地西他滨联合CAG方案治疗老年复发难治性急性髓细胞白血病的临床观察

目的:评价地西他滨结合CAG方案治疗老年复发难治性急性髓细胞白血病效果和药物不良反应.方法:回顾性分析2013年01月至2015年05月扬州大学附属泰兴医院血液科收治的12例老年复发难治性急性髓细胞白血病患者的临床资料,地西他滨结合CAG方案:地西他滨20mg/m2,静滴,第1~5天;阿克拉霉素20mg/m2,第1天、第3天、第5天、第7天;阿糖胞苷10mg/m2,1次/12小时,皮下注射,第1~14天;粒系集落刺激因子300μg,皮下注射,1次/天(依照骨髓抑制情况而调整用药剂量及用药次数).结果:12例患者均出现不同程度的骨髓抑制,在骨髓抑制期间,4例出现不明原因的发热,3例出现肺部感染,1例出现肛周感染,经升白细胞、抗感染治疗后症状得到控制,1例患者肝功能损害,经保肝降酶治疗后恢复,2例出现轻度胃肠道反应,经对症治疗后症状消失.12例病人中,完全缓解者6例,部分缓解3例,总有效率为75%.结论:地西他滨联合CAG方案治疗老年复发难治性急性髓细胞白血病效果确切、临床用药安全,在临床上可以推广应用.     

国产紫杉醇联合吉西他滨治疗晚期非小细胞肺癌20例临床观察

目的评价国产紫杉醇(Paclitaxel)联合吉西他滨(Gemcitabine)对晚期非小细胞肺癌的疗效和毒副作用。方法经病理组织学或细胞学证实的20例晚期非小细胞肺癌应用国产紫杉醇135mg／m^2静脉滴注，d1，吉西他滨(健择)1000mg／m^2静脉滴注，d2.9、16，4周为一周期，所有患者至少接受2周期治疗。结果可评价疗效20例，总有效率55．0％(均为部分缓解)，初治病例11例，有效率63．6％；复治病例9例，有效率44．4％。主要毒副作用是骨髓抑制，恶心呕吐，脱发，手足麻木，关节肌肉痛，心脏毒性反应等，但均可耐受。结论国产紫杉醇联合吉西他滨治疗晚期非小细胞肺癌具有良好的疗效，毒性可以耐受。     

地西他滨诱导宫颈癌细胞凋亡分子机制探讨

目的 地西他滨(decitabine, DAC)具有较好的抗肿瘤活性,其分子机制与DNA去甲基化有关,本研究通过DAC对腺瘤性结肠息肉病(adenomatous polyposiscoli,APC)基因的表达水平和去甲基化的影响,探讨DAC诱导宫颈腺癌Hela细胞凋亡分子机制.方法 不同浓度的DAC作用于宫颈腺癌Hela细胞24、36和48 h,MTT法检测对宫颈癌细胞的增殖抑制作用,观察DAC对Hela细胞增殖的浓度依赖效应和时间依赖效应.流式细胞术检测DAC对宫颈腺癌Hela细胞凋亡和细胞周期的影响.在DAC作用于宫颈腺癌Hela细胞前后,通过甲基化特异性PCR(Methylation specific PCR, MSP)检测APC基因的甲基化状态;RT-PCR法检测APC基因mRNA表达水平;蛋白质印迹法检测APC蛋白、β-catenin蛋白在胞内及核内表达的变化.结果 DAC对宫颈腺癌Hela细胞增殖抑制具有浓度依赖效应和时间依赖效应,Hela细胞半数抑制浓度(IC50) 24、36、48 h 分别为 28.23、7.65和5.64 μmol/L.DAC处理后的宫颈腺癌Hela细胞的凋亡率为(73.82±0.11)%,明显高于对照组的(12.41±0.24)%,P<0.001.DAC处理Hela细胞后,S期细胞比例(47.82±2.57)%和G2期细胞比例(30.87±2.28)%显著高于空白对照组的S期细胞比例(24.08±0.71)%和G2期细胞比例(2.52±0.84)%,P<0.001.DAC处理后,APC基因启动子区域去甲基化状态明显增高,APC mRNA表达量上升,处理前后比较差异有统计学意义,P<0.05.DAC处理后,胞内APC蛋白表达上调,而胞内和核内的β-catenin蛋白表达下调,差异均有统计学意义,P<0.05.结论 DAC可通过对APC基因的去甲基化作用,上调胞内APC蛋白表达,下调胞内和核内β-catenin表达,诱导宫颈癌细胞凋亡.     

