缺氧导致胃癌化疗耐药的研究进展

胃癌是严重危害人类健康的恶性肿瘤，其化疗耐药问题日趋严重，导致胃癌治疗有效率下降。胃癌局部微环境的缺氧是导致胃癌化疗耐药的一个重要原因，由于肿瘤内血管结构和功能的异常以及肿瘤细胞的快速增殖引起肿瘤细胞氧耗增加，导致肿瘤组织局部缺氧，结果肿瘤细胞更具有侵袭性，容易发生远处转移，并且对化疗产生抵抗。本文从导致胃癌组织内缺氧的原因及缺氧微环境的特征、缺氧引起胃癌化疗耐药的现状及原因、改善缺氧导致的胃癌化疗耐药的措施等几个方面就缺氧导致胃癌化疗耐药的研究进展进行综述。      

胃癌抗原和晚期胃癌全身化疗进展

2003年11月在广州召开的2003年全国肿瘤化疗学术会议上,第四军医大学西京医院的樊代明院士和北京肿瘤医院的金懋林教授,就胃癌肿瘤分子标记物方面的研究进展和对局部进展和转移期胃癌的化疗进展和经验进行了交流,现综述如下:     

青海地区胃癌相关性贫血的临床研究

目的：通过青海地区胃癌患者的贫血状况的分析,明确本地区贫血与胃癌分期及化疗效果的相关性。方法：收集2004年6月到2008年4月来院治疗的胃癌患者258例,检查血常规以了解贫血的状况,分析贫血发生率与肿瘤分期的关系。跟踪病例化疗情况,分析化疗后贫血发生率及其与预后间的关系。结果：样本中贫血发生率为43.8%。其中女性中为51.8%;男性中为41.6%,无显著性差异。在258例病人中具有完整TNM分期的195例,胃癌患者的贫血发生率根据肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄不同有显著性差异。肿瘤在胃贲门区、胃体部、胃窦区贫血发生率无显著性差异。258例胃癌患者接受三周期化疗后,贫血病人为161例。其中化疗后出现贫血的病人有46例,疾病控制率（DCR）为78.26%,客观缓解率（ORR）为21.74%。而化疗后无贫血的17例病人,疾病控制率（DCR）94.12%,客观缓解率（ORR）为52.94%。贫血组和非贫血组的DCR和ORR有显著性差异。在化疗过程中,15例病人接受了输血治疗,没有关于铁剂及促红细胞生成素（Erythropoietin,EPO）治疗的记录。结论：按NCI标准判断,青海地区胃癌相关性贫血的发生率与国内其他地区发生率相近。胃癌相关性贫血的发生率与肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄有关。化疗过程中发生贫血的病人对化疗的反应差,化疗过程中未发生贫血的病人疗效较好。本研究中贫血的发生率与患者性别及肿瘤的部位无关。     

青海地区胃癌相关性贫血的临床研究

目的:通过青海地区胃癌患者的贫血状况的分析,明确本地区贫血与胃癌分期及化疗效果的相关性。方法:收集2004年6月到2008年4月来院治疗的胃癌患者258例,检查血常规以了解贫血的状况,分析贫血发生率与肿瘤分期的关系。跟踪病例化疗情况,分析化疗后贫血发生率及其与预后间的关系。结果:样本中贫血发生率为43.8%。其中女性中为51.8%;男性中为41.6%,无显著性差异。在258例病人中具有完整TNM分期的195例,胃癌患者的贫血发生率根据肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄不同有显著性差异。肿瘤在胃贲门区、胃体部、胃窦区贫血发生率无显著性差异。258例胃癌患者接受三周期化疗后,贫血病人为161例。其中化疗后出现贫血的病人有46例,疾病控制率(DCR)为78.26%,客观缓解率(ORR)为21.74%。而化疗后无贫血的17例病人,疾病控制率(DCR)94.12%,客观缓解率(ORR)为52.94%。贫血组和非贫血组的DCR和ORR有显著性差异。在化疗过程中,15例病人接受了输血治疗,没有关于铁剂及促红细胞生成素(Erythropoietin,EPO)治疗的记录。结论:按NCI标准判断,青海地区胃癌相关性贫血的发生率与国内其他地区发生率相近。胃癌相关性贫血的发生率与肿瘤分化程度、肿瘤分期、浸润深度、淋巴结转移、远处转移、肿瘤大小、年龄有关。化疗过程中发生贫血的病人对化疗的反应差,化疗过程中未发生贫血的病人疗效较好。本研究中贫血的发生率与患者性别及肿瘤的部位无关。     

