晚期结直肠癌分子靶向治疗

晚期结直肠癌靶向治疗药物主要包括血管内皮生长因子抑制剂和表皮生长因子受体抑制剂.研究表明贝伐珠单抗和西妥昔单抗改善了晚期结直肠癌的预后,但在联合化疗药物方案的选择上稍有差异.西妥昔单抗和贝伐珠单抗改善K-ras野生型晚期结直肠癌患者总生存期相似.新的靶向药物阿柏西普、瑞格非尼等的出现,为晚期结直肠癌的靶向治疗提供了更多的选择.     

斑蝥酸钠维生素B6注射液联合FOLFOX4方案治疗晚期大肠癌疗效观察

新型药物和治疗方案的出现使晚期大肠癌的治疗效果得到一定提高,如贝伐珠单抗、西妥昔单抗等分子靶向药物与化疗药物的联合应用,但不可耐受的不良反应限制了其临床应用.目前,综合治疗已成为大肠癌治疗的指导原则.近年来,应用斑蝥酸钠维生素B6注射液联合化疗治疗晚期大肠癌取得了较好的疗效.     

抗EGFR靶向治疗胃癌

EGFR家族在胃癌形成中具有重要的作用.针对EGFR的分子靶向药物主要包括胞外单克隆抗体和胞内酪氨酸激酶抑制剂,许多新药如曲妥珠单抗、西妥昔单抗、帕尼单抗、拉帕替尼,已进入胃癌治疗的Ⅲ期临床研究阶段,而ToGA研究结果更给晚期胃癌患者带来希望.     

HER⁃2阳性乳腺癌免疫治疗药物的研究进展

曲妥珠单抗及帕妥珠单抗等药物的应用使HER?2阳性乳腺癌患者的生存得到了显著的提高,但靶向药耐药事件仍时有发生.免疫治疗作为一种新的治疗手段,对HER?2阳性乳腺癌患者具有重大临床意义.作为被动免疫治疗的一种有效手段,单克隆抗体曲妥珠单抗、帕妥珠单抗及T?DM1等药物的临床应用使HER?2阳性乳腺癌患者的生存有了明显改...     

膀胱癌的靶向药物治疗

全身化疗是能够改善膀胱癌生存的主要治疗方法,然而疗效有限,因此靶向药物治疗在膀胱癌中的应用逐渐引人关注.目前针对膀胱癌的靶向药物包括贝伐珠单抗、西妥昔单抗、舒尼替尼、吉非替尼、依维莫司和程序性死亡受体1及其配体抑制剂,其为晚期膀胱癌的治疗提供了新的方向.     

单克隆抗体3A5用于肿瘤区域性导向治疗及其临床前质控研究

单抗导向药物用于肿瘤治疗面临的一个重要问题是静脉给药时肿瘤组织单抗摄取量甚低,偶联物实际到达肿瘤细胞尤其是实体瘤深部细胞的数量有限,局部注射是可行的解决办法.平阳霉素(PYM)是研制局部注射用单抗偶联物较为理想的“弹头”药物,3A5是抗肝癌大鼠单克隆抗体,对人肝癌和人结肠癌具有强免疫反应性.本研究将单抗3A5与PYM偶联,探讨了3A5-PYM用于局部或腔内肿瘤治疗的可行性.并对单抗3A5及3A5-PYM偶联物进行了质量检测.     

贝伐珠单抗在结直肠癌治疗中的应用

近年来,随着对肿瘤生物学认识的深入,以贝伐珠单抗、西妥昔单抗为代表的分子靶向治疗药物正逐渐丰富着晚期结直肠癌的治疗选择.贝伐珠单抗是一种人源化、人鼠嵌合抗血管内皮生长因子的单克隆抗体,是第一个被美国FDA批准用于治疗晚期结直肠癌患者的抗血管生成药物,以贝伐珠单抗为基础进行的临床研究也证实了它能改善晚期结直肠癌患者的生存期.全文通过回顾近年来发布的结直肠癌治疗领域有关贝伐珠单抗的临床研究,对其在晚期结直肠癌一线、二线和维持治疗以及在结直肠癌术后辅助治疗领域中的应用做一系统综述.     

乳腺癌的靶向治疗

乳腺癌靶向治疗基于分子分型为乳腺癌患者提供了一个有效和个性化治疗的选择.目前用于乳腺癌靶向治疗的药物包主要括以人表皮生长因子受体2(HER2)为靶点的药物曲妥珠单抗、帕妥珠单抗、拉帕替尼、T-DM1和以血管内皮生长因子(VEGF)为靶点的贝伐珠单抗以及以雷帕霉素靶蛋白(mTOR)为靶点的依维莫司,多项研究表明靶向治疗联合化疗能显著提高患者的无进展生存期及总生存时间.     

