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CDK6 inhibits lymphoid cell infiltration and represents a prognostic marker in HPV+ squamous cell carcinoma of head and neck

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Chinese Journal of Cancer Research 2019年第6期31卷 901-909页

作者： Chuanhao Tang Li Lin Wei Zhou Xiang Liu Yali Fu Lingling Zhang Li Li Xiangyi Wang Libo Zhao Jun Liang Libo Zhao Jun Liang Department of medical oncology Peking University International Hospital

Objective:We investigated the correlations between cyclin-dependent kinase 4/6(CDK4/6)levels and human papillomavirus(HPV)infection state in head and neck squamous cell cancer(HNSCC).The aim was to explore the potential value of CDK4/6 inhibitors in the treatment of ***:Multiomic sequencing data for HNSCC were obtained from The Cancer Genome Atlas(TCGA),and the mRNA levels and copy number variations(CNVs)of CDK4 and CDK6 were strictly *** survival(OS)curves were produced using the Kaplan-Meier method,and survival differences between groups were assessed by the log-rank ***,gene set enrichment analysis(GSEA)was applied to interrogate CDK4/6-associated molecular pathways in HPV-positive(HPV+)and HPV-negative(HPV-)***,lymphoid cell infiltrates in each type of HNSCC were explored,and the correlations between CDK4/6 expression and lymphoid infiltrates were explored by Tumor Immune Estimation Resource(TIMER)***:Overexpression of either CDK6 or CDK4 was not a relevant factor for OS in HPV-HNSCC(CDK6:top 40%*** 40%,P=0.885;CDK4:top 40%*** 40%,P=0.267).In HPV+HNSCC,CDK6 but not CDK4 was a relevant factor for OS(CDK6:top 40%*** 40%,P=0.002;CDK4:top 40%*** 40%,P=0.452).GSEA found that overexpressed CDK6 in HPV+HNSCC inhibited pathways involved in the tumor immune response,suggesting its roles in antitumor *** analysis results revealed that CDK6 but not CDK4 accumulation was negatively correlated with the number of tumor-infiltrating lymphocytes specific for HPV+HNSCC,which led to tumor response ***:CDK6,but not CDK4,is a poor prognostic marker specific in HPV+HNSCC *** CDK6 might stimulate tumor progression by suppressing lymphocytes infiltration independent of its kinase *** abrogating its kinase activity using current CDK4/6 inhibitors was not enough to block its tumor promotion function.

关键词： HNSCC HPV CDK4/6 immune infiltration

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The prognostic value of programmed cell death ligand 1expression in non-Hodgkin lymphoma:a meta-analysis

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Cancer Biology & Medicine 2018年第3期15卷 290-298页

作者： Shu Zha Minghui Zhang Yu Zhang Hongxue Meng Yan Wang Yupeng Liu Jing Jing Lan Huang Mengqi Sun Yue Zhang Qingyuan Zhang Department of medical oncology Harbin Medical University Cancer Hospital Department of Radiotherapy Harbin Medical University Cancer Hospital Department of Pathology Harbin Medical University Cancer Hospital Department of medical oncology Heilongjiang Provincial Hospital Department of Epidemiology Public Health College of Harbin Medical University

Objective: Although the prognostic value of programmed cell death-ligand 1(PD-L1) expression in non-Hodgkin lymphoma(NHL) has been evaluated in many studies, the results remain controversial. To investigate the prognostic role of PD-L1 expression and the association between PD-L1 expression and clinicopathological features of NHL, we performed a ***: The Pub Med, EMBASE, and Cochrane Library databases were searched up to November 30, 2017. The hazard ratio(HR), 95% confidence interval(CI), and odds ratios(OR) with 95% CIs were combined to evaluate the association of PD-L1 expression with overall survival(OS) and clinicopathological features. Review manager 5.3 and STATA 12.0 were used in this ***: A total of 2,005 patients across nine studies were enrolled in our meta-analysis, and the pooled results showed that high PD-L1 expression was associated with a poor prognosis(HR=2.04, 95% CI: 1.18–3.54, P=0.01). In the subgroup analysis according to histology types, pooled results demonstrated that an increased PD-L1 expression was an unfavorable prognostic factor for diffuse large B-cell lymphoma(HR=1.92, 95% CI: 1.06–3.48, P=0.03) but not for natural killer/T-cell lymphoma(HR=2.41, 95%CI: 0.47–12.22, P=0.29). Pooled ORs indicated that PD-L1 expression was higher in NHL with international prognostic indices of≥3. However, PD-L1 expression had no correlation with gender, age, disease stage, lactate dehydrogenase level, B symptoms, and germinal center B-cell-like ***: High PD-L1 expression was a poor prognostic biomarker in patients with NHL. Because of our limited sample size,high-quality studies with larger sample sizes are needed to validate our results.

