Chemopreventive and therapeutic potential of curcumin in esophageal cancer: Current and future status

Esophageal cancer is a common malignant tumor with an increasing trend during the past three decades. Currently, esophagectomy, often in combination with neoadjuvant chemo- and radiotherapy, is the cornerstone of curative treatment for esophageal cancer. However, esophagostomy is related to significant risks of perioperative mortality and morbidity, as well as lengthy recovery. Moreover, the adjuvant therapies including chemotherapy and radiotherapy are associated with numerous side effects, limiting compliance and outcome. The dietary agent curcumin has been extensively studied over the past few decades and is known to have many biological activities especially in regard to the prevention and potential treatment of cancer. This review summarizes the chemo-preventive and chemotherapeutic potential of curcumin in esophageal cancer in both preclinical and clinical settings.     

Esophageal cancer management controversies: Radiation oncology point of view

Esophageal cancer treatment has evolved from single modality to trimodality therapy. There are some controversies of the role, target volumes and dose of radiotherapy (RT) in the literature over decades. The present review focuses primarily on RT as part of the treatment modalities, and highlight on the RT volume and its dose in the management of esophageal cancer. The randomized adjuvant chemoradiation (CRT) trial, intergroup trial (INT 0116) enrolled 559 patients with resected adenocarcinoma of the stomach or gastroesophageal junction. They were randomly assigned to surgery plus postoperative CRT or surgery alone. Analyses show robust treatment benefit of adjuvant CRT in most subsets for postoperative CRT. The Chemoradiotherapy for Oesophageal Cancer Followed by Surgery Study (CROSS) used a lower RT dose of 41.4 Gray in 23 fractions with newer chemotherapeutic agents carboplatin and paclitaxel to achieve an excellent result. Target volume of external beam radiation therapy and its coverage have been in debate for years among radiation oncologists. Pre-operative and post-operative target volumes are designed to optimize for disease control. Esophageal brachytherapy is effective in the palliation of dysphagia, but should not be given concomitantly with chemotherapy or external beam RT. The role of brachytherapy in multimodality management requires further investigation. On-going studies of multidisciplinary treatment in locally advanced cancer include: ZTOG1201 trial (a phase II trial of neoadjuvant and adjuvant CRT) and QUINTETT (a phase III trial of neoadjuvant vs adjuvant therapy with quality of life analysis). These trials hopefully will shed more light on the future management of esophageal cancer.     

Modern staging and utility of PET imaging in esophageal cancer management

Esophageal cancer is the eighth most common cancer worldwide, and one of the most fatal diseases despite modern medical treatment. Because correct staging and surveillance of neoadjuvant therapy for esophageal cancer is mandatory for further treatment planning, choosing a modern imaging system is important. The development of 18F-fluorodeoxyglucose positron emission tomography (18F-FDG-PET) has provided alternate means of tumor detection distinct from more conventional methods. This modality has extraordinary performance in detecting locoregional lymph node involvement and distant metastatic disease, and has been introduced as a powerful tool in many guidelines. However, some factors still lead to false-negative or -positive results, raising questions of its accuracy. This article discusses the clinical efficacy of PET in staging and surveillance of neoadjuvant therapy in esophageal cancer, comparing its accuracy with conventional imaging modalities.     

中国食管癌流行病学现状、诊疗现状及担任中华未来对策

食管癌发病率、死亡率高,危害严重,虽然诊疗方面已经取得一定进步,但存在的问题仍然较多.规范全国食管癌的诊治,尤其是食管癌的综合治疗和个体化治疗非常重要.本文就我国当前食管癌流行病学现状、诊疗现状、面临挑战与未来对策予以阐述.     

Curcumin analogs: Their roles in pancreatic cancer growth and metastasis

Curcumin is a polyphenolic constituent of turmeric that is known to have various molecular effects in preclinical models, leading to prevention and anticancer properties. In clinical trials, curcumin has failed to demonstrate activity against pancreatic cancer possibly due to its low bioavailability and potency. Using the curcumin molecular model, our group and others have synthesized several analogs with better bioavailability and higher potency in pancreatic cancer in vitro and xenograft models. This mini review summarizes some of the known molecular effects of curcumin analogs and their potential role as novel therapeutics for pancreatic cancer.     

晚期食管癌的姑息治疗

食管癌是常见的恶性肿瘤之一,手术治疗仍是首选的治疗手段,但多数病例属于进展期食管癌,只能采用姑息性治疗,以解决进食困难,维持营养,延长生存。近年来,随着食管支架的出现和发展以及新的再次造管治疗技术的应用,食管癌的姑息治疗方法越来越丰富,本文将对的各种方法进行综述。      

尼妥珠单抗在食管癌中的应用进展

食管癌是我国常见消化系统恶性肿瘤,对于不可手术切除的局部晚期食管癌,同期放化疗是较为公认的治疗方式,但疗效仍有待提高。尼妥珠单抗作为中国第一个治疗恶性肿瘤的人源化单克隆抗体,已应用于鼻咽癌、神经胶质瘤、胰腺癌等多种恶性肿瘤的治疗,且生存获益显著,不良反应轻微,因此越来越多的学者也关注到其在食管癌治疗中的价值。本文拟对尼...     

