Cyclo-oxygenase 2 inhibition in colorectal cancer therapy

BACKGROUND: Cyclo-oxygenase inhibition for the treatment of colorectal neoplasia has been studied with renewed interest since the discovery of cyclo-oxygenase (Cox) 2 and the introduction of specific Cox-2 inhibitors. These drugs have implications for both the prevention of colorectal carcinoma and the potential treatment of the disease. METHODS AND RESULTS: A Medline database search was performed for articles using the keywords "colonic, colon or rectal and neoplasia or cancer" and "cyclo-oxygenase or Cox-2." Cross-references of relevant historical papers were also included. There is substantial evidence that Cox-2 plays a role in the development and progression of colorectal cancer. The specific inhibition of this enzyme has been shown to inhibit cancer growth in in vitro and in vivo models. The mechanisms of action for these effects are poorly understood and potential clinical applications at present remain under investigation. CONCLUSION: Cox-2 inhibitors have great promise as useful additions to current cancer treatments. There is a need for randomized clinical trials to define a role for these drugs in chemoprevention, recurrence prophylaxis, and adjuvant therapy for colorectal and other solid tumours.     

高通量转录组测序初步研究结肠直肠癌新辅助治疗敏感性

目的 采用高通量转录组测序技术,通过生物信息学手段,初步筛选并鉴定结肠直肠癌病人术前新辅助治疗效果相关基因,并进行差异表达分析,为进一步阐明结肠直肠癌新辅助治疗敏感性的分子机制提供基础。方法 22例接受标准术前新辅助治疗的结肠直肠癌病人,根据肿瘤消退评级分为敏感组9例,不敏感组13例。提取肿瘤组织RNA,构建转录组文库,采用高通量测序平台进行测序。结合生物信息学等相关手段,筛除错误发生率（<0.05）的基因后对比组装,对得到的转录组样本进行分类和注释。对差异表达基因特征进行分析。结果 初步建立结肠直肠癌新辅助治疗敏感性基因数据库。从22例转录组标本中,发现89个基因表达出现显著上调,112个基因出现显著下调。结论 高通量测序分析提示,这些基因表达变化可能与结肠直肠癌新辅助治疗敏感性密切相关。     

结直肠癌的新辅助治疗

结直肠癌（colorectal cancer。CRC）的新辅助治疗（neoadjuvant therapy）是提高CRC根治性切除率、减少局部复发和增加保肛机会的主要途径和方法。新辅助治疗包括新辅助化疗（neoadjuvant chemotherapy,NC）、新辅助放疗（neoadjuvant radiotherapy,NR）和新辅助放化疗（neoadjuvant chemoradiotherapy,NCR）。在CRC肝转移和中低位局部进展期直肠癌的治疗中。新辅助治疗尤为重要。现就CRC肝转移和中低位直肠癌新辅助治疗的进展情况简述管见。     

客观评价和正确开展结直肠癌的新辅助治疗

结直肠癌的新辅助治疗应遵循以下原则：（1）对于II期,III期的直肠癌病人应进行术前新辅助治疗。具体方案可采用放疗或放化疗联合。但不推荐单纯化疗。（2）对于不伴有远处转移的结肠癌病人不推荐术前新辅助治疗。仅对于可切除结肠癌肝转移病人可行新辅助化疗,以达缩小病灶,杀灭潜在转移灶之目的。     

结直肠癌基因治疗研究进展

【摘要】〓结直肠癌是常见的消化道恶性肿瘤,传统治疗以外科手术为主,辅以放、化疗,术后5年生存率仅为50%左右。近年来结直肠癌基因治疗备受人们青睐,且有许多研究成果成功运用于临床。目前对结直肠癌基因治的方法主要有原癌基因治疗、抑癌基因治疗、免疫基因治疗以及多基因联合治疗等。     

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消化道癌肿一旦冠之以“晚期” ,就意味着医生已无能为力 ,病人也只能束手待毙。然而 ,随着科学的发展 ,一些原本认为无法治疗的病例通过综合治疗不但得到了缓解 ,甚至奇迹般地出现了 5年生存 ,给病人提供了延长生命的希望。本文就当前通过综合治疗改变晚期结直肠癌病人预后的新动向作一简要的概述。结直肠癌采用综合治疗取得显著疗效的例子已不为少数。直肠癌术后的局部复发一般认为都是致命的 ,仅早期发现非常局限的吻合口复发或小的会阴部复发还能一期切除 ,但即使如此 ,也罕有长期生存者。多数这类病人为了减轻症状 ,给予姑息性放射治疗…     

Systemic therapy for colorectal cancer]

Drug treatment of colorectal cancer has made impressive progress during the past 10 years. In addition to the traditional 5-fluorouracil, newer anticancer drugs are available including irinotecan and oxaliplatin. Monoclonal antibodies like bevacizumab and cetuximab have been integrated into modern treatment regimens. Based on randomized clinical trials we can formulate rational treatment strategies as outlined in this article.     

