Detection of Gastrin-Releasing Peptide mRNA in Small Cell Lung Carcinomas and Medullary Thyroid Carcinomas Using Synthetic Oligodeoxyribonucleotide Probes

Human gastrin-releasing peptide (GRP) mRNA was detected in thetumor tissues of medullary thyroid carcinomas and small celllung carcinomas using synthetic oligodeoxyribonucleotldes ashybridization probes. The amount of GRP mRNA was estimated byradiodensitometric hybridization assay. A good correlation wasfound between the amount of GRP mRNA and the concentration ofimmuno-reactive GRP in the tumor tissues.     

Meta-Analysis of Serum Gastrin-Releasing Peptide Precursor as a Biomarker for Diagnosis of Small Cell Lung Cancer

Background: The serum level of gastrin-releasing peptide precursor (proGRP) is generally. elevated in patients with small cell lung cancer (SCLC). However, the diagnostic sensitivity and specificity of serum proGRP in SCLC cases remains controversial. The study aimed to assess the diagnostic value of this biomarker by meta-analysis. Materials and Methods: The Cochrane, Clinical trials, Pubmed, Web of Science and Embase databases were searched and diagnostic values were calculated or extracted. Statistical analysis was accomplished with RevMan 5.3 and STATA 12.0 software. Results: A total of 27 studies with 7268 participants were included. The pooled sensitivity, specificity, PLR, NLR and DOR were 0.754 (95% CI: 0.700-0.802), 0.945 (95% CI: 0.916-0.965), 13.804 (95% CI: 9.096-20.948), 0.260 (95% CI: 0.213-0.317) and 53.101 (95% CI: 34.327-82.145) respectively. The AUC was 0.910 (95% CI: 0.880-0.930). Significant publication bias was not found (P =0.622). Conclusions: The meta-analysis indicated that serum proGRP is indeed a useful biomarker with good sensitivity and high specificity for diagnosis of SCLC. Therefore proGRP can be expected to be widely applied in the clinic for identification of lung cancer patients.     

局限期小细胞肺癌非手术综合治疗(附60例疗效与生存关系分析)

治疗局限期小细胞肺癌60例,联合化疗加胸部~(60)Co 照射和随机分预防性脑照射及非脑照射。CR49例,PR4例,NR7例,总有效率88%。生存范围7～58个月,中位数18个月,2年生存者21例(35%),3年无瘤生存7例(11%)。生存时间与 KPS 计分、组织学亚型及治疗前 CEA 值和化疗周期次数相关,但与是否预防性脑照射无关。     

小细胞肺癌合并抗利尿激素异常分泌综合征研究进展

小细胞肺癌患者常合并抗利尿激素异常分泌综合征(SIADH),其发生目前认为主要是肿瘤细胞分泌及药物应用引起体内抗利尿激素增多,引起体内水钠代谢平衡紊乱,导致不同程度的低钠血症,临床症状多样,表现无特异性,尤其与肿瘤引起的症状类似,极易造成误诊、漏诊.治疗上在积极治疗原发肿瘤基础上,严格限水是有效和主要的方法,小细胞肺癌患者合并抗利尿激素异常分泌综合征预后相关研究结果不一致,多认为是预后不良的独立因子.     

Small Cell Lung Carcinoma with Ectopic Adrenocorticotropic Hormone and Antidiuretic Hormone Syndromes: A Case Report

This report describes a 63-yr-old man with lung cancer accompanyinghypertension, hyperpigmentation, muscle weakness, psychosis,hypokalemia, hyperglycemia, hyponatremia, massive naturesisand lower serum osmolality than urine osmolality. Elevated levelsof plasma and urine corticosteroids and of plasma immunoreactiveadrenocorticotropic hormone (ACTH) were not altered by the administrationof large amounts of dexamethasone. Elevated plasma antidiuretichormone (ADH) values were also demonstrated. Postmortem examinationsrevealed small cell lung carcinoma with extensive metastasis,bilateral adrenocortical hyperplasia and Crooke's degenerationof the pituitary gland. Immunoradiological and immunohistochemicalstudies demonstrated the presence of immunoreactive ACTH, ADHand gastrin-releasing peptide in the tumor tissue. Beta-melanocyte-stimulatinghormone, calcitonin and carcinoembryonic antigen were also detectedby one of the methods. Hence, this is a rare case of lung cancerwith multiple hormone production and clinical and laboratoryevidence of both the ectopic ACTH and ADH syndromes. ^* Present address: Department of Internal Medicine, Keio UniversitySchool of Medicine, Tokyo, Japan     

Feasibility Study of Personalized Peptide Vaccination for Advanced Small Cell Lung Cancer

Introduction

The prognosis of patients with small cell lung cancer (SCLC) remains very poor. Therefore, the development of new therapeutic approaches, including immunotherapies, is desirable.

