Cancer colorectal

结直肠癌
  • 文章类型: Journal Article
    结直肠癌(CRC)是世界上癌症相关死亡的第二大原因,化疗,作为CRC治疗的重要组成部分,有一些缺点,包括全身毒性。因此,发现新的更有效的CRC治疗方案至关重要.大黄(R.horasanicum)是一种具有高类黄酮的药用植物,二苯乙烯,和蒽醌含量,因此它可能是抗氧化剂的潜在来源,可用于治疗目的并引发癌细胞凋亡。在这项研究中,我们研究了罗氏酵母水醇根提取物对诱导HT-29和Caco-2人结直肠腺癌细胞线粒体凋亡的影响。首先,测定总酚和黄酮含量。然后,K.对三种不同类型细胞的细胞毒作用,使用MTT测定评估包括HT-29和Caco-2结肠癌细胞以及正常3T3细胞。为了研究细胞死亡的特征,流式细胞术,并进行了蛋白质印迹。这项研究的结果表明,呼罗兰中相当多的酚类(356.4±9.4GAE/gDW)和类黄酮(934.55±17.1QE/gDW)含量。MTT分析的发现表明,100、60和30µg/mL浓度的霍拉西氏菌可显著降低HT-29和Caco-2细胞系中的细胞活力(P<0.05)。还揭示了在这些细胞系中,罗氏菌提取物诱导细胞凋亡而不是坏死。此外,Bcl-2在HT-29和Caco-2细胞系中的表达显著降低,而Bax和裂解的caspase-3的表达在霍氏弧菌治疗下显著飙升(P<0.05)。总之,我们的研究结果表明,高含量的horasanicum根提取物可能在HT-29和Caco-2结肠癌细胞的细胞毒性和凋亡诱导中起重要作用。
    Colorectal cancer (CRC) is the second greatest cause of cancer-related death in the world and chemotherapy, as an important part of CRC treatment, has some drawbacks, including systemic toxicity. Therefore, it is crucial to discover new and more effective CRC treatment plans. Rheum khorasanicum (R. khorasanicum) is a medicinal plant with high flavonoids, stilbenes, and anthraquinone contents, so it can be a potential source of antioxidants and can be used for therapeutic purposes and trigger apoptosis in cancer cells. In this study, we investigated the effects of hydroalcoholic root extract of R. khorasanicum treatment on inducing mitochondrial apoptosis of HT-29 and Caco-2 human colorectal adenocarcinoma cells. Firstly, the total phenolic and flavonoid content was determined. Then, the cytotoxic effects of R. khorasanicum on cells of three different types, including HT-29 and Caco-2 colon cancer cells as well as normal 3T3 cells were assessed using the MTT assay. To investigate the characteristics of cellular death, flow cytometry, and western blotting were performed. The results of this study indicated considerable phenolic (356.4±9.4 GAE/gDW) and flavonoid (934.55±17.1 QE/gDW) contents in R. khorasanicum. MTT assay\'s finding indicated that 100, 60, and 30μg/mL concentrations of R. khorasanicum reduce cell viability in HT-29 and Caco-2 cell lines significantly (P<0.05). It has been also revealed that R. khorasanicum extract induces apoptosis rather than necrosis in these cell lines. Moreover, Bcl-2 expression was significantly reduced in both HT-29 and Caco-2 cell lines, while Bax and cleaved caspase-3 expression soared considerably in the groups under R. khorasanicum treatment (P<0.05). In conclusion, our findings have suggested that high phenol and flavonoid contents of R. khorasanicum root extract possibly play an important role in cell cytotoxicity and apoptosis induction in HT-29 and Caco-2 colon cancer cells.
