结直肠肿瘤中APC基因突变研究进展

APC基因为结直肠腺瘤性息肉的易感基因，定位于人体5号染色体5q21上。APC基因不仅与家族性腺瘤性息肉病（FAP）有关，而且同部分散发性结直肠肿瘤也有关。本文对APC基因突变类型、功能、基因型-表型相关性、检测及临床应用作一扼要介绍。     

LAPTM4β在人结直肠癌耐药细胞株中的表达及意义

目的建立耐奥沙利铂(L-OHP)的人结直肠癌耐药细胞株(HT-29/L-OHP),检测相关耐药基因LAPTM4β的表达,探讨其在L-OHP耐药中的作用机制。 方法采用药物浓度梯度递增间歇诱导法建立人结直肠癌耐药株HT-29/L-OHP;应用LAPTM4β-35蛋白抑制剂作用于HT-29/L-OHP细胞株后,流式细胞技术检测细胞凋亡,比较其与HT-29/L-OHP细胞株对于L-OHP的耐药情况;应用RT-PCR检测LAPTM4β mRNA的表达;应用Western blot测定LAPTM4β-35蛋白的表达。 结果成功建立人结直肠癌耐药细胞株HT-29/L-OHP,流式细胞技术检测结果表明应用LAPTM4β-35蛋白抑制剂作用于HT-29/L-OHP细胞株后,其对于L-OHP的耐药明显低于HT-29/L-OHP细胞株。HT-29/L-OHP细胞株中LAPTM4β mRNA表达水平明显高于亲本细胞株HT-29,分别为5.613±0.139和1.105±0.187,(P<0.05),LAPTM4β-35蛋白在HT-29/L-OHP细胞和HT-29细胞的相对表达量2.203±0.080和1.033±0.070,(P<0.05)。 结论LAPTM4β在结直肠癌耐药细胞株中过表达,与结直肠癌奥沙利铂耐药密切相关,可以作为结直肠癌耐药的一个敏感的生物学标志物。     

遗传性结直肠肿瘤研究进展

结直肠癌是我国最常见的消化系恶性肿瘤之一,其发病率和死亡率都居全部恶性肿瘤的前列.约有1/3的结直肠癌是由遗传性结直肠肿瘤引起.遗传性结直肠肿瘤包括遗传性非息肉病性结直肠癌和遗传性结肠息肉病两大类.本文简要总结了近年来国内外学者在遗传性结直肠肿瘤的研究中所取得的共识与进展,并就其临床诊治进行讨论和展望.以期加深人们对他的认识,提高医务人员对上述疾病的临床诊治能力.     

结直肠肿瘤中医药治疗的研究进展

结直肠癌是我国发病率较高的恶性肿瘤之一.目前对结直肠癌的早期治疗西医以手术切除为主、中晚期以放化疗为主.随着中医药学的不断发展,在结直肠肿瘤的综合治疗中显示出独特的优势.在各阶段配合其治疗,可明显改善患者预后、延长患者的生存期、提高患者生活质量、减轻患者由于放化疗引起的不良反应并抑制肿瘤的复发和转移等.并且,随着中药有效成分研究的不断进展,亦在抑制肿瘤发生发展及诱导肿瘤细胞分化和凋亡等方面显示出了极好的疗效.合理的应用可极大地改善患者预后.本文从中医角度全面综述了结直肠肿瘤的病因病机、发生发展及辨证治疗等内容,旨在更好的指导临床治疗.     

结直肠肿瘤的遗传学和分子生物学研究进展

结直肠肿瘤的遗传学和分子生物学研究进展靳富有综述段芳龄审校（Ｖ．Ａ．ＭｅｄｉｃａｌＣｅｎｔｅｒ，ＬｏｎｇＢｅａｃｈＣＡ９０８２２ＵＳＡ，河南医科大学消化病研究所郑州４５０００３）流行病学研究确认高动物脂肪、低纤维素饮食在结直肠癌的发病中具有重要作用。...     

奥沙利铂对结直肠癌急慢性神经毒性的观察

[目的]观察并分析结直肠癌完全切除后奥沙利铂辅助化疗疗效及神经毒性。[方法]选取2014年1月~2014年12月我院肿瘤科接受结直肠癌手术完全切除的患者100例,患者肿瘤分期为高危II期及高危III期,接受奥沙利铂联合氟尿嘧啶辅助化疗,对患者应用2种不同的FOLFOX方案进行治疗。研究前期主要采用FOLFOX4方案,后期主要应用mFOLFOX6方案。参照美国癌症研究所常规毒性判定标准（NCI-CTCAE 3.0）进行分级,使用NTX-12自评量表对患者常见症状进行评分。[结果]患者急性神经毒性共发生49例,发生率49.00%,慢性神经毒性84例,发生率84.00%。≥60岁患者慢性神经毒性发生率与发生程度较〈60岁患者更高（χ2=4.645,P=0.031）,FOLFOX4和mFOLFOX6方案,后者较前者神经毒性发生率更高。NTX-12自评未发现≥60岁患者较〈60岁患者评分提高更多,但前者明显高于后者。[结论]奥沙利铂治疗结直肠癌神经毒性发生率高,但多数可在12个月内恢复。     

