食管癌患者血清TGF-α水平检测的临床价值

目的探讨食管癌患者手术前后血清转化生长因子α(TGF-α)水平检测的临床意义。方法应用放射免疫分析法(RIA法)检测30例正常人,58例食管癌患者血清TGF-α水平,并比较40例食管癌患者手术前后血清TGF-α水平。结果血清TGF-α水平与临床分期、细胞分化程度有关;与食管癌患者性别、年龄无关。食管癌患者血清TGF-α水平(9.01ng/L±1.37ng/L)明显高于正常对照组(6.77ng/L±0.72ng/L)(P<0.01);Ⅳ期食管癌血清TGF-α(11.03ng/L±0.48ng/L)明显高于Ⅰ、Ⅱ、Ⅲ期(7.23ng/L±0.45ng/L、8.73ng/L±0.47ng/L、9.35ng/L±0.44ng/L)(P<0.01),Ⅲ期明显高于Ⅱ期(P<0.05),Ⅱ期明显高于Ⅰ期(P<0.01),低分化食管鳞癌患者血清TGF-α水平(9.96ng/L±1.19ng/L)显著高于中、高分化食管鳞癌患者(9.00ng/L±1.10ng/L、8.35ng/L±1.06ng/L)(P<0.05～0.01);食管癌患者术后血清TGF-α水平(7.45ng/L±0.90ng/L)明显低于术前(8.38ng/L±1.00ng/L)(P<0.01)。结论血清TGFα检测对食管癌疗效观察、病情监测及和和预后判断有重要的参考意义。     

胃癌患者血清endostatin水平与临床及预后的关系

目的探讨血清内皮抑制素(endostatin)在健康者与胃癌患者水平、胃癌患者手术前后endostatin水平的变化及与临床病理特征和预后的关系。方法采用酶联免疫吸附法(EL ISA)检测33例健康对照组及67例胃癌患者手术前后血清内皮抑素的水平。结果健康对照组血清endostatin水平为(32.4±10.4)μg/L,明显低于胃癌患者手术前血清endostatin的水平(49.9±14.3)μg/L,P值<0.01,胃癌患者手术后4周endostatin的水平(52.5±14.2)μg/L高于手术前endostatin的水平(P=0.016);Ⅲ+Ⅳ期胃癌患者endostatin水平明显高于Ⅰ+Ⅱ者,分别为(52.9±14.8)μg/L与(45.4±12.6)μg/L,P<0.01,lauren分型中弥漫型胃癌患者血清endostatin水平(53.4±12.3)μg/L)明显高于肠型(46.0±15.5)μg/L,P<0.05。血清endostatin水平与性别、年龄、病理类型、肿瘤大小及局部血管浸润差异无显著性(P值均>0.05);手术前血清Endostatin低于平均值(49.9μg/L)患者5年生存率明显高于平均者(P<0.01),Cox比例风险模型对多因素分析结果显示TNM分期、手术前endostatin水平是影响生存的独立预后因素。结论胃癌患者外周血清endostatin水平明显高于健康者,并与胃癌TNM分期、L auren分型密切相关,检测胃癌患者外周血清endostatin水平不仅有助于进一步了解胃癌的生物学行为,也可作为预测肿瘤预后的指标。     

肝癌患者血清转化生长因子α检测的临床意义

目的 :探讨肝癌患者血清转化生长因子α检测的意义。方法 :采用放射免疫分析法检测 42例肝癌患者和 2 5例肝硬化患者血清中 TGF-α的水平 ,并与 AFP进行比较分析。结果 :对照组 TGF-α为 13.2 4± 4.10 ng/ L ,肝硬化组为 12 .10± 3.1ng/ L,与对照组无明显差异 ,P>0 .0 5 ;肝癌组为 18.85± 9.6 1ng/ L,明显高于对照组和肝硬化组 ,P<0 .0 1。结论 :TGF- α能配合 AFP检测肝癌 ,可作为肝癌诊断的一项检测指标。     

