小剂量IL-2和IFNα与TNFα联合治疗恶性肿瘤的免疫学与临床研究

目的:研究小剂量细胞因子在恶性肿瘤免疫治疗中的意义。方法:全身应用小剂量重组干扰素(ＩＦＮα２ｂ)、白细胞介素－２(ＩＬ－２)和肿瘤坏死因子(α－ＴＮＦ)联合治疗多种恶性肿瘤６０例。应用ＡＰＡＡＰ法和免疫单向扩散法(ＲＩＤ)分析了治疗前后患者外周血中Ｔ、Ｂ淋巳细胞、ＮＫ细胞、免疫球蛋白(Ｉｇ)和补体Ｃ３活性。结果:治疗１个疗程后外周血中ＣＤ４＋的Ｔ淋巴细胞和ＣＤ２３＋的Ｂ淋巴细胞显著的高于治疗前水平(Ｐ＜０．０５);ＣＤ４＋/ＣＤ８＋比值也明显增高(Ｐ＜０．０１)。免疫球蛋白(ＩｇＭ)活性亦显著的高于治疗前水平(Ｐ＜０．０５)。ＫＰＳ积分较治疗前明显增高(Ｐ＜０．００１)。治疗后细胞因子加化疗组的ＫＰＳ积分平均增高２８．５分(Ｐ＜０．００１);ＣＲ ２６例(６５．０%);ＰＲ １１例(２７．５%),总有效率８２．５%。单纯细胞因子治疗组的ＫＰＳ积分平均增高２３分(Ｐ＜０．００１);ＰＲ １３例(６５．０%),总有效率６５．０%。结论:本方案可以显著的提高多种恶性肿瘤患者的细胞免疫和体液免疫。有可能提高肿瘤的化疗效果和患者的生存质量,延长生存期。     

康莱特注射液联合化疗治疗非小细胞肺癌的

目的观察康莱特注射液与化疗联用对非小细胞肺癌(NSCLC)的治疗效果.方法将62例中晚期NSCLC患者随机分为康莱特联用诺维本+异环磷酰胺(NVB+IFO+NI)组和单纯NI化疗组.结果两组有效率分别为53.1%和36.6%,差异有显著性(P<0.05),联合组治疗前后KPS评分改善及稳定者明显高于单纯化疗组(P＜0.05).结论长期应用康莱特能使患者KPS提高或保持稳定,有助于提高疗效,延长缓解期.肿瘤防治杂志,2001,8(4)394-395     

力尔凡配合化疗治疗肿瘤的临床研究

目的观察链球菌制剂(力尔凡)配合化疗治疗肿瘤提高患者化疗后免疫功能及减轻化疗副作用的疗效。方法70例恶性肿瘤患者随机分为治疗组和对照组。治疗组(35例)采用力尔凡+化疗,对照组(35例)单用化疗,两组同一病种化疗方案相同。力尔凡给药方案化疗前3天开始5mg/d皮下注射,连用3天;然后5mg/d静滴,连用5天,再10mg/d静滴,连用20天,28天为1疗程。结果1)治疗组全部病例均如期进行下一周期化疗,化疗间歇期中血常规各项始终在正常范围,未使用任何注射用升白药物,对照组有4例患者因白细胞低于4.0×109/L,未能如期开始下一周期化疗,且另有12例患者化疗间歇期中因白细胞低于3.0×109/L而使用升白针剂;2)治疗组化疗期间恶心、呕吐Ⅰ度以上发生率68.0%(24/35),对照组为94.2%(33/35,P<0.05);3)治疗组治疗后与治疗前相比CD4、CD4/CD8、CD56值均明显升高(P<0.05),而对照组则相反,各项均下降(P<0.05),且两组治疗后上述指标相比差异显著(P<0.05)。结论力尔凡与化疗同时应用能明显减轻化疗副反应,改善患者生活质量,降低白细胞低于正常值的发生率,保证化疗如期进行,同时提高患者的免疫功能。     

