清肠解毒方对大肠癌术后复发化疗患者肿瘤标记物水平及生活质量的影响

摘 要 目的: 探讨清肠解毒方对大肠癌术后复发化疗患者的生活质量及肿瘤标记物水平的影响。方法:选取出现复发的大肠癌患者60例，随机分为观察组与对照组各30例。两组化疗方案均为奥沙利铂联合卡培他滨或者盐酸伊立替康联合卡培他滨，观察组加用清肠解毒方治疗。比较两组患者治疗前后血清CEA、AFP、CA 125、CA 199水平与ECOG评分变化。结果: 两组患者治疗后血清CEA、AFP、CA 125、CA 199水平显著低于治疗前（P＜0.05）。此外，治疗后观察组患者的血清CEA和CA 199水平显著低于对照组（P＜0.05）。生活质量方面，治疗后两组患者ECOG评分均显著低于治疗前，差异有统计学意义（P＜0.05）；且观察组患者治疗后ECOG评分显著低于对照组，差异有统计学意义（P＜0.05）。结论: 清肠解毒方能够明显改善大肠癌术后化疗患者的生活质量，降低血清肿瘤标记物浓度，值得临床应用。     

Oxaliplatin use in pressurized intraperitoneal aerosol chemotherapy (PIPAC) is safe and effective: A multicenter study

IntroductionPressurized intraperitoneal aerosol chemotherapy (PIPAC) is a new drug delivery method used in patients with peritoneal cancer (PC) of primary or secondary origin. Intraperitoneal use of oxaliplatin raises concerns about toxicity, especially abdominal pain. The objective of this study was to assess the tolerance of PIPAC with oxaliplatin (PIPAC-Ox) in a large cohort of patients and to identify the risk factors for high grade toxicity, discontinuation of treatment and impaired survival.Material and methodsThis retrospective cohort study included all consecutive patients treated with PIPAC-Ox (92 mg/m²) in five centers specialized in the treatment of PC. The procedure was repeated every 6 weeks. Outcomes of interest were Common Terminology Criteria for Adverse Events (CTCAE), symptoms and survival (Kaplan-Meier). Univariate risk factors were included in a multinominal regression model to control for bias.ResultsOverall, 251 PIPAC-Ox treatments were performed in 101 patients (45 female) having unresectable PC of various origins: 66 colorectal, 15 gastric, 5 ovarian, 3 mesothelioma, 2 pseudomyxoma, 10 other malignancies (biliary, pancreatic, endocrine) respectively. The median PCI was 19 (IQR: 10–28). Postoperative abdominal pain was present in 23 patients. Out of the 9 patients with grade 3 abdominal pain, only 3 needed a change of PIPAC drug. CTCAE 4.0 toxicity grade 4 or higher was encountered in 16(15.9%) patients. The patients had a mean of 2.5 procedures/patient (SD = 1.5). 50 subjects presented with symptom improvement.ConclusionsOxaliplatin-based PIPAC appears to be a safe treatment that offers good symptom control and promising survival for patients with advanced peritoneal disease.     

E-Cadherin in Colorectal Cancer: Relation to Chemosensitivity

Background

The conventional chemotherapy of colorectal cancer with irinotecan, 5-fluorouracil, and oxaliplatin remains one of the front-line treatments worldwide. However, its efficacy is quite low. Recently studies of the epithelial–mesenchymal transition (EMT) have become the focus of investigations into the cause of chemoresistance in several types of cancer, including colorectal cancer. The data about the role of EMT in chemosensitivity are controversial.

铂类药物在头颈部鳞癌治疗中的选择与应用

以铂类药物为基础的化疗成为晚期头颈部鳞癌（head and neck squamous cell carcinoma，HNSCC）综合治疗中不可缺少的部分。化疗可与放疗同步用于局部晚期HNSCC的根治性治疗，或用于具有高危因素的HNSCC术后辅助治疗，也可用于诱导化疗（新辅助化疗）或者放疗后的辅助化疗。同期放化疗在局部晚期HNSCC的治疗中尤其重要。几种常用的铂类药物在HNSCC的治疗中各有优势。本文简述铂类药物的药理作用及机制，比较铂类药物在HNSCC的疗效与毒性，并分析不同给药方式（单药或多药联合，每周或每3周）与给药剂量所带来的疗效与毒性差异，希望能对医师合理使用铂类药物治疗HNSCC有所裨益。     

Upregulation of miR-489-3p and miR-630 inhibits oxaliplatin uptake in renal cell carcinoma by targeting OCT2