Pain therapy in the recurrence of colorectal cancer

After exploiting all causal therapies there are other therapeutic methods only for soothing, viz. anodyne drug therapy using peripheral or central efficient analgesics, opiates and opioids as well. Procedures with destructing the pain-sensitive nerve path (chemical neurolysis using a method like conduction anaesthesia) and blockage of the sympathetic trunk and plexus coeliacus are preferred against intrathecal rhizolysis. Operative: Percutaneous cervical chordotomy. If insufficient analgesia results by these methods patients may get a peridural long acting catheter for applying local anaesthetics and/or opioide/opiate. Special importance is attached to the psychological care of all these patients.     

西妥昔单抗治疗晚期结肠直肠癌的研究进展

目前对晚期结肠直肠癌病人治疗的主要措施为化疗,化疗药物有3大类,即5-FU及其衍生物、第三代铂类(奥沙利铂,oxaliplatin)和拓扑异构酶Ⅰ抑制剂(伊立替康,irinote-can).     

Adjuvant therapy for patients with colorectal cancer

There are now excellent data that patients with stage III colon cancer or stage II and III rectal cancer live longer if they receive, respectively, systemic or regional and systemic therapy after surgery. In addition, disease-free survival, particularly freedom from the symptom of regional recurrence, in the high risk rectal cancer patient population has been markedly improved by application of multimodality treatment approaches. Newer prospective protocol testing variations in administration of systemic therapy, addition of 5-fluorouracil modulation techniques that proved effective in advanced disease settings, and the combination of therapy attempting to decrease single treatment toxicities while maintaining an antitumor effect have been built on the initial dramatic successes of the past 20 years. This paper concisely summarizes the data that should allow a marked decrease in mortality and morbidity if applied uniformly to patients who remain at high risk for recurrence after surgery for their colon or rectal adenocarcinomas.

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Resumen Se dispone de excelente información sobre pacientes con cáncer de colon en estado III o con cáncer rectal en estados II y III sobre una mejor supervivencia si reciben terapia sistémica o terapia regional y sistémica, respectivamente, luego de la cirugía. Además, la supervivencia libre de enfermedad, especialmente libre de los síntomas de recurrencia local en la población de pacientes de alto riesgo, ha mejorado considerablemente con aproches de terapia multimodal. Nuevos protocolos prospectivos para probar las variaciones en la administración de la terapia sistémica, la adición de técnicas de modulación con 5-FU que hayan demostrado efícacia en los estados avanzados de la enfermedad, y la combinación de terapias orientadas a disminuir la toxicidad propia de los tratamientos con agentes únicos al tiempo que se mantiene el efecto antitumoral, se implementan con base en el dramático éxito inicial de los últimos 20 años. El presente artículo resume la información que debe llevar a una marcada reducción de la mortalidad y la morbilidad, siempre y cuando sea aplicada en forma uniforme a los pacientes que siguen siendo del alto riesgo de recurrencia luego de cirugía para sus adenocarcinomas de colon o de recto.

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Résumé Il existe aujourd'hui d'excellents essais thérapeutiques qui démontrent que la survie des patients atteints de cancer colique stade III ou atteints de cancer rectal stades II et III du cancer rectal est améliorée dès lors qu'ils sont traités par, respectivement, une chimìothérapie systémique ou chimiothérapie systémique et radiothérapie régionale combinées. La survie sans maladie, et en particulier, la survie sans symptômes en rapport avec une récidive locale est nettement améliorée par une approche multidisciplinaire chez les patients à haut risque chirurgical. De nouveaux protocoles, les uns testant les différentes voies d'administration systémique et les modalités d'addition de 5-FU ayant déjà fait leurs épreuves dans la maladie évoluée et les autres testant les thérapeutiques combinées qui visent à dimineur la toxicité tout en gardant une efficacité antitumorale, ont vu le jour ces dernières vingt années. Cet article a pour but de résumer les données qui devraient amener à diminuer la mortalité et la morbidité chez le patient à haut risque de récidive, opéré de son cancer colique ou rectal et traité aìnsi.