肝纤维化内科治疗的研究

肝纤维化是各种慢性肝病向肝硬化发展的中间病理过程.此过程是一动态过程,是可逆性的.目前许多学者研究发现给予药物治疗、基因治疗、干细胞移植等方法 能有效预防肝纤维化的发生、延缓肝纤维化的进展或使肝纤维化逆转.     

中医药对防治高血压左室肥厚的研究进展

高血压是常见的心血管疾病,有25％～30％高血压患者合并左室肥厚（left ventricular hypertrophy,LVH）。LVH是增加心衰、心肌梗死、心律失常及猝死等心血管并发症及死亡率的一种独立的危险因素。所以使用各种药物逆转和预防LVH的发生,是高血压治疗目标之一。重新认识和积极防治逆转LVH已成为近年来中西医领域研究的焦点。近年来,中医药防治高血压LVH已取得了一定成效。     

重视消化系统肿瘤的化学预防

肿瘤化学预防由Sporn于1976年首先提出。目前公认的肿瘤化学预防概念是指应用天然或人工合成的化合物来阻断、逆转或预防侵袭性肿瘤的发生。研究消化系统肿瘤的化学预防，并通过预防来降低其发病率和死亡率，也是消化病学研究者及临床工作者所面临的任务之一。肿瘤的化学预防可分为三级：Ⅰ级预防是指对具有高危因素(如有不良饮食习惯、吸烟、酗酒或家族中有癌症患者)的健康人进行预防；Ⅱ级预防是指对癌前病变患者(如结肠腺瘤、萎缩性胃炎等)的预防；Ⅲ级预防则是指预防肿瘤复发或转移。     

lncRNA在钙化性主动脉瓣疾病中的作用研究新进展

钙化性主动脉瓣疾病是老年人群中最常见的一种心脏瓣膜疾病,目前尚无有效药物逆转或预防其发病过程。钙化性主动脉瓣疾病致病过程高度类似于骨代谢和骨发育,但其具体致病机制尚不完全清楚。lncRNA是一种长度大于200个核苷酸的非编码RNA,具有重要的生物学功能。诸多研究表明lncRNA在钙化性主动脉瓣疾病中有表达差异,并通过不同机制参与钙化性主动脉疾病的发生。本文将综述近年来lncRNA与钙化性主动脉瓣疾病的重要进展,为进一步理解钙化性主动脉瓣疾病发生发展的分子机制提供依据。     

食疗:辅助逆转肝纤维化的重要策略

<正>肝纤维化在新版的疾病国际统计分类中的编码为ICD-10 k 74.0,已成为一种独立疾病。目前,临床上较为理想的肝纤维化治疗药物不多。虽然肝纤维化发生的机制极为复杂,但氧化应激与炎症反应占有重要地位,而抑制氧化应激及炎症反应可在一定程度上实现肝纤维化的逆转[1~3]。一些食物具有较确切地对抗氧化应激或抑制炎症反应的特性,可辅助逆转肝纤维化,有望成为经典药物治疗学的延伸及有效补充。现谈谈可辅助逆转肝纤维化的几种食物。     

消化道肿瘤的化学预防

肿瘤的化学预防是指在目标群体中应用特异性药物或营养剂进行干预治疗，从而防止、推迟、减慢肿瘤的发生和发展。本文将对消化道肿瘤的化学预防作一综述。现阶段主要的消化道肿瘤预防药物有四类，分述如下。     

药物逆转左心室肥厚研究进展

高血压引起的左心室肥厚(LVH)已被公认为是心血管并发症的独立危险因素[1],引起高血压LVH的主要原因是血流动力学和神经内分泌激活两方面。高血压LVH时心脏的组织结构发生的改变,包括心肌细胞肥大和心肌间质纤维化。下面就药物逆转左心室肥厚研究进展简单综述如下。1血管紧张素转换酶抑制剂现已证实多种血管紧张素转换酶抑制剂如苯那普利、依那普利、赖诺普利,均能有效逆转高血压LVH。一项多研究分析表明,血管紧张素转换酶抑制剂是逆转高血压LVH的最有效药物[2]。以往认为血管紧张素转换酶抑制剂主要通过抑制AngⅡ形成来防止LVH,但…     

室性期前收缩性心肌病研究进展

室性期前收缩是临床上常见的心律失常之一,而近年来长期频发室性期前收缩引起的心肌病也得到大量研究的证实,即室性期前收缩性心肌病。此类心肌病的发病机制目前尚不明确,其预测因子仍是目前的研究热点。随着诊疗技术的不断发展,有效的药物或射频导管消融治疗能在一定程度上减少或抑制室性期前收缩,并改善心功能,甚至可逆转心室重构。     

