自体外周血干细胞移植治疗小细胞肺癌进展

自体外周血干细胞移植(APBSCT)联合大剂量化疗(HDC)可提高治疗小细胞肺癌(SCLC)的疗效,延长生存期。APRSCT还可联合放疗和手术治疗SCLC。年龄、化疗方案及疾病程度等因素可影响APBSCT疗效。APBSCT治疗SCLC既有直接的抗癌作用,也有其免疫治疗作用。     

重组人血管内皮抑素联合化疗治疗复发性小细胞肺癌三例

 目的　观察重组人血管内皮抑素（商品名：恩度）联合化疗治疗复发性小细胞肺癌（SCLC）的有效性及安全性。方法　3例为既往原发病灶均接受过放射治疗及三线或以上的方案化疗后病情进展的广泛期SCLC患者,2例重组人血管内皮抑素联合洛铂方案化疗,1例重组人血管内皮抑素联合HLF方案化疗,治疗1个周期后按美国国立癌症研究所常见不良事件分级标准（NCI CTC 3.0）评价毒性,2个周期后按实体瘤疗效评价标准（RECIST 1.0）评价疗效。结果　2例患者分别为微小缓解（MR）及部分缓解（PR）,1例疾病进展（PD）。2例死亡的患者疾病进展时间（TTP）分别为8个月和27周,总生存期（OS）分别为60个月和74个月,另1例生存时间已达78个月,近期疗效评价仍维持PR。结论　重组人血管内皮抑素联合化疗治疗复发转移性SCLC,尤其是三线或三线以上治疗失败的患者具有较好的近期疗效及耐受性。     

自体外周血干细胞移植治疗恶性血液病

 目的 观察自体外周血干细胞移植（APBSCT）治疗急性白血病及恶性淋巴瘤的疗效。方法 用APBSCT治疗急性白血病3例,恶性淋巴瘤5例,恶性淋巴瘤采用环磷酰胺联合粒细胞集落刺激因子（G-CSF）动员;3例白血病患者化疗缓解后,予5～9个疗程的化疗巩固治疗,再给予化疗加G-CSF动员。5例恶性淋巴瘤预处理方案为CBV,急性白血病预处理方案为MAC。结果 全部患者均获得完全缓解,随访时间4～12个月,全部病例无病生存,无移植相关死亡。结论 APBSCT是治疗急性白血病及恶性淋巴瘤、改善其预后的主要手段之一,APBSCT后对急性白血病患者应定期进行序贯化疗和免疫治疗,对难治的恶性淋巴瘤患者应进行补救治疗及免疫治疗。     

四种方法治疗鼻腔非霍奇金淋巴瘤的疗效比较

 目的 评价化疗、放疗、放疗加化疗及自体外周血干细胞移植（APBSCT）联合全身照射（TBI）4种治疗方法对原发鼻腔的非霍奇金淋巴瘤（N-NHL）的疗效。方法 1980年至2000年间我院收治的原发鼻腔非霍奇金淋巴瘤（N-NHL）138例进行回顾分析。放射治疗：主野鼻前"凸"字野,辅单或双侧耳前野,累及口咽者先用面颈联合野。鼻腔靶区中位剂量56.0（35.2～75.5）Gy。化疗：放射治疗前、中、后或单纯化疗,方案为COP,COPP,COMP,CHOP,COBDP。6例为APBST联合 TBI 。TBI组剂量为6MV X 线8 Gy,有两例原发灶加量30 Gy。结果 单化组、单放组、放疗加化疗组及APBST联合 TBI组局部控制率分别为12 %,69 %,76 %,83 %;5年总生存率分别为9 %,52 %,63 %,83 %。APBSCT联合TBI组生存率优于放疗加化疗组,而放疗加化疗组优于单放组,单放组优于单化组（P＜0.05）。结论 放化疗结合的治疗应成为N-NHL的主要治疗方法,而APBSCT联合TBI取得了更好的疗效。     

