is clarified using different *** results demonstrate that RD-KLA-Gffy is highly enriched in CNS-ALL lesions and induces tumor cell apoptosis,thus reducing CNS-ALL disease burden and prolonging the survival of CNS-ALL mice without obvious ***,the combined use of RD-KLA-Gffy and methotrexate(MTX)shows a potent antitumor effect in treating CNS-ALL,indicating that RD-KLA-Gffy plays an important role in suppressing CNS-ALL progression either as a single agent or in combination with MTX,which shows promise for application in CNS-ALL therapy.

关键词： Central nervous system acute lymphoblastic leukemia Integrinα6 Targeted peptide Proapoptotic Nanopeptide

Unlocking the potential of amorphous calcium carbonate: A star ascending in the realm of biomedical application

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Acta Pharmaceutica Sinica B 2024年第2期14卷 602-622页

作者： Han Liu Zhiyang Wen Zihan Liu Yanfang Yang Hongliang Wang Xuejun Xia Jun Ye Yuling Liu state key laboratory of Bioactive Substance and Function of Natural Medicines Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China Beijing key laboratory of Drug Delivery Technology and Novel Formulation Institute of Materia MedicaChinese Academy of Medical Sciences&Peking Union Medical CollegeBeijing 100050China

Calcium-based biomaterials have been intensively studied in the field of drug delivery owing to their excellent biocompatibility and ***-based materials can also deliver contrast agents,which can enhance real-time imaging and exert a Ca^(2+)-interfering therapeutic *** on these characteristics,amorphous calcium carbonate(ACC),as a brunch of calcium-based biomaterials,has the potential to become a widely used *** functional ACC can be either discovered in natural organisms or obtained by chemical synthesis However,the standalone presence of ACC is unstable in *** are required to be used as stabilizers or core-shell structures formed by permeable layers or lipids with modified molecules constructed to maintain the stability of ACC until the ACC carrier reaches its *** has high chemical instability and can produce biocompatible products when exposed to an acidic condition in vivo,such as Ca^(2+) with an immune-regulating ability and CO_(2) with an imaging-enhancing *** to these characteristics,ACC has been studied for selfsacrificing templates of carrier construction,targeted delivery of oncology drugs,immunomodulation,tumor imaging,tissue engineering,and calcium *** in this paper has been placed on the origin,structural features,and multiple applications of ***,ACC faces many challenges in clinical translation,and long-term basic research is required to overcome these *** hope that this study will contribute to future innovative research on ACC.

关键词： Amorphous calcium carbonate Drugdelivery system Nanoparticle Acid sensitivity Water instability,Tumortherapy Tissue engineering Calcium supplement

Complete blood and urine paraprotein tests as response assessments in multiple myeloma patients treated with bortezomib,cyclophosphamide,and dexamethasone

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Chronic Diseases and Translational Medicine 2024年第1期10卷 62-68页

作者： Xialu Lan Fujing Zhang Chen Yang Wei Su Jianhua Du Shuangjiao Liu Miao Chen Bing Han Daobin Zhou Junling Zhuang Department of Hematology Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina Department of Pathology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhouChina Department of laboratory Medicine Peking Union Medical College HospitalChinese Academy of Medical SciencesBeijingChina

Background: This study assessed the effect of standardized efficacy markers on prognosis in patients with newly diagnosed multiple myeloma(MM)during the induction phase of treatment with bortezomib,cyclophosphamide,and dexamethasone(BCD).Methods :We retrospectively analyzed clinical data in 197 newly diagnosed MM patients treated with BCD as front-line regimen at Peking Union Medical College Hospital from January 1,2013 to December 31,***: There were 107 patients with International Staging System(ISS)III and 51 with paraprotein of light *** these,77 completed nine cycles of the BCD *** the number of treatment cycles increased,the proportions of serum and urine immunofixation electrophoresis(IFE)tests elevated from 40.39%to 62.22%and 16.75%to 37.78%,*** than 90%of intact immunoglobulin chain MM patients were evaluated for blood M protein per cycle,but that of urinary M protein was less than 60%.The detection rate of urinary M protein in light chain MM was more than 70%per *** with a very good partial response(VGPR)had longer progression-free survival(PFS)than those with uncertain VGPR(32 vs.26 months,p=0.0336).Of the 141 patients who completed at least four cycles without undergoing autologous hematopoietic stem cell transplantation,those who were regularly assessed at every other cycle showed more favorable PFS than those who visited irregularly(27 vs.22 months,p=0.059).Conclusion: Urinary M protein detection rate is significantly lower than that in serum,leading to an overestimation of efficacy,premature reduction of treatment intensity,and shortened *** response assessments are critical to treatment decisions and clinical diagnoses.