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  • 文章类型: English Abstract
    经过十多年的良好结果,使用细胞减灭术(CRS)加腹腔热化疗(HIPEC)联合治疗结直肠起源的腹膜癌,PRODIGE7研究,专门评估了HIPEC的作用,与单独使用CRS相比,CRS+HIPEC组合在总体生存率和无病生存率方面未能显示出任何优势.这项研究构成了迄今为止观察到的知识和治疗态度的根本变化。在查阅文献和国内外专家的共识后,提供了一种合成,以及对提出的问题以及不久的将来的治疗试验和创新的展望。分析了由于新技术的出现而取得的最新进展,PIPAC,还提议,以及对该领域当前治疗试验的回顾。
    After more than a decade of good results using the combination of cytoreductive surgery (CRS) plus hyperthermic intraperitoneal chemotherapy (HIPEC) in the treatment of peritoneal carcinosis of colorectal origin, the PRODIGE7 study, which specifically evaluated the role of HIPEC, failed to show any superiority in terms of overall and disease-free survival for the CRS+HIPEC combination compared with CRS alone. This study constituted a radical change in the knowledge and therapeutic attitudes observed to date. After reviewing the literature and the consensus of national and international experts, a synthesis is provided, together with an outlook on the questions raised and the therapeutic trials and innovations of the near future. An analysis of recent advances due to the advent of a new technique, PIPAC, is also proposed, as well as a review of current therapeutic trials in this field.
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  • 文章类型: English Abstract
    在转移性结直肠癌(mCRC)感兴趣的分子亚组中,HER2(人类表皮生长因子受体2)过度表达的肿瘤正在进行创新.HER2蛋白的过表达涉及主要位于远端结肠和直肠的任何阶段的2-5%的CRC。诊断基于免疫组织化学,具有适当的结肠直肠定位标准的原位杂交,和分子生物学(NGS:下一代测序)。HER2的过表达是对靶向EGFR的治疗的抗性的预测因素,这在肿瘤是野生型RAS的情况下表明。它似乎与mCRC的不良预后有关,具有较高的脑转移风险。关于针对HER2的治疗,迄今为止尚未发表随机对照III期。然而,已在II期评估了几种组合,具有临床意义的客观缓解率:曲妥珠单抗-deruxtecan(45%),曲妥珠单抗-图卡替尼(46%),曲妥珠单抗-吡唑替尼(45%),曲妥珠单抗-帕妥珠单抗(30%)和曲妥珠单抗-拉帕替尼(30%)。在这篇文献综述中,我们在此介绍关于CRC中HER2过表达的诊断方法的现有知识,主要临床,分子和预后特征,以及不同治疗组合对HER2过表达mCRC患者的疗效结果。这证明了,尽管在法国和欧洲缺乏针对CRC中HER2的药物的营销授权,对HER2状态的系统评估,特别是NCCN(国家综合癌症网络)的建议。
    Among the molecular subgroups of interest in metastatic colorectal cancer (mCRC), innovations are underway for tumors with overexpression of HER2 (Human Epidermal Growth Factor Receptor 2). Overexpression of the HER2 protein concerns 2 to 5% of CRC at any stage mainly located in the distal colon and rectum. Diagnosis is based on immunohistochemistry, in situ hybridization with appropriate criteria for colorectal localization, and molecular biology (NGS: next-generation sequencing). Overexpression of HER2 is a predictive factor for resistance to treatments targeting EGFR which are indicated in the case where the tumor is wild-type RAS. It seems to be associated with a poor prognosis of mCRC with a higher risk of brain metastasis. Regarding treatments targeting HER2, no randomized controlled phase III has been published to date. However, several combinations have been evaluated in phase II with clinically meaningful objective response rates: trastuzumab-deruxtecan (45%), trastuzumab-tucatinib (46%), trastuzumab-pyrotinib (45%), trastuzumab-pertuzumab (30%) ou trastuzumab-lapatinib (30%). In this literature review, we present here the current state of knowledge on the diagnostic methods of HER2 overexpression in CRC, the main clinical, molecular and prognostic characteristics, and the efficacy results of the different therapeutic combinations for the patients with HER2 overexpressed mCRC. This justifies, despite the lack of marketing authorization in France and in Europe for agents targeting HER2 in CRC, the systematic evaluation of the HER2 status, as recommended in particular by the NCCN (National Comprehensive Cancer Network).