74例胃癌术后患者的预后因素分析

[目的]分析胃癌预后因素。[方法]对1998年～2005年我院收治的74例胃癌术后患者进行回顾性分析,采用LifeTable法、Kaplan-Meier和Cox回归分析对胃癌预后的影响进行评价。[结果]单因素分析显示临床分期、浸润深度、淋巴结转移、术后化疗和肿瘤残留情况与预后明显相关(P<0.05)。多因素分析显示术后化疗、肿瘤残留情况及临床分期为预后的独立因素(P<0.05)。[结论]术后化疗、肿瘤残留情况及临床分期是胃癌术后患者预后的独立危险因素。Ⅲ期胃癌术后患者接受辅助化疗具有明显的生存优势。     

不同CT测量方法在评价胃癌围手术期化疗效果中的应用研究

目的比较不同CT测量方法在评价胃癌围手术期化疗疗效中的作用,从而找出最有说服力的评价方法及其标准。方法选择2009年1月至2012年1月收治的胃癌患者42例,以门静脉期重建图像分别测量肿瘤的厚度、最大截面积和体积,分析化疗前后各项变化与预后的相关性。结果化疗前后肿瘤厚度、肿瘤最大截面积及肿瘤体积的差异均有统计学意义（P〈0.05）,其中以CT肿瘤体积减少率与预后的相关性最强（r=0.694）。结论采用CT测量胃癌患者化疗前后肿瘤体积的变化来预测患者的预后,指导进一步的临床治疗。     

晚期胃癌化疗进展

胃癌是人类常见的肿瘤之一.在过去的70年多年来尽管胃癌的发病率和死亡率已经显著下降[1],但胃癌仍旧 是全球第口大常见肿瘤和第二位的肿瘤相关死亡原因[2].在2002年,全球报道有1100万新发病例,有700万病人死亡[3].手术仍然是治愈胃癌的主要手段,化疗、放疗也占有重要地位,生物治疗、基因治疗等新手段也不断开展.本文就晚期胃癌化疗的进展状况进行分析和讨论.     

胃癌的化疗

进展型胃癌化疗疗效的评价标准可采用X线、内窥镜和活检多次检查,分为:完全缓解(CR);部分缓解(PR);没有变化(NC)和疾病进展(PD)四类。 胃癌化疗有单一药物化疗和联合化疗。东京肿瘤协作研究组10年来对165例胃癌采用的化疗方案如下:     

全身及腹腔化疗对胃癌腹腔游离癌细胞影响的实验研究

目的 研究全身及腹腔化疗对胃癌腹腔游离癌细胞的影响。方法 将2.0×10~4MFC前胃癌细胞注入Balb/c小鼠腹腔内,建立胃癌腹腔游离癌细胞模型。将小鼠分为3组:肿瘤对照组、全身化疗组入腹腔化疗组。全身化疗组经尾静脉注射5—FU1.0mg(0.1ml)只·天,腹腔化疗组注入腹腔5—FU1.0mg(0.6ml)/只·天,均连用5天。于第6日处死全部小鼠,腹水癌细胞计数。结果 肿瘤对照组、全身化疗组及腹腔化疗组游离癌细胞计数分别为1.78±1.05,0.52±0.29及0.26±0.19(单位10~5)。全身化疗组和腹腔化疗组较肿瘤对照组明显减少(P<0.05,P<0.01)。全身化疗组同腹腔化疗组间无差异(P>0.05)。结论 全身化疗及腹腔化疗均可抑制、杀灭胃癌腹腔内游离癌细胞。     

晚期胃癌常用化疗方案及其疗效

晚期胃癌常用化疗方案及其疗效林盛毅上海杨浦肿瘤医院（２０００８２）近年来国际上就晚期胃癌的化疗不断涌现新的方法。有的已为国内临床医生所应用，有的还有待于进一步开发研究。现就目前胃癌化疗的研究进展和临床应用情况综述如下。一、联合化疗方案治疗的近况现今国...     