关键词： bortezomib light chain subtype multiple myeloma response assessment

Impact of baseline steroids on the efficacy of neoadjuvant immunochemotherapy in locally advanced esophageal squamous cell carcinoma

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World Journal of Gastrointestinal oncology 2024年第9期16卷 3887-3897页

作者： Yuan-Heng Huang Guo-Zhen Yang Hui-Guo Chen Xiao-Jun Li Yong-Hui Wu Kai Zhang Jian-Nan Xu Jian Zhang Department of Cardiothoracic Surgery The Third Affiliated Hospital of Sun Yat-sen UniversityGuangzhou 510630Guangdong ProvinceChina state key laboratory of oncology in South China Collaborative Innovation Center of Cancer MedicineGuangzhou 510060Guangdong ProvinceChina Guangdong Esophageal Cancer Institute Guangzhou 510060Guangdong ProvinceChina

BACKGROUND Immunochemotherapy involving the combination of programmed cell death 1/programmed cell death ligand 1 inhibitors with chemotherapy has advanced the treatment of locally advanced esophageal squamous cell carcinoma(ESCC).The use of corticosteroids as pretreatment might reduce immunotherapy *** To investigate the impact of baseline corticosteroid use on neoadjuvant immunochemotherapy(nIC)outcomes in locally advanced ESCC *** Patients with locally advanced ESCC who received nIC at Sun Yat-sen University Cancer Center and the Third Affiliated Hospital of Sun Yat-sen University were *** were divided into dexamethasone and antihistamine groups on the basis of the administered *** efficacy and safety were evaluated,as well as its impact on short-term efficacy[complete pathological response(pCR),major pathological response(MPR)]and long-term efficacy[overall survival(OS),progression-free survival(PFS)]of *** From September 2019 to September 2023,142 patients were *** severe treatment-related adverse events or deaths were *** occurrence was greater in the antihistamine group(P=0.014).Short-term efficacy was not significantly different:The pCR rates were 29.9%and 40.0%,and the MPR rates were 57.9%and 65.7%in the dexamethasone and antihistamine groups,*** long-term efficacy was not significantly different:The 2 years OS rates were 95.2%and 93.5%,and the 2 years PFS rates were 90.3%and 87.8%.Subgroup analysis revealed no difference in OS between the 20 mg dexamethasone group and the<20 mg dexamethasone group,but PFS was significantly greater in the 20 mg dexamethasone group(93.9%vs 56.4%,P=0.001).CONCLUSION Dexamethasone or antihistamines can be used before nIC in locally advanced ESCC without affecting short-or long-term *** 20 mg dexamethasone before nIC may improve PFS in ESCC.

关键词： Esophageal squamous cell carcinoma Neoadjuvant immunochemotherapy Dexamethasone Antihistamines Treatment efficacy

CircMYBL2 facilitates hepatocellular carcinoma progression by regulating E2F1 expression

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oncology Research 2024年第6期32卷 1129-1139页

作者： JUNZHE YI BINBIN LI XIAOMIN YIN LINGRUI LIU CAILU SONG YING ZHAO MANBO CAI HAILIN TANG DONG CHEN NING LYU state key laboratory of oncology in South China Guangdong Provincial Clinical Research Center for CancerSun Yat-sen University Cancer CenterGuangzhou510060China Department of Medical oncology The Third People’s Hospital of YongzhouYongzhou425000China Department of Radiotherapy The First Affiliated HospitalHengyang Medical SchoolUniversity of South ChinaHengyang421001China Center of Hepato-Pancreato-Biliary Surgery The First Affiliated HospitalSun Yat-sen UniversityGuangzhou510080China

Circular RNAs(circRNAs)have been recognized as pivotal regulators in tumorigenesis,yet the biological functions as well as molecular mechanisms of the majority of circRNAs in hepatocellular carcinoma(HCC)remain *** sought to unveil the expression profile and biological role of circMYBL2 in *** microarray analyses were conducted to probe the expression profile of circMYBL2 in HCC cells,and qRT‒PCR analysis was then performed in HCC cell lines and tissues,revealing significant upregulation of *** experiments were conducted to evaluate the biological function of circMYBL2 in HCC ***,bioinformatics analysis,qRT‒PCR analysis,luciferase reporter assays,and western blot analysis were employed to investigate the interplay among circMYBL2,miR-1205,and ***2 was found to exhibit marked upregulation in tumor tissues as well as HCC cell *** expression of circMYBL2 increased the proliferation and migration of HCC cells,whereas circMYBL2 knockdown elicited contrasting ***,our results indicated that circMYBL2 promoted E2F1 expression and facilitated HCC progression by sponging *** findings revealed that circMYBL2 contributed to HCC progression through the circMYBL2/miR-1205/E2F1 axis,suggesting the potential of circMYBL2 as a novel target for HCC treatment or a prognostic biomarker for HCC.

