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HER2 over-expression and response to different chemotherapy regimens in breast cancer

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2008年第1期9卷 5-9页

作者： Jin ZHANG Yan LIU department of Breast cancer Cancer Institute and Hospital Tianjin Medical University Tianjin 300060 China

Purpose: To exam the relationship between HER2 over-expression and different adjuvant chemotherapies in breast cancer. Patients and Methods: A total of 1625 primary breast cancer patients who received post-surgery adjuvant chemotherapy in Tianjin cancer Hospital,China,from July 2002 to November 2005 were included in the study. Among them,600 patients were given CMF (CTX+MTX+5-Fu) regimen,600 given CEF (CTX+E-ADM+5-Fu) regimen,and 425 given anthracyclines plus taxanes regimen,with mean follow-up time of 42 months. Results: In CMF treatment group,the 3-year disease free survival (DFS) in HER2 over-expressed patients was lower than that of the HER2-negative ones (89.80% vs 91.24%,P=0.0348); in node-positive subgroup,the 3-year DFS was 84.72% in HER2 over-expressed patients,and 90.18% in the HER-2-negative ones (P=0.0271). Compared to CMF regimen,anthracyclines and anthracyclines plus taxanes regimens are more effective (Pcancer patients. HER2 over-expressed patients are resistant to CMF regimen chemo-therapy,but sensitive to anthracyclines-based or anthracyclines plus taxanes regimen. HER2 expression can be taken as a marker for therapies in breast cancer.

关键词： Breast cancer HER2 Chemotherapy

S-1 in the treatment of pancreatic cancer

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World Journal of Gastroenterology 2014年第41期20卷 15110-15118页

作者： Kentaro Sudo Kazuyoshi Nakamura Taketo Yamaguchi department of Gastroenterology Chiba Cancer Center

S-1 is an oral 5-fluorouracil(5-FU) prodrug,which is designed to improve the antitumor activity of 5-FU by inhibiting dihydropyrimidine dehydrogenase,the key enzyme of 5-FU ***,two important studies on the clinical use of S-1 for pancreatic cancer have been reported from *** the first study(GEST study),S-1 demonstrated non-inferiority to gemcitabine(GEM) in overall survival(OS) for metastatic or locally advanced pancreatic cancer,but combination chemotherapy with GEM and S-1 did not show superiority to GEM in *** the second study(JASPAC-01 study),S-1 showed superiority to adjuvant chemotherapy with GEM in OS in patients with resected pancreatic *** addition to GEM,S-1 is now regarded as the key drug in the management of pancreatic cancer in *** date,many studies have investigated the effectiveness of S-1 in various settings,such as first-line chemotherapy for metastatic or locally advanced pancreatic cancer,second-line chemotherapy after GEM failure,and chemoradiotherapy for locally advanced *** this review,we focus on recent clinical trials of S-1-based chemotherapy for advanced pancreatic cancer.

关键词： Pancreatic cancer S-1 Chemotherapy Randomized controlled trial Chemoradiotherapy Adjuvant therapy

Development and evaluation of the screening performance of a low-cost high-risk screening strategy for breast cancer

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cancer Biology & Medicine 2022年第9期19卷 1375-1384页

作者： Yubei Huang Huan Wang Zhangyan Lyu Hongji Dai Peifang Liu Ying Zhu Fengju Song Kexin Chen department of cancer Epidemiology and Biostatistics 2Department of Breast ImagingTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and Therapy of TianjinTianjin’s Clinical Research Center for CancerKey Laboratory of Cancer Molecular Epidemiology of TianjinKey Laboratory of Breast Cancer Prevention and TherapyMinistry of EducationTianjin 300060China