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  • 文章类型: Letter
    暂无摘要。
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  • 文章类型: Journal Article
    ADAM10在Notch信号传导的上游起作用,并在各种癌症中发挥致癌作用。Tetraspanin家族蛋白调节ADAM10的运输和活性。这里,我们旨在研究tetraspanin-29是否以及如何在结直肠癌(CRC)中调节ADAM10.我们发现ADAM10表达在CRC组织中上调,这在TCGACOAD数据集中得到了交叉验证。与对照细胞系相比,CRC细胞系中的ADAM10蛋白水平及其α-分泌酶活性得到增强。免疫共沉淀显示,在LoVo细胞系中,ADAM10与tetraspanin-29相互作用。Tetraspanin-29敲低降低了ADAM10的细胞表面运输和α-分泌酶活性。此外,tetraspanin-29敲低在荧光素酶报告基因测定中抑制Notch活性,并降低切割的Notch1和Notch靶基因的水平,例如HES2,c-MYC,和细胞周期蛋白D3。始终如一,tetraspanin-29过表达增加了切割的Notch1,并且这种作用被ADAM10抑制剂阻断。TCGACOAD数据集证实了tetraspanin-29与HES2,c-MYC,和细胞周期蛋白D3。因此,tetraspanin-29/ADAM10/Notch通路在CRC中发挥重要作用。
    ADAM10 acts upstream of Notch signaling and plays oncogenic roles in various cancers. Tetraspanin family proteins regulate ADAM10 trafficking and activity. Here, we aimed to investigate whether and how tetraspanin-29 modulates ADAM10 in colorectal cancer (CRC). We found that ADAM10 expression was upregulated in CRC tissues and this was cross-validated in the TCGA COAD data set. The ADAM10 protein level and its α-secretase activity were enhanced in CRC cell lines compared with control cell lines. Co-immunoprecipitation showed ADAM10 interacted with tetraspanin-29 in the LoVo cell line. Tetraspanin-29 knockdown reduced the cell surface trafficking and α-secretase activity of ADAM10. In addition, tetraspanin-29 knockdown inhibited Notch activity in a luciferase reporter assay and reduced the levels of cleaved Notch1 and Notch target genes such as HES2, c-MYC, and cyclin D3. Consistently, tetraspanin-29 overexpression increased cleaved Notch1 and this effect was blocked by ADAM10 inhibitors. The TCGA COAD data set confirmed the positive correlations of tetraspanin-29 with HES2, c-MYC, and cyclin D3. Thus, the tetraspanin-29/ADAM10/Notch pathway plays an important role in CRC.
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  • DOI:
    文章类型: English Abstract
    OBJECTIVE: The aim of this study was to describe the diagnostic and therapeutic aspects of the managment of obstructive colorectal cancer and to evaluate the different surgical methods.
    METHODS: This retrospective, descriptive and analytical study was carry out from january 2008 to december 2014 in the visceral surgery department of Hospital Principal of Dakar and included 37 patients treated for obstructive colorectal cancer. The parameters studied were age, gender, unit of provenance, antecedents, clinical and paraclinical examination data, treatment and evolution. The data entered on Excel, was analyzed with SPSS software. Intergroup comparisons were made through Pearson or Fisher tests for qualitative values and Student or ANNOVA tests for quantitative values. The threshold of significance of the statistical tests was 5% in a bilateral situation.
    RESULTS: We collected 22 men and 15 women. CT scan showed the tumor in 23 cases. In 14 cases, the tumor was seen on laparotomy. The tumeur was in left colon in 28 cases, in right colon in 4 cases, in rectum in 5 cases. The right colon tumor underwent palliative surgery in 3 cases (1 ileostomy, 1 internal diversion, 1 caecostomy) and staged surgery in 1 case (caecostomy followed by secondary hemicolectomy). In left colon tumor were performed, 5 one stage left colectomies, 2 Hartmann procedures, 1 Bouilly Wolkmann, 3 internal diversions and 17 primary colostomies in which 12 had a secondary tumor resection. In rectum tumor was done 5 colostomies without secondary tumor resection. Twenty seven patients had their histology in wich 26 was adenocarcinoma. Nine patients underwent chemotherapy. The global early morbidity and mortality were respectively 35% and 13,5%. In left colon tumor, morbidity and mortality of the primary colostomy followed by secondary resection were respectively 17,6% and 11,7%. In case of emergent one stage tumor resection it was respectively 40% and 20%.Survival at one year was 43,2%.
    CONCLUSIONS: Our results confirm the poor outcome of colorectal cancer obstruction and suggest that 2 stage tumor resection is safer in left colon cancer.
    OBJECTIVE: Décrire les aspects diagnostiques, thérapeutiques des cancers colorectaux en occlusion et évaluer les différentes modalités thérapeutiques chirurgicales.