Establishment of a Human Small Cell Lung Cancer Cell Line Producing a Large Amount of Anti-diuretic Hormone

A new cancer cell line (Lu-165) producing a large amount of anti-diuretic hormone (ADH, 2.8 μg/g protein) was established from a 50-year-old small cell lung cancer patient presenting with a syndrome of inappropriate anti-diuretic hormone secretion. These cells grew well in serum-supplemented medium and during more than 100 passages they continued producing a large amount of this hormone. This cell line will be a useful tool for studies of the biochemistry and pathology of ADH-producing cancer.     

Enzyme-linked Immunosorbent Assay of Pro-gastrin-releasing Peptide for Small Cell Lung Cancer Patients in Comparison with Neuron-specific Enolase Measurement

Our previous study demonstrated that pro-gastrin-releasing peptide(31–98), or ProGRP, is a specific tumor marker in patients with small cell lung carcinoma (SCLC). Using a newly developed, highly sensitive enzyme-linked immunosorbent assay (ELISA) for ProGRP, we analyzed 1,446 samples including those obtained from 478 lung cancer patients to evaluate the clinical usefulness of this ELISA. Several properties indicated that ProGRP is a useful tumor marker for SCLC. First, ProGRP was specifically elevated in SCLC patients. In non-SCLC patients and patients with non-tumorous lung diseases, its serum level was very rarely elevated. Secondly, ProGRP was a reliable marker, in terms of the marked elevation of serum ProGRP levels in SCLC patients. Thirdly, serum ProGRP levels were elevated in SCLC patients even at a relatively early stage of this disease. Fourthly, changes in the serum ProGRP level showed an excellent correlation with the therapeutic responses in SCLC patients. Neuron-specific enolase (NSE) is accepted as a tumor marker of SCLC patients. With the aim of comparing ProGRP and NSE as tumor markers for SCLC patients, we measured serum NSE levels in all samples collected in the present study. We found that ProGRP was superior to NSE in terms of sensitivity, specificity and reliability. Therefore, we consider that ProGRP can play a major role as a clinical tumor marker for SCLC patients.     

Long-Term Survival in Patients with Small Cell Lung Cancer

Of the 66 patients with small cell lung cancer (SCLC) who weretreated by combination chemotherapy with or without radiationtherapy from July 1978 to December 1983 at the National CancerCenter Hospital, Tokyo, 12 (18%) sur vived over two years andnine (14%) have remained disease-free over three years. Thetwo-year survival rates were compared according to the patientcharacteristics of sex, performance status (PS), extent of disease,histologic subtype, regimen of the initial chemotherapy andresponse to treatment. Sex, extent of disease and response tothe initial chemotherapy were the most important prognosticfactors. The prognosis for patients with liver or bone metastasis was poor. All disease-free survivors, except for two patientswho were treated by surgical resection after chemotherapy, achievedcomplete response (CR) with chemotherapy with or without radiationtherapy. Eleven of the 12 two-year survivors achieved CR. Becauseof the small number of patients in our study, it will be necessaryto evaluate further the influence of prognostic factors in patientswith SCLC in future studies.     

Clinical and Flow Cytometric Analyses of Renal Cell Carcinomas with Reference to Incidental or Non-incidental Detection

In recent years renal cell carcinomas have been diagnosed asincidental findings. The tumors are usually associated withlow stage and good prognosis. To find out if they might havea different malignant potential from suspected tumors, we retrospectivelycompared 56 cases of incidentally detected tumors with 84 casesof suspected tumors, with regard to tumor stage, nuclear grade,tumor size and DNA ploidy pattern as evaluated by flow cytometry.The incidentally detected tumors were lower in stage (P<0.01),smaller in size (P<0.01) and higher in probability of survival(P<0.02) than the suspected tumors, as other studies havereported. Meanwhile, there was no difference in nuclear grade,DNA ploidy pattern and survival in stage I tumors between thetwo groups of renal cancers. The results suggest that the betterprognosis in incidental renal cancer might be due to early detectionrather than lower malignant potential of this specific typeof renal cancer.     