顺铂、5-氟尿嘧啶持续动脉灌注化疗对口腔癌患者免疫功能的影响

目的 研究顺铂、5-氟尿嘧啶持续动脉灌注化疗对口腔癌患者免疫功能的影响.方法 选取30例口腔癌患者为治疗组,选取30例健康志愿者为对照组,给予治疗组顺铂、5-氟尿嘧啶持续动脉灌注化疗,观察治疗组化疗前后T淋巴细胞各亚群的改变、T细胞表型表达特点、细胞因子水平改变.结果 30例健康志愿者T淋巴细胞各表型占总细胞数的比例处于正常范围,化疗前治疗组CD3+、CD4+、CD4+/CD8+较对照组低(P<0.05),CD8+较对照组高(P<0.05),化疗后治疗组CD4+/CD8+较化疗前升高(P<0.05),CD8+较化疗前降低(P<0.05);化疗前治疗组CD4+/INF-y+INF-y+低于对照组(P<0.05),化疗后治疗组INF-y+较化疗前升高,且高于对照组(P<0.05),化疗后治疗组CD4+/INF-y+INF-y+较化疗前升高,但仍低于对照组(P<0.05);化疗前治疗组CD4+/IL-2+IL-2+低于对照组(P<0.05),化疗后治疗组CD4+/IL-2+IL-2+与化疗前比较有所上升,但仍低于对照组(P<0.05).结论 给予口腔癌患者手术治疗的同时,进行顺铂、5-氟尿嘧啶持续动脉灌注化疗,能够改善患者的免疫功能,有利于患者的预后.     

胃癌患者化疗前后Th1/Th2细胞因子的检测及其临床意义

目的 研究胃癌患者化疗前后CD4+T淋巴细胞中Th1、Th2类细胞因子的表达水平和Th1/Th2值的变化及其临床意义.方法 60例胃癌患者接受FOLFOX4方案化疗,应用流式细胞仪对化疗前后患者外周血特异性细胞因子的表达变化进行分析.结果 化疗后,全组胃癌患者外周血CD4+T淋巴细胞分泌的γ干扰素(IFN-γ)的表达水平为11.4%±5.0%,较化疗前升高(P＜0.05);白介素10(IL-10)的表达水平为3.6%±1.2%,较化疗前降低(P＜0.05);Th1/Th2(IFN-γ/IL-4)的值为3.4±1.0,与化疗前比较,无明显变化(P＞0.05).15例化疗后疗效为部分缓解的患者,外周血CD4+T淋巴细胞分泌的IFN-γ和肿瘤坏死因子-α(TNF-α)的表达水平分别为14.8%±8.0%和5.9%±2.0%,均较化疗前升高(均P＜0.05);Th1/Th2(IFN-γ/IL-4)的值为4.0±1.5,明显高于化疗前水平(P＜0.01).结论 有效的化疗可减轻患者机体的肿瘤负荷,降低Th1类细胞因子向Th2类细胞因子漂移的程度;但胃癌化疗的有效率较低,因此对胃癌化疗者,改善机体免疫功能仍是很重要的治疗措施.     

恶性肿瘤患者化疗前后的淋巴细胞亚群分析

目的:观察恶性肿瘤患者化疗前后淋巴细胞亚群的变化特征,探讨恶性肿瘤患者的机体免疫状况.方法:采用流式细胞术对100例住院恶性肿瘤患者的淋巴细胞亚群进行分析,观察患者化疗前后的淋巴细胞亚群的变化特征.同时收集30名健康体检者作为正常对照.结果:恶性肿瘤患者CD8+细胞、B细胞高于正常,而CD3+细胞、CD4+细胞、NK细胞及CD4+/CD8+比值显著低于正常水平(P<0.05);化疗后完全缓解组以上4项趋于正常(P>0.05);而未缓解组与完全缓解组及正常对照组相比有明显差异(P<0.05).结论:恶性肿瘤患者细胞免疫功能衰退,体液免疫功能略增高,化疗后缓解的病人各指标趋于正常,与病情发展一致,淋巴细胞亚群分析可作为监测恶性肿瘤患者免疫状态的指标.     

小剂量环磷酰胺通过抑制调节性T细胞提高小鼠肝癌阿霉素化疗效果

目的 探讨小剂量环磷酰胺是否可以提高小鼠肝癌阿霉素化疗效果,并对其机制进行探讨.方法 建立C57BL/6J小鼠皮下肝癌模型,待肿瘤长至100～150mm3体积大小时备用.10只小鼠随机分为2组,对照组不处理,观察组以2 mg/只的剂量腹腔注射环磷酰胺(CTX),4天后以流式细胞仪检测小鼠脾脏CD4+、CD8+T细胞和CD4+CD25high Treg淋巴细胞比例.32只小鼠随机分为4组:①对照组(PBS);②环磷酰胺组(CTX);③阿霉素组(DOX);④环磷酰胺+阿霉素组(CTX+DOX);观察小鼠皮下肿瘤生长情况和小鼠的生存期.结果 应用小剂量CTX后荷瘤小鼠脾脏CD4+和CD8+T淋巴细胞的浸润分别由17.62%、16.03%上升到24.54%和25.41%(P<0.05),而Treg则由用药前的11.92%降低为用药后的5.36%(P<0.05).CTX组肿瘤生长和对照组相比无统计学差异(P>0.05).DOX组、CTX+DOX组肿瘤生长均显著受到抑制,以CTX+DOX组更为显著(P<0.05).DOX组生存期显著改善(P=0.027),联合应用CTX后生存期亦有显著捉高(P=0.018).结论 小剂量CTX可以抑制小鼠脾脏Treg浸润,改善机体免疫微环境,并可以增强肝癌阿霉素化疗的效果.免疫化疗治疗晚期肝癌具有一定的应用前景.     

