白藜芦醇对人胃癌耐药细胞SGC-7901/5-FU生物学效应的影响及其作用机制

目的 探讨白藜芦醇(resveratrol,RES)对5-氟尿嘧啶(5-fluorouracil,5-FU)耐药胃癌细胞(SGC-7901/5-FU)生物学效应的影响及其作用机制.方法 用不同浓度(0μmol/L、10μmol/L、50μmol/L、200μmol/L、400μmol/L)的RES分别处理SGC-790...     

胃动脉插管化疗栓塞联合腹腔化疗治疗进展期胃癌

目的:为探讨对晚期进展期胃癌,进行胃动脉化疗栓塞并腹腔化疗双途径给药的可行性及临床疗效.方法:无法手术切除的进展期胃癌98例,随机分为三组,A组行胃动脉化疗栓塞并腹腔化疗;B组行腹腔化疗;c组行静脉化疗.结果:胃动脉化疗栓塞是可行的.A、B、C三组有效率分别为71.88%、38.7%和14.3%.A组与B、C组比较有明显差异(P<0.01).A组有5例完全缓解,且生存期延长.不良反应以胃肠道毒性和骨髓抑制为主.A组术后胃粘膜有损伤,四周后可恢复正常.结论:胃动脉化疗栓塞并腹腔化疗双途径给药是治疗晚期进展期胃癌的有效方法.     

Paclitaxel chemotherapy for the treatment of gastric cancer

A comprehensive review of phase I and phase II clinical trials of paclitaxel and paclitaxel-containing chemotherapy regimens for advanced gastric cancer was performed. Response rates, median progression-free survivals, and median overall survivals were examined, together with the treatment regimens and the numbers of patients registered in each trial. Although paclitaxel monotherapy produced considerable improvement in tumor response and prognosis, combination doublet or triplet chemotherapy with fluoropyrimidines and/or platinum compounds showed better results than the paclitaxel monotherapy. With regard to the schedule of paclitaxel administration, weekly injection seemed to show less toxicity and better results than administration every 3 weeks. Adjuvant therapies, chemoradiation therapies, and paclitaxel treatment for gastric ascites were also investigated and are discussed.     

乳腺癌干细胞抵抗放射治疗及化疗的调控机制

据中国城市癌症报告统计,乳腺癌是中国城市女性发病率最高的癌症。尽管乳腺癌早期原位切除及放射治疗和化疗(简称放化疗)后,患者的5年和10年生存率较好,但依旧有小部分癌细胞逃逸、潜伏和扩散,导致乳腺癌复发和转移。未治愈乳腺癌中,约70%发生肺转移,60%发生骨转移和肝转移,15%发生脑转移。肿瘤干细胞是肿瘤组织中存在的少量具有干细胞特征的细胞亚群,有极强的再生肿瘤能力以及天然放化疗抵抗能力,被视作乳腺癌复发、转移的主要原因。靶向肿瘤干细胞的研究,为人类彻底攻克恶性肿瘤带来了希望。乳腺癌组织中具备乙醛脱氢酶(＋)、CD44^＋ CD24^－Lin^－等特征的细胞亚群已经被证实是乳腺肿瘤干细胞。笔者总结了乳腺肿瘤干细胞的鉴定、起源、特征、调控机制、放化疗不敏感的原因及临床靶向治疗的研究进展,供同行参考。     

卵巢癌化疗耐药及逆转耐药基因水平研究进展

卵巢癌细胞对化疗产生耐药的机制主要有肿瘤细胞内有效药物浓度降低、DNA损伤修复功能异常和细胞凋亡调控异常3个方面.逆转卵巢癌细胞耐药主要包括反义基因治疗、RNA干预、化疗药物的联合应用等.     

Non-coding RNA in drug resistance of gastric cancer

Gastric cancer (GC) is the third leading cause of cancer-related mortality worldwide. The poorly prognosis and survival of GC are due to diagnose in an advanced, non-curable stage and with a limited response to chemotherapy. The acquisition of drug resistance accounts for the majority of therapy failure of chemotherapy in GC patients. Although the mechanisms of anticancer drug resistance have been broadly studied, the regulation of these mechanisms has not been completely understood. Accumulating evidence has recently highlighted the role of non-coding RNAs (ncRNAs), including long non-coding RNAs and microRNAs, in the development and maintenance of drug resistance due to their regulatory features in specific genes involved in the chemoresistant phenotype of GC. We review the literature on ncRNAs in drug resistance of GC. This review summarizes the current knowledge about the ncRNAs’ characteristics, their regulation of the genes involved in chemoresistance and their potential as targeted therapies for personalized treatment in resistant GC.     