关键词： Circular RNAs circMYBL2 miR-1205 E2F1 Hepatocellular carcinoma

Hemolysis attributed to high dose vitamin C:Two case reports

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World Journal of Clinical Cases 2024年第17期12卷 3168-3176页

作者： Shi-Wan Wang Xiao-Wei Zhang Jin-Xiu Qu Yi-Zhong Rao Shuai Lu Bing Wang Jia He Yuan Zhao Ben-Qiang Rao Center for oncology Nutrition and Metabolism Beijing Shijitan HospitalCapital Medical University/Key Laboratory of Cancer FSMP for State Market RegulationBeijing 100038China

BACKGROUND High-dose vitamin C treatment(HVCT)can reduce the adverse effect of chemotherapy and enhance the effect of antitumor therapy,which has been considered one of the safest alternative ***,the severity of its adverse effects may have been *** most serious adverse effect is hemolysis,which may result in acute kidney injury or *** glucose-6-phosphate dehydrogenase(G6PD)deficiency is considered to be the main cause,the probability and pathological mechanism are not completely understood,leading to a lack of effective and standardized treatment *** SUMMARY Two patients with colorectal cancer developed hemolytic anemia after using 1 g/kg *** contrast to previous cases,the lowest hemoglobin level in the two cases was<50 g/L,which was lower than previously *** may be because Case 1 had chronic hepatitis B for many years,which caused abnormal liver reserve function,and Case 2 had grade II bone marrow *** patients improved and were discharged after blood replacement *** cases had the most severe degree of hemolysis but the best prognosis,suggesting that our treatment may be helpful for rescue of drug-induced *** is the first review of the literature on hemolysis caused by HVCT,and we found that all patients with G6PD deficiency developed hemolysis after *** G6PD deficiency should be considered as a contraindication to HVCT,and it is not recommended for patients with bone marrow suppression,moderate-tosevere anemia,hematopoietic abnormalities,or abnormal liver and kidney *** blood purification and steroid therapy may avoid acute kidney injury or death caused by HVCT-related hemolytic anemia.

关键词： Hemolysis Vitamin C Adverse effects Acute kidney injury Cancer Case report

Aberrant epithelial cell interaction promotes esophageal squamous-cell carcinoma development and progression

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Signal Transduction and Targeted Therapy 2024年第1期9卷 279-294页

作者： Liping Chen Shihao Zhu Tianyuan Liu Xuan Zhao Tao Xiang Xiao Hu Chen Wu Dongxin Lin Department of Etiology and Carcinogenesis National Cancer Center/National Clinical Research Center for Cancer/Cancer HospitalChinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China key laboratory of Cancer Genomic Biology Chinese Academy of Medical Sciences and Peking Union Medical CollegeBeijing 100021China Collaborative Innovation Center for Cancer Personalized Medicine Nanjing Medical UniversityNanjing 211166China CAMS Oxford Institute Chinese Academy of Medical SciencesBeijing 100006China Sun Yat-sen University Cancer Center State Key Laboratory of Oncology in South ChinaGuangzhou 510060China

Epithelial-mesenchymal transition(EMT)and proliferation play important roles in epithelial cancer formation and progression,but what molecules and how they trigger EMT is largely *** we performed spatial transcriptomic and functional analyses on samples of multistage esophageal squamous-cell carcinoma(ESCC)from mice and humans to decipher these critical *** investigating spatiotemporal gene expression patterns and cell–cell interactions,we demonstrated that the aberrant epithelial cell interaction via EFNB1-EPHB4 triggers EMT and cell cycle mediated by downstream SRC/ERK/AKT *** aberrant epithelial cell interaction occurs within the basal layer at early precancerous lesions,which expands to the whole epithelial layer and strengthens along the cancer development and *** analysis revealed that the aberrant EFNB1-EPHB4 interaction is caused by overexpressedΔNP63 due to TP53 mutation,the culprit in human ESCC *** results shed new light on the role of TP53-TP63/ΔNP63-EFNB1-EPHB4 axis in EMT and cell proliferation in epithelial cancer formation.

