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SHR-A1811(antibody-drug conjugate)in advanced HER2-mutant non-small cell lung cancer:a multicenter,open-label,phase 1/2 study

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Signal Transduction and Targeted Therapy 2024年第8期9卷 3483-3492页

作者： Ziming Li Zhengbo Song Wei Hong Nong Yang Yongsheng Wang Hong Jian Zibin Liang Sheng Hu Min Peng Yan Yu Yan Wang Zicong Jiao Kaijing Zhao Ke Song You Li Wei Shi Shun Lu Shanghai Lung Cancer Center Shanghai Chest HospitalShanghai Jiaotong University School of MedicineShanghai 200030China Phase I Clinical Trial ward Zhejiang Cancer HospitalHangzhou 310000China Department of Thoracic oncology Zhejiang Cancer HospitalHangzhou 310000China Department of Lung&Gastrointestinal oncology Hunan Cancer HospitalChangsha 410031China Thoracic oncology ward/Cancer Center West China Hospital of Sichuan UniversityChengdu 610041China Department of Thoracic oncology The Fifth Affiliated Hospital of Sun Yat-Sen UniversityZhuhai 51900China Department of Medical oncology Hubei Cancer HospitalWuhan 43000China Department of oncology Renmin Hospital of Wuhan UniversityWuhan 430200China Department of Thoracic Medicine Harbin Medical University Cancer HospitalHarbin 150081China Department of Medical oncology Cancer HospitalChinese Academy of Medical SciencesBeijing 100021China Geneplus-Beijing CoLtd.Beijing 102206China Jiangsu Hengrui Pharmaceuticals Co.Ltd.Shanghai 200120China

A dose-escalation and expansion,phase 1/2 study(***,NCT04818333)was conducted to assess the novel antibodydrug conjugate SHR-A1811 in pretreated HER2-altered advanced non-small cell lung cancer(NSCLC).Here,we report results from the phase 1 *** who had previously failed or were intolerant to platinum-based chemotherapy were enrolled and received SHR-A1811 intravenously at doses of 3.2 to 8.0 mg/kg every 3 *** escalation followed a Bayesian logistic regression model that included overdose control,with subsequent selection of tolerable levels for dose ***,63 patients were enrolled,including 43 receiving a recommended dose for expansion of 4.8 mg/*** patients had HER2-mutant ***-limiting toxicity occurred in one patient in the 8.0 mg/kg dose ***≥3 treatment-related adverse events occurred in 29(46.0%)*** patient in the 6.4 mg/kg cohort died due to interstitial lung *** of April 11,2023,the 4.8 mg/kg cohort showed an objective response rate of 41.9%(95%Cl 27.0-57.9),and a disease control rate of 95.3%(95%Cl 84.2-99.4).The median duration of response was 13.7 months,with 13 of 18 responses *** median progression-free survival was 8.4 months(95%CI 7.1-15.0).SHR-A1811 demonstrated favourable safety and clinically meaningful efficacy in pretreated advanced HER2-mutantNSCLC.

关键词： SHR HER2 doses

Advancing RAS inhibition: broad-spectrum targeting and tumor-selective activity of RMC-7977 in cancer therapy

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Science China Life Sciences 2024年

作者： Qunli Xiong Yaguang Zhang Laboratory of Gastrointestinal Tumor Epigenetics and Genomics Frontiers Science Center for Disease-related Molecular Network West China Hospital Sichuan University Abdominal oncology ward Cancer Center West China Hospital Sichuan University

In cancer, the proto-oncogene RAS frequently mutates at codons 12, 13, and61, with these mutations propelling tumor progression by locking RAS proteins in their active, GTP-bound state(Pylayeva-Gupta et al., 2011; Yang et al.,2023). Despite the recent approval of small molecule inhibitors targeting KRAS(G12C) for non-small cell lung cancer(de Langen et al., 2023), a broadspectrum small molecule inhibitors for multiple RAS mutations have remained elusive.

