恶性胸液中GLUT-1和iNOS的表达及临床意义

目的探讨恶性胸液中葡萄糖转运蛋白-1(GLUT-1)和诱导型一氧化氮合成酶(iNOS)的表达水平及临床意义。方法检测70例胸腔积液患者(良性积液30例、恶性积液40例)血清和胸液中GLUT-1和iNOS的表达水平,并将检测结果进行对比。结果恶性组胸液中GLUT-1和iNOS水平显著高于良性组水平(P<0.01),血清中GLUT-1和iNOS水平略高于良性组,但无统计学意义(P>0.05),两组患者胸液中的GLUT-1和iNOS水平均高于同组血清中的水平。结论 GLUT-1和iNOS在恶性胸液中高表达,临床上检测二者的水平可能有助于恶性胸腔积液的诊断。     

HER-2蛋白检测对非小细胞肺癌所致恶性胸腔积液的诊断价值

目的探讨胸腔积液HER-2蛋白检测对非小细胞肺癌（NSCLC）所致恶性胸腔积液的诊断价值。方法分别应用酶联免疫吸附法和应用免疫组织化学方法（SP法）检测20例NSCLC所致恶性胸腔积液中HER-2蛋白水平和胸液沉渣细胞HER-2蛋白的表达，同期取20例良性胸腔积液作对照。结果NSCLC所致恶性胸腔积液患者胸液中HER-2水平（6．18±2．35）ng／ml显著高于结核性胸腔积液患者（3．06±1．18）．g／ml（P〈0．01），肺癌性胸液患者血清HER-2水平（3．89±1．98）ng／ml也显著高于结核组患者（2．31±O．65）ng／ml（P〈0．05）；20例NSCLC所致恶性胸液沉渣细胞HER-2蛋白阳性率（85．O％）与20例良性胸液细胞HER02蛋白检测率（O％）具有统计学差异（P＜O．01）。结论用酶联免疫吸附法和免疫组织化学方法（SP法）检测胸腔积液HER-2蛋白，对NSCLC所致恶性胸腔积液诊断具有重要的临床价值。     

α-烯醇化酶对非小细胞肺癌恶性胸腔积液患者的诊断价值

目的探讨α-烯醇化酶对原发性非小细胞肺癌恶性胸腔积液患者的诊断效果。方法选取我院2013年6月-2017年6月收治的非小细胞肺癌合并恶性胸腔积液患者68例为恶性胸腔积液组,选取同期住院的良性肺病良性胸腔积液的患者60例为良性胸腔积液组。检测两组患者胸腔积液中α-烯醇化酶表达水平。结果恶性胸腔积液组胸腔积液中α烯醇化酶水平(155.67±23.51)pg/mL显著高于良性胸腔积液组的(97.60±12.45)pg/mL(P0.05)。肺腺癌胸腔积液中α烯醇化酶水平(160.23±20.30)pg/mL显著高于肺鳞癌(129.22±15.45)pg/mL(P0.05)。α烯醇化酶诊断恶性胸腔积液AUC为0.891。选取76.68 pg/mL作为最佳截断值,其诊断灵敏度为97.10%和特异度为88.50%。结论良恶性胸腔积液中α烯醇化酶水平存在显著性差异,α-烯醇化酶可作为一种良恶性胸腔积液的有效诊断指标,同时对肺癌的组织分型具有一定的指导价值。     

分泌型白细胞蛋白酶抑制因子在胸腔积液中的水平及意义

目的 探讨各种疾病所致的胸腔积液中分泌型白细胞蛋白酶抑制因子的水平及其临床意义.方法 收集85例胸腔积液及其同源外周血(分为四组,其中结核性胸腔积液组为29例,恶性胸腔积液组30例,细菌性胸腔积液组15例,漏出液组11例).应用ELISA法测定胸水上清液和血清中分泌型白细胞蛋白酶抑制因子(SLPI)的浓度,并对结果及意义进行分析.结果 (1)胸腔积液间:结核组浓度(21 1710±29 130)pg/ml,分别与肿瘤组(99 274±21 807)pg/ml、细菌组(127 980±34 299)pg/ml及漏出液组(109 360±21 619)pg/ml相比,差异均有统计学意义(P<0.05);肿瘤组、细菌组及漏出液组三组之间相比差异均无统计学意义(P>0.05).(2)血清中:结核组(35 116±4 122.1)pg/ml及肿瘤组(2 5767±2 054)pg/ml分别与漏出液组(51 377±10 190)pg/ml相比差异有统计学意义(P<0.05);漏出液组与细菌组(52 396±8 954.5)pg/ml比较差异无统计学意义,结核组、肿瘤组及细菌组之间差异亦无统计学意义(P>0.05).(3)胸腔积液与血清液间:结核组、肿瘤组与漏出液组之间差异有统计学意义(P<0.05);而在细菌组差异无统计学意义(P>0.05).(4) 各组胸腔积液与同源外周血清之间无相关性(P>0.05).(5)受试者工作特征曲线(ROC曲线)结果显示:胸腔积液中SLPI浓度对结核性胸腔积液的最佳诊断阈值为23 6071 pg/ml,相应灵敏度和特异度分别为43.33%和96.77%.结论 白细胞蛋白酶抑制因子(SLPI)有可助于结核性与恶性、细菌性及漏出性胸腔积液的鉴别.SLPI浓度测定有可能成为结核性胸腔积液的新诊断方法.     