术后确诊的小细胞肺癌联合放化疗疗效分析

目的回顾性总结及评价手术后确诊的小细胞肺癌（SCLC）患者44例联合放化疗治疗的疗效。方法44例SCLC患者中,Ⅰ期15例（34.1%）,Ⅱ期13例（29.6%）,Ⅲ期12例（27.3%）,Ⅳ期4例（9.1%）,除肺段切除1例外均行肺叶或全肺切除,术后均用＂依托泊苷＋顺铂或卡铂＂或＂紫杉醇＋顺铂或卡铂＂方案化疗4～8个疗程,分别随访1,3,5年生存率。结果44例小细胞肺癌（SCLC）患者的1,3,5年总的生存率分别为84.3%、48.2%和18.1%。Ⅰ期、Ⅱ期患者采用术后联合放、化疗,可以获得较好疗效,Ⅲ期、Ⅳ期患者首选手术对生存率无益。结论手术后联合放、化疗对Ⅰ～II期的SCLC具有良好的治疗效果。     

免疫检查点抑制剂治疗小细胞肺癌疗效及预后生物标志物的研究进展

小细胞肺癌（SCLC）的治疗已经迈入免疫治疗时代,免疫疗法联合化疗的一线治疗新标准得以确立。然而并非所有 SCLC患者均能从免疫检查点抑制剂（ICI）中获益,缺乏有效的疗效和患者预后生物标志物在很大程度上限制了其临床应用。目 前,肿瘤相关生物标志物PD-L1表达水平在预测SCLC免疫治疗疗效及患者预后中最为常用;肿瘤突变负荷（TMB）、错配修复缺 陷（dMMR） 和微卫星高度不稳定（MSI-H）也可作为预测 ICI 治疗疗效及患者预后的潜在生物标志物。而 dMMR/MSI-H 因在 SCLC中的发生频率极低,限制了其应用;外周血免疫相关标志物因其便捷性而在SCLC免疫治疗中受到越来越多的关注;肿瘤 微环境相关的生物标志物也有助于识别从ICI治疗中获益的患者。因此,深入了解SCLC的一线免疫治疗现状和预测患者免疫 治疗疗效与预后的潜在生物标志物的研究进展,可为SCLC患者免疫治疗优化策略和分层管理提供思路和参考。     

小细胞肺癌的研究进展

七十年代以前,小细胞肺癌(SCLC)的主要治疗手段为手术、放疗,或手术 放疗。即使是可切除病例,5年生存率也仅达1—3％,因为确诊时往往已有扩散。七十年代以后,联合化疗对SCLC有较好的疗效,且可延长生存期,八十年代联合化疗已成为SCLC的标准治疗方法。一般采用化疗 放疗。近几年来,化疗结合手术治疗小细胞肺癌是可行的,可使早期SCLC5年生存率达40％左右,因而SCLC综合治疗有可能提高远期疗效。     

自体外周血造血干细胞移植治疗难治性恶性淋巴瘤的临床疗效

目的：探讨自体外周血造血干细胞移植（APBSCT）治疗难治性恶性淋巴瘤的临床疗效。方法：APBSCT治疗难治性恶性淋巴瘤26例,采用CHOP方案化疗加G-CSF动员外周血造血干细胞。结果：26例患者中25例获造血重建,16例获CR（61.53%）,9例PR（34.61%）,1例死于肝静脉闭塞,移植组3年无病生存率达41.70%。结论：对APBSCT治疗难治性恶性淋巴瘤具有较好疗效。明显优于常规化疗。     

沙利度胺联合EP方案治疗小细胞肺癌

目的：观察沙利度胺与EP方案联合治疗小细胞肺癌（small cell lung cancer,SCLC）的近期疗效及不良反应。方法：22例经病理或细胞学证实的SCLC患者,随机分为联合组和化疗组各11例,联合组接受沙利度胺联合EP方案,化疗组接受EP方案化疗,治疗2周期以后进行疗效评价。结果：联合组有效率54.55%,临床受益率90.91%;化疗组有效率54.55%,临床受益率81.82%（P〉0.05）;体重增加率联合组和对照组分别为72.73%和18.19%（P〈0.05）;联合组和对照组Karnofsky评分改善率分别为72.73%和27.23%（P〈0.05）;两组患者不良反应情况未见明显差异。结论：沙利度胺与化疗同时应用和单用化疗相比,可以提高恶性肿瘤患者治疗的临床受益率,同时提高患者生活质量,增加化疗耐受性。     

