肾癌根治术前肾动脉化疗栓塞的疗效观察

目的　评价根治术前化疗栓塞对肾癌预后的影响。方法　对 26例经术后病理证实并获随访的肾癌患者临床资料进行回顾性分析,分A、B两组,肾癌根治术前化疗栓塞组 16例(A组),单纯根治术组 10例(B)组。A组经肾动脉灌注化疗药物后,用碘油和化疗药物混合剂行末梢血管栓塞,用明胶海绵进行中心性栓塞,化疗栓塞后 2~5d行患肾根治术性切除。结果　A组术中出血量 150 ~500ml,平均 220ml;少于B组。A组 1、3、5年生存率分别为 86 .6%、72 .7%、58. 1%,两组比较,差别均有显著性意义 (P<0 .05 )。Cox模型分析表明,根治术前化疗栓塞是影响肾癌预后的独立因素。结论　肾癌根治术前化疗栓塞安全有效,对肾癌的治疗有积极意义。     

索拉非尼与舒尼替尼序贯治疗晚期肾癌1例

肾癌发病率约占成人癌症的3%.鉴于目前检查手段的进步和提高,近年来肾癌的发病率有所上升.肾细胞癌治疗以手术治疗为主.由于学界普遍认为肾癌细胞存在多药耐药基因-1及其产物P-糖蛋白的过度表达,因此肾癌细胞对化疗药物几乎普遍抗拒,疗效甚微.     

本期继续医学教育试题

1.目前,在肝癌临床研究中,所针对的靶点有:(多选题)AEGFRBVEGF/VEGFRCRaf/MAPK-ERKDHGF2.目前,用于治疗肾癌的靶向药物主要有:(多选题)A抗血管生成药B生长因子受体抑制剂C激酶抑制剂D肿瘤抗原抑制剂3.抗肿瘤药外渗是肿瘤患者化疗过程中常见的并发症,一旦发生,应立即处理。(判断     

转移性肾癌的内科治疗及相关研究进展

肾细胞癌简称肾癌,起源于肾实质中的肾小管上皮细胞.肾癌的主要病理亚型为透明细胞癌、乳头状细胞癌和嫌色细胞癌,其中,以透明细胞癌最多见.确诊时即存在远处转移或手术后出现转移的肾癌统称为转移性肾癌(mRCC),mRCC的预后较差.目前,mRCC的主要内科治疗方法包括细胞因子疗法和靶向药物治疗,免疫治疗也逐渐成为热点.肾癌存在多药耐药性及生物学异质性,对传统的放、化疗均不敏感,细胞因子治疗曾是肾癌的主要治疗方法,但是高剂量的白细胞介素-2(IL-2)所引起的不良反应也不容忽视.近年来,靶向治疗以其在实体肿瘤中明显的治疗效果和良好的耐受性越来越受到医务工作者的关注,根据作用机制的不同,肾癌的靶向治疗药物可分为三大类:酪氨酸激酶抑制剂(TKI)、雷帕霉素靶蛋白(MTOR)抑制剂及HGF/c-MET信号通路阻断剂.尽管以血管内皮细胞生长因子(VEGF)及血管内皮细胞生长因子受体(VEGFR)等为靶点的靶向治疗药物能够改善晚期肾癌患者的预后,但几乎所有的患者均对其产生耐药.因此,需要研究新的治疗策略以克服耐药,从而使患者获得持续性的疗效.程序性死亡受体1(PDCD1,也称PD-1)位于T细胞表面,程序性死亡受体配体1(PDCD1LG1,也称PD-L1)在大部分的肿瘤细胞中均有表达,PD-1与PD-L1结合后可抑制T细胞的活化甚至诱导T细胞衰竭.由于肿瘤细胞持续高表达PD-L1,可使其逃脱免疫监视,出现免疫逃逸现象.因此,阻止PD-1与PD-L1结合、重新激活衰竭的T细胞成为了研究的重点.本文就mRCC内科治疗的现状及研究进展作一综述.     

肝癌化疗的研究进展

尽管有各种治疗模式,不能切除肝细胞癌(UHCC)仍存在较差的自然病程,其治疗主要集中在化疗和化疗相关治疗.全身化疗和化疗相关治疗如肝动脉栓塞化疗(TACE)、肝动脉灌注化疗(HAI)、经皮注射化疗(PICT)和化学药物预防等,近年来发展迅速并有广阔的应用前景.     

贝伐珠单抗临床应用进展

贝伐珠单抗是一种重组人源化血管内皮生长因子受体单克隆抗体,与化疗药物联合应用治疗多种肿瘤如结直肠癌、肺癌、乳腺癌、肾癌、胶质母细胞瘤等,取得良好的疗效.主要表现为提高缓解率,延长无进展生存期和总生存期.     