肝癌患者血清TGF-α和IGF-Ⅱ检测的临床意义

目的　探讨转化生长因子 (TGF α)和胰岛素样生长因子 Ⅱ (IGF Ⅱ )在肝癌患者血清中的水平及临床意义。方法　采用放射免疫分析法 ,分组检测患者血清TGF α和IGF Ⅱ的水平 ,其中肝癌组 3 5例 ,肝转移癌组 3 2例及肝硬化组 3 0例。结果　肝癌及肝转移癌组血清TGF α水平分别为 ( 2 2 .0 2± 4.10 ) pg/ml和 ( 3 1.0 5± 3 8.2 4) pg/ml ,明显高于肝硬化组 ( 8.61± 2 .0 2 )pg/ml和对照组 ( 6.0 1± 1.5 8) pg/ml(P <0 .0 5和P <0 .0 1) ,肝硬化组血清TGF α水平 ( 8.61± 2 .0 2 )pg/ml与对照组 ( 6.0 1± 1.5 8)pg/ml比较无显著性差异 (P <0 .0 5 )。肝癌组IGF Ⅱ水平 ( 1.3 2± 0 .2 4)ng/ml明显高于肝硬化组 ( 0 .3 8± 0 .16)ng/ml和对照组( 0 .48± 0 .12 )ng/ml(P <0 .0 5 ) ,肝硬化组及肝转移癌组IGF Ⅱ水平分别为 ( 0 .3 8± 0 .16)ng/ml和 ( 0 .40± 0 .13 )ng/ml ,与对照组 ( 0 .48± 0 .12 )ng/ml比较无显著性差异 (P >0 .0 5 )。 结论　检测血清TGF α和IGF Ⅱ的水平有助于肝癌的诊断     

非小细胞肺癌患者手术前后血清中内皮抑素和VEGF水平变化及相关性研究

目的:探讨非小细胞肺癌(non-smallcell lung cancer,NSCLC)患者手术前后血清中内皮抑素(endostatin)和血管内皮生长因子(vasular endothelial growth factor,VEGF)水平的动态变化规律及两者水平变化的相关性。方法:用ELISA法检测46例NSCLC患者手术前后血清中endostatin和VEGF的水平。结果:1)NSCLC患者术后7d血清endostatin水平为(23·41±5·12)ng/mL,显著高于术前[(20·85±4·56)ng/mL]和术后1d[(18·89±4·67)ng/mL]血清endostatin水平,P值分别为0·011和0·000;术后7d血清VEGF水平为(3·75±0·71)ng/mL,显著高于术前[(1·72±0·46)ng/mL]和术后1d[(2·22±0·58)ng/mL]血清VEGF水平,P值均为0·000。2)NSCLC患者术前血清endostatin与VEGF水平呈非常显著负相关,r=-0·380,P=0·009。3)NSCLC患者术后7d血清endostatin水平与VEGF水平呈非常显著正相关,r=0·351,P=0·017。结论:NSCLC患者手术前、后血清endostatin和VEGF水平存在动态变化,且两者手术前后的水平变化有显著相关性,检测NSCLC患者手术前后血清中endostatin和VEGF水平可能是进一步预测肺癌恶性行为的有用指标。肿瘤防治杂志,2005,12(19):1441-1444     

