内皮素-1与非小细胞肺癌

肺癌是一种死亡率高、危害大的疾病,严重威胁人类健康,而非小细胞肺癌占肺癌的80%以上.近年来,研究发现内皮素-1与非小细胞肺癌关系密切.非小细胞肺癌患者体内内皮素-1水平升高,通过外周血、支气管镜等检查测定内皮素-1水平,有助于非小细胞肺癌的诊断和预后的评估.     

血管形成与非小细胞肺癌

肿瘤血管形成是指从宿主现存血管内皮建立新生血管的过程。肿瘤的生长一般经历生长缓慢的血管前期和生长迅速的血管期。当实体肿瘤直径大于 1ｍｍ～ 2ｍｍ后 ,它的生长就必须依靠新生血管。新生血管为肿瘤提供营养物质和氧以及排出代谢废物 ,并为肿瘤细胞的播散提供最直接的通道[1] ,而且新生血管对肿瘤生长有旁分泌作用 ,即通过内皮细胞分泌生长因子刺激肿瘤生长[2 ] 。因此新生血管形成是肿瘤发生、发展中的关键环节之一。自 2 0世纪 90年代以来 ,肿瘤血管形成成为国外医学研究的热门话题 ,近几年来国内亦有学者开始关注这方面的研究。在…     

Staging of non-small cell lung cancer

Accurate clinical staging is critical in the evaluation of any patient with non-small cell lung cancer (NSCLC). Staging for NSCLC is based on the tumor, node, metastasis (TNM) system used for most solid tumors. The clinical stage, as determined by all available clinical, radiographic, and biopsy data, provides patients and physicians with an overall assessment of disease extent and prediction of survival and enables the identification of appropriate therapies. It is thus imperative that staging be performed as accurately and comprehensively as possible while also maintaining efficiency. To do so requires an understanding of the staging system, the clinical clues that drive the staging evaluation, and a working knowledge of available noninvasive and invasive diagnostic modalities.     

非小细胞肺癌的化学治疗

在过去10多年中，非小细胞肺癌的化疗一直是一个有争议的问题。像新药吉西他宾，紫杉醇，异长春花碱等已经显示出它们是有前途的单一化疗药物，把它们应用到联合化疗方案中获得了更高的反应率和存活率。本文就单一化疗药物，新药和正在研究的药物，联合化疗，手术切除后的辅助化疗，非小细胞肺癌局部进展病变的化疗，非小细胞肺癌局部进展期诱导化疗和手术治疗，进展期（Ⅳ期）的化疗进行讨论。     

New antiangiogenetic agents and non-small cell lung cancer

New blood vessel formation, known as angiogenesis is a fundamental event in the process of tumor growth and metastatic dissemination. Due to its central role in tumor angiogenesis, the vascular endothelial growth factor (VEGF) and its receptor have been a major focus of basic research and drug development in the field of oncology, including the treatment of non-small cell lung cancer (NSCLC). Approaches targeting VEGF include monoclonal antibodies and vascular endothelial growth factor receptor-tyrosine kinase inhibitors (VEGFR-TKIs). Bevacizumab (Avastin) is an anti-VEGF recombinant humanized monoclonal antibody. A very recent randomized phase III trial demonstrated a statistically significant advantage in median survival favouring the combination of bevacizumab plus chemotherapy versus chemotherapy alone in the treatment of advanced non-squamous NSCLC. This study represents the first evidence of superior efficacy of targeted therapy combined with chemotherapy over chemotherapy alone in the treatment of NSCLC. ZD6474 is an orally bioavailable inhibitor of VEGFR-2 tyrosine kinase. First evidences of antitumor activity and its excellent toxicity profile make it a promising targeted agent for the treatment of NSCLC. A recent phase I/II study examined the combination of Epidermal Growth Factor Receptor (EGFR)-TKI erlotinib and bevacizumab in patients with non-squamous stage IIIB/IV NSCLC. Data on antitumor activity of this combination have to be considered very promising. Clinical trials of multiple targeted therapy may represent the second generation studies in the treatment of NSCLC.     