晚期肾癌的靶向治疗进展

由于肾癌对放化疗不敏感,以IL-2和IFN为主的免疫治疗成为主要的治疗手段,但是应用高剂量IL-2和IFN所产生的严重不良反应又限制了其应用.近年来,对肾癌的生物学和分子机制的研究发现,肾透明细胞癌发病机制与VHL(Von Hippel-Lindau)、Ras和PTEN等基因的突变有关,针对这些突变基因及其信号传导途径中的多种分子靶向治疗药物相继问世,并取得了良好的效果.2008年NCCN肿瘤治疗指南已经将靶向治疗药物,Sorafenib、Sunitinib、Temsirolimus应用到晚期.肾癌的一线治疗.在欧洲Bevacizumab联合干扰素已经批准应用在晚期肾癌的一线治疗.目前几种新的药物正在进行Ⅲ期临床试验.     

食管癌化疗的演变及其在综合治疗中的作用

本文评述食管癌化疗的前景与困难.全身化学治疗有可能提高食管癌患者缓解率,延长生存期和改善生活质量.联合化疗治疗食管癌有明显优越性.顺铂 氟尿嘧啶(加或不加醛氢叶酸)认为是最佳联合化疗药物,对食管鳞癌的有效率为42%～66%,对食管腺癌的有效率为27%～48%.评价较新的化疗药物,包括紫杉醇类和喜树碱类(如伊利替康)可有助于选择更为有效和较好耐受的全身治疗方案.由于单用手术或单用放疗的患者预后较差,推动食管癌的综合治疗.目前临床试验有术前(新辅助)化疗,术前同时联合化-放疗,或对局部区域病变单用化-放疗,以及对有高复发危险的患者行术后(辅助)化疗,将有助于为食管癌患者提供最佳的治疗方案.     

肾癌分子靶向治疗药物的不良反应及处理研究进展

目前分子靶向药物已成功地应用于肾癌临床治疗,且其不良反应的治疗也日益受到关注,本文就肾癌分子靶向治疗药物的不良反应及处理进行综述.     

肾动脉化疗栓塞结合手术治疗晚期肾癌

目的 :探讨动脉化疗栓塞 (LP TRAE)、手术综合治疗晚期肾癌的价值。方法 :先行肾动脉插管化疗栓塞 ,4周后行手术治疗。结果 :15例患者行根治性切除 9例 (60 .0 % ) ,姑息性切除 6例(4 0 .0 % )。 1、3、5年生存率分别为 10 0 %、66.6%、37.5 %。结论 :LP TRAE结合手术治疗晚期肾癌较单纯化疗、姑息性手术相比 ,疗效高 ,复发率低 ,生存期延长     

Role of natural and adaptive immunity in renal cell carcinoma response to VEGFR‐TKIs and mTOR inhibitor

Angiogenesis and immunosuppression work hand‐in‐hand in the renal cell carcinoma (RCC) microenvironment. Tumor growth is associated with impaired antitumor immune response in RCC, which involves T cells, natural killer cells, dendritic cells (DCs) and macrophages. Vascular endothelial growth factor receptor (VEGFR), such as sorafenib, sunitinib, pazopanib and axitinib, and mammalian target of rapamycin (mTOR) inhibitors, such as temsirolimus and everolimus, do exert both antiangiogenic and immunomodulatory functions. Indeed, these agents affect neutrophil migration, as well as T lymphocyte‐DC cross‐talk, DC maturation and immune cell metabolism and reactivity. In this review, we overview the essential role of innate and adaptive immune response in RCC proliferation, invasion and metastasis and the relationship between tumor‐associated immune cells and the response to targeted agents approved for the treatment of metastatic RCC.     

Increased Serum Levels of Vascular Endothelial Growth Factor in Patients with Renal Cell Carcinoma

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. One such factor, vascular endothelial growth factor (VEGF), is considered to exert a potent angiogenic activity, as indicated by immunohistochemical and molecular evidence. In this study we investigated the serum VEGF level (s-VEGF) in patients with renal cell carcinoma (RCC). s-VEGF in peripheral blood samples was analyzed in 40 RCC patients and 40 patients without cancer (controls) using a sandwich enzyme-linked immunoassay. In 20 RCC patients, serum samples were obtained separately from the bilateral renal veins. s-VEGF was also measured before, 4 and 8 weeks after nephrectomy in 11 patients. There were significant differences in s-VEGF between the RCC patients and the controls (207.3 ± 32.9 vs. 71.5 ± 9.1 pg/ml, mean ± SE) ( P < 0.005), between the tumor-bearing renal veins and the contralateral ones ( P < 0.01), between the pre- and post-nephrectomy situations ( P < 0.01) and among the various parameters of tumor status such as tumor extent ( P < 0.001) and existence of metastasis ( P < 0.001). s-VEGF significantly correlated with the tumor volume obtained by a three-dimensional measurement ( r = 0.802, P < 0.0001). The sensitivity and specificity of s-VEGF at the cut-off level of 100 pg/ml, as determined by the receiver-operating-characteristics curve, were 80.0% and 72.5%, respectively. The results indicate that tumor tissue of RCC liberates VEGF into the systemic blood flow and that s-VEGF is a possible marker for RCC.     