Objective:To develop and evaluate the screening performance of a low-cost high-risk screening strategy for breast cancer in low resource ***:Based on the Multi-modality Independent Screening Trial,6 questionnaire-based risk factors of breast cancer(age at menarche,age at menopause,age at first live birth,oral contraceptive,obesity,family history of breast cancer)were used to determine the women with high risk of breast *** screening performance of clinical breast examination(CBE),breast ultrasonography(BUS),and mammography(MAM)were calculated and compared to determine the optimal screening method for these high risk ***:A total of 94 breast cancers were detected among 31,720 asymptomatic Chinese women aged 45–65 *** to significantly higher detection rates(DRs)and suitable coverage of the population,high risk women were defined as those with any of 6 risk *** high risk women,the DR for BUS[3.09/1,000(33/10,694)]was similar to that for MAM[3.18/1,000(34/10,696)],while it was significantly higher than that for the CBE[1.73/1,000(19/10,959),P=0.002].Compared with MAM,BUS showed significantly higher specificity[98.64%(10,501/10,646)vs.98.06%(10,443/10,650),P=0.001],but no significant differences in sensitivity[68.75%(33/48)vs.73.91%(34/46)],positive prediction values[18.54%(33/178)vs.14.11%(34/241)],and negative prediction values[99.86%(10,501/10,516)vs.99.89%(10,443/10,455)].Further analyses showed no significant difference in the percentages of early stage breast cancer[53.57%(15/28)vs.50.00%(15/30)],lymph node involvement[22.73%(5/22)vs.28.00%(7/25)],and tumor size≥2 cm[37.04%(10/27)vs.29.03%(9/31)]between BUS and *** analyses stratified by breast densities or age at enrollment showed similar ***:The low-cost high-risk screening strategy based on 6 questionnaire-based risk factors was an easy-to-use method to identify women with high risk of breast ***,BUS and MAM had comparable screening

关键词： cancer screening breast cancer high risk mammography ultrasonography

Sintilimab for relapsed/refractory extranodal NK/T cell lymphoma: a multicenter, single-arm, phase 2 trial (ORIENT-4)

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Signal Transduction and Targeted Therapy 2021年第11期6卷 3341-3347页

作者： Rong Tao Lei Fan Yongping Song Yu Hu Wei Zhang Yafei Wang Wei Xu Jianyong Li department of Hematology Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghaiChina The First Affiliated Hospital of Nanjing Medical University Jiangsu Province HospitalCollaborative Innovation Center for Cancer Personalized MedicineNanjingChina The Affiliated cancer Hospital of Zhengzhou University and Henan cancer Hospital ZhengzhouChina Union Hospital Tongji Medical College Huazhong University of Science and Technology WuhanChina Peking Union Medical College Hospital BeijingChina Tianjin Medical University cancer Institute and Hospital TianjinChina

This study(ORIENT-4)aimed to assess the efficacy and safety of sintilimab,a humanized anti-PD-1 antibody,in patients with relapsed/refractory extranodal NK/T cell lymphoma(r/r ENKTL).ORIENT-4 is a multicenter,single-arm,phase 2 clinical trial(NCT03228836).Patients with r/r ENKTL who failed to at least one asparaginase-based regimen were enrolled to receive sintilimab 200 mg intravenously every 3 weeks for up to 24 *** primary endpoint was the objective response rate(ORR)based on Lugano 2014 ***-eight patients with r/r ENKTL were enrolled from August 31,2017 to February 7,***-one patients(75.0%,95%CI:55.1–89.3%)achieved an objective *** a median follow-up of 30.4 months,the median overall survival(OS)was not *** 24-month OS rate was 78.6%(95%CI,58.4–89.8%).Most treatment-related adverse events(TRAEs)were grade 1–2(71.4%),and the most common TRAE was decreased lymphocyte count(42.9%).Serious adverse events(SAEs)occurred in 7(25.0%)patients,and no patient died of adverse *** is effective and well tolerated in patients with r/r ENKTL and could be a novel therapeutic approach for the control of ENKTL in patients.