关键词： Meta-analysis non-Hodgkin lymphoma(NHL) programmed cell death ligand 1(PD-L1) prognosis

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Crizotinib-induced acute fatal liver failure in an Asian ALK-positive lung adenocarcinoma patient with liver metastasis: A case report

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World Journal of clinical Cases 2019年第9期7卷 1080-1086页

作者： Ying Zhang Yan-Yan Xu Yi Chen Jin-Na Li Ying Wang Department of oncology Shengjing Hospital of China Medical University

BACKGROUND Crizotinib-induce hepatotoxicity is rare and non-specific, and severe hepatotoxicity can develop into fatal liver failure. Herein, we report a case of fatal crizotinib-induced liver failure in a 37-year-old Asian *** SUMMARY The patient complained of dyspnea and upper abdominal pain for a week in August 2017. He was diagnosed with anaplastic lymphoma kinase-rearranged lung adenocarcinoma combined with multiple distant metastases. Crizotinib was initiated as a first-line treatment at a dosage of 250 mg twice daily. No adverse effects were seen until day 46. On day 55, he was admitted to the hospital with elevated liver enzymes aspartate aminotransferase(AST)(402 IU/L), alanine aminotransferase(ALT)(215 IU/L) and total bilirubin(145 μmol/L) and was diagnosed with crizotinib-induced fulminant liver failure. Despite crizotinib discontinuation and intensive supportive therapy, the level of AST(1075 IU/L),ALT(240 IU/L) and total bilirubin(233 μmol/L) continued to rapidly increase,and he died on day *** Physicians should be aware of the potential fatal adverse effects of crizotinib.

关键词： Fatal liver failure Crizotinib hepatotoxicity Liver metastases ALK rearrangement Lung adenocarcinoma Case report

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Which strategy after first-line therapy in advanced colorectal cancer?

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World Journal of Gastroenterology 2014年第27期20卷 8921-8927页

作者： Coinu Andrea Petrelli Fausto Borgonovo Karen Francesca Cabiddu Mary Ghilardi Mara Lonati Veronica Barni Sandro medical oncology Unit Oncology Department Azienda Ospedaliera di Treviglio Treviglio 24047 BG Italy

Second-line therapy for advanced colorectal cancer is an integral part of the treatment strategy that needs to be set from the beginning for each patient, bearing in mind the expected toxicities of chosen treatments, the patient's clinical condition, comorbidities, preferences, the aims of the treatment and the molecular status. Furthermore, the distinction between lines of therapy is no longer absolute. The perspective of "continuum of care" includes switching chemotherapy prior to disease progression, maintenance therapy, drug "holidays" if needed, surgical resection of metastases in selected patients, and seems to allow a tailored treatment, in which patients are more likely to benefit from exposure to all active agents, which is known to correlate with overall survival. The scenario of second-line treatment has changed dramatically over the years and could currently benefit from several options including chemotherapy with a single agent or in combination and the addition of molecular-targeted agents developed in the last decade, such as epidermal growth factor receptor antibodies(cetuximab, panitumumab) and vascular endothelial growth factor-targeting agents(bevacizumab, aflibercept), with the possibility of bevacizumab use even beyond first progression. The purpose of this review is to summarize the most important scientific data supporting the use of chemotherapy and the new biologic agents in the second-line setting in advanced colorectal cancer.