托马克联合治疗肺癌Ⅲ期临床观察

［目的］观察托马克（长春地辛VDS）对原发性肺癌的疗效。[方法]应用含托马克的联合化疗对59例晚期原发性支气管肺癌患者进行了Ⅲ期临床研究。其中非小细胞肺癌（NSCLC）50例，小细胞肺癌（SCLC）9例。（结果）肺癌化疗总有效率达54．2％，NSCLC及SCLC有效率分别为50．0％及77．8％。化疗毒副反应以骨髓抑制、胃肠道反应及脱发为主。［结论］托马克的临床疗效及毒副反应与国外长春地辛同类产品相似。可广泛应用于支气管肺癌的临床治疗中。     

Biomarkers in clear cell renal cell carcinoma

The treatment of advanced renal cell carcinoma (RCC) has evolved significantly following the identification of the von Hippel–Lindau (VHL) gene and the function of its protein, and subsequent development of antiangiogenic therapies. A series of clinical trials resulted in the approval of three new agents with significant activity in this disease. Additional studies are now underway to identify subsets of patients most likely to benefit. This article reviews the current therapy for advanced RCC and the development of biomarkers in RCC. This requires the identification of disease characteristics at a clinical, genetic and molecular level associated with response and/or surrogate measures of clinical benefit. Currently, a variety of prognostic factors (lactate dehydrogenase, performance status, disease-free interval, hemoglobin and calcium levels) are utilized to predict the survival of RCC patients. The use of validated biomarkers in either serum/plasma, urine or tissue could enhance this process, as well as define at the molecular and genetic levels, factors associated with response to therapy and/or the development of resistance. Examples include plasma VEGF levels, VHL gene mutation status and carbonic anhydrase IX levels in tumor tissue, among others. Validation of such biomarkers is crucial in order for them to be clinically useful.     

Biomarkers in clear cell renal cell carcinoma

The treatment of advanced renal cell carcinoma (RCC) has evolved significantly following the identification of the von Hippel-Lindau (VHL) gene and the function of its protein, and subsequent development of antiangiogenic therapies. A series of clinical trials resulted in the approval of three new agents with significant activity in this disease. Additional studies are now underway to identify subsets of patients most likely to benefit. This article reviews the current therapy for advanced RCC and the development of biomarkers in RCC. This requires the identification of disease characteristics at a clinical, genetic and molecular level associated with response and/or surrogate measures of clinical benefit. Currently, a variety of prognostic factors (lactate dehydrogenase, performance status, disease-free interval, hemoglobin and calcium levels) are utilized to predict the survival of RCC patients. The use of validated biomarkers in either serum/plasma, urine or tissue could enhance this process, as well as define at the molecular and genetic levels, factors associated with response to therapy and/or the development of resistance. Examples include plasma VEGF levels, VHL gene mutation status and carbonic anhydrase IX levels in tumor tissue, among others. Validation of such biomarkers is crucial in order for them to be clinically useful.     

Non-small and small cell lung carcinoma cell lines exhibit cell type-specific sensitivity to edelfosine-induced cell death and different cell line-specific responses to edelfosine treatment

