Production of platelet-derived growth factor by human lung cancer

The production of platelet-derived growth factor (PDGF) was studied in small cell lung carcinoma, lung squamous carcinoma and lung adenocarcinoma cell lines, and in seven human lung tissues obtained from each type of lung cancer. By indirect immunofluorescence, PDGF was detected in all the cell lines. Likewise, five out of seven biopsies derived from patients with adenocarcinoma and squamous carcinoma, and four out of seven specimens with small cell carcinoma displayed a positive pattern for PDGF. In addition, lung carcinoma cell lines expressed both PDGF-A and PDGF-B/sis genes, as judged by Northern blot analysis. Biologically active, serum-free conditioned media obtained from all three cell lines stimulated the incorporation of [3H]thymidine into quiescent BALB/c-3T3 cells. This effect was abolished when IgG-PDGF antiserum was used. These findings suggest that an abnormal expression of PDGF occurs in the three more frequent types of lung cancer, which can play a potential role in neoplastic transformation and uncontrolled cell growth.     

Expression and prognostic impact of DNA-PK in human lung cancer

Among all cancer patient’s lung cancer is the leading cause of death. Prognostic biomarkers continue to be investigated for the detection and stratification of lung cancer for clinical use. The DNA-dependent protein kinase is involved in mechanisms of DNA damage repair. Deregulation and overexpression of DNA-dependent protein kinase is associated with poor prognosis in various tumor entities. In this study, we investigated the expression of DNA-dependent protein kinase in relation to clinicopathological features and overall survival in patients with lung cancer.By immunohistochemistry, expression of DNA-dependent protein kinase was analyzed in 205 cases of lung cancer; 95 cases of adenocarcinoma, 83 cases of squamous cell lung carcinoma and 27 cases of small cell lung cancer and correlated with clinicopathological characteristics as well as patient’s overall survival.In patients with adenocarcinoma, a significant correlation between strong expression of DNA-dependent protein kinase and worse overall survival was found. No significant association was observed in patients with squamous cell lung carcinoma and small cell lung cancer. Strong detection of DNA-dependent protein kinase expression was most evident in small cell lung cancer (81.48 %), followed by squamous cell lung carcinoma (62.65 %) and adenocarcinoma (61.05 %).In our study, expression of DNA-dependent protein kinase was associated with poor overall survival in patients with adenocarcinoma. DNA-dependent protein kinase could serve as a new prognostic biomarker.     

A statistical analysis of serum sialyl Lewis X-1 (SLX), CEA, SCC and NSE levels in patients with lung cancer]

Serum SLX, CEA, SCC and NSE levels were serially measured in 266 patients with lung cancer and compared with those in 345 patients with benign respiratory disorders (BRD). The positive rate for CEA in lung cancer (44.4%) and the false-positive rate in BRD (15.3%) were the highest among the 4 markers. The positive rate for SLX in lung cancer (32.0%) was lower than that of CEA, while the false-positive rate for SLX in BRD (7.2%) was lower than that of CEA. The positive rate for SLX was highest in adenocarcinoma and correlated better with the clinical stages than did CEA. SCC and NSE were specifically elevated in squamous cell carcinoma and small cell carcinoma, respectively. Using these 4 markers, only 70.2% of patients were correctly diagnosed as having lung cancer or BRD. In monitoring treatment effect, only SLX showed a statistically significant correlation with regression and progression in adenocarcinoma, while NSE and SLX showed such a correlation in small cell carcinoma. Serum tumor markers seem to be less sensitive for the diagnosis of lung cancer than chest X-ray and sputum cytology, indicating that a search for more specific markers is still required. However, in monitoring treatment effect, SLX appeared to be suitable for adenocarcinoma, while NSE and SLX seemed to be useful in small cell carcinoma.     

Plasma levels of thrombin-activatable fibrinolysis inhibitor in primary and secondary thrombocytosis.