胃癌细胞多药耐药机制及耐药性逆转

 中国胃癌的发病例数占全球总数的1／3。化疗是治疗胃癌的有效手段，但由于肿瘤细胞多药耐药性（MDR）的产生，化疗疗效往往不佳。深入探讨胃癌MDR产生机制，寻找有效低毒的多药耐药逆转剂，对提高化疗的有效性，延长患者的生存期有着重要的意义。从转运蛋白有关的耐药机制、酶系统有关的耐药机制、细胞凋亡与耐药、细胞因子等四方面肿瘤细胞MDR产生的机制做一简要综述。     

胃癌多药耐药相关机制

多药耐药(MDR)是导致胃癌化疗失败的主要原因.研究表明,胃癌MDR的发生机制与多个因素相关,主要有P-糖蛋白(P-gp)和多药耐药相关蛋白(MRP)过表达、谷胱甘肽转移酶-π(GST-π)活性增强、拓扑异构酶Ⅱ(TopoⅡ)含量减少、DNA损伤修复能力增强.     

Neoadjuvant or adjuvant therapy for gastric cancer

Currently, there is no international consensus on the best treatment regimen for patients with advanced resectable gastric carcinoma. In the United States, where a limited lymph-node dissection is frequently performed, adjuvant chemoradiotherapy after surgery is the standard treatment. In Europe, intensified perioperative chemotherapy is commonly administered. In Japan and South Korea, postoperative S-1-based adjuvant chemotherapy after surgery with D2 lymph-node dissection is the standard treatment. Several ongoing trials are currently evaluating the optimal sequence of chemotherapy, radiotherapy, and surgery, as well as the place of targeted therapeutic agents in the treatment of advanced gastric carcinoma.     

Molecular biology of gastric cancer

Abstract Despite its decreasing incidence overall, gastric cancer is still a challenging disease. Therapy is based mainly upon surgical resection when the tumour remains localised in the stomach. Conventional chemotherapy may play a role in treating micrometastatic disease and is effective as palliative therapy for recurrent or advanced disease. However, the knowledge of molecular pathways implicated in gastric cancer pathogenesis is still in its infancy and the contribution of molecular biology to the development of new targeted therapies in gastric cancer is far behind other more common cancers such as breast, colon or lung. This review will focus first on the difference of two well defined types of gastric cancer: intestinal and diffuse. A discussion of the cell of origin of gastric cancer with some intriguing data implicating bone marrow derived cells will follow, and a comprehensive review of different genetic alterations detected in gastric cancer, underlining those that may have clinical, therapeutic or prognostic implications. *Supported by an unrestricted educational grant from Sanofi-Aventis.     

高压氧联合化疗治疗转移性胃癌的临床分析

目的：观察高压氧联合顺铂（DDP）、氟尿嘧啶（5-FU）、甲酰四氢叶酸（CF）组成的FLP方案治疗转移性胃癌的临床疗效及其毒副反应。方法：40例转移性胃癌患者随机分为治疗组和对照组,治疗组采用高压氧联合FLP方案治疗,对照组单用FLP化疗方案,并进行疗效和毒副反应评价。结果：治疗组有效率为55％,对照组有效率为50％,两者比较无显著性差异（P〉0．05）;生存时间：治疗组（8．35±3．91）个月,对照组为（6．83±3．20）个月,两者比较有显著性差异（P〈0．05）;白细胞减少分级评分：治疗组为1．00±0.79,对照组为1．65±0．59,两者比较有显著性差异（P〈0．05）;恶心、呕吐分级评分：治疗组为1．05±0．76,对照组为3．3±0．73,两组比较有显著性差异（P〈0．05）。结论：高压氧联合FLP方案治疗转移性胃癌有效率较高,生存时间延长,患者耐受性较好。     

Silencing MRP4 by small interfering RNA reverses acquired DDP resistance of gastric cancer cell