肺气肿预防研究的新进展

近年来对预防肺气肿的研究取得了一些进展。基于弹性蛋白酶及其抑制因子失平衡理论,可通过测定弹性蛋白分解产物达到早期监测肺气肿的发生,可使用弹性蛋白酶抑制剂、升高体内α_1 AT的药物或补充α_1 AT 以预防肺气肿。本文综述这项研究的一些新进展及目前在临床上的应用情况。     

茶多酚抗白血病作用分子机制研究进展

茶多酚是自绿茶提取的一种有效的抗癌产物,已有研究表明对白血病细胞具有明显的增殖抑制作用和逆转耐药作用.其抑制白血病增殖作用与诱导细胞凋亡有关,可能的抗白血病的作用机理是调节凋亡相关基因的表达、抑制造血生长因子及其受体、抑制端粒酶活性和肿瘤血管生成等,有望成为一种廉价高效的治疗肿瘤的化疗药物或辅助治疗药物.     

Lung cancer chemoprevention

Lung cancer is the leading cause of cancer death in the United States, and the majority of diagnoses are made in former smokers. Although avoidance of tobacco abuse and smoking cessation clearly will have the greatest impact on lung cancer development, effective chemoprevention could prove to be more effective than treatment of established, advanced-stage disease. Chemoprevention is the use of dietary or pharmaceutical agents to reverse or block the carcinogenic process and has been successfully applied to common malignancies other than lung (including recent reports on the prevention of breast cancer in high-risk individuals). Despite previous studies in lung cancer chemoprevention failing to identify effective agents, our ability to define the highest-risk populations and the understanding of lung tumor and premalignant biology continue to make advances. Squamous cell carcinogenesis in the bronchial epithelium starts with normal epithelium and progresses through hyperplasia, metaplasia, dysplasia, and carcinoma in situ to invasive cancer. Precursor lesions also have been identified for adenocarcinoma, and these premalignant lesions are targeted by chemopreventive agents in current and future trials. Chemopreventive agents can currently only be recommended as part of well-designed clinical trials, and multiple trials have recently been completed or are enrolling subjects.     

Prevention of lung cancer

Lung cancer is the major cause of death in industrialized western societies. Its link to tobacco abuse is well established and efforts should be made to eliminate this potent environmental carcinogen. The concept of chemoprevention, the use of agents to inhibit and reverse lung cancer carcinogenesis, has great appeal. The CARET study, conducted in 18,000 high-risk smokers in the US, found that a combination of beta-carotene and retinyl palmitate resulted in a 28% increase in the incidence of lung cancer. A similar study conducted in Finland, the ATBC trial utilizing alpha tocopherol and beta-carotene, had similar findings for the group taking beta-carotene. These two trials have caused a rethinking of the use of natural compounds as chemoprevention agents. These agents should no longer be regarded as harmless, but as having potential toxicities. A new approach in the chemoprevention of cancer has been the concept of surrogate endpoints, biological changes that are on the pathway to cancer. Trials are underway to determine what are appropriate surrogate endpoints for lung cancer chemoprevention trials.     

Chemoprevention of lung cancer

PURPOSE OF REVIEW: Lung cancer is one of the major causes of cancer-related deaths. Grim mortality figures argue powerfully for new approaches to control this disease. Chemoprevention is the use of specific natural or synthetic chemical agents to reverse, suppress, or prevent carcinogenic progression to invasive cancer. The current article focuses on the field of lung cancer chemoprevention and recent advances. Lung cancer biology and general principles of prevention strategies are also described. RECENT FINDINGS: Trials in lung cancer chemoprevention have so far produced either neutral or harmful primary end point results whether in the primary, secondary and tertiary settings. The data suggest that lung cancer was not prevented by beta-carotene, alpha-tocopherol, retinal, retinyl palmitate, N-acetylcysteine, or isotretinoin in smokers. The results from the recently completed Canadian study of anethole dithiolethione in smokers with bronchial dysplasia as well secondary analyses of the phase III trials involving selenium and data from the US Intergroup NCI-91-0001 supporting treatment with isotretinoin in never and former smokers are hopeful and may help define new avenues of chemopreventive treatment after scientists and clinicians analyze the information generated. SUMMARY: The concept of chemoprevention in lung cancer is still in its infancy but one day may have a significant impact on the incidence and mortality of this leading cancer threat. An improved understanding of carcinogenesis and cancer prevention mechanisms will no doubt aid in the design of future clinical trials and in the validation of candidate agents as well as the development of new targets. Planned or ongoing trials currently are targeting important molecular markers of lung carcinogenesis and progression including cyclooxygenase-2, the ras-signaling pathway through farnesyl transferase inhibitors and the tyrosine kinase/epidermal growth factor receptor pathway. Until such studies are completed however, no drug or drug combination should be used for lung cancer prevention outside of a clinical study.     

