c-myc和K-ras对小鼠卵巢上皮细胞体外转化和体内致瘤的研究

目的探讨癌基因c-myc和K-ras在卵巢癌发生发展中的作用。方法用逆转录病毒转基因系统,将正常的c-myc基因和突变的K-ras基因先后导入小鼠卵巢上皮（MOSE）细胞,建立表达c-myc和K-ras基因的细胞株,分别称为MOSE-Myc细胞、MOSE-Ras细胞和MOSE-RM细胞。通过细胞增殖实验、克隆形成实验、体外侵袭实验以及体内成瘤实验,研究转基因后MOSE细胞生物学特性的改变及恶性转化。结果c-myc和K-ras基因容易被重组逆转录病毒导入MOSE细胞,转导后靶细胞内分别有相应的c-myc或K-ras mRNA转录,以及相应的c-myc（62ooo）和K-ras（21000）蛋白的表达。MOSE-Ras组和MOSE-RM（MOSE-Ras／Myc）组细胞增殖能力显著强于MOSE和MOSE-Myc组（P〈0．01）,MOSE-RM组细胞增殖能力显著强于MOSE-Myc组（P〈0．05）。MOSE-Ras和MOSE-RM组在软琼脂培养中均能形成克隆集落,而MOSE组和MOSE-Myc组不能形成克隆集落。MOSE-Ras组和MOSE-RM组能够穿透Matrigel,具有侵袭能力。MOSE-Ras组和MOSE-RM组细胞在裸鼠体内形成肿瘤,且肿瘤组织细胞仍然可见有K-ras和c-myc蛋白的表达;而MOSE组和MOSE-Myc组无肿瘤形成。结论重组逆转录病毒载体作为转基因的工具,转导效率高,可稳定表达,可以感染正常的细胞;突变的K-ras可使MOSE发生恶性转化,在体内形成肿瘤;c-myc作为一个核转录调节因子,不能使MOSE发生恶性转化,但可协同其他因子,加强其他因子的功能。     

重组人血管内皮抑制素联合全身化疗治疗转移性乳腺癌的临床疗效观察

目的评价重组人血管内皮抑制素联合全身化疗治疗转移性乳腺癌的有效性和安全性。方法 14例转移性乳腺癌患者均接受重组人血管内皮抑制素联合全身化疗方案的治疗。重组人血管内皮抑制素7.5mg/m2,加入500mL生理盐水中,静脉滴注3～4h,连续用药14d,间歇7d重复。化疗方案则根据患者既往治疗方案选用可能有效的化疗方案,按照RECIST 1.1标准评价疗效及NCI-CTC 3.0评价毒性。结果 14例患者均为女性,其中11例患者可评价疗效,6例PR,3例疾病稳定(SD),2例疾病进展(PD),客观缓解率为54.5%(6/11),疾病控制率为81.8%(9/11),无疾病进展生存时间(PFS)为3～35个月,中位PFS为6个月。主要不良反应有中性粒细胞减少、贫血、血小板减少、脱发、乏力、恶心呕吐。此外阴道流血1例,尿路及肺部感染各1例,各种不良反应经对症处理均可恢复,未发现心脏、肝脏及肾脏等器官的功能损害。结论重组人血管内皮抑制素联合全身化疗治疗转移性乳腺癌疗效肯定,不良反应可耐受,安全性高。     

谷氨酰胺强化的营养支持对围手术期肿瘤患者预后影响的Meta分析

目的系统评价谷氨酰胺（Gin）强化的营养支持对围手术期肿瘤患者预后的影响。方法检索6个生物医学数据库（《Pubmed数据库》、《Springer Link数据库》、《中国生物医学文献数据库》、《Cochrane Library》、《中国学术期刊全文数据库》等）的文献资料。按照Cochrane系统评价员手册,对纳入随机对照研究进行方法学质量评定,应用RevMan5．2软件进行Meta分析。结果共纳入9项符合标准的RCT相关文献（n=921）。Meta分析显示,谷氨酰胺增强化的实验组与对照组比较可使患者临床感染率降低至65％,95％CI[0．47,0．90],P=0．010,具有统计学意义;患者总住院时间平均缩短1．95d,95％CI[-3．03,-0．87],P=0．0004,具有统计学差异;患者的IgG平均增加1．27g／L,95％CI[0．80,1．73],P〈0．00001,具有统计学意义。结论谷氨酰胺强化的营养支持,能有效地降低外科腹部手术患者术后感染风险,提高免疫功能,缩短患者住院时间,具有一定的卫生经济学意义。谷氨酰胺强化的营养支持是一种安全有效的营养治疗方法,有利于围手术期肿瘤患者的康复。     

广西社区肝癌和鼻咽癌联合筛查研究

目的在社区建立动态的肝癌和鼻咽癌（简称“两癌”）高危人群队列,并通过定期复查以期早发现、早治疗肿瘤患者,从而提高“两癌”患者的生存率;评估在肝癌、鼻咽癌高发区实施联合筛检方案的可行性。方法在广西某社区对参与体检的自然人群采用“乙肝两对半”和“VCA—IgA抗体”的方法进行初筛。动员符合标准的肝癌、鼻咽癌高危人群参与每半年一次复查,对指定指标异常者做进一步的检测。结果目前建立了1546例肝癌高危人群和649例鼻咽癌高危人群队列,筛检出肝癌患者4例,总检出率为81．00／10万人年,规范化参加筛检的肝癌高危人群检出率为159．49／10万人年,中断检查的检出率为69．59／10万人年;筛检出鼻咽癌患者1例．总检出率为89．30／10万人年。结论按照规范化筛检的高危人群早中期肿瘤的检出率明显高于中断筛检者和普通人群,并随着复检次数的增加肿瘤检出率呈上升趋势。     

