Pressurized intraperitoneal aerosol chemotherapy (PIPAC) of peritoneal metastasis from gastric cancer: a descriptive cohort study.
胃癌腹膜转移的加压腹腔气溶胶化疗 (PIPAC): 一项描述性队列研究。
- 作者列表："Ellebæk SB","Graversen M","Detlefsen S","Lundell L","Fristrup CW","Pfeiffer P","Mortensen MB
:Pressurized intraperitoneal aerosol chemotherapy (PIPAC) represents a novel approach to deliver intraperitoneal chemotherapy. We report our experience with PIPAC in patients with peritoneal metastasis (PM) from gastric cancer (GC). Data from GC patients (n = 20) included in the prospective PIPAC-OPC1 and PIPAC-OPC2 studies are reported. All patients had received prior systemic chemotherapy. The mean peritoneal cancer index (PCI) was 10.5 (range 0-39) and nine patients had diffuse GC. PIPAC with cisplatin 7.5 mg/m2 and doxorubicin 1.5 mg/m2 were administered at 4-6-week intervals. Outcome criteria were objective tumour response, survival and adverse events. Twenty patients had 52 PIPAC procedures with a median follow-up of 10.4 months (3.3-26.5). Median survival from the time of PM diagnosis and after the first PIPAC procedure was 11.5 months and 4.7 months, respectively. Fourteen patients had repeated PIPAC (> 2), and the objective tumour response according to the histological peritoneal regression grading score (PRGS) was observed in 36%, whereas 36% had stable disease. Ten patients completed the three prescheduled sessions (per protocol group) and 40% of those displayed an objective tumour response, while 20% had stable disease. Only minor postoperative complications were noted, and none were considered causally related to the PIPAC treatment. PIPAC with low-dose cisplatin and doxorubicin can induce a quantifiable objective tumour response in selected patients with PM from GC. Survival data are encouraging and warrant further clinical studies.
: 加压腹膜内气溶胶化疗 (PIPAC) 代表了一种提供腹腔内化疗的新方法。我们报告了我们在胃癌 (GC) 腹膜转移 (PM) 患者中使用 PIPAC 的经验。本文报告了前瞻性 PIPAC-OPC1 和 PIPAC-OPC2 研究中 GC 患者 (n = 20) 的数据。所有患者均既往接受过全身化疗。平均腹膜癌指数 (PCI) 为 10.5 (范围 0-39)，9 例患者有弥漫性 GC。PIPAC 联合顺铂 7.5 mg/m2 和多柔比星 1.5 mg/m2，间隔 4-6 周。结果标准为客观肿瘤反应、生存和不良事件。20 例患者进行了 52 次 PIPAC 手术，中位随访时间为 10.4 个月 (3.3-26.5)。从 PM 诊断开始和第一次 PIPAC 手术后的中位生存期分别为 11.5 个月和 4.7 个月。14 例患者重复 PIPAC (> 2)，根据组织学腹膜回归分级评分 (PRGS) 观察到的客观肿瘤反应为 36%，而 36% 的患者病情稳定。10 例患者完成了 3 次预先安排的治疗 (按方案组)，40% 的患者显示客观的肿瘤反应，而 20% 的患者疾病稳定。仅观察到轻微的术后并发症，无一例被认为与 PIPAC 治疗有因果关系。PIPAC 联合低剂量顺铂和多柔比星可以在来自 GC 的 PM 患者中诱导可量化的客观肿瘤反应。生存数据令人鼓舞，需要进一步的临床研究。
METHODS::Diffuse gastric cancer (DGC) is a lethal malignancy lacking effective systemic therapy. Among the most provocative recent results in DGC has been that the alter of the cellular cytoskeleton and intercellular adhesion. CD2-associated protein (CD2AP) is one of the critical proteins regulating cytoskeleton assembly and intercellular adhesion. However, no study has investigated the expression and biological significance of CD2AP in gastric cancer (GC) to date. Therefore, the aim of our study was to explore if the expression of CD2AP is associated with any clinical features of GC and to elucidate the underlying mechanism. Immunohistochemistry of 620 patient tissue samples indicated that the expression of CD2AP is downregulated in DGC. Moreover, a low CD2AP level was indicative of poor patient prognosis. In vitro, forced expression of CD2AP caused a significant decrease in the migration and invasion of GC cells, whereas depletion of CD2AP had the opposite effect. Immunofluorescence analysis indicated that CD2AP promoted cellular adhesion and influenced cell cytoskeleton assembly via interaction with the F-actin capping protein CAPZA1. Overall, the upregulation of CD2AP could attenuate GC metastasis, suggesting CD2AP as a novel biomarker for the prognosis and treatment of patients with GC.
METHODS::Aim: To identify the methylated-differentially expressed genes (MDEGs) that may serve as diagnostic markers and therapeutic targets in Epstein-Barr virus-associated gastric cancer (EBVaGC) and to explore the methylation-based pathways for elucidating biological mechanisms of EBVaGC. Materials & methods: Gene expression and methylation profiles were downloaded from GEO database. MDEGs were identified by GEO2R. Pathway enrichment analyses were conducted based on DAVID database. Hub genes were identified by Cytoscape, which were further verified by The Cancer Genome Atlas database. Results: A total of 367 hypermethylated, lowly expressed genes were enriched in specific patterns of cell differentiation. 31 hypomethylated, highly expressed genes demonstrated enrichment in regulation of immune system process. After validation using The Cancer Genome Atlas database, seven genes were confirmed to be significantly different hub genes in EBVaGC. Conclusion: EBVaGC-specific MDEGs and pathways can be served as potential biomarkers for precise diagnosis and treatment of EBVaGC and provide novel insights into the mechanisms involved.
METHODS:Gastric adenocarcinoma, like other cancers, is a multifactorial genetic disease, andmetastasis of cancer cells is one of the main features of this illness. The expressionlevels of the CFL1 gene have been modulated in this pathway. Using small interferingRNA (siRNA) in the treatment of gastric cancer is considered a hopeful genetherapeutic approach. The present study reported the level of CFL1 genes betweentumor and margin and healthy tissue of gastric cancer. Also, the features of a cationicnanoparticle with a polymer coating containing polyacrylic acid and polyethylenei-mine that were used in the delivery of CFL1 siRNA, were shown. Then thecytotoxicity, cellular uptake, and gene silencing efficiency of this nanoparticle wereevaluated with CFL1siRNA. Method:In this study, the CFL1 gene expression was measured in 40 gastricadenocarcinoma, marginal and 15 healthy biopsy samples by a real‐time polymerasechain reaction. Physicochemical characteristics, apoptosis, and inhibition of migrationof the delivery of CFL1 siRNA by nanoparticle and lipofectamine were investigated ingastric cancer cells. Result:The CFL1 expression was remarkably increased in gastric cancer tissues incomparison with the marginal samples and normal tissues (p< .05) and the biomarkerindex for CFL1 was obtained as 0.94, then this gene can be probably used as abiomarker for gastric cancer. After treatment of the AGS cell line by CFL1 siRNA, theCFL1 expression level of mRNA and migration in AGS cells were remarkablysuppressed after transfection. Furthermore, the amount of apoptosis increased(p< .05). Conclusion:Our results demonstrated that CFL1 downregulation in AGS cells caninterdict cell migration. Finally, our outcomes propose that CFL1 can function as anoncogenic gene in gastric cancer and would be considered as a potential purpose ofgene therapy for gastric cancer treatment