肺癌患者免疫功能变化的初步研究

目的 :通过测定肺癌患者外周血清白细胞介素 8(interleukin 8、IL 8)、白细胞介素 10 (interleukin 10、IL 10 )和转化生长因子 β1(transforminggrowthfactor β1,TGF β1)的水平 ,探讨肺癌患者的免疫功能变化及IL 8、IL 10和TGF β1在肺癌形成过程中的可能作用。方法 :用酶联免疫吸附法 (ELISA法 )测定 32例肺癌患者及 2 0例健康人血清IL 8、IL 10和TGF β1水平。统计学处理用两样本均数的t检验和方差分析。结果 :肺癌组血清IL 8、IL 10和TGF β1水平分别为 10 3.91± 30 .80pg/ml、5 0 .46± 13.18pg/ml、48.6 2± 9.35ng/ml。健康对照组血清IL 8、IL 10和TGF β1水平分别为 5 2 .5 6± 8.40pg/ml、2 8.49± 2 .85pg/ml、2 6 .89± 4.83ng/ml。结果 :肺癌组IL 8、IL 10和TGF β1水平明显高于健康对照组 ,差异有显著性 (P <0 .0 1) ,且血清IL 8、IL 10和TGF β1水平与其病理分型无关 (P >0 .0 5 ) ,与肺癌的TNM分期有关 ,随肺癌的进展各项指标的水平逐步增高 (P <0 .0 1)。结论 :上述结果提示 ,肺癌患者存在免疫功能异常 ,IL 8、IL 10和TGF β1可能在肺癌的发生、发展过程中起着一定作用。动态观察IL - 8、IL 10和TGF - β1水平将有助于肺癌的诊断及疗效评价     

血清TGF-α水平对肝癌临床诊断的意义

目的 :检测血清TGF -α在肝癌临床的应用价值。方法 :采用放射免疫法检测 38例原发性肝癌、16例肝转移癌、2 0例肝硬化及 2 5例正常人的血清TGF -α含量 ,并与AFP值进行比较。数据用x±s表示 ,以正常人x± 2s作为上限计算TGF -α阳性率 ,以 4 0 0 μg/L为上限计算AFP阳性率。 结果 :肝硬化组与正常对照组血清TGF -α比较无显著性差异 (P >0 0 5 )。原发性肝癌组、肝转移组血清TGF -α水平显著高于正常对照组 (分别P <0 0 5、P <0 0 1) ;原发性肝癌Ⅲ期组血清TGF-α水平高于Ⅱ期 ,但无明显差别 (P >0 0 5 ) ;原发性肝癌组肝转移组血清TGF -α水平无显著性差异 (P >0 0 5 ) ;肝转移组血清TGF -α和AFP阳性率分别为 6 8 8%和 0 % ;原发性肝癌组血清TGF -α和AFP阳性率分别为 78 9%和 6 8 4 %。结论 :肝癌患者血清TGF -α明显升高 ,血清TGF -α检测有助于肝癌的诊断、鉴别诊断 ,效果优于AFP ,但对原发性肝癌临床分期意义不大     

鼻咽癌患者血浆可溶性P-选择素的测定及其意义

目的 :探讨鼻咽癌患者血浆可溶性P -选择素 (solubleP selectin ,sP selectin)的意义。方法 :采用ELISA法对 78例不同期别的鼻咽癌患者和 3 0位正常对照者血浆sP selectin水平进行了测定。结果 :各期鼻咽癌患者血浆sP selectin水平 ( 97 76± 5 6 5 7)ng/mL均显著高于正常对照组 ( 2 5 63± 8 86)ng/mL ,P <0 0 1;颈淋巴结转移组( 13 7 5 4± 62 48)ng/mL高于非转移组( 72 3 1± 3 9 86)ng/mL ,P <0 0 1。Ⅲ期( 15 9 76± 79 5 8)ng/mL与Ⅱ期( 12 2 69± 5 1 76)ng/mL患者sP selectin的含量均高于Ⅰ期 ( 67 5 4± 3 4 47)ng/mL ,P <0 0 1,且Ⅲ期高于Ⅱ期 ,P <0 0 5。结论 :sP selectin水平与鼻咽癌的发生及发展有关     