关键词： Advanced colorectal cancer Second-line Targeted agents Polychemotherapy Overall survival

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Effects of Aromatherapy on Physical and Mental Health of Cancer Patients Undergoing Radiotherapy and/or Chemotherapy: A Meta-Analysis

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Chinese Journal of Integrative Medicine 2024年第5期30卷 449-457页

作者： XIE Shuang-ran MA Liang XU Xin-yu ZHOU Shu XIE Hui-miao XIE Chang-sheng The First clinical medical College Zhejiang Chinese Medical UniversityHangzhou 310053China Department of medical oncology Hangzhou Traditional Chinese Medicine Hospital Affiliated to Zhejiang Chinese Medical UniversityHangzhou 310007China Department of Dermatology the Third Xiangya HospitalCentral South UniversityChangsha 410013China Department of Famous Chinese Medicine clinic the Second Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310005China Department of medical oncology the First Affiliated Hospital of Zhejiang Chinese Medical UniversityHangzhou 310006China

Backgroup:Currently,aromatherapy is being increasingly utilized in clinical practice,particularly in managing the side effects associated with radiotherapy and ***,it remains to be established whether aromatherapy can effectively alleviate these ***:To investigate the effects of aromatherapy on the physical and mental health of patients with cancer undergoing radiotherapy and ***:Seven databases were researched from inception until September 29,2023,including PubMed,Scopus,and Web of Science,Chinese National Knowledge Infrastructure,Wanfang database,China Biology Medicine disc and VIP Chinese medical Journal *** Manager version 5.3 was utilized for data *** Cochrane Risk of Bias tool RoB2 was employed to evaluate the quality of the literature included in the *** quality rating was assessed using the Grading of Recommendations Assessment,Development,and Evaluation(GRADE) approach through the GRADEpro GDT online ***:Nineteen studies involving 1,541 patients were *** can alleviate nausea [relative risk(RR)=0.64,95% confidence interval(CI):0.53 to 0.78,P<0.05,I^(2)=46%;standardized mean difference(SMD)=-0.86,95% CI:-1.21 to-0.51,P<0.05,I^(2)=64%] and vomiting(RR=0.54,95% CI:0.42 to 0.69,P<0.05,I^(2)=35%;SMD=-1.28,95% CI:-1.52 to-1.03,P<0.05,I^(2)=92%),improve sleep disorders [mean difference(MD)=-3.39,95% CI:-3.95 to-2.84,P<0.05,I^(2)=0%],relieve pain(SMD=-1.58,95% CI:-1.96 to-1.21,P<0.05,I^(2)=0%),mitigate fatigue(SMD=-1.28,95% CI:-2.44 to-0.11,P<0.05,I^(2)=93%) and enhance quality of life(SMD=0.50,95% CI:0.22 to 0.79,P<0.05,I^(2)=0%) in cancer patients after radiotherapy and chemotherapy,but it may not have a significant effect on *** risk of bias was high in the included studies using the Cochrane Risk of Bias tool RoB2,and no studies were considered to be of high grade according to the GRADE ***:Aromatherapy is an efficacious,safe a

关键词： aromatherapy cancer chemoradiotherapy physical psychological

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Study of primary leiomyosarcoma induced by MNNG in BALB/C nude mice

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World Journal of Gastroenterology 2000年第1期6卷 128-130页

作者： Zhu JS Su Q Zhou JG Hu PL Xu JH Institute of oncology Hengyang Medical CollegeHengyang 421001China

INTRODUCTIONIt has been well known that MNNG is one of thestrong and multipotential carcinogens that havebeen frequently reported inducing malignant *** have successfully induced rat and doggastric adenocarcinomas,squ... 详细信息

关键词： Subject headings leiomyosarcoma stomach neoplasms MNNG BALB/C nude mice

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Role of Akt signaling in resistance to DNA-targeted therapy

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World Journal of clinical oncology 2016年第5期7卷 352-369页

作者： Abolfazl Avan Ravi Narayan Elisa Giovannetti Godefridus J Peters Department of medical oncology VU University Medical Center Department of Radiation oncology VU University Medical Center