地西他滨治疗成人急性髓细胞白血病的临床观察

目的:探讨地西他滨治疗成人急性髓细胞白血病(acutemyeloid leukemia,AML)的临床疗效和安全性。方法:收集2009年8月—2010年10月在本科接受地西他滨治疗的15例AML患者(年龄>18岁)的临床资料,评价其疗效和不良反应。结果:15例患者中,完全缓解3例,部分缓解5例,总有效率为53.3%。在12例可行细胞遗传学评价的患者中,1例(8.3%)获得完全细胞遗传学缓解。中位总生存期为123d(27～509d),中位无复发生存期为70d(19～306d),中位反应持续时间为33d(11～176d)。Ⅳ级血液学不良反应发生率为93.3%,Ⅲ～Ⅳ级感染发生率为33.3%,无Ⅲ～Ⅳ级出血、恶心呕吐和肝功能损伤。早期死亡1例。结论:地西他滨可有效治疗成人急性髓细胞白血病,血液学不良反应较重,必须给予积极的支持治疗。     

地西他滨在恶性血液肿瘤治疗中的应用

 地西他滨（DAC）是一种甲基化抑制剂,其不同于传统的化疗药物,具有独特的作用机制,并代表了新的治疗观念。甲基化存在于几乎所有的细胞内,通过抑制DNA甲基转移酶,引起DNA低甲基化和细胞分化或凋亡来发挥抗肿瘤作用。现就甲基化抑制剂DAC在恶性血液肿瘤治疗方面的应用进行综述。     

地西他滨联合三氧化二砷对NB4细胞凋亡作用的研究

 目的　研究去甲基化制剂地西他滨（DAC）单用或联合三氧化二砷（As2O3）对NB4细胞凋亡的作用机制。方法　将不同浓度的DAC、As2O3以及两药联合作用于NB4细胞,不加药为对照组,采用四甲基偶氮唑蓝（MTT）法检测细胞增殖抑制作用,流式细胞术检测细胞凋亡。结果　DAC与As2O3单药对NB4细胞的抑制作用呈浓度时间依赖性（DAC 1 μmol／L作用24、48、72 h的抑制率分别为12.18 %、22.72 %、35.54 %;DAC 2 μmol／L作用24、48、72 h的抑制率分别增高为22.14 %、31.18 %、45.21 %;As2O3 0.5 μmol／L作用24、48、72 h的抑制率分别21.09 %、32.43 %、44.93 %;As2O3 1.0 μmol／L作用24、48、72 h的抑制率分别增高为31.69 %、41.12 %及54.27 %）,两药联合抑制作用较单药明显（DAC 1 μmol／L+As2O3 0.5 μmol／L作目的　研究去甲基化制剂地西他滨（DAC）单用或联合三氧化二砷（As2O3）对NB4细胞凋亡的作用机制。方法　将不同浓度的DAC、As2O3以及两药联合作用于NB4细胞,不加药为对照组,采用四甲基偶氮唑蓝（MTT）法检测细胞增殖抑制作用,流式细胞术检测细胞凋亡。结果　DAC与As2O3单药对NB4细胞的抑制作用呈浓度时间依赖性（DAC 1 μmol／L作用24、48、72 h的抑制率分别为12.18 %、22.72 %、35.54 %;DAC 2 μmol／L作用24、48、72 h的抑制率分别增高为22.14 %、31.18 %、45.21 %;As2O3 0.5 μmol／L作用24、48、72 h的抑制率分别21.09 %、32.43 %、44.93 %;As2O3 1.0 μmol／L作用24、48、72 h的抑制率分别增高为31.69 %、41.12 %及54.27 %）,两药联合抑制作用较单药明显（DAC 1 μmol／L+As2O3 0.5 μmol／L作用24、48、72 h抑制率分别为42.10 %、48.75 %、60.78 %）（P＜0.05）,各浓度组与对照组比较差异均有统计学意义（P值均＜0.05）;As2O3 1 μmol／L作用于NB4细胞株48 h可见5.8 %的细胞凋亡,联合组增高为17.3 %。结论　DAC能显著抑制NB4细胞的增殖并诱导其凋亡,DAC联合As2O3对NB4细胞增殖抑制及诱导凋亡有协同作用。用24、48、72 h抑制率分别为42.10 %、48.75 %、60.78 %）（P＜0.05）,各浓度组与对照组比较差异均有统计学意义（P值均＜0.05）;As2O3 1 μmol／L作用于NB4细胞株48 h可见5.8 %的细胞凋亡,联合组增高为17.3 %。结论　DAC能显著抑制NB4细胞的增殖并诱导其凋亡,DAC联合As2O3对NB4细胞增殖抑制及诱导凋亡有协同作用。     

