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。     

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。     

Chemotherapy rechallenge in metastatic colon cancer: A case report and literature review

BACKGROUNDColorectal cancer (CRC) is the third leading cause of cancer-related death in males and females in the United States. Approximately, 20%-22% of patients have metastatic disease at the time of presentation, and 50%-60% will develop metastasis over the course of their disease. Despite advances in systemic therapies, there remains a paucity of effective third- and later-line therapies for patients with ongoing disease progression. However, rechallenging chemo-resistant CRC tumors with previously administered therapies is an emerging concept that may be a life-prolonging option for heavily treated metastatic colorectal cancer (mCRC).CASE SUMMARYA 41-year-old man with no previous medical history initially presented with worsening diffuse abdominal tenderness. Computed tomography was significant for a splenic flexure mass and hepatic lesions concerning for metastatic disease. He underwent a colectomy with anastomosis. Postoperative pathology was diagnostic for moderately to well-differentiated adenocarcinoma (T4bN1bM1a). He received adjuvant 5-fluorouracil, leucovorin, and oxaliplatin (FOLFOX), but therapy was discontinued due to the development of atrial fibrillation. Additional workup indicated a carcinoembryonic antigen level of 508.2 ng/mL, and mutational analysis found that the tumor was microsatellite instability-high and KRAS/BRAF wild-type. He was started on irinotecan with oxaliplatin (IROX), and bevacizumab (14 cycles), developed disease progression, was transitioned to FOLFOX and cetuximab, and then eventually three cycles of pembrolizumab. Following disease progression, he was rechallenged with IROX therapy, as he previously responded well to oxaliplatin-based therapy. The IROX rechallenge provided this patient with a ten-month survival benefit, decreased metastatic burden, and marked improvement in his clinical condition.CONCLUSIONRechallenge of previous lines of well-tolerated systemic chemotherapy regimens may be a valuable therapeutic strategy in patients with heavily-treated mCRC.     

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.     

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。     

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.     

替吉奥联合奥沙利铂对比替吉奥联合顺铂治疗晚期胃癌的Meta分析

目的评价替吉奥联合奥沙利铂（SOX方案）对比替吉奥联合顺铂（SP方案）治疗晚期胃癌（AGC）的疗效及安全性。 方法在PubMed、Embase、Web of Science、中国期刊全文数据库（CNKI）、中国生物医学文献数据库（CBM）、万方数据库、维普中文科技期刊数据库中检索2022年7月前公开发表的有关替吉奥联合奥沙利铂（SOX组）对比替吉奥联合顺铂（SP组）治疗AGC的相关研究,按照Cochrane Handbook 5.1的临床试验质量评价标准对文献进行质量评价,采用RevMan 5.4软件进行Meta分析。 结果共有14篇2 650例AGC患者纳入研究,其中SOX组1 334例,SP组1 316例。与SP组比较,SOX组的总生存期（HR=0.87,95% CI：0.78~0.97,P=0.01）、无进展生存期（HR=0.87,95% CI：0.78~0.97,P=0.01）、完全缓解（OR=1.43,95% CI：1.02~2.00,P=0.04）、部分缓解（OR=1.64,95% CI：1.18~2.29,P=0.003）、疾病进展（OR=0.55,95% CI：0.34~0.87,P=0.01）、疾病控制率（OR=1.64,95% CI：1.04~2.56,P=0.03）和疾病稳定（OR=0.67,95% CI：0.53~0.83,P=0.000 4）方面比较,差异均有统计学意义,而两组客观有效率差异无统计学意义（OR=1.57,95% CI：0.85~2.90,P=0.15）。安全性方面,3级及以上不良反应中,SOX组白细胞减少（OR=0.20,95% CI：0.13~0.30,P<0.000 01）、贫血（OR=0.52,95% CI：0.32~0.86,P=0.01）、肌酐升高（OR=0.21,95% CI：0.07~0.61,P=0.004）的发生率更低,而周围感觉神经病（OR=10.64,95% CI：1.85~61.10,P=0.008）的发生率更高。 结论SOX方案可提高AGC的治疗有效率,改善无进展生存期和总生存期,但可能增加周围感觉神经病的发生率。