The unique signal transduction pathways that distinguish non-small cell lung carcinoma (NSCLC) from small cell lung carcinoma (SCLC) are poorly understood. We investigated the ability of edelfosine, an inhibitor of phosphatidylinositol-specific phospholipase C (PLC) to inhibit cell viability among four NSCLC cell lines and four SCLC cell lines. The differential sensitivity of cells to edelfosine's cytostatic and cytotoxic effects has been attributed to edelfosine-induced changes in the activities of many enzymes, including c-Jun NH2-terminal kinase (JNK), extracellular signal-regulated kinases (ERK), p38 kinase, and poly(ADP-ribose) polymerase (PARP). To investigate the role of these enzymes in edelfosine-induced cytotoxicity, we correlated edelfosine-induced changes in enzyme activity and cell viability among the different NSCLC and SCLC cell lines. We found that NSCLC cells are much more susceptible to the cytotoxic effects of this drug than are SCLC cells. Three out of the four edelfosine-sensitive NSCLC cell lines (NCI-H157, NCI-H520, NCI-H522) exhibit G2/M arrest, significant apoptosis and some degree of JNK activation in response to drug treatment. In contrast, none of the SCLC cell lines exhibit edelfosine-induced G2/M arrest or significant apoptosis. A comparison of the edelfosine-induced effects among the sensitive and resistant lung cancer lines indicates that there is little correlation between edelfosine-induced cytotoxicity and altered activities of JNK, ERK, p38, or cleavage of PARP. These results demonstrate that edelfosine-induced changes in JNK, ERK, p38, or PARP are not good predictors of cell susceptibility to edelfosine-induced cytotoxicity. Thus, edelfosine-induced inactivation of PLC may disrupt signaling cascades downstream of PLC that are unique to individual cellular environments. These findings also identify edelfosine as one of the few potential chemotherapeutic agents that has a greater cytotoxic effect against NSCLC cells than SCLC cells.     

桥接整合因子1通过AKT-mTOR通路诱导非小细胞肺癌H1975细胞周期阻滞

目的：研究桥接整合因子1（bridging intergrator 1,Bin1）基因过表达后对非小细胞肺癌细胞株H1975细胞周期的影响及其作用机制。方法：构建携带Bin1基因的CMV-MCS-GFP-SV40-Neomycin-Bin1质粒,并转染H1975细胞（Bin1+组）,另设置空白质粒转染组（Bin1-组）及空白对照组（Ctrl组）,利用RT-PCR和Western blotting分别检测3组细胞中Bin1在mRNA和蛋白质水平的表达情况。流式细胞术检测不同处理组H1975细胞周期的变化,Western boltting分别检测各组中AKT、mTOR磷酸化水平及细胞周期相关蛋白（周期蛋白D1、CDK4、Rb）的表达情况。结果：与Bin1-组、Ctrl组比较,Bin1+组H1975细胞中Bin1在mRNA、蛋白水平表达明显上调（均P<0.05）; H1975细胞阻滞在G1期\[（60.53±1.89）% vs（46.14±1.56）%、（47.33±2.07）%,均P<0.05\]; Bin1+组H1975细胞内p-AKT、p-mTOR表达下调（均P<0.05）,AKT、mTOR表达变化无统计学差异（P>0.05）;周期蛋白D1、CDK4的表达量均明显下调(P<0.05),Rb表达量明显增加（P<0.05）。结论：Bin1基因在H1975细胞株过表达后明显诱导细胞周期阻滞,其机制可能是通过抑制AKT-mTOR通路及其细胞周期相关蛋白实现的。     

Inhibition of S-adenosylhomocysteine hydrolase decreases cell mobility and cell proliferation through cell cycle arrest

S-adenosylhomocysteine hydrolase (AHCY) hydrolyzes S-adenosylhomocysteine to adenosine and l-homocysteine, and it is already known that inhibition of AHCY decreased cell proliferation by G2/M arrest in MCF7 cells. However, the previous study has not indicated what mechanism the cell cycle arrest is induced by. In this study, we aimed to investigate the different cell cycle mechanisms in both p53 wild-typed MCF7 and p53 mutant-typed MCF7-ADR by suppressing AHCY. We extensively proved that AHCY knockdown has an anti-proliferative effect by using the WST-1 assay, BrdU assay, and cell cytometry analysis and an anti-invasive, migration effect by wound-healing assay and trans-well analysis. Our study showed that down-regulation of AHCY effectively suppressed cell proliferation by regulating the MEK/ERK signaling pathway and through cell cycle arrests. The cell cycle arrest occurred at the G2/M checkpoint by inhibiting degradation of cyclinB1 and phosphorylation of CDC2 in MCF7 cells and at the G1 phase by inhibiting cyclinD1 and CDK6 in MCF7-ADR cells. Finally, we determined that AHCY regulates the expression of ATM kinase that phosphorylates p53 and affects to arrest of G2/M phase in MCF7 cells. The findings of this study significantly suggest that AHCY is an important regulator of cell proliferation through different mechanism in between MCF7 and MCF7-ADR cells as p53 status.