联合检测胸水脱落细胞Survivin基因及血清Survivin抗体在恶性胸腔积液诊断中的意义

目的:探讨胸水Survivin基因及血清Survivin抗体诊断恶性胸腔积液的可行性。方法:选择恶性胸腔积液患者50例(非小细胞肺癌胸水组)及结核性胸腔积液患者50例(对照组),检测并比较2组胸水脱落细胞Survivin基因表达水平和血清Survivin抗体水平。结果:恶性胸水组脱落细胞Survivin基因表达阳性患者12例(24%)明显高于对照组(0%),恶性胸水组血清Survivin抗体浓度(102.10±94.53)pg/m L明显高于对照组(56.32±19.37)pg/mL(P0.01)。当血清Survivin抗体浓度80 pg/m L时,对癌性胸水诊断的敏感性及特异性均较好,分别为88.0%和84.6%。结论:胸水脱落细胞Survivin基因联合血清Survivin抗体检测在肺癌性胸腔积液诊断中有一定的临床意义。     

胸腔积液中白细胞介素6、18的变化与意义

目的　探讨胸腔积液患者血清及胸腔积液中白细胞介素6(IL -6)、白细胞介素1 8(IL -1 8)的变化及其临床意义,并明确其在胸腔积液免疫发病机理中的作用。方法　应用双抗体夹心酶联免疫吸附测定法(ELISA)检测2 0例结核性胸腔积液患者、2 0例恶性胸腔积液和1 5例漏出性胸腔积液患者血清及胸腔积液中IL -6、IL -1 8的水平。结果　结核组胸腔积液中IL -6、IL- 1 8水平分别为(468.1±1 4 2 .4)和(759.3±2 85 .1 )pg/ml显著高于恶性组(2 2 0 .8±50 .7)和(2 73 .7±93 .7)pg/ml及漏出液组(36 .4±4 .8)和(40 .6±5 .4)pg/ml。结论　IL- 6、IL -1 8在结核性、肿瘤性和漏出性胸腔积液患者的表达水平不同,可作为临床上鉴别诊断的参考指标,在结核和肿瘤性胸膜病变局部的免疫病理生理过程中起着重要作用。     

AMPK信号通路在中老年肺癌患者恶性质胸腔积液中表达及临床意义

目的 研究腺苷酸活化蛋白激酶(AMPK)信号通路在中老年肺癌患者胸腔积液中的表达,从分子水平探明其在良、恶性胸腔积液中的影响。方法 以中老年肺癌患者胸腔积液为研究对象,其中恶性胸水78例,良性胸水42例;将良性胸水作为良性组,恶性(腺癌)胸水为恶性组,分别抽提两组细胞总RNA与总蛋白,RT-PCR检测肝激酶(LK)B1、AMPKα1和AMPKα2 mRNA表达情况,Western印迹检测LKB1、AMPKα1、AMPKα2和P-AMPKα蛋白表达情况。结果 与良性组比较,恶性组LKB1、AMPKα1、AMPKα2 mRNA表达明显下降(P<0.05,P<0.01);与良性组比较,恶性组LKB1蛋白表达降低(P<0.001);AMPKα1、AMPKα2蛋白表达有所降低,但差异无统计学意义(P>0.05);p-AMPKα水平表达差异有统计学意义(P<0.05)。结论 AMPK信号通路对鉴别良、恶性胸腔积液具有一定的临床提示价值。     