2008年转移性结直肠癌个体化治疗进展回顾

含草酸铂或伊立替康的化疗方案作为晚期结直肠癌的标准治疗方案,使得患者总生存期超过20个月,靶向治疗药物西妥昔单抗和贝伐单抗的加入进一步提高了疗效.2008年结直肠癌治疗的重要进展是确定KRAS基因状态与抗EGFR抗体疗效的相关性.CRYSTAL、OPUS和CELIM等随机研究显示,通过K-ras检测可筛选出能从分子靶向治疗药物中获益的人群,西妥昔单抗无论是联合以奥沙利铂为基础、还是联合以伊立替康为基础的一线化疗方案,都能使KRAS野生型患者疗效显著提高,显示出西妥昔单抗在mCRC一线治疗中的优势.     

转移性结直肠癌分子靶向治疗临床研究进展

 转移性结直肠癌应用最多的靶向药物包括贝伐珠单抗和西妥昔单抗。贝伐珠单抗和西妥昔单抗均是单克隆抗体,作用靶点分别为血管内皮生长因子（VEGF）和表皮生长因子受体（EGFR）。在转移性结直肠癌,无论是一线还是二线治疗,靶向药物联合化疗均可增加疗效,延长患者的生存。靶向药物联合化疗增加肝转移灶的切除率。k-ras基因突变是西妥昔单抗的疗效预测因子。对于贝伐珠单抗目前尚无明确的疗效预测因子。     

Anti-sense oligodeoxynucleotides--promises and pitfalls.

The high specificity of binding of oligodeoxynucleotides to their target mRNA has resulted in suggestions that these compounds may be useful as therapeutic agents against human cancer. While many successful anti-sense experiments have been reported in the literature, significant obstacles to widespread therapeutic use remain. These include nuclease sensitivity, non-sequence specificity, and uncertainties regarding optimum choice of mRNA target. Other significant problems include lack of information concerning cellular pharmacology and pharmacokinetics, and relatively little data concerning optimum dosing schedules. This review attempts to provide current information about these issues, which have such a strong impact on this exciting and rapidly growing field.     

Imaging of ovarian teratomas: Appearances and complications

Ovarian teratomas are the most common germ cell neoplasm. Subtypes of teratoma include mature cystic, immature and the monodermal teratomas. The benign cystic teratoma shows typical imaging manifestations and can be complicated by torsion, rupture and uncommonly malignant degeneration. Uncommon subtypes of teratomas include the immature, which is usually malignant at diagnosis. The growing teratoma syndrome is an uncommon complication reported in patients treated for immature teratomas. The monodermal teratomas which include the struma ovarii may also have specific imaging characteristics that should be recognised on imaging. This paper aims to provide a comprehensive review describing the spectrum of imaging findings of these ovarian tumours and associated complications     

Fruit and vegetables and cancer risk

The possibility that fruit and vegetables may help to reduce the risk of cancer has been studied for over 30 years, but no protective effects have been firmly established. For cancers of the upper gastrointestinal tract, epidemiological studies have generally observed that people with a relatively high intake of fruit and vegetables have a moderately reduced risk, but these observations must be interpreted cautiously because of potential confounding by smoking and alcohol. For lung cancer, recent large prospective analyses with detailed adjustment for smoking have not shown a convincing association between fruit and vegetable intake and reduced risk. For other common cancers, including colorectal, breast and prostate cancer, epidemiological studies suggest little or no association between total fruit and vegetable consumption and risk. It is still possible that there are benefits to be identified: there could be benefits in populations with low average intakes of fruit and vegetables, such that those eating moderate amounts have a lower cancer risk than those eating very low amounts, and there could also be effects of particular nutrients in certain fruits and vegetables, as fruit and vegetables have very varied composition. Nutritional principles indicate that healthy diets should include at least moderate amounts of fruit and vegetables, but the available data suggest that general increases in fruit and vegetable intake would not have much effect on cancer rates, at least in well-nourished populations. Current advice in relation to diet and cancer should include the recommendation to consume adequate amounts of fruit and vegetables, but should put most emphasis on the well-established adverse effects of obesity and high alcohol intakes.     