Increased serum levels of vascular endothelial growth factor in patients with renal cell carcinoma.

Neovascularization, an essential event for the growth of solid tumors, is regulated by a number of angiogenic factors. One such factor, vascular endothelial growth factor (VEGF), is considered to exert a potent angiogenic activity, as indicated by immunohistochemical and molecular evidence. In this study we investigated the serum VEGF level (s-VEGF) in patients with renal cell carcinoma (RCC). s-VEGF in peripheral blood samples was analyzed in 40 RCC patients and 40 patients without cancer (controls) using a sandwich enzyme-linked immunoassay. In 20 RCC patients, serum samples were obtained separately from the bilateral renal veins. s-VEGF was also measured before, 4 and 8 weeks after nephrectomy in 11 patients. There were significant differences in s-VEGF between the RCC patients and the controls (207.3+/-32.9 vs. 71.5+/-9.1 pg/ml, mean+/-SE) (P<0.005), between the tumor-bearing renal veins and the contralateral ones (P<0.01), between the pre- and post-nephrectomy situations (P<0.01) and among the various parameters of tumor status such as tumor extent (P<0.001) and existence of metastasis (P<0.001). s-VEGF significantly correlated with the tumor volume obtained by a three-dimensional measurement (r=0.802, P<0.0001). The sensitivity and specificity of s-VEGF at the cut-off level of 100 pg/ml, as determined by the receiver-operating-characteristics curve, were 80.0% and 72.5%, respectively. The results indicate that tumor tissue of RCC liberates VEGF into the systemic blood flow and that s-VEGF is a possible marker for RCC.     

抑癌基因甲基化在肾细胞癌研究中的新进展

抑癌基因启动子高度甲基化被认为是除突变和缺失以外的抑癌基因功能失活的关键机制,在肿瘤的发生和发展中起重要作用,已成为目前肿瘤病因学基础研究的热点.肾细胞癌是泌尿系统最常见的恶性肿瘤之一,近年来也有许多文献报道了肾细胞癌中抑癌基因的异常甲基化情况.肾细胞癌临床发病隐匿,出现症状时多为晚期,肾细胞癌相关基因异常甲基化检测有望为肾癌的早期无创诊断提供新的途径.针对肾癌对放、化疗效果均不敏感的特点,改变DNA甲基转移酶活性和抑癌基因甲基化状况可作为肾细胞癌辅助治疗的一种新思路.本文对抑癌基因甲基化与肾细胞癌关系的研究进展作一综述,介绍DNA甲基化在肿瘤发生过程中的作用及机理;总结近7年来肾细胞癌中抑癌基因甲基化的研究情况和肾细胞癌独特的甲基化谱,并着重介绍了新近报道的HOXB13,HAI2/SPINT2,CDH1,CTNNG/JUP四个基因启动子异常甲基化与肾细胞癌的关系;阐述DNA甲基化研究对肾细胞癌的临床意义.     

Evolving classification of renal cell neoplasia

The development of consensus classifications for renal epithelial neoplasia in 1996 and 1997 led to the recognition of renal adenoma, renal oncocytoma and metanephric adenoma/adenofibroma as benign tumors and conventional (clear cell) renal cell carcinoma (RCC), papillary RCC, chromophobe RCC and collecting duct carcinoma as malignant morphotypes. While the overwhelming majority of renal adenomas and metanephric adenomas are benign, malignant transformation of both types have been described and genetic predictors of malignant transformation are as yet unknown. The main groups of malignant renal tumors are associated with characteristic genetic changes; conventional RCC (-3p), papillary RCC (+7, +17, -Y), chromophobe RCC (hypodiploid). Recent studies have also shown focal loss of heterozygosity of 3p segments in papillary and chromophobe RCC, indicating that 3p mutations are not confined to the conventional RCC morphotype and suggesting the presence of an important tumor suppressor gene at this site. Sarcomatoid metaplasia may occur in any morphotype and this is associated with a poor prognosis. More recently additional varieties of conventional RCC (multilocular cystic RCC), collecting duct carcinoma (medullary renal carcinoma) and papillary RCC (Types 1 and 2), each showing a characteristic morphology, have been recognized.     