联合测定分泌型白细胞蛋白酶抑制因子和腺苷脱氨酶在结核性胸腔积液中的诊断意义

目的探讨联合测定胸腔积液中分泌型白细胞蛋白酶抑制因子（SLPI）和腺苷脱氨酶（ADA）浓度对结核性胸腔积液的诊断价值。方法收集103例胸腔积液及其同源外周血,其中结核性胸腔积液组为45例,恶性胸腔积液组31例,细菌性胸腔积液组16例,漏出液组11例。应用ELISA法测定胸水上清液和血清中SLPI的浓度,用比色法测定ADA水平,并对结果及意义进行分析。结果 （1）结核组SLPI浓度（193790±15476）pg/ml,与恶性组（121700±13101）pg/ml、细菌组（92885±26962）pg/ml、漏出液组（109360±21619）pg/ml相比差异均有统计学意义（P〈0.05）;恶性组、细菌组及漏出液组间相比差异均无统计学意义（P〉0.05）。结核组及细菌组ADA水平与恶性组及漏出液组比较差异有统计学意义（P〈0.05）。（2）受试者工作特征曲线（ROC曲线）结果显示,胸腔积液SLPI浓度对于诊断结核性胸腔积液的最佳阈值为236071pg/ml,曲线下面积（AUC）为69.9%（95%可信区间为58.2%～81.6%）,灵敏度和特异度分别为43.2%和91.4%（P〈0.05）;ADA对于诊断结核性胸腔积液的曲线下面积、灵敏度、特异度、诊断阈值分别是71.9%（可信区间60.9%～82.8%）、75%、64.2%和29.5（P〈0.001）;SLPI和ADA同时高于各自的诊断阈值,得出最佳诊断特异度为95%;SLPI或ADA高于诊断阈值,得出最佳诊断灵敏度为89%。结论单独测定SLPI及ADA均有助于诊断结核性胸腔积液,但联合测定更能提高诊断效能。     

Tenascin-c和癌胚抗原检测在恶性胸腔积液中的诊断价值

目的探讨肌腱蛋白C(Tenascin C,Tn-C)和癌胚抗原(CEA)联合检测在肺癌所致胸腔积液中的表达及其临床意义。方法采用酶联免疫吸附(ELISA)法及电化学发光法分别检测60例肺部良性疾病所致胸腔积液和60例恶性胸腔积液中Tn-C和癌胚抗原(CEA)的表达,分析Tn-C蛋白的表达与临床特征及肺癌诊断的关系。结果恶性组患者胸腔积液中Tn-C的表达水平高于对照组(P0.05),Tn-C在胸水中的表达与患者的性别、吸烟状况、肿瘤大小、病理分期及病理分型无关(P0.05),与淋巴结的转移有关(P0.05);两组患者的Tn-C血清浓度无统计学差异(P0.05)。根据ROC曲线,以Tn-C浓度为41.508ng/ml为最佳诊断临界点,此点所对应的诊断恶性胸腔积液(MPE)敏感性为90%,特异度为46.67%,联合CEA诊断的灵敏度为80%,特异度为98.3%。结论 Tn-C在肺癌所致恶性胸腔积液中的表达水平较高,与CEA联合检测可提高恶性胸腔积液的诊断灵敏度及特异度,故Tn-C可作为肺癌诊断的良好标记物。     

可溶性髓系细胞触发受体-1表达水平与胸腔积液性质的相关性

目的:探讨可溶性髓系细胞触发受体-1(sTREM-1)表达水平与胸腔积液性质的相关性。方法:选择胸腔积液患者84例为研究对象(分为4组:结核性胸水24例;细菌性胸水22例;肿瘤性胸水16例;漏出液22例)。用酶联免疫吸附法(ELISA)分别检测患者胸水和血清中sTREM-1的表达水平,并分析比较。结果:4组患者胸水中,细菌性胸水组sTREM-1表达增高最显著,肿瘤性胸水组次之,漏出液胸水sTREM-1表达最低。4组患者血清中,细菌性胸水组sTREM-1的表达增高也最为显著,其他3组间差异无统计学意义。结论:sTREM-1表达水平对细菌性胸水、结核性胸水、肿瘤性胸水以及漏出液的鉴别诊断有较好价值,特别是对以胸膜细菌感染时胸水的诊断有较重要意义。     

Identification of tumor-associated,MHC class II-restricted phosphopeptides as targets for immunotherapy