Prognostic Factors in Small Cell Lung Cancer

Extent of disease and clinical performance status have been used traditionally for prognostic stratification of patients with small cell lung cancer. A plethora of other prognostic attributes reflecting host factors, tumor factors, and serological and hematological parameters have been described over the last decade. Attempts to assess the contribution of the latter attributes to prognostication in small cell lung cancer have lead to the formation of multivariate prognostic models. These models invariably describe prognostic groupings that are not identified by the conventional two-stage classification currently in use. Consensus for application of a new prognostic classification is evolving with analysis of prognostic data from diverse clinical centers.     

Immunotherapy in Extensive-Stage Small Cell Lung Cancer

Small cell lung cancer (SCLC) remains a poorly understood disease with aggressive features, high relapse rates, and significant morbidity as well as mortality, yet persistently limited treatment options. For three decades, the treatment algorithm of SCLC has been stagnant despite multiple attempts to find alternative therapeutic options that could improve responses and increase survival rates. On the other hand, immunotherapy has been a thriving concept that revolutionized treatment options in multiple malignancies, rendering previously untreatable diseases potentially curable. In extensive stage SCLC, immunotherapy significantly altered the course of disease and is now part of the treatment algorithm in the first-line setting. Nevertheless, the important questions that arise are how best to implement immunotherapy, who would benefit the most, and finally, how to enhance responses.     

Surgery for Small Cell Lung Cancer

Retrospective analyses have shown that, following surgical resection, patients with early-stage small cell lung cancer have a survival rate comparable to that seen with non-small cell lung cancer, especially if combined modality therapy is used. Surgery has been employed in three specific instances: primary surgery followed by postoperative chemotherapy and, when indicated, mediastinal irradiation for tumors presenting as peripheral nodules; multimodality therapy including induction chemotherapy followed by surgery; and radiotherapy in "resectable," very limited disease and "salvage surgery" for patients with limited disease previously treated, recurring at the primary site. The results of such surgery in very selected patients yields the best reported results in the treatment of small cell lung cancer. These approaches are worthy of further study.     

双特异性抗体治疗小细胞肺癌的实验研究

目的：探讨双特异性抗体在小细胞肺癌免疫治疗中的应用价值。方法：制备既抗小细胞肺癌表面抗原又抗T细胞表面CD3抗原的双特异抗体（简称双抗，BSAb),分别进行体外实验与运输实验。结果：体外实验显示，加入双抗的较未加入双抗的LAK细胞对小细胞肺癌细胞杀伤活性明显提高（P＜0．05）。显示杀伤活性与效靶比例呈正相关。在肿瘤生长的动物实验中，接种后第7－10天双抗组肿瘤发生率明显低于未用双抗组（P＜0．05）；裸鼠生存动物实验中，双抗组平均存活为58．4天，是对照组的1．5倍。结论：双特异性抗体能提高LAK细胞对小细胞肺癌的治疗效果。     

冰片逆转小细胞肺癌顺铂耐药的研究

摘 要：［目的］ 评价冰片对小细胞肺癌（SCLC）顺铂（DDP）耐药的逆转作用及其对P糖蛋白（P-glycoprotein,P-gp）和小凹蛋白-1 (Caveolin-1)表达的影响。［方法］ 利用前期建立的SCLC DDP耐药细胞株LTEP-P/DDP,四甲基偶氮唑盐微量酶反应比色法（MTT）检测冰片和/或DDP的抗肿瘤活性,流式细胞仪检测细胞周期和凋亡率,Western blotting检测P-gp和Caveolin-1的表达。［结果］冰片联合DDP对LTEP-P/DDP-0.75 细胞的增殖抑制作用较单用DDP显著性增加（P<0.05）,耐药逆转指数为2.246。LTEP-P/DDP-0.75细胞经冰片联合DDP处理细胞后,较单用DDP处理组的G0/G1期和S期降低,G2/M期升高,差异有显著性（P<0.05）。冰片和DDP联合处理后,LTEP-P/DDP-0.75细胞凋亡显著性上升（P<0.05）,LTEP-P/DDP-0.75细胞Caveolin-1相比LTEP-P细胞显著性上升（P<0.05）,冰片或DDP单独用药组Caveolin-1显著性变化,冰片联合联合DDP组相比对照组能显著性降低LTEP-P/DDP-0.75细胞Caveolin-1表达（P<0.05）,而对P-gp无显著性抑制作用。［结论］ 冰片能在一定程度上逆转LTEP-P/DDP-0.75对DDP的耐药,其作用可能与抑制Caveolin-1表达有关。