小剂量地西他滨联合阿糖胞苷治疗骨髓增生异常综合征临床观察

目的：探讨小剂量地西他滨联合阿糖胞苷治疗骨髓增生异常综合征（MDS）的临床疗效和安全性。方法收集2012年1月至2015年1月接受小剂量地西他滨联合阿糖胞苷方案治疗的15例MDS 患者临床资料,评价其疗效和不良反应。结果15例患者中完全缓解4例,部分缓解5例,稳定、进展和无效6例,总有效率为60.0%（9／15）。总感染率为40.0%（6／15）,其中肺部感染率为26.7%（4／15）,Ⅲ～Ⅳ度骨髓抑制率为73.3%（11／15）。患者经积极抗感染、刺激造血及输血等支持治疗后感染得到控制。15例患者均无严重肝损害,未出现化疗相关死亡。结论小剂量地西他滨单药联合阿糖胞苷方案治疗 MDS 有一定疗效,可延缓疾病进展,患者能耐受化疗不良反应,无化疗相关死亡。     

地西他滨联合CAG或HAAG方案治疗老年白血病疗效比较

目的:观察地西他滨(DAC)+CAG方案与地西他滨(DAC)+HAAG方案治疗初治老年急性非淋巴细胞白血病(AML)的疗效与安全。方法:回顾性分析我院血液科近5年的58例老年初治急性非淋巴细胞白血病患者,其中35例接受DAC+CAG方案诱导化疗,23例接受DAC+HAAG方案诱导化疗。结果:DAC+CAG及DAC+HAAG组缓解率分别为51.4%及60.9%,差异无统计学意义(P=0.592),两组有效率分别为62.9%及69.6%,差异无统计学意义(P=0.779)。经过平均12个月(1~60个月)的随访,两组的2年存活率分别为23.5%及33.3%,差异无统计学意义(P=0.591)。结论:DAC+CAG与DAC+HAAG方案对于诱导老年急性非淋巴细胞白血病缓解的疗效差异并不明显,两种方案对患者的长期生存并无明显影响。     

吉西他滨联合卡铂或紫杉醇与紫杉醇联合卡铂治疗晚期非小细胞肺癌的随机对照研究

非小细胞肺癌(NSCLC)是威胁中国人群生命健康的重要疾病,由于诊断技术的限制,80％的NSCLC患者确诊时已处于晚期,失去了最佳手术时机.姑息性化疗已经成为治疗晚期NSCLC的重要手段,以铂类为基础的化疗方案对提高患者生存率和改善患者生活质量具有重要意义.我们比较了吉西他滨联合卡铂或紫杉醇与紫杉醇联合卡铂对晚期NSCLC的治疗作用,现将结果报告如下.     

低剂量地西他滨联合伊马替尼对K562细胞的增殖抑制作用

 目的　研究低剂量地西他滨（DAC）联合伊马替尼（IM）对K562细胞株的增殖抑制作用及对bcr-abl表达的影响。方法　单药及两药联合后,通过四甲基偶氮唑蓝（MTT）法观察药物对K562细胞株的增殖抑制作用,流式细胞术检测药物对K562细胞株早期凋亡率及细胞周期,巢式反转录-聚合酶链反应（RT-PCR）半定量检测药物对K562细胞株bcr-abl mRNA表达。结果　DAC与IM单药对K562细胞的抑制作用呈浓度时间依赖性。两药联合用药抑制作用较单药组明显（F＝43.947、165.580、321.193、296.101,均P＜0.05）,24、 48、72 h各浓度组与对照组比较差异均有统计学意义（F＝202.759、168.457、417.538,均P＜0.05）。DAC及IM单药作用药物对K562细胞株均使G1期细胞明显增多,IM 0.2 μmol／L作用于K562细胞株48 h可见6.7 %早期凋亡细胞,IM 0.2 μmol／L联合DAC 4 μmol／L早期凋亡细胞增加至8.4 %。bcr-abl mRNA表达水平降低,DAC 4 μmol／L作用48 h后可降低K562细胞中bcr-abl mRNA表达（约14 %）,IM 0.2 μmol／L降低约40 %,联合用药表达量明显降低（约60 %）。联合用药组与单药组比较差异有统计学意义（F＝71.981,P＜0.05）。结论　DAC 对K562细胞的增殖抑制作用与细胞周期阻滞、诱导凋亡及降低bcr-abl mRNA表达有关,两药联合可显著抑制K562细胞增殖。     