鸦胆子油逆转奥沙利铂耐药胃癌SGC-7901细胞对奥沙利铂的敏感性

目的探讨鸦胆子油增加奥沙利铂(OXA)耐药胃癌SGC-7901细胞(SGC-7901/COXA)对OXA敏感性的效果。方法 (1)建立SGC-7901/COXA细胞株。首先通过让细胞持续接触药物的培养方法,并逐渐增加OXA的浓度,建立SGC-7901/COXA细胞株。(2)计算鸦胆子油及OXA对SGC-7901/COXA细胞增殖抑制率及药物的IC_(50)。取对数生长期SGC-7901/COXA细胞,培养24 h,然后加入不同浓度的鸦胆子油、OXA,继续培养48 h后应用CCK8试剂测定各孔光吸收值(A),取平均值,计算两药单独对SGC-7901/CDDP细胞增殖抑制率及药物的IC_(50)。(3)计算两药联合后SGC-7901/COXA细胞增殖抑制率、IC_(50)逆转倍数。选择适宜的鸦胆子油浓度与不同浓度OXA联合,重复CCK8法,计算两药联合后SGC-7901/COXA细胞增殖抑制率、IC_(50)、逆转倍数。结果鸦胆子油、OXA对SGC-7901/COXA细胞增殖具有抑制作用,该作用与浓度呈正相关。鸦胆子油、OXA对SGC-7901/COXA细胞的IC_(50)分别为91.39μg/ml和5.37μg/ml。鸦胆子油联合不同浓度OXA后对SGC-7901/COXA细胞增殖抑制作用明显增强,联合用药后OXA的IC_(50)降为1.29,逆转耐药倍数为4.16,因此SGC-7901/COXA对OXA敏感性明显增强。结论鸦胆子油与OXA联合后SGC-7901/COXA对OXA的敏感性增加,相对单独使用易产生耐药性的缺点,两者联合后能有效提高SGC-7901/COXA对OXA的敏感性。     

肿瘤干细胞学说与结直肠癌的形成和多药耐药

对化疗药物耐药是肿瘤化疗失败的主要原因,肿瘤干细胞理论为重新认识肿瘤化疗药物的耐药机制提供了新思路。近年,许多学者从结直肠肿瘤组织中分离出肿瘤干细胞,并提出肿瘤干细胞致瘤模型和耐药模型学说,很好地解释了药物治疗后肿瘤复发的最根本原因。本文就肿瘤干细胞与结直肠癌的形成和多药耐药作一综述,旨在为进一步研究肿瘤干细胞与结直肠癌的内在联系提供参考。     

脂代谢与结直肠肿瘤关系的研究进展

近年来结直肠肿瘤(colorectal carcinoma,CRC)的发病率和死亡率每年呈上升趋势,严重威胁着人类的健康.在对CRC的发生发展的研究中,脂代谢与CRC的关系受到人们的越来越多关注.目前研究发现高脂饮食更易导致CRC,而且血脂中的不同成分在CRC的形成和发展中,可能发挥了完全相反的作用,对于这些作用发生的机制有多种推测,还需要进一步的研究证实.因此,对于脂代谢异常对结直肠肿瘤的形成和进展中的作用及机制的研究对结直肠癌的诊断和治疗具有重要意义.     

肠干细胞与结直肠肿瘤干细胞研究进展

干细胞(stem cell,SC)是一群结构和功能未特化的原始细胞,具有长期自我更新潜能和产生至少一种终末分化细胞的能力.而肠干细胞是位于小肠隐窝下部潘氏细胞上方及结直肠隐窝的底部的成体干细胞,具有增殖和自我维持、能产生许多子代细胞并能在受损伤后再生的特性.近年较多的文献报道结直肠癌组织中存在肿瘤干细胞,而这些具有干细胞特性的瘤细胞可能来自突变的肠干细胞,本文就肠干细胞和结直肠癌肿瘤干细胞的研究进展作一综述.     

Emerging roles of non-coding RNAs in colorectal cancer oxaliplatin resistance and liquid biopsy potential

Colorectal cancer (CRC) is one of the most common malignancies of the digestive tract,with the annual incidence and mortality increasing consistently.Oxaliplatinbased chemotherapy is a preferred therapeutic regimen for patients with advanced CRC.However,most patients will inevitably develop resistance to oxaliplatin.Many studies have reported that non-coding RNAs (ncRNAs),such as microRNAs,long non-coding RNAs,and circular RNAs,are extensively involved in cancer progression.Moreover,emerging evi...     