An elevated platelet count is a common finding in both hospitalized and ambulatory patients. Thrombosis and bleeding complications are more frequently observed in patients with clonal thrombocytosis than secondary thrombocytosis. The aim of this study was to investigate the behaviors of thrombin-activatable fibrinolysis inhibitor (TAFI) activity, the inhibitor of fibrinolysis, and also prothrombin time (PT), active partial thromboplastin time, and D-dimer and fibrinogen levels in 21 patients affected with clonal thrombocytemia as compared with 21 patients with reactive thrombocytosis and 21 healthy controls. In the clonal thrombocytemia group, plasma levels of TAFI activity were significantly higher than in both the reactive thrombocytosis and the control group. Plasma levels of leukocyte and platelet counts were significantly higher in the clonal thrombocytemia group than in the other two groups and also higher in the reactive thrombocytosis group than in the control group, which was also significant. Fibrinogen and D-dimer levels were higher in patients than in the control group but showed no significant difference between the clonal and secondary thrombocytosis groups. Plasma levels of PT and aPTT were higher in secondary thrombocytosis group than the clonal thrombocytosis group. The results of this study showed for the first time that TAFI activity is increased in patients with clonal thrombocytosis. These increased levels in clonal thrombocytosis can be considered a factor to explain the thrombotic tendency in myeloproliferative disorders.     

Fenofibrate improves endothelial function and decreases thrombin-activatable fibrinolysis inhibitor concentration in metabolic syndrome

Procoagulant state, inflammation, and endothelial dysfunction have been documented in metabolic syndrome. Endothelial dysfunction is a strong predictor of cardiovascular events. Studies on the association of thrombin-activatable fibrinolysis inhibitor and thrombosis are still controversial, but substantial evidence suggests that increased thrombin-activatable fibrinolysis inhibitor or thrombin-activatable fibrinolysis inhibits or protects against arterial thrombosis. This study aimed to assess concomitantly the effects of fenofibrate therapy on thrombin-activatable fibrinolysis inhibitor concentrations and endothelial functions in patients with metabolic syndrome. Twenty-five patients (16 women; mean age 50.4 +/- 7.0) were enrolled in the study. Plasma thrombin-activatable fibrinolysis inhibitor, C-reactive protein, and fibrinogen levels were measured before fenofibrate administration and after 8 weeks of fenofibrate treatment. Endothelial function was assessed by endothelial-dependent flow-mediated dilatation from brachial artery. Pretreatment (baseline) thrombin-activatable fibrinolysis inhibitor level was 52.3 (1.2-119.7) decreasing to 7.7 (0.9-51.2; P < 0.001) after 8 weeks of fibrate treatment. Endothelial functions, which were measured with flow-mediated dilatation, were significantly improved after treatment (mean flow-mediated dilatation was 6.76 +/- 2.21 at baseline and 10.66 +/- 1.17% after 8 week of fenofibrate treatment, P < 0.001). Fenofibrate decreases thrombin-activatable fibrinolysis inhibitor levels and improves endothelial function in metabolic syndrome and, thus, suggests a potential for protection against cardiovascular effects. Further studies are warranted to confirm the effects of fibrates on thrombin-activatable fibrinolysis inhibitor and for conclusive evidence on the association between thrombin-activatable fibrinolysis inhibitor and thrombosis.     

384例男性肺癌支气管镜下特征及临床特点分析

目的探讨男性肺癌支气管镜下特征及临床特点。方法对384例男性肺癌患者支气管镜检查资料进行分析。结果 384例男性肺癌患者中鳞癌204例（53.13%）,小细胞癌118例（30.73%）,腺癌55例（14.32%）,其他7例（1.83%）。老年组与中年组比较,鳞癌检出率上升,小细胞癌检出率下降。均好发于右肺及双肺上叶。支气管镜下表现以直接征象为主占92.19%;鳞癌以增生性改变为主占70.59%;小细胞癌增生性改变稍高于浸润性改变;腺癌以浸润性改变为主占52.73%。结论男性肺癌的临床表现和镜下改变有一定的特殊性,了解上述规律,对临床有指导意义。     

Association of serum reactive oxygen metabolite levels with different histopathological types of lung cancer

BACKGROUND: Oxygen is required for respiration and the energetic processes that enable aerobic life. Costs associated with oxygen use are free radical and reactive oxygen metabolite (ROM) formations, which create oxidative stress and contribute to various processes including aging, degenerative diseases and cancer. Additionally, they may have a role in the pathogenesis of lung cancer with different histopathological types. OBJECTIVES: In this study, we aimed to investigate the degree of oxidative stress in different types of carcinoma such as small cell carcinoma and non-small cell carcinoma, including epidermoid carcinoma and adenocarcinoma, and to find out whether the degree of oxidative stress shows any difference among them and whether it can be used as an index for their differential diagnosis. METHODS: Thirty-eight patients with lung cancer and 26 healthy persons were included in the study. Of the patients with lung cancer, 14 had epidermoid carcinoma, 12 adenocarcinoma and 12 small cell carcinoma. Serum ROM levels were detected by using an available commercial kit according to the manufacturer's instructions. RESULTS: The ROM levels were significantly lower in the controls than in the patients (p<0.001). Although all subtypes had significantly high ROM levels compared with the controls, the highest significance was found in the small cell carcinoma (p<0.001), and then in the adenocarcinoma and epidermoid carcinoma (p<0.01 and p<0.01, respectively). CONCLUSIONS: In the light of these data, it might be possible to conclude that the serum ROM levels increase in patients with different types of lung cancers and may be an index parameter for lung cancer. It could be thought that this increase, particularly in small cell carcinoma, may contribute to its poor progression.     