The activation and recruitment of CD4⁺ T cells are critical for the development of efficient antitumor immunity and may allow for the optimization of current cancer immunotherapy strategies. Searching for more optimal and selective targets for CD4⁺ T cells, we have investigated phosphopeptides, a new category of tumor-derived epitopes linked to proteins with vital cellular functions. Although MHC I-restricted phosphopeptides have been identified, it was previously unknown whether human MHC II molecules present phosphopeptides for specific CD4⁺ T cell recognition. We first demonstrated the fine specificity of human CD4⁺ T cells to discriminate a phosphoresidue by using cells raised against the candidate melanoma antigen mutant B-Raf or its phosphorylated counterpart. Then, we assessed the presence and complexity of human MHC II-associated phosphopeptides by analyzing 2 autologous pairs of melanoma and EBV-transformed B lymphoblastoid lines. By using sequential affinity isolation, biochemical enrichment, mass spectrometric sequencing, and comparative analysis, a total of 175 HLA-DR-associated phosphopeptides were characterized. Many were derived from source proteins that may have roles in cancer development, growth, and metastasis. Most were expressed exclusively by either melanomas or transformed B cells, suggesting the potential to define cell type-specific phosphatome “fingerprints.” We then generated HLA-DRβ1*0101-restricted CD4⁺ T cells specific for a phospho-MART-1 peptide identified in both melanoma cell lines. These T cells showed specificity for phosphopeptide-pulsed antigen-presenting cells as well as for intact melanoma cells. This previously undescribed demonstration of MHC II-restricted phosphopeptides recognizable by human CD4⁺ T cells provides potential new targets for cancer immunotherapy.     

Obstruction of the pancreatic duct by a granular cell tumor

Summary A 31-year-old woman presented with constant epigastric pain. Obstruction of the pancreatic duct was observed by ultrasonography and CT scan and was further defined by ERCP. Surgical exploration of the pancreas revealed a tumor in the pancreatic head. Histologic and immunocytochemical examination revealed a benign granular cell tumor, a neoplasm not previously described as causing obstruction in the pancreas.     

Recurrent endobronchial inflammatory myofibroblastic tumors: Novel treatment options

Endobronchial inflammatory myofibroblastic tumors (IMTs) rarely occur in children younger than 10 years of age and have intermediate malignant potential. A 7‐year‐old girl initially presented with pneumonia. After failing outpatient treatment, she re‐presented in status asthmaticus. Computed tomography showed a left mainstem endobronchial mass which was resected bronchoscopically. Pathology was consistent with IMT. Surveillance bronchoscopy identified a recurrence. Despite a left upper lobectomy, recurrence led to further treatment with celecoxib and argon plasma coagulation. Follow‐up bronchoscopy revealed complete resolution. She remains disease and symptom‐free at her six‐year follow‐up.     

Circulating tumour cells: insights into tumour heterogeneity

Tumour heterogeneity is a major barrier to cure breast cancer. It can exist between patients with different intrinsic subtypes of breast cancer or within an individual patient with breast cancer. In the latter case, heterogeneity has been observed between different metastatic sites, between metastatic sites and the original primary tumour, and even within a single tumour at either a metastatic or a primary site. Tumour heterogeneity is a function of two separate, although linked, processes. First, genetic instability is a hallmark of malignancy, and results in ‘fixed’ genetic changes that are almost certainly carried forward through progression of the cancer over time, with increasingly complex additional genetic changes in new metastases as they arise. The second type of heterogeneity is due to differential but ‘plastic’ expression of various genes important in the biology and response to various therapies. Together, these processes result in highly variable cancers with differential response, and resistance, to both targeted (e.g. endocrine or anti‐human epithelial growth receptor type 2 (HER2) agents) and nontargeted therapies (e.g. chemotherapy). Ideally, tumour heterogeneity would be monitored over time, especially in relation to therapeutic strategies. However, biopsies of metastases require invasive and costly procedures, and biopsies of multiple metastases, or serially over time, are impractical. Circulating tumour cells (CTCs) represent a potential surrogate for tissue‐based cancer and therefore might provide the opportunity to monitor serial changes in tumour biology. Recent advances have enabled accurate and reliable quantification and molecular characterization of CTCs with regard to a number of important biomarkers including oestrogen receptor alpha and HER2. Preliminary data have demonstrated that expression of these markers between CTCs in individual patients with metastatic breast cancer reflects the heterogeneity of the underlying tumours. Future studies are designed to determine the clinical utility of these novel technologies in either research or routine clinical settings.     

Solitary concomitant endocrine tumor and ductal adenocarcinoma of pancreas

Pancreatic tumors with combined exocrine and endocrine features are rare.Most reported cases are classified as mixed exocrine and endocrine carcinoma of the pancreas.We report the first case of solitary concomitant endocrine tumor and ductal adenocarcinoma of the pancreas.A 58-year-old patient was admitted for uncontrolled diabetes mellitus and body weight loss.The tumor was fortuitously discovered in the pancreatic tail after a tumor survey panel.Grossly,the solitary tumor had a central fibrous band that c...     