The Akt signal transduction pathway controls most hallmarks of cancer. Activation of the Akt cascade promotes a malignant phenotype and is also widely implicated in drug resistance. Therefore, the modulation of Akt activity is regarded as an attractive strategy to enhance the efficacy of cancer therapy and irradiation. This pathway consists of phosphatidylinositol 3 kinase(PI3K), mammalian target of rapamycin, and the transforming serine-threonine kinase Akt protein isoforms, also known as protein kinase B. DNA-targeted agents, such as platinum agents, taxanes, and antimetabolites, as well as radiation have had a significant impact on cancer treatment by affecting DNA replication, which is aberrantly activated in malignancies. However, the caveat is that they may also trigger the activation of repairing mechanisms, such as upstream and downstream cascade of Akt survival pathway. Thus, each target can theoretically be inhibited in view of improving the potency of conventional treatment. Akt inhibitors, e.g., MK-2206 and perifosine, or PI3K modulators, e.g., LY294002 and Wortmannin, have shown some promising results in favor of sensitizing the cancer cells to the therapy in vitro and in vivo, which have provided the rationale for incorporation of these novel agents into multimodality treatment of different malignancies. Nevertheless, despite the acceptable safety profile of some of these agents in the clinical studies, with regard to the efficacy, the results are still too preliminary. Hence, we need to wait for the upcoming data from the ongoing trials before utilizing them into the standard care of cancer patients.

关键词： Phosphatidylinositol 3 kinase/Akt Platinum Taxane Antimetabolite Radiation

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The application of Tau protein testing to gastric cancer patients treated with paclitaxel

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Chinese Science Bulletin 2013年第36期58卷 4641-4646页

作者： WANG Qiong WANG NanYao SHAO GuoYi QIAN JianZhong YUAN Ming LI SuYi Department of oncology the Affiliated Jiangyin Hospital of Southeast University Medical College Department of Surgery the Affiliated Jiangyin Hospital of Southeast University Medical College Department of Pathology the Affiliated Jiangyin Hospital of Southeast University Medical College Department of oncology the Affiliated Zhongda Hospital of Southeast University Medical College

Paclitaxel is one of the main drugs used to treat gastric cancer,but many tumors develop drug resistance,resulting in treatment *** levels of expression of Tau protein in breast tumors have been found to be related to paclitaxel resistance,suggesting that Tau protein expression may predict breast cancer sensitivity to paclitaxel *** determine whether Tau protein expression can predict gastric cancer sensitivity to paclitaxel,we assayed Tau protein expression levels in gastric cancer specimens from 70 *** observed Tau protein expression in 54 of 70(77.1%)*** in gastric cancer cell lines showed that Tau protein expression was significantly lower in BGC823 than in MKN45 cells(P=0.0147).MTT assays showed that different concentrations of paclitaxel inhibited the growth of MKN45 and BGC823 cells,but inhibition and apoptosis were more obvious in cells expressing low levels of Tau *** chemotherapy was effective in 34 of the 70 patients(48.6%)and was significantly correlated with low expression of Tau protein(P<0.01).These findings indicate that Tau protein is expressed in a high percentage of gastric cancers,with paclitaxel being more effective in tumors with low Tau expression.

关键词： Tau蛋白紫杉醇胃癌治疗患者蛋白表达测试应用

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Efficacy and safety of duloxetine in Chinese breast cancer patients with paclitaxel-induced peripheral neuropathy

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Chinese Journal of Cancer Research 2017年第5期29卷 411-418页

作者： Jiani Wang Qing Li Binghe Xu Tongtong Zhang Shanshan Chen Yang Luo Department of medical oncology National Cancer Center/Cancer Hospital Chinese Academy of Medical Sciences and Peking Union Medical College