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Massive simultaneous hepatic and renal perivascular epithelioid cell tumor benefitted from surgery and everolimus treatment:A case report

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World Journal of Gastrointestinal Surgery 2024年第10期16卷 3334-3342页

作者： Han-Teng Yang Fu-Rong Wang Na He Yuan-Hua She Yong-Yue Du Wen-Gui Shi Jing Yang Gang Chen Shu-Ze Zhang Feng Cui Bo Long Ze-Yuan Yu Jun-Min Zhu Geng-Yuan Zhang Department of General Surgery Lanzhou University Second HospitalLanzhou 730030Gansu ProvinceChina Department of Pathology Lanzhou University Second HospitalLanzhou 730030Gansu ProvinceChina oncology Department ward Lanzhou University Second HospitalLanzhou 730030Gansu ProvinceChina Cuiying Biomedical Research Center Lanzhou University Second HospitalLanzhou 730030Gansu ProvinceChina

BACKGROUND Perivascular epithelioid cell tumor(PEComa)is a rare mesenchymal neoplasm that predominantly affects the kidney and *** occurrence of this tumor in the liver,particularly with simultaneous involvement of the liver and kidney,is exceedingly *** diagnosis is the gold *** usually show positive immunohistochemical staining for melanocytic(HMB-45,Melan-A)and myoid(SMA,muscle-specific actin)*** SUMMARY We presented a noteworthy case of malignant PEComa affecting both the liver and kidney in a 53-year-old man with tuberous sclerosis complex(TSC).FAT2 and TP73 mutations in the kidney were identified and positive expression of diagnostic markers including HMB-45,Melan A,and TFE3 were *** addition,we demonstrated that hepatic artery perfusion chemotherapy was ineffective for hepatic PEComa,while surgery remained the most effective *** showed an excellent efficacy in the postoperative treatment of the *** Surgical treatment is preferred for malignant PEComa affecting liver and kidney,especially with TSC;everolimus is effective postoperatively.

关键词： Perivascular epithelioid cell tumor Hepatic Renal Surgery Case report

Establishing prognostic models for intrahepatic cholangiocarcinoma based on immune cells

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World Journal of Gastrointestinal oncology 2024年第10期16卷 4092-4103页

作者： Zhuo-Ran Wang Cun-Zhen Zhang Zhan Ding Yi-Zhuo Li Jian-Hua Yin Nan Li Department of Hepatic Surgery I(ward I)Shanghai Eastern Hepatobiliary Surgery Hospital Navy Medical UniversityShanghai 200433China Key Laboratory of Biological Defense Ministry of EducationNavy Medical UniversityShanghai 200433China Shanghai Key Laboratory of Medical Bioprotection Navy Medical UniversityShanghai 200433China Department of Epidemiology Faculty of Navy MedicineNavy Medical UniversityShanghai 200433China Department of oncology 905 Hospital of People’s Liberation Army NavyShanghai 200050China Department of Hepatobiliary Surgery The Second Affiliated HospitalWenzhou Medical UniversityWenzhou 325000Zhejiang ProvinceChina

BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant liver tumor that is challenging to treat and manage and current prognostic models for the disease are inefficient or ***-associated immune cells are critical for tumor development and *** main goal of this study was to establish models based on tumor-associated immune cells for predicting the overall survival of patients undergoing surgery for *** To establish 1-year and 3-year prognostic models for ICC after surgical *** Immunohistochemical staining was performed for CD4,CD8,CD20,pan-cytokeratin(CK),and CD68 in tumors and paired adjacent tissues from 141 patients with ICC who underwent curative *** of variables was based on regression diagnostic procedures and goodness-of-fit tests(PH assumption).Clinical parameters and pathological diagnoses,combined with the distribution of immune cells in tumors and paired adjacent tissues,were utilized to establish 1-and 3-year prognostic *** This is an important application of immune cells in the tumor ***4,CD8,CD20,and CK were included in the establishment of our prognostic model by stepwise selection,whereas CD68 was not significantly associated with the prognosis of *** integrating clinical data associated with ICC,distinct prognostic models were derived for 1-and 3-year survival outcomes using variable *** 1-year prediction model yielded a C-index of 0.7695%confidence interval(95%CI):0.65-0.87 and the 3-year prediction model produced a C-index of 0.69(95%CI:0.65-0.73).Internal validation yielded a C-index of 0.761(95%CI:0.669-0.853)for the 1-year model and 0.693(95%CI:0.642-0.744)for the 3-year *** We developed Cox regression models for 1-year and 3-year survival predictions of patients with ICC who underwent resection,which has positive implications for establishing a more comprehensive prognostic model for ICC based on tumor immune microenvironment an