CIK细胞对一线化疗后晚期非小细胞肺癌维持治疗的疗效分析

目的 探讨细胞因子诱导的杀伤细胞(CIK)维持治疗一线化疗后晚期非小细胞肺癌(NSCLC)的疗效及安全性.方法 收集96例ⅢB~Ⅳ非小细胞肺癌患者,一线治疗为4~6个周期的含铂两药方案化疗,将疗效达稳定或以上的患者随机分两组,一组给予CIK免疫治疗,一组给予支持治疗,比较两组的PFS、有效率、外周血T淋巴细胞亚群、KPS评分及评估安全性.结果 CIK组和对照组的中位PFS分别为8.0个月(95%CI 7.3~8.7)和6.0个月(95%CI 4.8~7.2)(P=0.002).CIK组疾病控制率为81.25%,显著高于对照组的62.50%(P<0.05).CIK治疗组患者外周血CD3+、CD3+/CD4+细胞比率较治疗前显著上升,对照组T淋巴细胞亚群没有变化.CIK细胞治疗后患者KPS评分为(71.53±7.96)分,较治疗前显著提高(P<0.05).CIK治疗组中3例出现一过性发热,3例皮疹,2例肌肉痛.结论 CIK维持治疗一线化疗后稳定的晚期非小细胞肺癌患者,可提高PFS及近期疾病控制率,改善免疫功能及生活质量,安全性好.     

化疗对乳腺癌患者外周血中Treg细胞数目的影响及意义

目的研究化疗药物对乳腺癌患者根治术后外周血中Treg(CD4 CD25 调节性T细胞)的影响及意义.方法采集52例乳腺癌术后患者化疗前1天及化疗后第10天外周静脉血,应用流式细胞技术检测外周血中Treg细胞以及CD3 、CD4 、CD8 T细胞占T淋巴细胞百分比,采用ELLSA法检测外周血中IL-4、IL-10、TGF-β1和IFN-γ的表达水平.结果化疗后乳腺癌患者外周血中Treg细胞占T淋巴细胞百分比(4.75±1.60)%较化疗前(5.59±1.81)%减少(P＜0.05),且与淋巴结有无转移、转移数量以及绝经状态无关(P＞0.05).化疗前后CD3 细胞占T淋巴细胞比例分别为(64.690±7.469)%,(64.357±9.356)%(P＞0.05).化疗前后CD4 T细胞占T淋巴细胞比例分别为(38.048±10.671)%,(36.536±9.664)%(P＞0.05).化疗后CD8 T细胞占T淋巴细胞比例(28.129±10.900)%较化疗前(24.876±6.631)%升高(P＜0.05).化疗后CD4 /CD8 (1.506±0.691)较化疗前(1.680±0.704)降低(P＜0.05).化疗后乳腺癌患者外周血中IL-4、IL-10、TGF-β1浓度较化疗前降低,而IFN-γ浓度增高(P均＜0.05).化疗前后Treg细胞比例变化与细胞因子IL-4、IL-10、TGF-β1和IFN-γ浓度变化无关(P＞0.05).结论化疗可使乳腺癌患者外周血中Treg细胞占T淋巴细胞比例降低,从而达到治疗肿瘤的效果.     

胸腺五肽辅助化疗对肺癌患者免疫功能和生活质量的影响及意义

目的 探讨胸腺五肽辅助化疗对肺癌患者免疫功能和生活质量的影响及意义.方法 将78例肺癌患者随机分为治疗组和对照组,每组各39例.对照组采取单纯化疗,治疗组采用胸腺五肽联合化疗.观察和比较治疗前后2组患者的淋巴细胞比例变化、补体C3、C4和免疫球蛋白等免疫功能指标的变化,以及对其生活质量的影响.结果 治疗组患者治疗后CD3+、CD4+、CD4+/CD8+明显高于治疗前,CD8+低于治疗前(P＜0.05);与对照组比较差异有统计学意义(P＜0.05).治疗前后2组患者的补体和免疫球蛋白的变化没有统计学差异(P＞0.05).治疗后,2组患者的生活质量得到明显改善,治疗组的改善程度大于对照组(P＜0.05).2组患者的不良反应发生率无统计学差异(P＞0.05).结论 胸腺五肽辅助化疗可促进肺癌患者免疫功能的恢复,提高患者生活质量,值得临床广泛应用.     