Objective： Chemotherapy with paclitaxel is associated with significant neurotoxicity that may offset patients＇ quality of life and therapeutic benefits. This prospective, non-randomized control study evaluated the efficacy and safety of an antidepressant drug, duloxetine, at 30 or 60 mg/d, in the treatment of paclitaxel-induced peripheral neuropathy（PIPN） in Chinese breast cancer ***：A total of 102 patients with a median age of 50（range,25–60）years,treated in the Department of medical oncology,National Cancer Center/Cancer Hospital,Chinese Academy of medical Sciences and Peking Union medical College,between November 2014 and January 2017 were finally *** by baseline characteristics,the patients were classified into two groups,receiving either duloxetine or alternative antineurotoxicity *** the course of the paclitaxel regimen,the eligibility criteria included sensory neuropathy,as evaluated by the National Cancer Institute-Common Toxicity Criteria for Adverse *** treatment consisted of receiving 30 mg duloxetine（for the first 4 weeks）and 60 mg duloxetine for an additional 8 weeks,or any other anti-neurotoxicity drug daily during the same crossover *** improvement associated with PIPN from the patient’s perspective were assessed by the Functional Assessment of Cancer Therapy-Taxane（FACT-Tax）Scales,which contained questions scored from 0 to 4（0,not at all;4,very much;total score range,0–44）.Results：Duloxetine was more effective in decreasing PIPN（odds ratio=5.426;95%confidence interval,1.898–15.514;P=0.002）.Between duloxetine group and control group,the median（25th–75th percentiles）decreasing difference in the FACT-Tax pain score was 4（2–6）vs.1（0–4）（P=0.005）.Conclusions：Duloxetine is a promising and safe option with tolerable toxicity at a dose of 60 mg/d for Chinese breast cancer patients with ***-neuropathy adverse events were mild and similar in both *** major toxicities of duloxetine included nausea,c

关键词： Duloxetine FACT-Tax Scales paclitaxel peripheral neuropathy

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THE CORRELATION BETWEEN THE EXPRESSION OF MULTIDRUG RESISTANCE RELATED GENE AND CELL APOPTOSIS AND clinicAL SIGNIFICANCE IN NON-SMALL CELL LUNG CANCER

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Chinese Journal of Cancer Research 2000年第4期12卷 273-277页

作者：王洁刘叙仪李西平蒋薇梁莉 Department of medical oncology The School of Oncology Peking University Beijing China

Objective: To explore the correlation and clinical significance between expression of MDR (multidrug resistance) related gene MRP, MDR1, C-erbB-2 and cell apoptosis in non-small cell lung cancer (NSCLC). Methods: RT-PCR, Immunohistochemistry were used to examine the expression of mRNA and protein in the MDR and apoptosis related gene. Apoptosis cells were assayed by Terminal deoxynucleotidyl transferase (TdT)- mediated biotin dUTP nick end-labeling (TUNEL). Results: The positive rates of MRP, MDR1, C-erbB-2, bc1-2, C-myc mRNA in 63 cases NSCLC were 81.0% (51/63), 38.1%(24/63), 47.6%(30/63), 65.1%(41/63), 76.2%(48/63) respectively. Their levels were higher than those of corresponding proteins (74.6%, 34.9%, 46.0%, 61.9%, 71.4%, respectively). The significant association was found between the mRNA level and the protein expression (r =+0.764, P<0.02). The C-myc expression in 2 cases adjacent and benign lung tissue were light positive, and another 3 cases were negative. The positive correlation were demonstrated between C-myc and C-erbB-2 (r=+0.547, p=0.001) as well as bcl-2 and C-erbB-2 (r =+0.486, p=0.023) in NSCLC. There is no any correlation among bcl-2, C-myc and MRP or MDR1. There exists inverse correlation between apoptotic index and bcl-2 (r = -0.587, p = 0.017), and no any correlation among apoptotic index and MRP or MDR1 or C-erbB-2 or C-myc. The average apoptotic index were higher in the effective chemotherapy group (27.2( 2.1, 30.5(1.8) than that in the non-effective chemotherapy group (9.4( 1.3, 12.6( 2.4) with adenocarcinoma and squamous cell carcinoma (p =0.01, p=0.004). The positive rates of bcl-2, MRP, C-erbB-2 expression in the effective chemotherapy group (31.8%, 40.9%, 22.7%, respectively) were lower than those in the non-effective chemotherapy group (77.4%, 90.3%, 67.7%, respectively) (p=0.036, p=0.012, p=0.01), but MDR1 and C-myc expression have no any significant difference (p=0.067, p=0.282). The median survival time in the patients with coexpres

关键词： Lung cancer Multidrug resistance Apoptosis Related genh

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