Impact of perioperative intraperitoneal chemotherapy on the treatment of primary gastric cancer

Perioperative intraperitoneal chemotherapy provides effective prevention of peritoneal recurrence after resection in advanced gastric cancer, especially in gastric cancer with serosal invasion. With improved local-regional control, improved survival rate for advanced gastric cancer is achieved. This type of regional chemotherapy is an independent treatment-related prognostic factor for advanced gastric cancer. There are several methods of perioperative intraperitoneal chemotherapy. Among them, early postoperative intraperitoneal chemotherapy is simple and easy to perform.     

Long- and short-term survivors after chemotherapy among patients with advanced or recurrent gastric cancer in our hospital

Since S-1 was approved in 1999, the response rate and the disease control rate of this chemotherapy for advanced or recurrent gastric cancer has been improved. Aa a result, we can plan for chemotherapy in patients with advanced or recurrent gastric cancer, because the median survival time (MST) with advanced or recurrent gastric cancer was over 20 months. We examined the characteristic findings of long- and short-term survivors in chemotherapy patients with advanced or recurrent gastric cancer. The prognosis for advanced gastric cancer is better than that for recurrent gastric cancer (p <0.02). In patients with only recurrent gastric cancer, the interval from surgery to recurrence is a significant prognostic factor. We thus show the results of chemotherapy for advanced or recurrent gastric cancer in our hospital and the characteristic findings in long- and short-term survivors for chemotherapy, and discuss effective planning of chemotherapy for each patient with advanced or recurrent gastric cancer.     

Second malignancy after gastrectomy for early gastric cancer-is there any evidence that adjuvant chemotherapy for early gastric cancer causes a second malignancy ?

The common causes of post-operative death in early gastric cancer are other diseases and second malignancy. In Japan, adjuvant chemotherapy using oral administration of 5-fluorouracil is widely accepted in spite of no statistical evidence until the presentation by Kinoshita in 2005. In 1999, Fujimoto mentioned that adjuvant chemotherapy and chemo-immune-therapy cause a second malignancy. Adjuvant chemotherapy was once the standard treatment for early gastric cancer patients. So, we investigated the relation between adjuvant chemotherapy and second malignancy for early gastric cancer patients. As a result, adjuvant chemotherapy using 5-fluorouracil(Tegafur)did was not cause second malignancy under multivariate analysis. The most important factor in second malignancy with post-operative early gastric cancer patients was heredity(cancer within first-degree relatives). From this point of view, early gastric patients after gastrectomy and endoscopic treatment are necessary in regular examinations to detect other organ cancers and remnant gastric cancer, especially in patients with hereditary factors.     

Combination chemotherapy of S-1 +CPT-11 (q 4-5 w) for metastatic gastric cancer

The effectiveness of systemic chemotherapy for metastatic gastric cancer has already been established. However, a standard chemotherapy still remains uncertain. New agents such as S-1, CPT-11 and taxanes are markedly improving the response rates for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard regimen to treat gastric cancer will be reported. In this article, we described the current state of S-1 +CPT-11 combination chemotherapy for gastric cancer. Among various CPT-11 based chemotherapy, S-1 +CPT-11 appears to be the most effective and less toxic treatment.     

晚期胃癌靶向治疗进展

胃癌化疗敏感性较低, 存在明显的异质性, 传统化疗疗效极其有限。以分子表型为指引的靶向治疗是进一步提高胃癌治疗效果的重要途径。曲妥珠单抗已被证明与化疗联合可以提高初治HER-2阳性胃癌患者的生存。相对于安慰剂, Ramucirumab延长了二线治疗患者的生存。抗C-MET单克隆抗体Rilotumumab在Ⅱ期研究中显示出良好的前景。然而, 大多数的靶向药物都未能在胃癌的临床研究中获得成功。寻找胃癌关键的靶基因, 开发更有效靶向药物仍任重道远。      