Piperlongumine and its analogs down-regulate expression of c-Met in renal cell carcinoma

The c-Met protein, a transmembrane receptor tyrosine kinase, is the product of a proto-oncogene. Its only known ligand, hepatocyte growth factor (HGF), regulates cell growth, motility, migration, invasion, proliferation, and angiogenesis. The aberrant expression of c-Met is often associated with poor prognosis in multiple cancers, including renal cell carcinoma (RCC). Silencing or inactivation of c-Met leads to decreased viability of cancer cells, thereby making ablation of c-Met signaling an attractive concept for developing novel strategies for the treatment of renal tumors. Naturally-occurring products or substances are the most consistent source of drug development. As such, we investigated the functional impact of piperlongumine (PL), a naturally occurring alkaloid present in the Long pepper (Piper longum) on c-Met expression in RCC cells and demonstrated that PL and its analogs rapidly reduce c-Met protein and RNA levels in RCC cells via ROS-dependent mechanism. PL-mediated c-Met depletion coincided with the inhibition of downstream c-Met signaling; namely Erk/MAPK, STAT3, NF-κB and Akt/mTOR. As such, PL and PL analogs hold promise as potential therapeutic agents for the treatment of metastatic RCC and the prevention of postoperative RCC recurrence.     

Evolving classification of renal cell neoplasia

The development of consensus classifications for renal epithelial neoplasia in 1996 and 1997 led to the recognition of renal adenoma, renal oncocytoma and metanephric adenoma/adenofibroma as benign tumors and conventional (clear cell) renal cell carcinoma (RCC), papillary RCC, chromophobe RCC and collecting duct carcinoma as malignant morphotypes. While the overwhelming majority of renal adenomas and metanephric adenomas are benign, malignant transformation of both types have been described and genetic predictors of malignant transformation are as yet unknown. The main groups of malignant renal tumors are associated with characteristic genetic changes; conventional RCC (-3p), papillary RCC (+7, +17, -Y), chromophobe RCC (hypodiploid). Recent studies have also shown focal loss of heterozygosity of 3p segments in papillary and chromophobe RCC, indicating that 3p mutations are not confined to the conventional RCC morphotype and suggesting the presence of an important tumor suppressor gene at this site. Sarcomatoid metaplasia may occur in any morphotype and this is associated with a poor prognosis. More recently additional varieties of conventional RCC (multilocular cystic RCC), collecting duct carcinoma (medullary renal carcinoma) and papillary RCC (Types 1 and 2), each showing a characteristic morphology, have been recognized.     

Parathyroid hormone-related protein in human renal cell carcinoma

Parathyroid hormone-related protein (PTHrP), a polyprotein discovered in 1987, plays crucial roles not only in development and in various physiological events associated with normal life, but also in a number of pathological conditions such as cancer. PTHrP appears as the major causative agent in humoral hypercalcemia of malignancy (HHM) associated to a broad range of tumors. However, this is only one aspect of the multiple facets of PTHrP in cancer biology. Indeed, the complex growth factor-like properties of PTHrP has shed new light onto potential roles of this peptide in the regulation of tumor growth and invasion. Initial studies in breast, prostate and lung cancer and recent results in renal cell carcinoma (RCC) suggest such roles and highlight the therapeutic potential of PTHrP-targeting strategies in human cancer including RCC. In this review, the role of PTHrP in RCC tumorigenesis and its potential as a therapeutic target will be discussed.     

Temsirolimus in metastatic chromophobe renal cell carcinoma after interferon and sorafenib therapy

Chromophobe renal cell carcinoma (chRCC) is a common subtype of renal cell carcinoma (RCC), occurring in 6-11% of renal carcinoma patients. Limited clinical trial data have shown minimal activity with cytokines and chemotherapy, although small-molecule inhibitors of the vascular endothelial growth factor and platelet-derived growth factor pathways such as sunitinib and sorafenib, which are associated with significant clinical activity in clear-cell RCC (ccRCC), have been associated with a 25% response rate in chRCC. The mammalian target of rapamycin kinase inhibitor temsirolimus demonstrates good clinical activity in ccRCC patients with poor prognosis, with further data suggesting it is an effective treatment for all RCC tumour histologies. This report describes the case of a patient with chRCC who experienced rapid improvement in his general condition and stable disease on treatment with temsirolimus, following disease progression on interferon alfa and sorafenib treatment. This case report suggests that temsirolimus is an effective and appropriate treatment for this RCC tumour subtype.     

肾癌靶向治疗的常见不良反应及其治疗策略

 随着对肾癌(RCC)分子机制研究的深入,针对血管内皮生长因子（VEGF）及其受体等为靶点的肾癌靶向治疗药物取得重大进展,极大改善了进展期或转移性肾癌患者的预后。但临床试验表明,靶向治疗药物会导致高血压、骨髓抑制、肺炎等药物相关性不良反应,临床中及时发现并采取有效干预措施,对改善患者生活质量和提高靶向治疗效果尤为重要。