Targeting cancer stem cells by curcumin and clinical applications

Curcumin is a well-known dietary polyphenol derived from the rhizomes of turmeric, an Indian spice. The anticancer effect of curcumin has been demonstrated in many cell and animal studies, and recent research has shown that curcumin can target cancer stem cells (CSCs). CSCs are proposed to be responsible for initiating and maintaining cancer, and contribute to recurrence and drug resistance. A number of studies have suggested that curcumin has the potential to target CSCs through regulation of CSC self-renewal pathways (Wnt/β-catenin, Notch, sonic hedgehog) and specific microRNAs involved in acquisition of epithelial–mesenchymal transition (EMT). The potential impact of curcumin, alone or in combination with other anticancer agents, on CSCs was evaluated as well. Furthermore, the safety and tolerability of curcumin have been well-established by numerous clinical studies. Importantly, the low bioavailability of curcumin has been dramatically improved through the use of structural analogues or special formulations. More clinical trials are underway to investigate the efficacy of this promising agent in cancer chemoprevention and therapy. In this article, we review the effects of curcumin on CSC self-renewal pathways and specific microRNAs, as well as its safety and efficacy in recent human studies. In conclusion, curcumin could be a very promising adjunct to traditional cancer treatments.     

食管癌围手术期治疗的研究现状和进展

食管癌是我国常见的恶性肿瘤之一。西方国家以腺癌为主,亚洲地区则以鳞癌为主,我国食管癌中鳞癌患者约占95％。手术为食管癌的主要治疗方法,但单纯手术的效果并不尽如人意,5年生存率不足30％。为了提高手术效果,国内外很多研究探索了手术联合围手术期治疗的综合治疗模式。目前认为,在确保疗前准确分期的基础上,对于Ⅰ期及ⅡA期的患者可直接行手术治疗;对于ⅡB期及Ⅲ期的患者可行新辅助化疗或同步放化疗后进行手术。关于术后辅助治疗,目前尚缺乏有力的循证医学证据支持,但一些研究已初步证实术后辅助治疗的有效性。此外,围手术期分子靶向药物的应用及新辅助治疗疗效预测因子的研究也越来越成为研究的热点。     

老年食管癌的放射治疗研究进展

随着社会老龄化现象加剧，老年食管癌发病率逐年升高，已成为临床常见疾病。由于老年患者生理机能减退，往往有较多的合并症，因此对患者进行全面评估后需谨慎选择治疗方案和治疗强度，目前以放射治疗为主的综合治疗是重要手段。本文以老年食管癌治疗为中心，从手术、放射治疗、联合化疗以及其他治疗手段的进展等方面进行综述。      

食管癌围术期治疗的争议与共识

食管癌是全球排名第七的恶性肿瘤,在癌症相关的死亡原因中排名第六。手术治疗是可切除食管癌的主要治疗方式,但对于局部晚期食管癌患者,单纯手术治疗后,局部复发和远处转移缩短了患者的生存期,因此除极早期肿瘤外,所有患者推荐术前行新辅助放化疗或新辅助化疗。但是仍然有一部分患者未能在术前行新辅助治疗,这就需要术后辅助治疗来改善患者预后。本文系统回顾了食管癌围术期治疗的研究进展,包括新辅助治疗和辅助治疗,并结合指南对食管癌围术期的治疗方案进行了总结。     

Molecular targets of curcumin for cancer therapy: an updated review

In recent years, natural edible products have been found to be important therapeutic agents for the treatment of chronic human diseases including cancer, cardiovascular disease, and neurodegeneration. Curcumin is a well-known diarylheptanoid constituent of turmeric which possesses anticancer effects under both pre-clinical and clinical conditions. Moreover, it is well known that the anticancer effects of curcumin are primarily due to the activation of apoptotic pathways in the cancer cells as well as inhibition of tumor microenvironments like inflammation, angiogenesis, and tumor metastasis. In particular, extensive studies have demonstrated that curcumin targets numerous therapeutically important cancer signaling pathways such as p53, Ras, PI3K, AKT, Wnt-β catenin, mTOR and so on. Clinical studies also suggested that either curcumin alone or as combination with other drugs possess promising anticancer effect in cancer patients without causing any adverse effects. In this article, we critically review the available scientific evidence on the molecular targets of curcumin for the treatment of different types of cancer. In addition, we also discuss its chemistry, sources, bioavailability, and future research directions.     

Radiotherapy for Carcinoma of the Esophagus： Progress of Treatment and Research in China

ABSTRACT Carcinoma of the esophagus is a common malignancy in China. Radiotherapy is one of the most important modalities of treatment. This article provides a review of the natural history of this disease, the results of radiotherapy for esophageal cancer and the recent advances in radiation techniques in China. Significant progress has been made in this area of research and treatment. Combined treatment modalities and new therapies are being evaluated and may be expected to contribute to improved patient outcomes and better palliation of symptoms in the future.     