凝血酶激活的纤溶抑制物与肺部疾病的关系

凝血酶激活的纤溶抑制物是近年发现的血浆羧肽酶原,在调节血浆凝块的纤溶过程中有着重要的作用,而最近研究发现,其生理功能并不限于控制纤溶系统,还有更广泛的抗炎作用.现就凝血酶激活的纤溶抑制物与肺血栓栓塞症、ALI、肺间质纤维化、支气管哮喘等肺部疾病的相关性作一综述.     

Prognostic significance of hemostatic parameters in patients with lung cancer

There is a subclinical activation of coagulation and fibrinolysis system in lung cancer. Alterations in hemostatic system are seen frequently in lung cancer correlated with the prognosis of disease. In this prospective study, our purpose was to investigate the prognostic significance of hemostatic markers in patients with lung cancer. The study comprised 58 patients (22 squamous cell carcinoma, 16 adenocarcinoma, 20 small cell carcinoma). There were 55 men (95%)and 3 women (5%) with a mean age of 61 years range (36-74). Plasma level of platelets (PLT), prothrombin time (PT), active partial thromboplastin time (aPTT), antithrombin III (AT III), fibrinogen (F) and D-dimer level were measured before the initiation of any therapy. Patients were followed up for 17 (12-20) months. The median survival was determined as 6.4 months. Three histopathologic groups; squamous cell carcinoma, adenocarcinoma and small cell carcinoma were compared for the hemostatic parameters. There were no statistically significant differences among the histopathologic types for any of the parameters (P > 0.05). Patients were divided into two groups as patients without distant metastasis (stages I,II,III) and with distant metastasis (stage IV). The group with distant metastasis had higher level of D-dimer than the other group (P < 0.05). However, there were no statistically significant differences for D-dimer level between stages IIIB and IV (P > 0.05). Patients having high D-dimer and low AT III level had poor survival in our study. Thus, high level of D-dimer and low AT III level were determined as correlated with short survival (P < 0.05). These results suggest that elevated plasma level of D-dimer and low AT III level might be a sign of poor prognosis in patients with lung cancer.     

LKB1、VEGFR2在非小细胞肺癌组织中表达及临床意义的研究

目的探究人Liver kinase B1(LKB1)与血管内皮生长因子受体-2(VEGFR2)在非小细胞肺癌组织中的表达情况,并探究其临床意义。方法采用免疫组化方法测定65例非小细胞肺癌组织及40例癌旁组织LKB1、VEGFR2表达情况。分析LKB1、VEGFR2表达情况与临床病理特征的相关性。结果肺癌组织中LKB1阳性率低于癌旁组织,VEGFR2阳性率高于癌旁组织。LKB1在腺癌中的表达阳性率高于鳞癌,VEGFR2在腺癌中的表达阳性率低于鳞癌。在具有吸烟史、淋巴转移、临床低分期以及低分化程度中LKB1阳性率更低,VEGFR2阳性率更高,差异均有统计学意义(均P0.05)。结论腺癌组织中LKB1表达水平高于鳞癌组织;非小细胞肺癌组织中LKB1、VEGFR2呈现相反的表达趋势。LKB1低表达与VEGFR2高表达提示肺癌患者具有吸烟史、出现淋巴转移、高临床分期以及低分化程度。     

Research on the reactivation of Syk expression caused by the inhibition of DNA promoter methylation in the lung cancer