Differentiating mTOR inhibitors in renal cell carcinoma

PI3K/Akt/mTOR signalling is dysregulated in many cancers, including renal cell carcinoma (RCC), and activation of this pathway has been suggested to correlate with aggressive behavior and poor prognosis in RCC tumors. mTOR inhibition plays a principal role in the targeted treatment of many cancer types, including RCC. Although mTOR inhibitors share the same mechanism of action, differences in metabolism, formulation and dosing schedule underpin distinct PK/PD profiles such that they may be differentiated for use in a variety of treatment niches. Approved mTOR inhibitors temsirolimus and everolimus serve as important therapeutic options within the current RCC treatment paradigm, although their recommended applications differ in setting and patient population characteristics. Clinical practice guidelines recommend temsirolimus for use in treatment-naive patients with poor-prognosis metastatic RCC of any histology (predominant clear cell or non-clear cell histology). Everolimus provides a standard-of-care therapy for patients with metastatic RCC whose disease has progressed after previous vascular endothelial growth factor receptor-tyrosine kinase inhibitor therapy. As therapeutic failure impacts the vast majority of patients with RCC, sequencing strategies of available agents or simultaneous targeting of multiple members of the PI3K/Akt/mTOR pathway may provide additional clinical benefit. Various classes of agents targeting the PI3K/Akt/mTOR pathway are currently being investigated, including mTORC1/mTORC2 kinase domain inhibitors, mTOR/PI3K dual inhibitors, PI3K-selective inhibitors, and programmed cell death 6 modulators. Clinical trials of mTOR inhibitors in a variety of tumor types are ongoing, and the role of mTOR inhibitors continues to evolve across the RCC treatment landscape.     

Combined cytotoxic action of paclitaxel and ceramide against the human Tu138 head and neck squamous carcinoma cell line

Purpose: Paclitaxel, a chemotherapeutic agent used in the treatment of recalcitrant ovarian and breast as well as other neoplasms, is being investigated for the treatment of squamous cell carcinoma of the head and neck. Our previous studies have demonstrated that exogenously added ceramide enhances apoptosis in paclitaxel-exposed human leukemic cells. In this study, we showed that exogenous ceramide augmented paclitaxel-induced apoptosis in Tu138 cells in vitro when added simultaneously in combination with the paclitaxel. Methods: The combined cytotoxic effects of paclitaxel and ceramide exposure against Tu138 cells were assessed by an MTT dye assay, cell cycle analysis, TUNEL (terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling) assay, and isobologram analysis for synergistic activity. Results: The MTT dye assay results indicated augmentation of time- and concentration-dependent paclitaxel-mediated cell cytotoxicity by simultaneous ceramide treatment. Paclitaxel treatment of Tu138 cells also resulted in an accumulation of cells in the G₂-M phase of the cell cycle. This paclitaxel-mediated G₂-M phase accumulation decreased significantly with the addition of ceramide, indicating that combined paclitaxel/ceramide treatment resulted in the elimination of Tu138 cells from the S and/or G₂-M phases of the cell cycle. Furthermore, ceramide enhancement of paclitaxel-mediated apoptosis was also detected by the TUNEL assay. Conclusion: Our results suggest that paclitaxel/ceramide combination therapy may be an attractive alternative to conventional methods of chemotherapy for head and neck cancer, and should be further explored. Received: 22 April 1999 / Accepted: 14 March 2000     