Combined use of lysyl oxidase,carcino-embryonic antigen,and carbohydrate antigens improves the sensitivity of biomarkers in predicting lymph node metastasis and peritoneal metastasis in gastric cancer

The purpose of this study was to determine whether lysyl oxidase (LOX) is a useful marker of metastasis in gastric cancer (GC) patients in combination with tumor markers carcino-embryonic antigen (CEA), carbohydrate antigen 724 (CA724), carbohydrate antigen 19-9 (CA19-9), and carbohydrate antigen 125 (CA125). There were 215 GC patients (67 without metastasis, 102 with lymph node metastasis, and 46 with peritoneal metastasis) who presented to the Affiliated Cancer Hospital of Guangxi Medical University between May 2009 and November 2012 that were enrolled in this study. The LOX expression level and the serum concentration of the four tumor markers were evaluated preoperatively. All patients underwent computed tomography (CT) and ultrasonography (US) before surgery. Statistical analysis, including receiver operating characteristic (ROC) curve analysis, area under the curve (AUC) analysis, and logistic regression analysis, was performed to evaluate the diagnostic value of these markers in predicting metastasis in GC. For predicting lymph node metastasis in GC, the sensitivity of LOX, CEA, CA724, CA199, and CA125 was 44.12, 12.75, 21.57, 23.53, and 15.69 %, respectively, and increased to 79.41 % in combination. For predicting peritoneal metastasis in GC, the sensitivity of these markers was 56.52, 23.91, 34.78, 36.96, and 34.78 %, respectively, and increased to 91.30 % in combination. Combining LOX with CEA, CA724, CA199, and CA125 could increase the sensitivity of predicting lymph nodes metastasis and peritoneal metastasis in GC. Surgeons can use these markers to determine the best treatment options for patients. Additional large-scale, prospective, multicenter studies are urgently needed to further confirm the results of this study.     

腹腔镜子宫切除术治疗妇科良性疾病疗效的系统评价

目的系统评价腹腔镜子宫切除术治疗妇科良性疾病的疗效和安全性。方法计算机检索CENTRAL（Cochrane图书馆2012年第5期）、MEDLINE、EMbase、CNKI、WanFangData、VIP和CBM数据库,检索时间从建库截至2012年5月,同时手T检索相关灰色文献,查找腹腔镜与开腹手术切除子宫治疗妇科良性病的随机对照试验。南2位研究者按照纳入排除标准筛选文献、提取资料并评价质量后,采用RevMan5．1软件进行Meta分析。结果纳入22个RCT,共3304例患者。Meta分析结果显示：与开腹术相比,腹腔镜子宫切除术的住院时间[MD=-2．31,95％CI（-3．03,-1．60）,P〈0．00001]和术后恢复正常活动的时间更短[MD=-13．86,95％CI（-17．70,-10．03）,P〈0．00001],术后发热及其他非特异性感染发生率更低[OR=0．72,95％CI（O．54,O．95）,P=0．02],但术中泌尿系损伤发生率更高[OR=2．41,95％CI（1．21,4．82）,P=0．012]且手术时间延长[MD=20．27,95％CI（3．95,36．59）,P=0．03]。,两组在术中肠道损伤、血管损伤、术后瘘管形成、术后排尿功能障碍及术后阴道残端感染等并发症发生率方面,其差异均无统计学意义（P〉0．05）。结论本系统评价结果显示,腹腔镜子宫切除术治疗妇科良性疾病在缩短住院时间及术后恢复正常活动时间优于传统开腹手术,且术后发热及其他非特异性感染发生率更低,但术巾泌尿系损伤发生率更高且手术时间更长：由于缺乏术后长期生活质量结局指标的结果,期待未来更多高质量的随机对照试验结果验证。     

Chronic stress increases experimental pancreatic cancer growth,reduces survival and can be antagonised by beta-adrenergic receptor blockade

Background/objectivesChronic stress could promote tumour growth and reduce survival of pancreatic cancer patients via beta-adrenergic receptors of tumour cells. We have tested the impact of chronic acoustic and restraint stress on tumour development in an orthotopic syngeneic murine model of pancreatic cancer.Methods and resultsTumour-bearing C57BL/6 mice exposed to chronic stress had 45% (p = 0.0138) higher circulating steroid and 111% (p = 0.0052) higher adrenal tyrosine hydroxylase levels. Their immune response was significantly suppressed: The in vitro LPS response of splenocytes was significantly reduced regarding Th1- and Th2-cytokines including IFN-gamma, IL-6, IL-10 and MCP-1 (0.0011 < p < 0.043). Also, tumours of stressed mice showed a tendency towards fewer total CD4 cells, more regulatory T cells (Treg), less T cell/tumour cell contacts and a reduction of CTLA-4 in CD4 cells (p > 0.05). TGF-beta in vitro was increased by 23.4% using catecholamines (p < 0.012) and in vivo employing chronic stress (p < 0.001). After 5 weeks tumour volumes were 130% (p = 0.0061) larger and median survival reduced by 13.5% (p = 0.0058). Tumours expressed more VEGF (p = 0.0334), had greater microvessel densities (p = 0.047), and an increased MMP-9 expression (p = 0.0456). Beta-catecholamines increased proliferation in tumour cells by 18% (p < 0.0001) and migration by 78% (p = 0.0348) whereas the beta-blocker propranolol reduced these effects by 25% (p < 0.0001) and 53% (p = 0.045), respectively. When stressed tumour-bearing animals were treated with propranolol tumour volumes were reduced by 69% (p = 0.0088) and survival improved by 14% (p < 0.0058).ConclusionsThe potential treatment with beta-blockers of patients with pancreatic cancer or other malignancies should be further evaluated as an adjuvant anti-neoplastic agent in clinical trials.