A cisplatin (DDP) resistant cell line (SGC7901/DDP) from a Chinese gastric cancer cell line (SGC7901) was established by step-increasing DDP treatment, and the resultant cell line showed an over 21.9-fold increased resistance to DDP. To identify the mechanism of DDP resistance, the differential gene expression panel was examined by Affymetrix microarray. Among the identified differential genes, 681 genes expression were increased and 1139 genes were decreased. To confirm these gene changes furtherly, one of the upregulated gene, MRP4 was identified with increased mRNA and protein level of SGC7901/DDP by RT-PCR and Western-blot analysis compared with its parental cell line. By using the small interfering RNA (RNAi) to decrease the MRP4 expression, the DDP resistance phenotype of SGC7901/DDP was reversed. These data suggest that MRP4 is a DDP resistance candidate gene of SGC7901 gastric cancer cell line.     

Multidisciplinary therapy for treatment of patients with peritoneal carcinomatosis from gastric cancer

There is no standard treatment for peritoneal carcinomatosis (PC) from gastric cancer. A novel multidisciplinary treatment combining bidirectional chemotherapy [neoadjuvant intraperitoneal-systemic chemotherapy protocol (NIPS)], peritonectomy, hyperthermic intraperitoneal chemoperfusion (HIPEC) and early postoperative intraperitoneal chemotherapy has been developed. In this article, we assess the indications, safety and efficacy of this treatment, review the relevant studies and introduce our experiences. The aims of NIPS are stage reduction, the eradication of peritoneal free cancer cells, and an increased incidence of complete cytoreduction (CC-0) for PC. A complete response after NIPS was obtained in 15 (50%) out of 30 patients with PC. Thus, a significantly high incidence of CC-0 can be obtained in patients with a peritoneal cancer index (PCI) ≤ 6. Using a multivariate analysis to examine the survival benefit, CC-0 and NIPS are identified as significant indicators of a good outcome. However, the high morbidity and mortality rates associated with peritonectomy and perioperative chemotherapy make stringent patient selection important. The best indications for multidisciplinary therapy are localized PC (PCI ≤ 6) from resectable gastric cancer that can be completely removed during a peritonectomy. NIPS and complete cytoreduction are essential treatment modalities for improving the survival of patients with PC from gastric cancer.     

Phase II study of docetaxel and cisplatin combination chemotherapy in metastatic gastric cancer

Purpose: Docetaxel, as a single agent, has demonstrated activity in patients with advanced gastric cancer and cisplatin has shown lack of overlapping toxicities with docetaxel. Therefore, we conducted a phase II study to assess the efficacy and the toxicity of a combination regimen of docetaxel plus cisplatin in patients with advanced gastric cancer who have never been treated with palliative chemotherapy. Methods: Ninety-two patients with metastatic gastric cancer were enrolled from April 2000 to March 2004. Patients with histologically confirmed gastric adenocarcinoma, at least one bi-dimensionally measurable lesion, no prior palliative chemotherapy and at least 6 months from the end of adjuvant chemotherapy were eligible for study entry. Docetaxel 75 mg/m² and cisplatin 75 mg/m² were given on day 1. The cycle was repeated every 3 weeks. The objective response was evaluated after three cycles of chemotherapy. Toxicity was assessed according to the National Cancer Institute common toxicity criteria scale version 2.0. Results: In total, 401 cycles were administered, with a median of 5 cycles per patient (range 1–9 cycles). The median age was 56 years (range 31–76). Eighty-six patients were evaluable for treatment response. The objective response rate was 43.5% (95% CI, 33.4–53.6) with one complete response and 39 partial responses. Twenty patients (21.7%) had stable disease and 26 patients (28.3%) had a progression. The median time to progression was 7.0 months (95% CI, 5.0–9.0) and the median overall survival was 11.5 months (95% CI, 9.5–13.4). The chemotherapy was generally well tolerated and the most common grade 3–4 toxicities were neutropenia (17.4%), nausea/vomiting (13.0%) and diarrhea (7.6%). Conclusion: The combination chemotherapy of docetaxel with cisplatin in advanced gastric cancer was tolerable for most patients and showed a promising antitumor activity as a first-line therapy.Keon Woo Park and Jin Seok Ahn contributed equally to this work.     