关键词： lymphoma relapse nodal

Radical treatment of stage Ⅳ pancreatic cancer by the combination of cryosurgery and iodine-125 seed implantation

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World Journal of Gastroenterology 2012年第47期18卷 7056-7062页

作者： Ji-Bing Chen Jia-Liang Li Li-Hua He Wei-Qun Liu Fei Yao Jian-Ying Zeng Yi Zhang Ke-Qiang Xu Li-Zhi Niu Jian-Sheng Zuo Ke-Cheng Xu Central Lab of Guangzhou Fuda cancer Hospital Medical Information department of Guangzhou Fuda cancer Hospital Cryosurgery Institute of Guangzhou Fuda cancer Hospital

AIM:To investigate the therapeutic effect of radical treatment and palliative treatment in stage Ⅳ pancreatic cancer ***:81 patients were enrolled in the *** treatment was performed on 51 patients,while 30 patients were put under palliative *** procedural safety and interval survival for stage Ⅳ pancreatic cancer(IS-Ⅳ) was assessed by almost 2.5 years of *** IS-Ⅳ of patients under the two kinds of treatment,and the effects of treatment timing and frequency on IS-Ⅳ,were ***:The IS-Ⅳ of patients who received radical treatment was significantly longer than those who received palliative treatment(P < 0.001).The IS-Ⅳ of patients who received delayed radical or palliative treatment was longer than those who received accordingly timely treatment(P = 0.0034 and 0.0415,respectively).Multiple treatments can play an important role in improving the IS-Ⅳ of patients who received radical treatment(P = 0.0389),but not for those who received palliative treatment(P = 0.99).CONCLUSION:The effect of radical treatment was significantly more obvious than that of palliative treatment,and multiple radical treatments may contribute more to patients than a single radical treatment.

关键词： Cryosurgery Stage Ⅳ pancreatic cancer Iodine-125 seed

Oncoprotein HBXIP promotes tumorigenesis through MAPK/ERK pathway activation in non-small cell lung cancer

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cancer Biology & Medicine 2021年第1期18卷 105-119页

作者： Jun Zhang Bei Sun Xianhui Ruan Xiukun Hou Jingtai Zhi Xiangrui Meng Xiangqian Zheng Ming Gao department of Breast cancer Key Laboratory of Breast Cancer Prevention and TherapyTianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China department of Outpatient Office Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China department of Thyroid and Neck Tumor Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China department of Lymphoma Tianjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerKey Laboratory of Cancer Prevention and TherapyTianjinTianjin’s Clinical Research Center for CancerTianjin 300060China

Objective:The oncoprotein,hepatitis B X-interacting protein(HBXIP),has been reported to play an important role in human ***,its functions in non-small cell lung cancer(NSCLC)are poorly *** goal of the present study was to identify the role of HBXIP in the regulation of NSCLC ***:The level of HBXIP expression in NSCLC tissue was assessed by immunohistochemical and Western blot analyses,and its relationships with clinicopathological features and outcomes were statistically *** effects of HBXIP on NSCLC cell progression were assessed through cell viability,colony formation,and flow cytometry analyses in *** mechanism by which HBXIP regulated the MAPK pathway was studied by Western blot,immunofluorescence,and immunoprecipitation *** addition,in vivo experiments were performed to evaluate the progression of NSCLC and ERK signaling pathway activation after HBXIP ***:HBXIP was overexpressed in human NSCLC and was correlated with the invasiveness of *** high expression of HBXIP in NSCLC was significantly correlated with gender(P=0.033),N stage(P=0.002),and tumor-node-metastasis stage(P=0.008).In vitro experiments using an NSCLC cell line revealed that HBXIP knockdown resulted in the suppression of cell proliferation and colony formation,which was consistent with the enhanced cell cycle arrest in G1 *** results of a mechanistic investigation suggested that binding of HBXIP to MEK1 protein promoted MAPK/ERK signaling pathway activation in NSCLC by preventing the proteasome-mediated degradation of *** addition,the results obtained using in vivo subcutaneous tumor xenografts confirmed that HBXIP deficiency decreased MEK1 protein levels and NSCLC tumor ***:Taken together,our results showed that the HBXIP-MEK interaction promoted oncogenesis via the MAPK/ERK pathway,which may serve as a novel therapeutic target for cancers in which MAPK/ERK signaling is a dominant featur

关键词： HBXIP non-small cell lung cancer MEK1 tumor progression

Poly （ADP-ribose） polymerase inhibitor： an evolving paradigm in the treatment of prostate cancer

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Asian Journal of Andrology 2014年第3期16卷 401-406页

作者： Jingsong Zhang department of Genitourinary Oncology and department of cancer Imaging and Metabolism H Lee Moffitt Cancer Center and Research Institute Tampa FL USA.