关键词： esophageal TP53 squamous

MicroRNAs as novel molecular targets of green tea polyphenol epigallocatechin-3-gallate(EGCG): relevance and importance to nutrition sciences and cancer prevention

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Food Science and Human Wellness 2024年

作者： Yu Li Q.Ping Dou Bo Li Yongli Wang Xiushan Wang Hui Guan Dapeng Li Feng Li College of Food Science and Engineering， Shandong Agricultural University key laboratory of Food Nutrition and Human Health in Universities of Shandong Barbara Ann Karmanos Cancer Institute， Departments of oncology， Pharmacology and Pathology， Wayne state University School of Medicine Jinan Vocational College of Nursing

MicroRNAs (miRNAs) are a class of single-stranded and non-coding endogenous RNAs with 18-25 nucleotides in length. By binding to the complementary sequences in the 3’untranslated region (3’UTR) of protein coding genes， miRNAs regulate posttranscriptionally the mRNA expression of target genes and enzymes involved in various biological processes. The application of high-throughput sequencing， bioinformatics analysis， and novel detection methods has high-lighted promising roles of miRNAs as both novel biomarkers for tumor diagnosis and critical regulators involved in almost all stages of carcinogenesis including cancer initiation， promotion and progression. Epigallocatechin-3-gallate (EGCG)， the most investigated active catechin in green tea， has been linked to various health-promoting benefits including chemoprevention and treatment of cancers. In this review， we first present a brief description of EGCG and its major metabolic pathway. It is followed by reviewing the roles of EGCG in the modulation of oncogenic and tumor suppressing miRNAs in some common cancers. These findings suggest that the capacity of EGCG to regulate expression of specific miRNAs provides insights of its new mechanisms of action underlying its chemopreventive and potential beneficial activities against various cancers.

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Single-cell transcriptomics reveals cell atlas and identifies cycling tumor cells responsible for recurrence in ameloblastoma

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International Journal of Oral Science 2024年第2期16卷 251-264页

作者： Gan Xiong Nan Xie Min Nie Rongsong Ling Bokai Yun Jiaxiang Xie Linlin Ren Yaqi Huang Wenjin Wang Chen Yi Ming Zhang Xiuyun Xu Caihua Zhang Bin Zou Leitao Zhang Xiqiang Liu Hongzhang Huang Demeng Chen Wei Cao Cheng Wang Hospital of Stomatology Sun Yat-sen UniversityGuangzhouChina Guangdong Provincial key laboratory of Stomatology Sun Yat-sen UniversityGuangzhouChina Guanghua School of Stomatology Sun Yat-sen UniversityGuangzhouChina Department of Periodontics Affiliated Stomatology Hospital of Guangzhou Medical UniversityGuangzhou Key Laboratory of Basic and Applied Research of Oral Regenerative MedicineGuangzhouChina Institute for Advanced Study Shenzhen UniversityShenzhenChina Center for Translational Medicine The First Affiliated HospitalSun Yat-sen UniversityGuangzhouChina state key laboratory of Ophthalmology Zhongshan Ophthalmic CenterSun Yat-sen UniversityGuangzhouChina Department of Oral and Maxillofacial Surgery Nanfang HospitalSouthern Medical UniversityGuangzhouChina Department of Oral and Maxillofacial&Head and Neck oncology Shanghai Ninth People’s HospitalShanghai Jiao Tong University School of MedicineShanghaiChina National Center for Stomatology National Clinical Research Center for Oral diseasesShanghai Key Laboratory of StomatologyShanghaiChina

Ameloblastoma is a benign tumor characterized by locally invasive phenotypes,leading to facial bone destruction and a high recurrence ***,the mechanisms governing tumor initiation and recurrence are poorly ***,we uncovered cellular landscapes and mechanisms that underlie tumor recurrence in ameloblastoma at single-cell *** results revealed that ameloblastoma exhibits five tumor subpopulations varying with respect to immune response(IR),bone remodeling(BR),tooth development(TD),epithelial development(ED),and cell cycle(CC)*** note,we found that CC ameloblastoma cells were endowed with stemness and contributed to tumor recurrence,which was dominated by the EZH2-mediated *** EZH2 effectively eliminated CC ameloblastoma cells and inhibited tumor growth in ameloblastoma patient-derived *** data described the tumor subpopulation and clarified the identity,function,and regulatory mechanism of CC ameloblastoma cells,providing a potential therapeutic target for ameloblastoma.

关键词： inhibited cycling eliminated