CNS listeriosis confused with leptomeningeal carcinomatosis in a patient with a malignant insulinoma

We describe a case of presumed listeria monocytogenes rhomboencephalitis, which was initially confused with leptomeningeal carcinomatosis in a patient with a malignant carcinoid tumor. Long-term corticosteroid treatment and immunosuppression caused by malignancy predisposed the patient to developing listeriosis. The clinical and radiologic features of this illustrative case are described. Listeriosis is an important treatable differential diagnosis in patients with malignancy presenting with neurologic signs.     

Development of a Nephrotic Syndrome in a Patient with Gastrointestinal Stromal Tumor during a Long-Time Treatment with Sunitinib

A patient with advanced gastrointestinal stromal tumor (GIST) receiving second-line treatment with sunitinib developed edema, increase of the serum creatinine, weight gain, nephrotic syndrome with proteinuria of 12 g/24 h, dyslipidemia, hypoalbuminemia and also presented with hypertension. A kidney biopsy showed an immunocomplex glomerulonephritis. Steroid treatment was started, but the clinical conditions and laboratory values did not improve. So in the hypothesis that the nephrotic syndrome was induced by sunitinib, sunitinib was temporarily discontinued with a subsequent reduction of proteinuria and improvement in blood pressure control. In the last years, the introduction of sunitinib has modified the natural history of advanced GIST. However, due to chronic and prolonged intake of this drug, there is increasingly frequent detection of late and unknown toxicities in clinical practice. In particular, the late renal toxicity from sunitinib may be the primary clinical problem with this drug in the case of prolonged treatment. Monitoring of kidney function and blood pressure should be performed for early detection of side effects such as hypertension and kidney dysfunction in advanced GIST patients receiving long-term treatment with sunitinib. A clinical collaboration between oncologists and nephrologists could be useful with the objective to optimize the management of sunitinib.Key words: Gastrointestinal stromal tumor, Sunitinib, Nephrotic syndrome, Vascular endothelial growth factor, Proteinuria, Renal toxicity     

术者之行始于扶镜

胸外科手术技术已发生革命性变化,胸腔镜手术（video-assisted thoracic surgery, VATS）已经、正在成为各类胸部手术的主流方式。安全、高质、艺术化的VATS离不开扶镜手与术者默契的团队配合,如果说优秀的开放手术是术者脑、眼、手、体并用并无缝连接的整体配合的结果,那么,VATS的扶镜手则担负着两个人的眼睛,即本人和术者,这比照顾一个人脑、眼、手、体更为精细,更为困难。当然,优秀的扶镜手必将成长为不久将来优秀的术者。     

ALKoma: a cancer subtype with a shared target

Anaplastic lymphoma kinase (ALK) is a receptor-type protein tyrosine kinase that is currently the focus of much attention in oncology. ALK is rendered oncogenic as a result of its fusion to NPM1 in anaplastic large cell lymphoma, to TPM3 or TPM4 in inflammatory myofibroblastic tumor, to EML4 in non-small cell lung carcinoma, and to VCL in renal medullary carcinoma. It is also activated as a result of missense mutations in neuroblastoma and anaplastic thyroid cancer. Whereas these various tumors arise in different organs, they share activated ALK, and a marked clinical efficacy with ALK inhibitors has already been shown for some of the tumors with ALK fusions. One of such compound, crizotinib, is now approved in the United States for the treatment of lung cancer positive for ALK rearrangement. I propose that tumors carrying abnormal ALK as an essential growth driver be collectively termed "ALKoma."     

Dramatic Response to Platinum in a Patient with Cancer with a Germline BRCA2 Mutation

We present a case of dramatic response of poor prognosis cancer in a lady with a germline mutation in the BRCA2 gene who was exposed to platinum containing chemotherapy. She is cancer-free 10 years’ later. Such cases provide clinical scenarios for the basis of trials of platinum-like agents in individuals with BRCA mutations who develop cancer.     

Histiocytic lymphoma with sclerosis arising from a nodular lymphoma with a special stromal reaction.

Histiocytic lymphoma with sclerosis was found together with a small nodular lymphoma in a cervical lymph node biopsy from a 48-year-old man. Since the cellular origin of this entity is unclear and its ultrastructure has not been described before, we processed formalin-fixed samples for electron microscopy, which revealed three cell types: small lymphocytes with cleaved nuclei, large lymphocytes with vesticular noncleaved nuclei, and mesenchymal stromal cells occasionally bearing desmosomes or hemidesmosomes. In addition, there was an increase of the intercellular connective tissue, which consisted of a mixture of normal and fibrous long spacing collagen fibers. The results indicate that histiocytic lymphoma with sclerosis can evolve from a nodular lymphoma, and that diagnostic information can be obtained by electron microscopy of tissue samples previously fixed in formalin.