Recent phase I studies have reported single-agent activities of poly （ADP-ribose） polymerase （PARP） inhibitor in sporadic and in BRCA-mutant prostate cancers. Two of the most common genetic alterations in prostate cancer, ETS gene rearrangement and loss of PTEN, have been linked to increased sensitivity to PARP inhibitor in preclinical models. Emerging evidence also suggests that PARP1 plays an important role in mediating the transcriptional activities of androgen receptor （AR） and ETS gene rearrangement. In this article, the preclinical work and early-phase clinical trials in developing PARP inhibitor-based therapy as a new treatment paradigm for metastatic prostate cancer are reviewed.

关键词： biomarker PARP inhibitor prostate cancer therapy

PI3K/Akt/mTOR inhibitors in breast cancer

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cancer Biology & Medicine 2015年第4期12卷 342-354页

作者： Joycelyn JX Lee Kiley Loh Yoon-Sim Yap department of Medical Oncology National Cancer Center Singapore

Activation of the phosphoinositide 3 kinase(PI3K)/Akt/mammalian target of rapamycin(mTOR) pathway is common in breast cancer. There is preclinical data to support inhibition of the pathway, and phase Ⅰ to Ⅲ trials involving inhibitors of the pathway have been or are being conducted in solid tumors and breast cancer. Everolimus, an mTOR inhibitor, is currently approved for the treatment of hormone receptor(HR)-positive, human epidermal growth factor receptor 2(HER2)-negative breast cancer. In this review, we summarise the efficacy and toxicity findings from the randomised clinical trials, with simplified guidelines on the management of potential adverse effects. Education of healthcare professionals and patients is critical for safety and compliance. While there is some clinical evidence of activity of mTOR inhibition in HR-positive and HER2-positive breast cancers, the benefits may be more pronounced in selected subsets rather than in the overall population. Further development of predictive biomarkers will be useful in the selection of patients who will benefit from inhibition of the PI3K/Akt/mTOR(PAM) pathway.

关键词： Breast cancer phosphoinositide 3 kinase(PI3K)/Akt/ mammalian target of rapamycin(mTOR) everolimus

Imatinib as preoperative therapy in Chinese patients with recurrent or metastatic GISTs

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Chinese Journal of cancer Research 2013年第1期25卷 63-70页

作者： Chunmeng Wang Biqiang Zheng Yong Chen Xi Cao Ruming Zhang Yingqiang Shi Gastric cancer and Soft Tissue Sarcoma department Fudan University Shanghai Cancer Center Department of Oncology Shanghai Medical College Fudan University

Objective： Imatinib has dramatically altered the options for management of patients with gastrointestinal stromal turnouts. However, it has become clear that secondary resistance to the drug develops during long- term therapy. The purpose of our study was to retrospectively analyze safety and long-term outcomes in Chinese patients with recurrent or metastatic GISTs treated with imatinib preoperatively. Methods： Between June 2003 and June 2011, 22 patients underwent surgery for recurrent or metastatic GISTs after preoperative treatment with imatinib. Results： Complete resection was accomplished in 8 of the 10 responsive disease （RD） patients （80%）, and in 3 of the 12 patients （25%） who had progression disease （PD）. The amount of blood loss during the operation in PD patients was higher than in RD patients. There was 1 hospital death in PD group related to surgery, while the other patients recovered with conservative therapy because complications were mild. The difference in median PFS between patients with RD and those with PD was significant （24.8 vs. 2.81 months, P〈0.001）. The difference in 2-year OS rate between patients with RE） and those with PD was not significant （100% vs. 87.5%, P〉0.05）. Conclusions： Our study indicates that surgical intervention can improve the PFS of Chinese patients with recurrent or metastatic GISTs responsive to imatinib, but does not prolong OS as well as in patients who develop imatinib resistance. Surgical resection following imatinib treatment is feasible and can be considered for patients with advanced GISTs responsive to imatinib.

关键词： Gastrointestinal stromal tumor imatinib targeted therapy surgical intervention pathology