塞来昔布对乳腺癌细胞株的放射增敏作用

背景与目的:塞来昔布(celecoxib)能有效增强放射线对肿瘤的作用,但其作用机制尚不清楚.本研究探讨塞来昔布对人乳腺癌MDA-MB-231细胞放射增敏的作用机制.方法:取对数生长期MDA-MB-231细胞株2×106个,分为对照组、药物组、照射组及实验组(照射线联合塞来昔布),流式细胞分析法(flowcytometry,FCM)检测各组细胞凋亡率;克隆形成实验检测放射增敏作用;Western blot法检测Akt、pAkt蛋白表达.结果:实验组凋亡率[(31.20±1.27)%]显著高于照射组[(17.99±1.01)%](t=14.01,P<0.05);与照射组相比较,实验组反映放射敏感性的指标准域剂量(Dq)、平均致死剂量(D0)、2 Gy照射的存活分数(SF2)值均显著降低(0.437 vs 1.175,1.874 vs 2.394,0.52 vs 0.79),放射增敏比(SERD0)为1.277;各组Akt蛋白表达无明显差异,但塞来昔布能抑制pAkt的表达,而放射线能上调其表达,两者联合使用对pAkt表达有明显抑制作用(P<0.05).结论:塞来昔布对人乳腺癌MDA-MB-231细胞有放射增敏作用,其可能的机制是阻断PI3K/Akt信号通路的活化,从而提高乳腺癌放射敏感性.     

Small cell carcinoma of the esophagus responding to fourth-line chemotherapy with weekly paclitaxel

A patient was diagnosed with a small cell carcinoma of the esophagus (T4N1M1b by the International Union Against Cancer [UICC] classification) in October 2002, and initially received two courses of concurrent chemotherapy with 5-fluorouracil (5-FU; 400 mg/m² by continuous infusion; days 1–5 and 8–12) and cisplatin (40 mg/m² by drip infusion; days 1 and 8) and radiation therapy (2 Gy/day, days 1–5, 8–12, and 15–19; total, 30 Gy per course) with the second course given after a 2-week interval. Two courses of chemotherapy with 5-FU (800 mg/m²; days 1–5) and cisplatin (80 mg/m²; day 1) given after this was completed. Although a complete response had been confirmed, recurrence with multiple liver and lymph node metastases was detected 3 months after the cessation of the second course of chemotherapy. Although the patient received second-line chemotherapy with irinotecan (150 mg/m²; every 2 weeks) from June 2003, the disease progressed. Brain metastases developed during third-line chemotherapy with gemcitabine (1000 mg/m² weekly by drip infusion). The symptoms were attenuated after whole-brain radiation (30 Gy), and fourth-line chemotherapy using paclitaxel (80 mg/m²; weekly) was initiated from November 2003. A computed tomography scan 1 month after the first course of paclitaxel showed remarkable regression of the liver metastases. The treatment strategy used for treating small cell carcinomas of the lung may be applicable for these carcinomas of the esophagus.     

Decreased expression of thrombomodulin is correlated with tumor cell invasiveness and poor prognosis in nonsmall cell lung cancer

Thrombomodulin (TM) plays a role in coagulation, inflammation, and cell adhesion. Reduction of TM expression plays an important role in the tumor metastatic process; however, insufficient information is available regarding the expression of TM in nonsmall cell lung cancer (NSCLC). Sixty NSCLC patients who underwent surgery were reviewed for TM expression and multiple variables were assessed by univariate and multivariate analyses. The expression level of TM and its metastatic ability were examined in vitro using the human NSCLC A549 cell line. TM expression in NSCLC was significantly correlated with survival; the 5‐yr survival rates of patients with high and low TM expression were 23% and 18% (P < 0.01), respectively. Distribution of TM was detected predominantly in the normal lung tissue compared with lung cancer tissue. Western blot analysis showed, on average, decreased expression levels of TM protein in the lung cancer tissues of patients with NSCLC. An in vitro study also showed that overexpression of TM can inhibit the invasiveness and migration ability of the A549 cell line, whereas silencing of TM significantly enhanced these processes. This inhibition of cellular migration by overexpression of TM was significantly prevented by the selective inhibitors of PI3K and Akt, but not by MAPK inhibitors. This study demonstrates that a decrease in TM expression may be an indicator in the prognosis of NSCLC patients and provides new insights into the molecular mechanisms of TM in the metastasis of NSCLC. © 2010 Wiley‐Liss, Inc.     