The aim of this study was to study the expression of Syk gene and methylation in its promoter region in the lung cancer and to investigate the relationship between silencing of the Syk gene and DNA methylation of the Syk promoter region in lung cancer cell lines. Real-time PCR and immunohistochemistry were used to examine the Syk expression in specimens from 3 lung cancer cell lines and 16 lung cancer patients (tumor tissues and adjacent normal tissues). MSP was used to analyze the methylation status of the Syk promoter region. We also investigated the role of restoring Syk expression by using a DNA methyltransferase inhibitor, 5-aza-CdR, in suppressing invasion of lung cancer cell lines. No expression of the Syk gene was detected in the 3 lung cancer cell lines. In the 16 lung cancer patient samples, Syk expression was significantly lower in the tumor tissues than that in their adjacent normal tissues (P<0.05). Consistently, immunohistochemistry analysis of Syk protein expression showed that in the lung cancer tissues Syk protein expression was also significantly lower than that in their adjacent normal tissues. In the two lung cancer cell lines (NL9980, YTMLC-9) that lack the endogenous Syk expression, 4uM demethylation agent 5-aza-CdR treatment was able to reactivate the Syk gene expression, but not NCI-H446. In conclusion, hypermethylation leads to silencing of the Syk gene in human lung carcinoma cell lines. Methylation of the Syk promoter and loss of Syk expression in lung cancer cell lines are independent biomarkers. Syk may be a potential tumor suppressor in human lung cancer.     

肺癌组织中内皮素1阳性表达及定量分析

目的了解内皮素１（ＥＴ－１）在肺癌组织中表达及定量分析与肺癌分型、分级的关系。方法采用免疫组织化学ＡＢＣ染色及图像分析技术测定ＥＴ－１阳性率及含量。结果１０４例不同类型肺癌ＥＴ－１阳性表达主要分布在胞浆内，腺癌、鳞癌和大细胞肺癌ＥＴ－１表达较高，分别为７１．４％（２０／２８），５７．１％（１６／２８）和４０．０％（８／２０）。小细胞肺癌表达低为２１．４％（６／２８）。对腺癌、鳞癌阳性表达的图像分析表明，肿瘤分化程度越低ＥＴ－１含量越高，分化程度越高ＥＴ－１含量越低。结论ＥＴ－１普遍存在于肺癌细胞中，腺癌和鳞癌高表达，表明ＥＴ－１含量与肿瘤分化程度有一定关系，ＥＴ－１可作为腺癌、鳞癌恶性生长的一个监测指标。     

经纤维支气管镜确诊的青年肺癌与中老年肺癌的对比研究

目的 探讨经纤维支气管镜确诊的青年肺癌患者的临床特点.方法 回顾性分析本院1882例经纤维支气管镜确诊的有组织学或细胞学结果的肺癌患者的临床资料,根据年龄分为青年组(＜40岁)和中老年组(≥40岁),对比分析其临床特点.结果 肺癌以中老年多发(91.1%);青年组咯血、胸痛发生率高于中老年组;青年组以小细胞癌最多(57.7%),其次为鳞癌(22.0%)和腺癌(10.1%).而中老年组以鳞癌最多(63.2%),其次为小细胞癌(19.2%)和腺癌(6.5%).结论 青年肺癌有其不同的临床特点,应加强对青年肺癌的认识,提高早期诊断率以使青年肺癌患者得到及时的诊治.     

Coagulation disorders and arterial thromboembolic events in non-small-cell lung cancer. A case report

Certain coagulation disorders can occur in patients with cancer and thromboembolic complications are frequent. We report the case of a 53-Year-old patient with metastatic adenocarcinoma of the lung treated with chemotherapy who presented several cerebral arterial thromboembolic events leading to death a few weeks after the initial diagnosis of cancer. This case illustrates the important role of certain satellite disorders related to coagulation activation: non-bacterial thrombotic endocarditis, disseminated intravascular coagulation, anti-phospholipid antibody syndrome. The role of anticancer chemotherapy as a favoring factor for thromboembolic events is also emphasized in patients with non-small-cell lung cancer.     

肺癌患者外周血中MDR1的表达及临床意义

目的 检测多药耐药基因-1（MDR1）在肺癌患者外周血中的表达,探讨MDR1的表达水平与肺癌病理类型及临床化疗进程之间的关系.方法 应用荧光定量PCR（qRT-PCR）技术,动态监测45例肺癌患者化疗前后外周血中MDR1的表达水平,并与48例健康者进行对照比较.结果 肺癌组化疗前MDR1的阳性率28.89%（13/45）,明显高于健康对照组2.08%（1/48）,差异显著（P〈0.05）;各种病理类型的肺癌随着化疗次数的增多MDR1的表达均增强;化疗前后各期MDR1的表达程度：非小细胞肺癌（NSCLC,肺鳞癌和肺腺癌）明显高于小细胞肺癌（SCLC）,差异具有统计学意义（P〈0.05）,而肺鳞癌和肺腺癌之间MDR1的表达程度相当,无显著差异,（P＞0.05）.结论 化疗可诱导各种病理类型肺癌MDR1表达增加;病理类型不同诱导化疗耐药的机制可能不同：NSCLC可能为原发性MDR,SCLC可能为获得性MDR;动态检测肺癌患者外周血中MDR1的表达水平,有利于进行肺癌耐药的监测与评价.     