Renal cell carcinoma (RCC) is one of the most common malignant tumors affecting the urogenital system, accounting for 90% of renal malignancies. Traditional chemotherapy options are often the front-line choice of regimen in the treatment of patients with RCC, but responses may be modest or limited due to resistance of the tumor to anticarcinogen. Downregulated expression of organic cation transporter OCT2 is a possible mechanism underlying oxaliplatin resistance in RCC treatment. In this study, we observed that miR-489-3p and miR-630 suppress OCT2 expression by directly binding to the OCT2 3′-UTR. Meanwhile, via 786-O-OCT2-miRNAs stable expression cell models, we found that miRNAs could repress the classic substrate 1-methyl-4-phenylpyridinium (MPP⁺), fluorogenic substrate N,N-dimethyl-4-(2-pyridin-4-ylethenyl) aniline (ASP⁺), and oxaliplatin uptake by OCT2 both in vitro and in xenografts. In 33 clinical samples, miR-489-3p and miR-630 were significantly upregulated in RCC, negatively correlating with the OCT2 expression level compared to that in adjacent normal tissues, using tissue microarray analysis and qPCR validation. The increased binding of c-Myc to the promoter of pri-miR-630, responsible for the upregulation of miR-630 in RCC, was further evidenced by chromatin immunoprecipitation and dual-luciferase reporter assay. Overall, this study indicated that miR-489-3p and miR-630 function as oncotherapy-obstructing microRNAs by directly targeting OCT2 in RCC.     

奥沙利铂通过调控miRNA-7-5p/RAF-1促进胃癌SGC-7901细胞凋亡的研究

目的探讨奥沙利铂如何调控MAPK通路,抑制胃癌细胞的增殖。方法NCBI检索文献,利用TargetScan、StarBase和miRBase数据库,进行GO分析与KEGG通路富集,找到相关miRNAs,预测靶基因。应用Real-time PCR、MTT、Hoechst33258、流式细胞术、细胞划痕实验、Western blot等方法分析人胃癌SGC-7901细胞的增殖、细胞周期、侵袭及蛋白表达情况。结果胃癌细胞中miR-7-5p显著低表达,RAF1与miR-7-5p存在互靶关系。miR-7-5p mimics与奥沙利铂均可促进SGC-7901细胞的凋亡,提高G1期细胞百分率(P<0.05),降低侵袭、迁移速度。caspase3、caspase9蛋白表达升高,Bcl-2/Bax比值降低(P<0.05)。结论过表达miR-7-5p与奥沙利铂均可促进胃癌SGC-7901细胞的凋亡,提示奥沙利铂可能通过上调miRNA-7-5p促进SGC-7901细胞的凋亡,降低侵袭、迁移速度。     

Targeting the PI3K/AKT/mTOR pathway in biliary tract cancers: A review of current evidences and future perspectives

Biliary tract cancers (BTCs) are a group of invasive neoplasms, with increasing incidence and dismal prognosis. In advanced disease, the standard of care is represented by first-line chemotherapy with cisplatin and gemcitabine. In subsequent lines, no clear recommendations are currently available, highlighting the need for novel therapeutic approaches.The PI3K/AKT/mTOR pathway is a core regulator of cell metabolism, growth and survival, and is involved in BTCs carcinogenesis and progression. Mutations, gene copy number alterations and aberrant protein phosphorylation of PI3K, AKT, mTOR and PTEN have been thoroughly described in BTCs and correlate with poor survival outcomes.Several pre-clinical evidences state the efficacy of PI3K/AKT/mTOR pathway inhibitors in BTCs, both in vitro and in vivo. In the clinical setting, initial studies with rapamycin analogs have shown interesting activity with an acceptable toxicity profile. Novel strategies evaluating AKT and PI3K inhibitors have risen serious safety concerns, pointing out the need for improved patient selection and increased target specificity for the clinical development of these agents, both alone and in combination with chemotherapy.This review extensively describes the role of the PI3K/AKT/mTOR pathway in BTCs and examines the rationale of its targeting in these tumors, with particular focus on clinical activity, toxicities and perspectives on further development of PI3K/AKT/mTOR pathway inhibitors.     

结直肠癌中葡萄糖转运蛋白-12作为化疗联合用药靶点的研究

目的 研究葡萄糖转运蛋白-12（GLUT12）在结直肠癌（CRC）细胞和组织中的表达与功能,探讨其作为联合用药治疗靶点的可能性。方法 分别采用RT-PCR和蛋白免疫印迹法检测CRC及正常结肠中GLUT12基因和蛋白水平。通过荧光免疫及蛋白印迹法观察槲皮素（QC）对肿瘤细胞中GLUT12定位的调节作用。四氮唑（MTT）比色法和克隆形成实验（CFA）观察QC和奥沙利铂（OXA）联合使用对CRC细胞增殖的影响。结果 GLUT12基因在肿瘤组织中的相对表达水平高于正常组织[（3.2±0.3）vs（0.5±0.6）,P<0.05]。高糖培养液能改变GLUT12在细胞中的定位及表达水平,QC能抑制高糖对GLUT12蛋白的调节作用。MTT和CFA试验显示,OXA和QC联用能使CRC细胞的活力降低[OXA+OC：（63.3±7.1）%vs OC：（88.7±4.2）%,P< 0.05]。QC和OXA联用能抑制结肠癌细胞群落的增殖能力。结论 QC能有效抑制CRC细胞GLUT12蛋白的功能,能增加OXA杀伤CRC的作用。