肾细胞癌中HSPgp96的免疫组化研究

 目的　研究HSPgp96在人肾细胞癌组织中的表达及其与临床分期、病理分级、细胞类型的相关性。方法　应用免疫组化S P法检测 5 4例人肾细胞癌组织标本中HSPgp96的表达情况。 结果　在人肾细胞癌组织中HSPgp96表达阳性率为88.9% ,表达强度明显较正常肾组织增高 (P <0 .0 5 ) ,但其高表达却与临床分期、病理分级及细胞类型无明显相关性 (P >0 .0 5 )。结论　人肾细胞癌组织中HSPgp96高表达在肿瘤的发生、发展中具有重要的促进作用。     

Microarray analysis of microRNA expression in renal clear cell carcinoma

Aim

To explore the microRNA (miRNA) expression in renal clear cell carcinoma (RCCC).

Methods

We compared the miRNA expression profiles in 11 pairs of RCCC and adjacent nontumorous tissue (NT) from 11 RCCC patients, using a mammalian miRNA microarray containing whole human mature and precursor miRNA sequences. To verify microarray results, Northern blotting was carried out on 5 randomly selected miRNAs.

Results

Totally 81 miRNAs were identified valid expression in RCCC samples, 48 of which specifically detected in RCCC samples, 17 of which detected downregulated in RCCC compared to NT sample, 2 upregulated and 14 without significant difference. MiRNAs in RCCC tissues exhibit an overall higher expression level than NT tissue. The chip results were confirmed by northern blot analysis.

Conclusion

Our study may help to clarify the molecular mechanisms involved in the pathogenesis of RCCC, and miRNAs potentially serve as a novel diagnostic biomarker of RCCC.     

Macrophage-derived exosomal miR-342-3p promotes the progression of renal cell carcinoma through the NEDD4L/CEP55 axis

Due to its difficulty in early diagnosis and lack of sensitivity to chemotherapy and radiotherapy, renal cell carcinoma (RCC) remains to be a frequent cause of cancer-related death. Here, we probed into new targets for its early diagnosis and treatment for RCC. microRNA (miRNA) data of M2-EVs and RCC were searched on the Gene Expression Omnibus database, followed by the prediction of the potential downstream target. Expression of target genes was measured via RT-qPCR and Western blot, respectively. M2 macrophage was obtained via flow cytometry with M2-EVs extracted. The binding ability of miR-342-3p to NEDD4L and to CEP55 ubiquitination was studied with their roles in the physical abilities of RCC cells assayed. Subcutaneous tumor-bearing mouse models and lung metastasis models were prepared to observe in vivo role of target genes. M2-EVs induced RCC growth and metastasis. miR-342-3p showed high expression in both M2-EVs and RCC cells. M2-EVs carrying miR-342-3p promoted RCC cell abilities to proliferate, invade and migrate. In RCC cells, M2-EV-derived miR-342-3p could specifically bind to NEDD4L and consequently elevate CEP55 protein expression via suppressing NEDD4L, thereby exerting tumor-promoting effects. CEP55 could be degraded by ubiquitination under the function of NEDD4L, and miR-342-3p delivered by M2-EVs facilitated the RCC occurrence and development by activating the PI3K/AKT/mTOR signaling pathway. In conclusion, M2-EVs promote RCC growth and metastasis by delivering miR-342-3p to suppress NEDD4L and subsequently inhibit CEP55 ubiquitination and degradation via activation of the PI3K/AKT/mTOR signaling pathway, strongly driving the proliferative, migratory and invasive of RCC cells.     

肾癌的靶向治疗

 目前转移性肾癌是最难治的恶性肿瘤之一。基于肾癌发生的分子机制的阐明，从而导致发展有希望治疗靶点的新药。在临床研究中，舒尼替尼和索拉芬尼是治疗晚期或转移性肾癌有明显的效果和可处理的毒性，它属于口服的多靶点酪氨酸激酶抑制剂，抑制血管内皮生长因子受体与血小板衍生的生长因子受体和C-KIT受体酪氨酸激酶。这两种药很快批准作为第二线药物治疗肾癌，并将用作第一线治疗。舒尼替尼或索拉芬尼作为单剂治疗与联合方案治疗肾癌值得进一步研究