Adjuvant chemotherapy for gastric cancer: a comprehensive review

The role of adjuvant chemotherapy in gastric cancer has been studied extensively over the past three decades in an attempt to further improve the prognosis of patients with gastric cancer who have undergone curative surgery. To date, no definitive conclusions have been drawn from randomized clinical trials of adjuvant chemotherapy for gastric cancer, because few studies have shown a significant positive impact on survival as compared with surgery alone. The negative results of most previous clinical studies do not necessarily mean that the adjuvant chemotherapy approach to treatment of gastric cancer does not work. Recent published reports of meta-analyses concerning adjuvant chemotherapy of gastric cancer revealed small but clear survival advantages for adjuvant therapy over surgery alone. The positive data from meta-analyses suggests that there are potential survival advantages of adjuvant chemotherapy, but this must be proven in the future by well-designed clinical trials that compare adjuvant chemotherapy with surgery alone, in which sufficient numbers of patients are enrolled and effective chemotherapeutic regimens with appropriate dose intensity are employed. Newly developed anticancer agents and/or newer therapeutic combinations or strategies (neoadjuvant chemotherapy, chemoradiotherapy, intraperitoneal chemotherapy) have the potential to benefit high-risk patients. Received: June 6, 2001 / Accepted: August 24, 2001     

Gastric cancer treatment: a systematic review

Gastric cancer remains one of the leading causes of cancer related deaths worldwide. The overall 5-year survival rate in the United States and most of the Western World ranges from 5 to 15%. The only potentially curative treatment for localized gastric cancer is complete surgical resection. Meta-analyses of adjuvant systemic chemotherapy in gastric cancer have shown at best marginal benefits, neoadjuvant chemotherapy and chemoradiotherapy are also feasible and are the subject of several ongoing studies. In metastatic disease, chemotherapy confers benefit when compared with best supportive care alone. This review will focus on the several treatment modalities available for gastric cancer patients: surgery, adjuvant, neoadjuvant and palliative chemotherapy as well as new target agents.     

The present state and future of home care for gastric cancer patients

Recently, cancer treatment has been shift from inpatient chemotherapy to outpatient chemotherapy, because of various medical circumstances. In chemotherapy of gastric cancer, outpatient chemotherapy was not spread in the last decade, because the chemotherapy protocol of gastric cancer was not fit for outpatient chemotherapy. But the development of new drugs as TS-1 make outpatient chemotherapy more frequent. So home care of patients has been important for management of gastric cancer. Various symptoms due to obstruction at primary lesion or other lesion prevent patients from living at home in gastric cancer. But recently, technical development and spread of home parenteral nutrition make a possible home care of patients with gastric cancer. It is necessary to make a system that supports patient life at home.     

１８９例Ⅱ期胃癌患者的预后因素及辅助化疗价值

目的　分析Ⅱ期胃癌患者的临床预后因素,探讨辅助化疗能否对这部分患者带来生存获益,并寻找合理的治疗形式。方法　收集并回顾性分析１９９５年５月至２００５年１１月在中山大学肿瘤防治中心确诊为Ⅱ期胃癌并行根治性手术的患者,术后观察或接受辅助化疗。最终可供分析的有１８９例,统计并分析患者的临床资料。结果　本中心Ⅱ期胃癌患者的５年生存率为６９.３％。单因素和多因素分析显示,术前体重下降程度、肿瘤大小、淋巴结清扫术式、肿瘤浆膜外侵犯或脉管浸润是Ⅱ期胃癌５年生存率的独立预后因素,术后接受辅助化疗的患者预后较好。进一步分析,使用氟尿嘧啶类单药与联合方案的患者无明显生存差异。接受化疗６～８个疗程者５年生存率明显优于未化疗或化疗不足３个疗程者。结论　Ⅱ期胃癌患者术前体重改变程度、淋巴结清扫术式、肿瘤浆膜外侵犯或脉管浸润是５年生存率的独立影响因素,辅助化疗对该期患者有生存获益,建议患者接受６～８个疗程的辅助化疗。     

CPT-11 combined chemotherapy for metastatic gastric cancer

The effectiveness of chemotherapy for metastatic gastric cancer has been already revealed. But a standard chemotherapy has not been established yet. New agents such as TS-1, CPT-11 and taxanes are improving the response rates and also the survivals for gastric cancer. Including these new drugs, several randomized phase III trials are ongoing in Japan. In the near future, the candidate for standard resume will be sent abroad. In this article, we described the current state of CPT-11 combined chemotherapy for gastric cancer. Among various CPT-11- combined chemotherapy, CPT-11 + TS-1 is the most effective and less toxic treatment.