Cdc25A 与非小细胞肺癌

肺癌是目前全世界范围内发病率及病死率最高的恶性肿瘤,其中非小细胞肺癌占肺癌总数80%以上。Cdc25A 是 Cdc25磷酸酶3种同源物之一,是一种双特异性蛋白激酶,也是最重要的细胞周期调节因子和凋亡因子。研究发现 Cdc25A 在多种肿瘤中表达上调,发挥癌基因作用。Cdc25A被认为是细胞发育和肿瘤形成、进展和转移中必不可少的调控因子,但其在非小细胞肺癌发生中的确切作用机制和临床意义仍不十分明确。     

癌基因信号转导和转录激活因子3与非小细胞肺癌

信号转导和转录激活因子3(STAT3)信号传导通路接受生长因子、细胞因子等细胞外信号刺激,作用于细胞核内特异的DNA片段,调控靶基因的转录,直接影响细胞的增殖分化和凋亡。研究结果显示STAT3异常激活与多种恶性肿瘤的发生发展密切相关,被定义为癌基因,目前已有学者以STAT3为靶点进行肿瘤治疗研究,取得了初步结果,本文就癌基因STAT3与非小细胞肺癌关系的研究进展作一综述。     

Molecular epidemiology of non-small cell lung cancer

Although smoking is the primary risk factor for most lung cancers, genetic predisposition may play an important role. Familial aggregation studies suggest a greater genetic component in the risk for younger individuals developing lung cancer, for lifetime nonsmokers, and possibly for women. Low-penetrance, high-prevalence polymorphic genes may explain part of this genetic predisposition. Functional polymorphisms of xenobiotic metabolism may alter the total exposure of tobacco carcinogens in the host. Subtle alterations in the DNA repair, inflammatory, and cell cycle pathways may also alter lung cancer susceptibility. The role of individual polymorphisms has been evaluated for several genes including the CYP and glutathione s-transferase superfamilies, and the NAT genes; DNA repair genes such as XPD (nucleotide excision pathway), XRCC1 (base excision pathway), and MGMT; and tumor suppressor or cell cycle genes such as p53. Molecular epidemiological studies are now focused on building larger databases from existing smaller studies and developing strategies to simultaneously evaluate multiple polymorphisms and genes within the same pathway.     

Novel therapies for non-small cell lung cancer

Lung cancer is the leading cause of cancer-related death in the United States. Emerging technologies for the treatment of early-stage non-small cell lung cancer are currently focused on less invasive approaches to obtaining local tumor control, including minimally invasive and less radical resections, as well as image-guided ablative therapies. Targeted chemotherapeutic agents represent the newest area of treatment for advanced non-small cell lung cancer. These novel agents capitalize on our increased understanding of the diverse biology of the disease. Each of these advanced modalities works best for only a small subset of the population with lung cancer, and efficacious use is highly dependent on appropriate patient selection.     

非小细胞肺癌研究新进展

2011年美国临床肿瘤学会（Ameriean Soeiety of elinieal Oneology, ASCO）年会于2011年6月在美国召开,大会内容非常丰富。本届ASCO年会在非小细胞肺癌（non-small cell lung cancer, NSCLC）方面发布了大量的一线、二线、维持治疗的新进展。现就此次大会关于NSCLC的内科研究进展做一总结摘录,并按NSCLC的一线治疗,二线治疗,维持治疗等分类综述如下。     

Interdisciplinary treatment of non-small cell lung cancer

At the time of diagnosis of non-small cell lung cancer, about two thirds of the patients manifest tumor disease limited to the lungs without distant metastases. In this group localized tumor spread (stages I and II) can be distinguished from locally advanced spread including lymph node metastases (stages IIIA and B). In stages I and II with sufficient cardiopulmonary function, surgical resection is considered the standard treatment approach. If lobe resection is not possible due to comorbidities or limited pulmonary function, parenchyma-sparing resection or definitive radiotherapy is advocated. Postoperative adjuvant chemotherapy is recommended for individual cases in stage IB and as the standard treatment in stage II. In stages IIIA and IIIB interdisciplinary consultation involving pneumologists/oncologists, surgeons, and radiation oncologists is necessary to reach decisions on treatment recommendations. Generally multiple treatment modalities are employed in these stages, such as induction chemotherapy followed by surgery and subsequent irradiation or simultaneous chemoradiotherapy. These treatment combinations with curative intent should be differentiated from the numerous treatment methods with palliative intent.     