Mucin-producing bile duct tumors: radiological–pathological correlation and diagnostic strategy

Mucin-producing bile duct tumors are characterized by intraductal papillary tumors producing large amounts of mucin. The tumor comprises macroscopically prominent intraductal papillary neoplastic epithelia and produces a large amount of viscid mucin, resulting in dilatation of the bile ducts. The surface of the tumor is frond-like, velvety, or serrated. The tumor exhibits five intraductal growth patterns; polypoid intraductal growth, mucosal spreading growth, cast-like intraductal growth, cystic tumor, and intraductal floating tumors. Imaging features reflect the interplay between the morphology of the tumor, the amount of mucin production, and biliary dilatation. This review article describes the radiological manifestations of the tumor, based on pathological-radiological correlation and biological behavior.     

A case of coexisting malignant carcinoid tumor and adenocarcinoma in the papilla of vater

A 47-year-old Japanese woman in whom obstructive jaundice had already been diagnosed, was found to have a dome-shaped elevated tumor approximately 3 cm in diameter located in the area very close to the papilla of Vater on endoscopical and radiographical investigations. Histopathologically, the resected tumor was composed mainly of solid nests of atypical argyrophilic cells, and partially of an area of well differentiated tubular adenocarcinoma, showing mutual transition in the mucosal layer. Both immunohistochemical and ultrastructural analyses confirmed the difference in character of tumor cells between these two areas; neuroendocrine cell carcinoma and tubular adenocarcinoma of common type in the intestine. To the best of our knowledge, this is only the third case reported to be a coexisting malignant carcinoid tumor and adenocarcinoma arising in the periampullary region.     

Metastatic germ cell tumor to the heart presenting with syncope.

Malignant nonseminomatous germ cell tumors (NSGCT) rarely metastasize to the heart. The first such case presenting with syncope is described. Eight previously described cases of NSGCT with intracaval metastasis to the heart are reviewed and the literature to date is discussed. Transesophageal echocardiography is the diagnostic study of choice and treatment consists primarily of platinum-based chemotherapy followed by surgical resection of residual deposits.     

Calcified Amorphous Tumor of the Heart: Case Report and Review of the Literature

Calcified amorphous tumor of the heart (cardiac CAT) is a rare non-neoplastic cardiac mass that mimics malignancy on imaging and can cause symptoms due to flow obstruction or embolization of calcific fragments. We report a 57-year-old female with multiple medical problems affected by cardiac CAT. The echocardiogram showed a 2 x 1.7 cm right atrial mass. Under the clinical diagnosis of cardiac myxoma, a mass resection was performed. Microscopic examination of the resected mass showed nodular calcified amorphous debris with admixed degenerated fibrin and focal chronic inflammation. At the 1-year follow-up, the patient was free of disease.We performed a literature review of 16 previously reported cases. Histologically, a cardiac CAT consists of calcification and eosinophilic amorphous material in the background of dense collagenous fibrous tissue. A review of these cases shows a wide range of age at diagnosis and slight female predominance. The patients are either asymptomatic at presentation or complain of shortness of breath. The tumors have been found in all chambers of the heart, most commonly in the left ventricle. The sizes of the tumors range from 0.17 to 4 cm, with 62.5% of the tumors being mobile. Among the nine cases with documented follow-up study, all but one was free of disease and only one case of relapse was recorded. In conclusion, cardiac CATs are frequently asymptomatic at presentation, size is equal to or less than 4 cm, they can be located in all four chambers and are usually mobile, and they may relapse when not completely excised.     

Sulfiredoxin is an AP-1 target gene that is required for transformation and shows elevated expression in human skin malignancies

Previous studies have shown that a dominant negative form of c-Jun (TAM67) suppresses mouse skin carcinogenesis both in vitro and in vivo. The current study identifies Sulfiredoxin (Srx) as a unique target of activator protein-1 (AP-1) activation and TAM67 inhibition. Manipulation of Srx levels by ShRNA or over-expression demonstrates that Srx is critical for redox homeostasis through reducing hyperoxidized peroxiredoxins. In JB6 cells, knockdown of Srx abolishes tumor promoter-induced transformation and enhances cell sensitivity to oxidative stress. Knockdown of Srx also impairs c-Jun phosphorylation, implicating a role for Srx in the feedback regulation of AP-1 activity. Screening of patient tissues by tissue microarray reveals elevated Srx expression in several types of human skin cancers. Our study indicates that Srx is a functionally significant target of AP-1 blockade that may have value in cancer prevention or treatment.