不可切除的结直肠癌肝转移灶局部治疗进展

肝脏是结直肠癌发生转移最主要的靶器官,手术切除是治疗肝转移最理想的方式,但对于不可切除的肝转移,局部控制是治疗的首要目标,在全身化疗的基础上,局部治疗发挥了重要的强化和补充作用。目前常用的局部治疗方式包括消融治疗、肝脏导向化疗、放射治疗等。近年来这些方式在低毒副作用、高可重复性、长期控制等方向均有一定的进展。     

结直肠癌转移复发的转化医学研究

结直肠癌复发转移是患者死亡的主因,早期发现肿瘤转移的证据能提高复发肿瘤的疗效。寻找结直肠癌复发转移的分子标志物是结直肠癌转化医学研究的重要内容之一。结直肠癌复发转移分子标志物转化研究的一般过程包括高通量数据处理基础上的分子标志物发掘,分子功能的鉴定,单中心小样本验证和多中心大样本的确认等四个关键步骤。     

奥沙利铂和伊利替康交替化疗治疗晚期大肠癌36例疗效观察

目的 评价奥沙利铂和伊利替康交替化疗治疗晚期大肠癌的有效性和安全性.方法 伊利替康125mg/m2,LV100mg/m2,5-FU 500mg/m2,第1 d,第8 d给药;奥沙利铂65mg/m2,LV 100mg/m2,5-FU500mg/m2,第15 d,第16 d给药.结果 入组36例患者,有效率(RR)50.00%,临床获益率(CBR)88.89%.总生存(OS)6～28个月,平均生存时间(MST)15个月,中位疾病进展时间(mTTP)10.3个月.常见的不良反应是感觉神经毒性、血液学毒性、腹泻、恶心呕吐,均较轻微.结论 此方案治疗晚期大肠癌具有良好的疗效和安全性.     

Application of nanotechnology in reversing therapeutic resistance and controlling metastasis of colorectal cancer

Colorectal cancer(CRC) is the most common digestive malignancy across the world. Its first-line treatments applied in the routine clinical setting include surgery, chemotherapy, radiotherapy, targeted therapy, and immunotherapy. However, resistance to therapy has been identified as the major clinical challenge that fails the treatment method, leading to recurrence and distant metastasis. An increasing number of studies have been attempting to explore the underlying mechanisms of the resistance o...     

Clinical pharmacokinetics of oxaliplatin and 5-fluorouracil administered in combination with leucovorin in Korean patients with advanced colorectal cancer

Purpose: Oxaliplatin and 5-fluorouracil (5-FU) act synergistically in colorectal cancer. Here, we evaluated the pharmacokinetics of oxaliplatin and 5-FU administered in combination with leucovorin in Korean advanced colorectal cancer patients. Methods: Nine patients with advanced colorectal cancer were included in this study. The 3-week regimen consisted of oxaliplatin (2-h infusion, 130 mg/m² on day 1) followed by 5-FU and leucovorin (2-h infusion, 425 and 20 mg/m², respectively, from day 1 to day 5). Blood samples were taken and platinum concentrations in total plasma, plasma ultrafiltrate, and RBCs were determined. Plasma concentrations of 5-FU were also determined. Results: The C _max of oxaliplatin was observed at the end of infusion, with mean values of 4.66, 0.84, and 2.69 μg/ml for total plasma, plasma ultrafiltrate, and RBC samples, respectively. C _max ratios of total/free were significantly higher than those reported in other ethnic groups. An accumulation of platinum was observed in RBCs, but not in total plasma and plasma ultrafiltrate samples. A significant correlation was found between the total body clearance of ultrafiltrable platinum and creatinine clearance. The C _max of plasma 5-FU ranged from 23.9 to 533.8 ng/ml, indicating large inter-patient pharmacokinetic variations. Conclusions: This study shows that pharmacokinetics of oxaliplatin in Korean patients is comparable with that of other ethic groups, except for the higher C _max ratios of total/free. The C _max of 5-FU in plasma showed large variations among patients. Antitumor efficacy in Korean advanced colorectal cancer patients given oxaliplatin and 5-FU should be further evaluated with respect to pharmacokinetic variabilities.     