关键词： Intrahepatic cholangiocarcinoma Tumor immune cells Biomarkers Prognosis Prediction models

Development and Application of Procedures for the Management of Skin Toxicity Related to Immune Checkpoint Inhibitors in Patients with Lung Cancer

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Journal of Biosciences and Medicines 2024年第7期12卷 289-300页

作者： Qianru Xu Qiong Wen Department of oncology First Peoples Hospital of Jingzhou City Jingzhou China

Objective: To establish the procedures for the management of skin toxicity related to immune checkpoint inhibitors in patients with lung cancer and explore the effect of application. Methods: A total of 24 evidence-based evidences were collected from 7 aspects, including risk factors, baseline screening, ICIs monitoring, daily skin care, multidisciplinary management, symptom management and health education. A total of 157 lung cancer patients and 94 nurses from 8 wards of the oncology department of our hospital from November 2022 to May 2023 were selected by convenience sampling. A total of 77 patients and 46 nurses from ward 1 - 4 were divided into the baseline group. There were 80 patients and 48 nurses in ward 5 - 8 as the evidence-based practice group. In the baseline group, patients were treated with routine methods such as assessing skin symptoms, taking medication according to symptoms, guiding to keep skin clean and moist, eating a light diet, and avoiding scratching. The evidence-based practice group adopts an evidence-based continuous improvement model for nursing. The differences in the severity of symptoms of skin toxicity in the second cycle of medication and the knowledge and practice of self-care of skin toxicity were compared between the two groups before and after the use of the syndrome, as well as the differences in the implementation rate of review indicators, evidence-based ability and knowledge and practice of skin toxicity care before and after the use of the syndrome. Results: The incidence and severity of cutaneous toxicity were significantly lower after treatment than before treatment (P P < 0.05). Conclusion: The implementation of immune checkpoint inhibitor-related skin toxicity management procedures can effectively reduce the incidence and severity of skin toxicity symptoms, optimize the clinical pathway, and improve the quality of care.

关键词： Lung Cancer Immune Checkpoint Inhibitors Skin Toxicity Process Management Nurse

A pilot study of precision treatment for patients with lung cancer pain by Longteng Tongluo recipe(龙藤通络方) using serum genomics

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Journal of Traditional Chinese Medicine 2024年第5期44卷 1006-1016页

作者： WU Ruixin FANG Qingliang GUAN Sisi WEI Xianglong SHAN Mengjun MAO Zhujun GONG Yabin XU Ling ZHOU Di DONG Changsheng Preclinical Department Shanghai Municipal Hospital of Traditional Chinese MedicineShanghai University of Traditional Chinese Medicine School of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Department of oncology Longhua HospitalShanghai University of Traditional Chinese Medicine Department of oncology the Third Affiliated Hospital of Henan University of Traditional Chinese Medicine Department of oncology Yueyang Hospital of Integrated Traditional Chinese and Western MedicineShanghai University of Traditional Chinese Medicine Cancer Institute of Traditional Chinese Medicine/Department of oncology Longhua HospitalShanghai University of Traditional Chinese Medicine