    UNASSIGNED: Il s\'agissait d\'une étude rétrospective, descriptive et analytique effectuée dans le service de chirurgie viscérale de l\'Hôpital Principal de Dakar, de janvier 2008 à décembre 2014, incluant 37 patients pris en charge pour cancer colique ou rectal en occlusion. Les paramètres étudiés étaient l\'âge, le genre, l\'unité de provenance, les antécédents, les données de l\'examen clinique et paraclinique, le traitement et l\'évolution. Les données saisies sur Excel, étaient analysées avec le logiciel SPSS. Des comparaisons intergroupes étaient effectuées grâce aux tests de Pearson ou de Fisher pour les valeurs qualitatives, de Student ou ANNOVA pour les valeurs quantitatives, avec un seuil de significativité de 5% en situation bilatérale.
    UNASSIGNED: Les dossiers cliniques de 22 hommes et 15 femmes étaient colligés. L\'âge moyen des patients était de 61,2 ans. Le diagnostic d\'occlusion tumorale était tomodensitométrique dans 23 cas et dans 14 cas per opératoire. Quatre tumeurs siégeaient au côlon droit, 28 au côlon gauche et 5 au rectum. Pour les tumeurs du rectum, étaient réalisées 5 colostomies de décharge en urgence sans résection tumorale secondaire. Pour les tumeurs coliques droites, un patient avait bénéficié d\'une caecostomie en urgence suivie d\'une hémicolectomie droite et 3 patients d\'une chirurgie palliative en urgence (dérivation interne, caecostomie, iléostomie dans 1 cas respectivement). Pour le siège colique gauche, une résection tumorale en urgence était réalisée dans 8 cas (5 colectomies gauches idéales, 2 Hartmann, 1 Bouilly Wolkman). Dix sept patients avaient bénéficié d\'une colostomie de décharge en urgence suivie d\'une résection tumorale secondaire chez 12 d\'entre eux. Trois patients avaient bénéficié d\'une dérivation interne. L\'histologie obtenue dans 27 cas, était en faveur d\'un adénocarcinome dans 26 cas. Neuf patients avaient bénéficié d\'une chimiothérapie. La morbidité et la mortalité globale était respectivement de 35% et 13,5%. Pour les localisations coliques gauches, cette morbi-mortalité en cas de stratégie en 2 temps était respectivement de 17,6% et 11,7%. En cas de colectomie idéale en urgence, elle était respectivement de 40% et 20%.La survie globale à 1 an était de 43,2%.
    CONCLUSIONS: Nos résultats confirment la gravité du cancer colorectal en occlusion et plaident pour la colostomie première suivie de la résection tumorale secondaire pour les tumeurs au côlon gauche.
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  • 文章类型: Journal Article
    大约四分之一接受结直肠癌手术的患者年龄超过75岁。因此,必须调整他们的护理,以尽量减少他的功能后果,这在老年患者中可能更重要。
    Approximately a quarter of patients undergoing colorectal cancer surgery are over 75 years of age. Their care must therefore be adapted to minimise his functional consequences, which can be more significant in an elderly patient.
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  • 文章类型: Journal Article
    在结肠癌的治疗中,在几种情况下讨论了化学疗法的药物治疗。在佐剂设置中,在淋巴结受累的情况下,应考虑使用5FU±奥沙利铂进行6个月的化疗。在转移性环境中,存在几种协议。治疗的选择应基于反应和生存增益方面的预期目标,也是患者的耐受性和生活质量。彻底的老年病学评估有助于更好地定义治疗方案。在整个治疗过程中继续进行老年随访表明,在生活质量和治疗耐受性方面对患者有益。
    Medical treatment with chemotherapy is discussed in several situations in the treatment of colon cancer. In the adjuvant setting, chemotherapy with 5FU±oxaliplatin for six months should be considered in the case of lymph node involvement. In the metastatic setting, several protocols exist. The choice of treatments should be based on the expected objectives in terms of response and survival gain, but also of tolerance and quality of life for the patient. A thorough oncogeriatric assessment helps to better define the therapeutic programme. The continuation of geriatric follow-up throughout the treatment process shows a benefit for the patient in terms of quality of life and tolerance of treatments.