A long-term survivor of metastatic gastric cancer treated by chemotherapy: case report

A long-term survivor of advanced gastric cancer with multiple metastases to the liver treated by chemotherapy is described. Chemotherapy comprising a combination of uracil and tegafur with mitomycin C achieved a complete response in the patient which lasted for approximately four years. Four years after initiation of the chemotherapy, a unique form of cancer recurrence occurred on the skin, showing infiltrative erythema. Cancer metastases developed further despite more treatment, and the patient died of generalized metastasis four years six months after the initiation of chemotherapy. It is significant that, at autopsy, no cancer cells were revealed in the primary lesion or in the liver which had been present before the initial chemotherapy.     

Prospective randomized trial of short-term neoadjuvant chemotherapy for advanced gastric cancer

Background

We performed short-term neoadjuvant chemotherapy (s-NAC) to examine whether anticancer drugs can change the proliferative ability of cancer cells in gastric cancer patients.

Methods

Chemotherapy was performed for 72 h before gastrectomy in 63 gastric cancer patients. Patients were classed into four groups: Group F, 16 cases who received a single administration of 5-fluorouracil (5-FU); Group C, 15 cases who received a single administration of cis-diamminedichloroplatinum (CDDP; cisplatin); Group FC, 16 cases who received both 5-FU+CDDP; and a Control group, 16 cases who did not receive chemotherapy. We reviewed neoadjuvant biopsy tissue and gastric cancer tissue delivered by operation in these cases. The TUNEL method and immunohistochemistry with an anti-MIB-1 antibody were used to evaluate cellular apoptosis and proliferative ability, respectively. The apoptotic index (AI) and an MIB-1 index (MI) were also calculated.

Results

There were no differences in AI or MI in biopsy tissue between the groups. The AI of gastric cancer tissue in Group FC was significantly higher than in the other groups (P < 0.01). The MI of Group FC was significantly lower than in the other groups (P < 0.05). In addition, after s-NAC operation there was a significant inhibition of proliferative potency and an induction of apoptosis in Group FC.

Conclusion

Combination of CDDP and 5-FU reduced proliferative potency and increased cellular apoptosis in gastric cancer cells.     

Multimodal treatment in oligometastatic gastric cancer

Gastric cancer is generally diagnosed at an advanced stage, especially in countries without screening programs. Previously, the metastatic stage was synonymous with palliative management, and surgical indications were only for symptomatic relief. However, this therapeutic option is associated with poor prognosis. A subgroup of patients with limited metastatic disease could benefit from intensive treatment. A combination of chemotherapy, immunotherapy, and targeted therapy could help either maintain a resectable state for oligometastatic disease or diminish the metastasis size to obtain a complete resection configuration. This latter strategy is known as conversion therapy and has growing evidence with favorable outcomes. Oncosurgical approach of metastatic disease could prolong survival in selected patients. The challenge for the surgeon and oncologist is to identify these specific patients to offer the best multimodal management. We review in this article the actual evidence for the treatment of oligometastatic gastric cancer with curative intent.     

不同术后辅助化疗方案对胃癌患者远期生存的影响

  目的  观察化疗期间肠外营养对中晚期胃癌患者免疫功能的影响。   方法  收集江苏省如皋市人民医院自2008年3月至2010年9月间收治的63例接受化疗的中晚期胃癌患者,随机分为观察组（化疗同时给予肠外营养）36例和对照组（化疗期间未给予肠外营养）27例。观察两组患者化疗疗效、平均化疗周期、无进展生存期,检测化疗前后两组患者营养状况和淋巴细胞亚群情况。   结果  两组患者近期疗效无显著性差异;观察组平均化疗周期和无进展生存期显著优于对照组;化疗后观察组患者营养状况显著优于对照组;淋巴细胞亚群检测显示观察组患者免疫功能得到改善,显著优于对照组。   结论  对中晚期胃癌患者化疗期间给予适当的肠外营养可改善患者的营养状态和免疫功能,患者易于耐受化疗,可取得更好的疗效。     

凋亡机制异常导致的肿瘤耐药

肿瘤耐药是导致肿瘤治疗失败的重要原因.近年研究发现,肿瘤细胞的死亡受体及线粒体凋亡途径均可表现多重的异常机制,并导致其对化疗耐药.深入了解肿瘤发生凋亡异常的机制,才能使针对性的抗癌治疗得到发展.针对凋亡变异机制设计的新药物,部分已上市或进入临床试验阶段.