OBJECTIVE: To investigate the efficacy of Longteng Tongluo recipe(龙藤通络方, LTTL) combined with threestep analgesia for the treatment of lung cancer pain, and the changes in serum miRNA expressions before-and after treatment with LTTL and its correlation with lung cancer pain. The possible mechanism underlying LTTL effects on the treatment of lung cancer pain was conducted. METHODS: The pilot study was conducted at the oncology ward of the Yueyang Hospital and the Longhua Hospital between March 2018 and October 2019. A prospective, single-blind, placebo controlled, randomized clinical trial of LTTL or placebo combined with three-step analgesia treatments were administered to 24 cancer pain patients diagnosed with lung cancer. Analgesic efficacy was investigated as the primary outcome. Equivalent morphine consumption and numerical rating scale(NRS) scores were used as the secondary outcome. In the present study, we utilized deep sequencing techniques to compare the differential miRNA expressions in serum samples obtained from two groups: the lung cancer pain treatment group(LTTL + three-step analgesia) and the control group(placebo + three-step analgesia). Next, we employed the target prediction database to investigate the target genes for differential miRNA expressions and Gene Ontology(GO) analysis along with Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis to examine the roles and the major biochemical and signaling pathways related to the differentially expressed target genes, respectively. RESULTS: LTTL treatment significantly reduces the NRS score(P = 0.021) as compared to those before treatment, along with significant reductions in the total morphine equivalent consumption(P = 0.007) and the average daily equivalent morphine consumption(P = 0.003) as opposed to the control group. The expressions of 31 miRNAs differed considerably between the two groups of patients( ≥ 2 times up-modulated or down-regulated between these groups, P < 0.05).

关键词： Longteng Tongluo recipe MicroRNA-chip Supporting information high-throughput nucleotide sequencing lung neoplasms neoplasm metastasis pain

Effect of lamivudinein in BeAg-positive chronic hepatitis B: Discordant effect on HBeAg and HBV DNA according to pretreatment ALT level

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World Journal of Gastroenterology 2005年第22期11卷 3346-3350页

作者： Tomoko Kurihara Fumio Imazeki Osamu Yokosuka Kenichi Fukai Tatsuo Kanda Shigenobu Kawai Hiromitsu Saisho Department of Medicine and Clinical oncology Graduate School of Medicine Chiba University 1-8-1 Inohana Chuou Ward Chiba 260-8670Japan

AM: To clarify differences in antiviral effect of the drug in patients with different ALT levels, we examined the changes in HBV markers in patients with high or low ALT levels with or without lamivudine treatment. METHODS: Thirty-seven HBeAg-positive patients were studied. Ten patients with ALT levels higher than 200 IU/L (group 1) and 8 patients with ALT below 200 IU/L (group 2) were treated orally with 100 mg/d of lamivudine. As untreated control, 9 patients with ALT above 200 IU/L (group 3) and 10 patients with ALT below 200 IU/L (group 4) were examined. ALT level, HBeAg/HBeAb status, and HBV DNA level were examined monthly for 11.9±0.4 mo. RESULTS: The ALT level normalized in all 10 patients of group 1, 7/8 of group 2, 4/9 of group 3, and 1/10 of group 4 within 6 mo (groups 1 vs2, P= NS; groups 1 vs 3, P= 0.002; groups 1 vs4, P2, 0/9 of group 3, and 0/10 of group 4 within 6 mo (groups 1 vs 2, P - NS). HBeAg became seronegative in 7/10 patients of group 1, 1/8 of group 2, 3/9 of group 3, and 0/10 of group 4 within 12 mo (groups 1 vs2, P= 0.02; groups 1 vs 3, P= NS). CONCLUSION: Our data suggest that HBeAg-positive patients with higher ALT levels can be considered good candidates for lamivudine therapy, probably because lamivudine accelerates the natural seroconversion of HBeAg, accompanied by HBV DNA loss, in these patients.