Conventional and new treatment options for myelofibrosis with myeloid metaplasia

The pathogenetic mechanisms underlying the clonal myeloproliferation and reactive marrow fibrosis that characterize myelofibrosis with myeloid metaplasia (MMM) are poorly understood. Recent advances into the pathophysiology of the disease have not yet translated into effective therapeutic options for patients. There is no standard treatment, and no therapies identified yet, besides allogeneic stem cell transplantation, that will significantly change the natural history of MMM. Treatment is therefore palliative and is geared towards alleviating symptoms of the disease and improving blood counts. Conventional therapies for anemia include androgens and corticosteroids. Cytoreductive agents such as hydroxyurea are indicated for symptomatic organomegaly and the control of leucocytosis or thrombocytosis. Several novel agents have been investigated in the recent past, and include antiangiogenic agents and signal transduction inhibitors that target the angiogenic and fibrogenic cytokines that have been implicated in the pathogenesis of the detrimental bone marrow stromal reaction. Ultimately, an improved understanding of the biological factors that cause the clonal myeloproliferation in MMM will lead to the development of effective therapeutic interventions.     

An Overview of the Effects of Dioxins and Dioxin-Like Compounds on Vertebrates,as Documented in Human and Ecological Epidemiology

Dioxins and dioxin-like compounds are primary examples of persistent organic pollutants that induce toxicity in both wildlife and humans. Over the past 200 years these compounds have been almost exclusively generated by human activity and have left a string of disasters in the wake of their accidental release. Most recently, the contamination of the Irish pork supply with dioxins resulted in an international recall of all Irish pork products. Epidemiologic data on human and ecological dioxin exposures have revealed a common pattern of biological response among vertebrate species, which is mediated through activation of the Aryl hydrocarbon Receptor (AhR). These AhR-mediated effects include profound consequences on the vertebrate individual exposed in early life with respect to myriad developmental endpoints including neurologic, immunologic, and reproductive parameters. Humans appear to be susceptible to these effects in a manner similar to that of the laboratory and wildlife species, which have demonstrated such outcomes. Furthermore, epidemiologic data suggest that there is little or no margin of exposure for humans with respect to these developmental effects. Given these concerns, prudent public health policy should include the continued reduction of exposures.     

Malignant melanoma prognostic factors 6: distant metastases and length of survival

Surgical resectability is the most important prognostic factor for determining the length of survival following distant metastases. Other important factors that derive prognostic significance from their correlation with surgical resectability include (1) number of metastatic sites, (2) performance status, (3) initial site of metastases, (4) interval between initial diagnosis of primary tumor and onset of distant metastases. Factors which have little or no prognostic value include location of the primary tumor, sex, age and histological characteristics of the primary tumor.     

Depression and pancreatic cancer

Although pancreatic carcinoma and depression have been linked for years, the prevalence and relationship of these often coexisting diseases are still poorly understood. A clinical gestalt asserts that many patients present with depression before pancreatic carcinoma is diagnosed. Published studies reviewing this issue have found that many patients with pancreatic cancer are depressed. If the definition of depression is broadened to include mild depression in addition to major depression, these numbers increase. This article reviews the literature linking pancreatic carcinoma and depression.     

Eicosanoids and HB-EGF/EGFR in cancer

Eicosanoids are bioactive lipids that play crucial roles in various pathophysiological conditions, including inflammation and cancer. They include both the COX-derived prostaglandins and the LOX-derived leukotrienes. Furthermore, the epidermal growth factor receptor (EGFR) pathways family of receptor tyrosine kinases also are known to play a central role in the tumorigenesis. Various antitumor modalities have been approved cancer treatments that target therapeutically the COX-2 and EGFR pathways; these include selective COX-2 inhibitors and EGFR monoclonal antibodies. Research has shown that the COX-2 and epidermal growth factor receptor pathways actively interact with each other in order to orchestrate carcinogenesis. This has been used to justify a targeted combinatorial approach aimed at these two pathways. Although combined therapies have been found to have a greater antitumor effect than the administration of single agent, this does not exempt them from the possible fatal cardiac effects that are associated with COX-2 inhibition. In this review, we delineate the contribution of HB-EGF, an important EGFR ligand, to the cardiac dysfunction related to decreased shedding of HB-EGF after COX-2/PGE2 inhibition. A better understanding of the molecular mechanisms underlying these cardiac side effects will make possible more effective regimens that use the dual-targeting approach.     

肿瘤免疫检查点抑制剂治疗不良反应及其治疗——皮肤

免疫检查点抑制剂(ICPIs)已成功应用于多种恶性肿瘤的治疗,但在应用的过程中也会发生免疫相关不良反应(irAEs)。皮肤不良反应为常见的irAEs,病变较轻者主要表现为斑丘疹、苔藓样皮炎、大疱性类天疱疮、白癜风、银屑病和硬皮病;病情较重甚至危及生命的皮肤不良反应包括史提芬强生症候群和中毒性表皮坏死松解症;其他包括药疹伴嗜酸性粒细胞增多和系统症状、Sweet′s 综合征、秃头症、Grover′s病和副肿瘤综合征等。本文将对ICPIs治疗相关皮肤不良反应诊治进行综述。