Prospects for chemoprevention of cancer

The recent progress in molecular biology and pharmacology has increased the likelihood that cancer prevention will rely increasingly on interventions collectively termed 'chemoprevention'. Cancer chemoprevention is the use of agents to inhibit, delay or reverse carcinogenesis. A number of potential targets for chemoprevention have recently been identified. Many classes of agents including antioestrogens, anti-inflammatories, antioxidants and other diet-derived agents have shown a great deal of promise. In this review, we will begin by describing the general classes of chemopreventive agents and the mechanisms by which these agents act. We will then describe the opportunities that presently exist for chemoprevention of specific cancers.     

Chemoprevention of colorectal cancer

Colorectal cancer is the third most incident cancer in the United States and is second only to lung cancer as a cause of cancer-related mortality. Colorectal cancer develops through a multistep process characterized by histopathological precursor lesions and molecular genetic alterations. This sequential process of tumorigenesis provides opportunities for the development and testing of both primary and secondary prevention strategies. This review focuses on chemoprevention, which is defined as the use of natural or synthetic agents to reverse the process of carcinogenesis. Epidemiological studies have consistently shown that chronic intake of nonsteroidal anti-inflammatory drugs (NSAIDs), principally aspirin, can reduce the incidence of colorectal adenomas and carcinomas. Evaluation of NSAIDs, including newer selective cyclo-oxygenase-2 inhibitors, in carcinogen-induced and genetically manipulated animal models of colorectal cancer demonstrates that these drugs are effective chemopreventive agents. In humans, the NSAID sulindac has been studied in familial adenomatous polyposis patients and was found to regress colorectal adenomas in a placebo-controlled trial. More recently, the selective cyclo-oxygenase-2 inhibitor Celebrex was also shown to be effective in familial adenomatous polyposis and was approved by the Food and Drug Administration as a adjuct to usual care in these patients. NSAIDs, as well as other chemopreventive agents, are currently being studied in patients at increased risk of colorectal cancer, including those with sporadic adenomas. The outcome of these studies has the potential to impact patient management practices. However, chemopreventive agents cannot be recommeded at present for average-risk individuals or for those with sporadic colorectal neoplasia. In addition to demonstrating efficacy, chemopreventive agents must be safe and well tolerated for chronic administration and should be relatively cost-effective. Although still in its infancy, the field of chemoprevention is an exciting and rapidly advancing area of investigation. Chemopreventive strategies, if effective, offer the promise of producing a paradigm shift in our current approach to colorectal cancer.     

Chemoprevention of Colorectal Cancer

Colorectal cancer is a major public health concern in all developed countries. Despite decades of advances in the treatment and prevention of colorectal cancer, it remains the second most common cause of cancer death. However, the optimal method for early detection remains unknown and patient compliance with screening recommendations remains poor. This has led to the development of complementary strategies, such as chemoprevention to reduce morbidity and mortality from colorectal cancer. Chemoprevention is defined as the use of specific pharmacologic or nutrient agents to prevent, reverse, or inhibit the process of carcinogenesis. This review was designed to discuss the most promising agents in colorectal chemoprevention. Supported by grants from the NIH K07 CA092445, The Cancer Research Prevention Foundation, and The Eleanor Naylor Dana Charitable Trust. Presented at the Colorectal Disease Symposium, Ft. Lauderdale, Florida, February 12 to 14, 2005.     

Inflammation in lung carcinogenesis: new targets for lung cancer chemoprevention and treatment

Lung carcinogenesis is a complex process involving the acquisition of genetic mutations that confer cancer development and the malignant phenotype, and is critically linked to apoptosis resistance, unregulated proliferation, invasion, metastasis, and angiogenesis. Epithelial mesenchymal transition (EMT) in cancer is an unregulated process in a host environment with deregulated inflammatory response that impairs cell-mediated immunity and permits cancer progression. Given the immunosuppressive tumor environment, strategies to reverse these events by stimulating host immune responses are an important area of investigation. Cyclooxygenase 2 (COX-2) and its downstream signaling pathways are potential targets for lung cancer chemoprevention and therapy. Clinical trials are underway to evaluate COX-2 inhibitors as adjuvants to chemotherapy in patients with lung cancer and to determine efficacy in prevention of bronchogenic carcinoma. The understanding of molecular mechanisms involved in inflammation and lung carcinogenesis provide insight for new drug development that target reversible, non-mutational events in the chemoprevention and treatment of lung cancer.     