关键词： Lamivudine Chronic hepatitis B HBeAg HBV DNA ALT

Modified R-CODOX-M/IVAC chemotherapy regimens in Chinese patients with untreated sporadic Burkitt lymphoma

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Cancer Biology & Medicine 2021年第3期18卷 833-840页

作者： Meiting Chen Zhao Wang Xiaojie Fang Yuyi Yao Quanguang Ren Zegeng Chen Ying Tian Fei Pan Xiaoqian Li Zhiming Li Qingqing Cai He Huang Tongyu Lin Department of Medical oncology Sun Yat-sen University Cancer CenterState Key Laboratory of Oncology in South ChinaCollaborative Innovation Center for Cancer MedicineGuangzhou 510060China Senior ward/PhaseⅠClinical Trial ward Sichuan Cancer Hospital&InstituteSichuan Cancer CenterSchool of MedicineUniversity of Electronic Science and Technology of ChinaChengdu 610041China

Objective:To characterize modified R-CODOX-M/IVAC-based chemotherapy to lower the severe adverse events in Chinese adult patients with sporadic Burkitt ***:We enrolled a retrospective cohort including 123 adult patients with untreated sporadic Burkitt lymphoma from August 2008 to September 2019 at Sun Yat-sen University Cancer *** studied a dose-modified and long-course R-CODOX-M/IVAC regimen utilizing a low dose of 1.0 g/m2/cycle cyclophosphamide,2 g/m2/cycle methotrexate,4,500 mg/m2/cycle ifosfamide,and 4.0 g/m2/cycle ***-nine patients with low risk disease underwent 4–6 cycles of dose-modified R-CODOX-M-based ***-four patients with high risk disease underwent 6–8 cycles of dose-modified alternating R-CODOX-M/IVAC ***:The objective remission was 87.0%.The event-free survival rate and overall survival at 3 years were 81.2%and 92.1%,*** grade 3–4 adverse events included leukopenia(91.9%),anemia(58.5%),thrombocytopenia(73.2%),and febrile neutropenia(48.8%).A total of 26.0%and 37.4%of patients received red blood cell and platelet transfusions,*** observed 4 cases(3.3%)of septic shock after *** treatment-related deaths occurred from severe ***:The modified R-CODOX-M/IVAC chemotherapy regimen was effective for sporadic Burkitt lymphoma in the Chinese population,with a lower toxicity than standard regimens.

关键词： Sporadic Burkitt lymphoma modified chemotherapy toxicity R-CODOX-M/IVAC adults

Effects of hypoxia inducible factor-1alpha siRNA on theinvasion of human Hela cells and expression of relatedproteins

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Frontiers of Medicine 2009年第3期3卷 303-308页

作者： Bin YANG Xianglin YUAN Yanmei ZOU Qingsong XI Guoxian LONG Qiang FU Guangyuan HU Center of oncology Tongji HospitalTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China First ward of Internal Medicine Tumor Hospital of Hubei ProvinceWuhan 430067China

The effects of hypoxia on the invasion and the related protein expression of Hela cells and the role of hypoxia inducible factor-1α(HIF-1α)were *** Hela cells were divided into three groups,namely,H0(non-transfected Hela cells),H1(pGenesil-1 empty plasmid-transfected Hela cells),and H2(HIF-1α-shRNA plasmid-transfected Hela cells),and were cultured under hypoxia(1%O2)and normoxia for 48 *** expression of HIF-1α,E-cadherin,β-catenin,and actin was detected using Western *** scratch test and the invasion assay were applied to examine the invasion in each *** expression of HIF-1α,E-cadherin,andβ-catenin in tumor grafts was assayed *** blot results revealed that the bands of HIF-1α,E-cadherin,β-catenin,and actin proteins were detected in the H0 and H1 groups under hypoxia for 48 *** expression of E-cadherin,β-catenin,and actin was detected in the H2 group under hypoxia for 48 h,and *** the H0,H1,and H2 groups under normoxia,and the H2 group under hypoxia for 48 h,no expression of HIF-1αwas *** scratch test showed that the invasive ability in the H2 group was signiﬁcantly ***-cally,it was found that there was a signiﬁcant difference in the expression of HIF-1α,E-cadherin,andβ-catenin between the H1 and H2 groups(P<0.05),but the difference was not signiﬁcant between the H0 and H1 *** was concluded that the effects of hypoxia on the invasion of human cervical cancer Hela cells and the expression of related proteins(E-cadherin,β-catenin,and actin)depend on HIF-1α.

关键词： hypoxia actin β-catenin E-cadherin inva-sion