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  • 文章类型: Journal Article
    目的:这项全国性调查的主要目的是确定黎巴嫩的结直肠癌筛查知识和接受水平。
    方法:共有1200名参与者参加了这项针对50岁及以上黎巴嫩人口的横断面家庭调查。使用两阶段分层整群抽样方法招募样本。
    结果:在总样本中,38.3%的人知道任何结直肠癌筛查测试,但只有7.5%的人曾经使用过任何筛查测试。39%的参与者认为他们患结肠直肠癌的风险很低或很低,只有53.5%对他们进行筛查测试的能力有信心。几乎所有参与者都同意医疗建议和测试报销将鼓励他们进行筛查测试。在多变量分析层面,在过去两年中,我们听到了一项宣传活动,结果显示,与结直肠癌筛查测试知识的相关性最强,估计ORadj=5.12(95CI:3.67~7.15).与此知识变量显着相关的其他因素包括:结直肠癌家族史,个人结直肠病史,有健康保险,了解结直肠癌的体征和症状。
    结论:这项全国性研究突出表明,尽管结直肠癌是黎巴嫩最普遍的癌症之一,并且其患病率在过去几年中一直在不断增加,但人们对结肠直肠癌筛查测试的了解不足和知识水平低下。证据表明,有结肠直肠癌诊断测试经验的人,无论是个人还是通过家庭成员,在过去的两年中,那些听说过关于结直肠癌的宣传运动的人更有可能知道它的筛查测试。
    结论:黎巴嫩的结直肠癌筛查知识和吸收是有限的,因此需要采取公共卫生干预措施。这项研究提供了证据,加上医疗提供者的参与和筛查测试费用的报销,将减轻黎巴嫩结肠直肠癌的负担。
    OBJECTIVE: The main aim of this national survey was to identify the levels of colorectal cancer screening knowledge and uptake in Lebanon.
    METHODS: A total of 1200 participants were enrolled in this cross-sectional household survey targeting the Lebanese population aged 50 years and above. The sample was recruited using a two-stage stratified cluster sampling approach.
    RESULTS: Of the total sample, 38.3% knew about any screening test for colorectal cancer but only 7.5% had ever used any. Thirty-nine percent of the participants rated their risk of getting colorectal cancer as very low or low, and only 53.5% were confident in their ability to undertake a screening test. Almost all participants agreed that medical advice and test reimbursement would encourage them to do a screening test. At the multivariate analysis level, hearing of an awareness campaign in the last two years showed the strongest association with the knowledge of a colorectal cancer screening test with an estimated ORadj = 5.12 (95%CI: 3.67 - 7.15). Other factors that were significantly associated with this knowledge variable included: a family history of colorectal cancer, a personal history of colorectal illness, having a health coverage, and knowledge of colorectal cancer signs and symptoms.
    CONCLUSIONS: This national study highlights an alarming lack of uptake and low levels of knowledge of colorectal cancer screening tests even though it is among the most prevalent cancers in Lebanon and its prevalence has been continuously increasing in the past years. The evidence suggests that people who had an experience with colorectal cancer diagnostic tests, either personally or through a family member, and those who have heard of an awareness campaign about colorectal cancer in the last two years are more likely to know its screening tests.
    CONCLUSIONS: Colorectal cancer screening knowledge and uptake in Lebanon are limited and justify the need for public health interventions. This study gives evidence that awareness campaigns, coupled with the involvement of medical providers and the reimbursement of screening test fees, would alleviate the burden of colorectal cancer in Lebanon.
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  • 文章类型: Case Reports
    Immunotherapies are part of the therapeutic strategy in many cancers and are indicated for metastatic colorectal adenocarcinoma with loss of expression of MisMatch Repair system proteins or with microsatelite instability (dMMR/MSI) in the United States. The rate of pathological response to immunotherapy remains poorly documented, but several cases of complete or major pathological response have recently been described. We decided to report the case of a complete pathological response to immunotherapy of a dMMR/MSI colorectal adenocarcinoma in a 74-year-old patient, initially inoperable due to duodenal invasion. Three months after the introduction of immunotherapy, the patient developed drug-induced colitis that contraindicated further treatment. Histological examination of the subtotal colectomy specimen revealed no residual tumour cells. The patterns of tumour regression were mainly represented by colloid regression, infarctoid-type necrosis and a resorptive inflammatory reaction. Although the operative indications for patients with metastatic dMMR/MSI colorectal cancer treated by immunotherapy are still very limited, the number of such specimens is expected to increase rapidly. The management of these specimens, as well as the possibility of a complete histological response, must be known by pathologists who play a key role in the pathophysiological knowledge of these lesions.
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