Esophageal cancer: A Review of epidemiology,pathogenesis, staging workup and treatment modalities

Esophageal cancer is a serious malignancy with regards to mortality and prognosis. It is a growing health concern that is expected to increase in incidence over the next 10 years. Squamous cell carcinoma is the most common histological type of esophageal cancer worldwide, with a higher incidence in developing nations. With the increased prevalence of gastroesophageal reflux disease and obesity in developed nations, the incidence of esophageal adenocarcinoma has dramatically increased in the past 40 years. Esophageal cancer is staged according to the widely accepted TNM system. Staging plays an integral part in guiding stage specific treatment protocols and has a great impact on overall survival. Common imaging modalities used in staging include computed tomography, endoscopic ultrasound and positron emission tomography scans. Current treatment options include multimodality therapy mainstays of current treatment include surgery, radiation and chemotherapy. Tumor markers of esophageal cancer are an advancing area of research that could potentially lead to earlier diagnosis as well as playing a part in assessing tumor response to therapy.     

Radiation therapy in the management of rectal cancer.

Substantial advances have been made in the adjuvant management of patients with resectable rectal cancer. Increasing interest in patient quality of life has promoted the use of radiation therapy to enhance sphincter-preserving surgical approaches as an alternative to the standard abdominoperineal resection. Because of the suggestion of enhanced sphincter preservation with preoperative therapy and the potential advantage of decreased acute morbidity, randomized trials comparing preoperative and postoperative adjuvant combined modality therapy are ongoing. Recent progress in adjuvant postoperative treatment regimens relates to the integration of systemic therapy to radiation, and redefining the techniques for both modalities. The incorporation of improved radiation planning may reduce treatment-related bowel toxicity. The integration of novel chemotherapeutic agents in the adjuvant therapy of rectal cancer remains an active area of investigation.     

Multiple and metachronous esophageal intramural metastases from a gastric adenocarcinoma

Esophageal squamous cell carcinoma is often accompanied by intramural metastases, and it has been reported to carry a poor prognosis. Intramural metastasis from gastric cancer to the esophageal wall, however, has rarely been reported. We herein report a rare case of a 46-year-old man with an elevated esophageal lesion, resembling a 0-IIa-type esophageal cancer, which was discovered 13 months after a total gastrectomy performed for gastric cancer. The esophageal tumor, resected by endoscopic mucosal resection (EMR), was an adenocarcinoma with the same histology as the previously resected primary gastric cancer, and it showed massive lymphatic permeation. Soon after the EMR, other similar lesions emerged on the esophageal wall. We therefore considered the esophageal tumor to be a systemic expansion of the primary gastric cancer, and we administered the anticancer drug, S-1. Esophageal intramural metastases from a gastric cancer imply a systemic expansion of the gastric cancer, and portend a poor prognosis.     

Adjuvant Treatment of Colorectal Cancer: Towards Tumor-specific Immunotherapies

Colorectal cancer is one of the leading causes of cancer-related mortality. After a series of clinical trials, the adjuvant 5-FU based chemotherapy has established a definitive role in the management of stage III colon cancer. The precise role for chemotherapy in stage II disease remains under investigation and less toxic treatment modalities like active specific immunotherapy have emerged as potentially attractive alternatives. It is most likely that the adjuvant treatment of colon cancer will move towards more tumor-specific immunotherapies using antibody- or vaccination-based strategies. Phase II/III clinical trials investigating these different modalities in colorectal cancer are reviewed.     

Progress of postoperative adjuvant therapies for esophageal cancer

Among the gastrointestinal cancers, esophageal cancer is supposed to be relatively sensitive to both radiotherapy and chemotherapy. The efficacy of combined chemo-radiotherapy in unresectable patients has been confirmed by several investigators. However, no prospective randomized controlled trials with surgery alone as a control had demonstrated significant survival benefit by postoperative adjuvant radiotherapy or chemotherapy in resectable patients. Only a slight prolongation of disease-free survival has been demonstrated with postoperative CDDP + 5-FU therapy. Thus, at present time, postoperative adjuvant therapy is not considered to be a standard therapy for resectable esophageal cancer. Clinical trials with more active combination chemotherapy including new anticancer drugs and new therapeutic strategies such as specific cancer immunotherapy and molecular targeting agents are hoped for in the future.     

Dose-escalation and pharmacokinetic study of nanoparticle curcumin,a potential anticancer agent with improved bioavailability,in healthy human volunteers

Background  

More and more preclinical studies support the idea that curcumin, a plant-derived natural polyphenol, could be a promising anticancer drug. However, poor bioavailability has limited its efficacy in clinical trials, and plasma curcumin levels remain low despite patients taking gram doses of curcumin.