免疫靶向治疗在非小细胞肺癌中的研究进展

随着对肿瘤分子发病机制的研究深入,肿瘤发生和发展的免疫学机制逐渐成为研究热点。近年来,肿瘤的免疫靶向治疗取得显著进展,有望成为晚期非小细胞肺癌治疗的一种重要手段。本文简要综述了近年来有关非小细胞肺癌免疫靶向治疗方面的研究进展。     

Skin metastases in non-small cell lung cancer

Skin metastasis associated with lung cancer is an uncommon manifestation and usually portends an aggressive clinical course. It can be either synchronous with the underlying malignancy or be the sign of recurrence. Solitary metastases can be treated with surgical resection or radiation therapy, but multiple lesions are usually treated with palliative chemotherapy. With standard platinum-based doublet regimens, treatment results are usually poor. With the advent of newer agents like pemetrexed, bevacizumab and erlotinib, perhaps results may improve with ongoing clinical trials.     

Cetuximab in advanced non-small cell lung cancer

Non-small cell lung cancer (NSCLC) remains a major problem in the western civilization and developing countries. Since most patients with NSCLC have advanced disease at diagnosis, to date, chemotherapy, with third-generation platinum-based doublets, represents the standard of care. Advances in the knowledge of tumour biology and mechanisms of oncogenesis has granted the singling out of several molecular targets for NSCLC treatment. Epidermal growth factor receptor (EGFR), a member of ErbB family, is one of the most studied target. Cetuximab is a chimeric (human-murine) monoclonal antibody directed against the extracellular domain of the EGFR that blocks ligand (TGF-alpha, EGF) access to the receptor. In the present paper we discuss about the activity, tolerability and efficacy of cetuximab, the EGFR monoclonal blocking antibody with the largest amount of clinical data being available on the treatment of advanced NSCLC.     

Chemotherapy in advanced non-small cell lung cancer

Although patients with advanced non-small cell lung cancer (NSCLC) cannot be cured, cytotoxic chemotherapy in patients with reasonable performance status can improve overall survival and quality of life. No one regimen has demonstrated superior efficacy results, and platinum-based doublets remain the current standard of care. The toxicity profiles of acceptable regimens differ, allowing treatment to be tailored to a specific patient. The duration of first-line chemotherapy should not exceed four to six cycles. Second- and third-line treatment regimens also have established survival benefits, which has led to increasing improvements in overall survival for patients with advanced NSCLC. Treatment approaches in patients with borderline performance status remain controversial. Although the optimal treatment approach for elderly patients has not yet been established, it is clear that the elderly do benefit from chemotherapy, and fit elderly patients can be treated with the same regimens as younger patients. It is critical that all patients with advanced NSCLC be referred to medical oncologists. Patients considering chemotherapy must have a clear understanding of the expected benefits, limitations, and toxicities.     

Active-specific immunotherapy for non-small cell lung cancer

Non-small cell lung cancer constitutes about 85% of all newly diagnosed cases of lung cancer and continues to be the leading cause of cancer-related deaths worldwide. Standard treatment for this devastating disease, such as systemic chemotherapy, has reached a plateau in effectiveness and comes with considerable toxicities. For all stages of disease fewer than 20% of patients are alive 5 years after diagnosis; for metastatic disease the median survival is less than one year. Until now, the success of active-specific immunotherapy for all tumor types has been sporadic and unpredictable. However, the active-specific stimulation of the host’s own immune system still holds great promise for achieving non-toxic and durable antitumor responses. Recently, sipuleucel-T (Provenge^®; Dendreon Corp., Seattle, WA) was the first therapeutic cancer vaccine to receive market approval, in this case for advanced prostate cancer. Other phase III clinical trials using time-dependent endpoints, e.g. in melanoma and follicular lymphoma, have recently turned out positive. More sophisticated specific vaccines have now also been developed for lung cancer, which, for long, was not considered an immune-sensitive malignancy. This may explain why advances in active-specific immunotherapy for lung cancer lag behind similar efforts in renal cell cancer, melanoma or prostate cancer. However, various vaccines are now being evaluated in controlled phase III clinical trials, raising hopes that active-specific immunotherapy may become an additional effective therapy for patients with lung cancer. This article reviews the most prominent active-specific immunotherapeutic approaches using protein/peptide, whole tumor cells, and dendritic cells as vaccines for lung cancer.