Lung cancer: genetics of risk and advances in chemoprevention

PURPOSE OF REVIEW: The current article reviews recent advances in genetic susceptibility and chemoprevention of lung cancer. RECENT FINDINGS: Linkage analysis has identified a locus on chromosome 6q23-25 that determines susceptibility to lung cancer in families with multiple members with cancer of the lung, throat, and larynx. Obligate gene carriers are sensitive to even small tobacco smoke exposure in terms of increased lung cancer risk. Variation in other genes, particularly those regulating the activation or inactivation of carcinogens, has been implicated in determining lung cancer risk. Epidemiologic and preclinical studies suggest that chemoprevention of lung cancer is an achievable goal. Early trials with beta-carotene supplementation, however, have revealed a harmful effect. Promising new agents must be evaluated in both preclinical models and in intermediate end point biomarker trials before being taken to large primary prevention trials, and lung cancer chemoprevention should only be attempted within controlled clinical trials. SUMMARY: We are poised to learn a great deal about the genetic susceptibility to lung cancer, which will not only allow definition of groups with extremely high risk, but may also yield new insights into processes that determine innate susceptibility or resistance to lung carcinogenesis. Chemoprevention of lung cancer is not yet ready for clinical application. As a result of the large number of lung cancer deaths and the large number of at-risk individuals, even modestly effective chemoprevention could save many lives.     

Role of biomarkers for early detection of lung cancer and chemoprevention.

Lung cancer is the leading cause of cancer deaths in developed countries. The poor prognosis associated with this disease is closely related to the fact that most lung cancer patients are not identified until their malignancy has reached an advanced stage. Recent advances have added to the understanding of the morphological and molecular characteristics of preinvasive bronchial lesions and early lung cancers. Such information is being used to provide new tests for the detection of lung cancer at early or preinvasive stages, and for identifying targets for therapeutic intervention that can prevent progression to advanced disease. Laser induced fluorescence endoscope bronchoscopy has improved the sensitivity with which preinvasive dysplastic bronchial lesions and early invasive malignancies can be detected. Morphological features of such lesions have been described and can be monitored by follow-up bronchoscopies in order to validate potential chemoprevention treatments. Distinct morphological characteristics such as angiogenic squamous dysplasia also suggest that processes like angiogenesis are present early in the development of lung cancer. Furthermore, tissue obtained from these early lesions has been used to describe alterations in the expression of a number of factors that distinguish these early lesions from normal bronchial epithelium. This could provide molecular markers and targets for the detection and treatment of early lung cancer. Studies to detect these alterations by polymerase chain reaction and/or immunhistochemical analyses of easily obtained specimens such as sputa are helping identifing molecular markers that could be utilized in effective screening programmes. The current article reviews new findings regarding the molecular biology of preinvasive bronchial lesions and early lung cancers, and describes new developments regarding their application in the early detection and chemoprevention of lung cancer.     

Chemoprevention of colorectal cancer: an update

Colorectal cancer (CRC) is the leading cause of cancer-related mortality in western countries. Adjuvant treatment does not seem to be highly effective and recurrent or metastatic disease occurs in half of the new cases within one year of diagnosis and median survival does not exceed 18 months. CRC represents an optimal model for primary and secondary prevention, given the availability of effective screening procedures and of a well defined multi-step carcinogenic pathway. Colon cancer is supposed to arise as the result of a series of genetic mutations, which parallel histopathologic and molecular changes, from normal colonic epithelium to invasive carcinoma, with adenomatous polyps as an intermediate step. A growing body of evidence has shown a wide variety of effective compounds, in vitro in animal models and in human clinical trials. The more studied agents are the non-steroidal anti-inflammatory drugs. Among those, aspirin has been shown, in two recent randomised trials, to lower the incidence on polyps vs. placebo. Intervention studies on diet showed disappointing results, but diet micronutrients are promising agents in CRC prevention. Calcium, vitamin D and folic acid in different proportions in different populations have been shown to have a certain degree of action in preventing cancer development in epidemiological studies and in randomised trials. Also oestrogens or, rather, hormone replacement therapy for the menopause can protect against CRC. In conclusion, the rapid growth of information and knowledge in chemoprevention, especially for CRC, is very encouraging and gives us hope that soon this approach will be applicable in a larger scale population.