结直肠癌浸润转移与癌胚抗原的关系

目的研究结直肠癌浸润转移患者与癌胚抗原（ＣＥＡ）的关系．方法结直肠癌患者６０例，男３６例，女２４例；年龄２７岁～８０岁，平均５４９岁±１３２岁，皆经手术及病理证实．ＤｕｋｅｓＡ１６例，Ｂ２０例，Ｃ１４例，Ｄ１０例．用ＲＩＡ测定血清ＣＥＡ水平，并用免疫组织化学方法检测肿瘤组织ＣＥＡ的表达．结果血清ＣＥＡ水平及肿瘤组织ＣＥＡ表达均与肿瘤浸润及转移有关．有转移的患者血清ＣＥＡ水平（１１４６μｇ／Ｌ±７９１μｇ／Ｌ）明显高于无转移的患者（４５３μｇ／Ｌ±３２３μｇ／Ｌ，Ｐ＜００１），肿瘤组织ＣＥＡ表达强度在有转移与无转移患者中亦有明显差异（强阳性率８７５ｖｓ３８９％，Ｐ＜００１）．肿瘤组织ＣＥＡ表达类型也与肿瘤转移有关，呈胞浆型表达者发生淋巴结转移（５４１％）及远处转移（２７０％）明显高于呈顶端型表达者（１９０％，０％，Ｐ＜００１）．结论ＣＥＡ与结直肠癌浸润转移呈正相关，肿瘤组织ＣＥＡ表达类型亦可作为一项预后指标     

Inhibition of Girdin enhances chemosensitivity of colorectal cancer cells to oxaliplatin

AIM: To investigate the effect of Girdin knockdown on the chemosensitivity of colorectal cancer cells to oxaliplatin and the possible mechanisms involved.METHODS: Four siRNAs targeting Girdin were transfected into the chemoresistant colorectal cancer cell line DLD1. Real-time polymerase chain reaction (PCR) was employed to assess Girdin mRNA expression and the most effective siRNA was chosen for conversion into shRNA. Then, DLD1 cells were infected with lentiviruses expressing the Girdin shRNA and a scramble control, respectively, and Girdin mRNA and protein expression levels were assessed by real-time PCR and Western blotting. Furthermore, microarray experiments were used to assess global gene expression profile after Girdin suppression in DLD1 cells. Finally, the cytotoxic effect of simultaneous treatment with oxaliplatin and adriamycin (an inhibitor of a significantly downregulated gene after Girdin suppression in DLD1 cells) was examined by MTT assay.RESULTS: The most effective siRNA suppressed Girdin expression with an inhibition efficiency of 57%. Compared with the scramble control, DLD1 cells infected with the Girdin shRNA displayed decreased Girdin mRNA and protein levels (P < 0.05), and Girdin knockdown significantly enhanced chemosensitivity to oxaliplatin in colorectal cancer cells (P < 0.05). Microarray data revealed that 381 and 162 genes were upregulated and downregulated in response to Girdin reduction, respectively, with ratios > 1.2 or < 0.8 (P < 0.01). Interestingly, TOP2B (DNA topoisomerase 2-β) was downregulated (ratio = 0.78, P = 0.0001) and oxaliplatin/adriamycin combination resulted in increased cell death compared with treatments with individual agents (P < 0.05).CONCLUSION: Girdin knockdown enhances chemosensitivity of colorectal cancer cells to oxaliplatin via TOP2B down-regulation. These findings provide a promising approach to overcome the chemoresistance of colorectal cancer cells.     

Hepatectomy for liver metastasis of colorectal cancer

Objective  The objective of this study was to investigate whether hepatic resection (HR) can increase the survival of liver metastasis of colorectal cancer (CRC). Materials and methods  CRC patients (n = 669) with liver metastasis treated at the Zhongshan Hospital, Fudan University from 1/2000 to 7/2007 were included in the study to investigate the relationship between HR and cancer survival. Results  CRC patients (n = 669) with liver metastases who had primary tumor resection were grouped in synchronous liver metastasis (SLM; 56.7%, n = 379) and metachronous liver metastasis (MLM) groups (43.3%, n = 290). Hepatic resection rates were lower (32.5%, n = 123) in the SLM than the MLM group (44.8%, n = 130, P < 0.05). The 30-day mortality rate in the MLM (2.3%) was significantly lower than SLM (2.4%) groups. The 5-year survival rates (36.6%) was same compared to SLM group (33.1%, P > 0.05). One-, 2-, and 3-year survival of stages I and II operation cases were 92.5% vs 86.5%, 0.7% vs 58.0%, and 42.1% vs 44.9% (P > 0.05) in the SLM group, respectively. Recurrence after first hepatic resection associated with a 2.23-fold increased risk of death (P < 0.01). Incision margins larger than 1 cm and HR for recurrence associated with 34% and 27% (P < 0.05) decreased death risk. Conclusions  Hepatic resection could help the survival of liver metastasis of colorectal cancer, and stage I surgery is safe for this disease. Xu Jianmin, Wei Ye, and Zhong Yunshi contributed equally to this paper.