肺癌359例分析

目的了解各种类型肺癌发病年龄及患病高峰。方法对2003~2006年收治的359例明确诊断肺癌患者的发病年龄及男女比例进行分析。结果肺癌患者男女比例为3.5∶1,在鳞癌高达11∶1。鳞癌患者占全部肺癌的53%。结论男性患病率明显高于女性,在鳞癌特别突出。鳞癌是最常见的肺癌。鳞癌患者发病年龄明显高于小细胞肺癌和腺癌。     

以精神异常为首发表现肺癌的临床分析

目的提高临床医生对以精神异常为首发表现肺癌的认识。方法分析以精神异常为首发表现的4例肺癌患者资料。结果 4例患者病初都出现不同程度的精神异常。其中3例有病理结果,腺癌2例,小细胞肺癌1例。结论以精神异常为首发表现的肺癌,因其临床表现不典型,易误诊、漏诊,提高对本病的认识有利于早期诊断及治疗。     

The expression of HER2/neu in patients with lung cancer and its associated factors

Background and objectives

Lung cancer is the most common cause of cancer-related death worldwide in both sexes. Evidence suggests the role of genetic factors in lung cancer. Studying of such factors can help understand the cancer prognosis. Overexpression of the human epidermal growth factor receptor-2 (HER2/neu) protein is considered an important prognostic factor in breast cancer, but its role has not been confirmed in lung cancer. Therefore, the present study aimed to investigate the role of its expression in patients with lung cancer.

Materials and methods

In this cross-sectional study, patients aged >18 years who were referred to Afzalipoor Hospital, Kerman, Iran, from 2016 to 2017, and were diagnosed with lung cancer were enrolled into the study if they had a pathological sample of their cancerous lung. Their demographics were recorded, and the sample was sectioned and stained to measure HER2/neu gene expression according to DAKO instructions using heat-induced antigen retrieval (HIER) enzyme marker.

Results

The samples of 100 patients with lung cancer were evaluated (84% men and 16% women) with a mean age of 61.34 years (standard deviation of 12.51 years). HER2/neu expression was significantly associated with the type of cancer and was highest in adenocarcinoma and zero in small cell carcinoma (P < 0.001), but not with patients' sex, age, smoking status and family history of cancer (P > 0.05).

Conclusion

These results emphasized the overexpression of HER2/neu in different types of lung cancer, which can be used further for therapeutic purposes. The results showed that HER2/neu was overexpressed not only in adenocarcinoma but also in other types, like squamous cell carcinoma. Therefore, all subtypes of non-small cell lung carcinoma should be considered for anti-HER2 therapies, and further research is required for small cell lung carcinoma.     

耐多药相关蛋白在人非小细胞肺癌组织中的表达

目的　检测人非小细胞肺癌组织中耐多药相关蛋白（ＭＲＰ） 的表达,探讨其与瘤组织学类型、分化程度、临床分期及预后的关系。方法　采用免疫组化方法及逆转录聚合酶链反应（ＲＴＰＣＲ）技术,分别检测了９２ 份人非小细胞肺癌石蜡组织中ＭＲＰ的表达及１６ 份人非小细胞肺癌新鲜组织中ＭＲＰ基因的表达。结果　９２ 份人非小细胞肺癌组织中（ 鳞癌４３ 例,腺癌４９ 例）ＭＲＰ表达阳性检出率为５４％（５０／９２） ,１６ 份人非小细胞肺癌组织中ＭＲＰ基因表达阳性检出率为３１％ （５／１６）。ＭＲＰ在腺癌中的表达阳性率明显高于鳞癌（ Ｐ＜ ０－０５） ,ＭＲＰ表达与瘤分化程度、肿瘤大小及淋巴结转移无显著相关。ＭＲＰ阳性患者术后５ 年生存率为１６％ （８／５０）,ＭＲＰ 阴性患者术后５ 年生存率为５２％ （２２／４２） ,二者经统计学处理,差异有显著性（ Ｐ＜ ０－０５）。ＭＲＰ阳性患者术后５ 年生存率有随其瘤组织中该蛋白表达阳性程度的增加而降低之趋势。结论　非小细胞肺癌患者瘤组织中ＭＲＰ的表达与瘤组织学类型及预后明显相关。