胃癌患者血清睾酮变化的临床意义

目的 :本文观察了 70例进展期胃癌手术前后血清睾酮的变化。方法 :采用放射性免疫化学方法测定进展期胃癌和对照组手术前后血清睾酮的变化。结果 :52例男性胃癌患者手术前血清睾酮( 32 63± 5 62 )nmol/L , x±s)与良性疾病对照组 ( 4 2 92± 8 93)nmol/L相比明显降低 (P <0 0 1) ;手术后 3个月复查血清睾酮 ( 4 0 84± 6 53)nmol/L比术前升高 (P <0 0 1) ;与良性疾病对照组入院时已无明显差别 (P >0 0 5) ;术后复发组血清睾酮 ( 2 8 66± 8 74 )nmol/L与术后 3个月时相比再次下降 (P <0 0 1)。女性胃癌患者术后血清睾酮 ( 2 32± 0 4 7)nmol/L比术前 ( 1 73± 0 34 )nmol/L也明显升高 (P<0 0 1)。结论 :结果提示血清睾酮可以做为胃癌诊断、治疗和观察复发的一个辅助指标     

血液肿瘤患者血清TNF、TGF-α的水平及临床意义

目的　探究TNF和TGF α在血液肿瘤性疾病中的变化和病情及预后的关系。方法　用放射免疫分析法检测了血液肿瘤性疾病患者 (63例 )和正常健康人 (3 0例 )血清TNF和TGF α水平 ,对治疗前后、病情变化进行了比较。结果　血液肿瘤性疾病患者治疗前TNF水平都明显高于正常组 (P <0 .0 1) ,治疗缓解后比治疗前明显降低 (P <0 .0 1)。急、慢性白血病和非何杰金氏淋巴瘤患者治疗前血清TGF α水平都明显高于正常组 (P <0 .0 5 ) ,而多发性骨髓瘤和骨髓增生异常综合症患者治疗前血清TGF α水平低于正常组 (P >0 .0 5 ) ,急、慢性白血病、非何杰金氏淋巴瘤和多发性骨髓瘤治疗缓解后比治疗前明显降低 (P <0 .0 1) ,骨髓增生异常综合症患者血清TGF α水平治疗后比治疗前降低但差异不显著 (P >0 .0 5 )。急、慢性白血病患者恶化后血清TNF和TGF α水平均升至治疗前水平。结论　检测血液肿瘤性疾病患者血清TNF和TGF α水平 ,有助于了解这种病人的病情变化及其预后。     

Detection of transforming growth factor-alpha in the serum of gastric carcinoma patients.

Transforming growth factor-alpha (TGF-alpha) is a ligand for epidermal growth factor receptor (EGFR) and it is overexpressed in various malignancies including lung, esophageal, colorectal, ovarian and gastric carcinomas. In patients with gastric carcinoma, its overexpression may be associated with advanced stage or poor prognosis. We have recently demonstrated that the mean serum level for EGFR in gastric carcinoma patients was significantly elevated compared with that of healthy controls. Using the enzyme-linked immunosorbent assay, the levels of TGF-alpha were determined in serum from 40 patients with gastric carcinoma (5 patients with stage I, 2 stage II, 4 stage III, and 29 stage IV patients) and 33 healthy controls. The mean serum level for TGF-alpha in the gastric carcinoma patients was significantly elevated as compared with that of healthy controls (104 +/- 235 vs. 22 +/- 16 pg/ml; p = 0.03). Eleven patients with gastric carcinoma (27.5%) showed elevated serum TGF-alpha levels above the cutoff value of 54 pg/ml (defined as 2 standard deviations above the mean of the control group). No significant association was noted between the positivity of TGF-alpha and clinicopathologic characteristics including gender, age and stage. However, poorly differentiated adenocarcinoma showed a higher positivity of serum TGF-alpha (43.8%) compared with other histologic types, which was marginally significant (p = 0.06). These results suggest that serum TGF-alpha could be useful as a tumor marker of gastric carcinoma for predicting prognosis and follow-up after surgery in patients whose initial serum TGF-alpha levels are elevated.     

Transforming growth factor-alpha: an oncodevelopmental growth factor

Transforming growth factor-alpha (TGF-alpha) is a 50-amino-acid mitogenic peptide that is structurally and, in some cases, functionally related to members of the epidermal growth factor (EGF) family of peptides. TGF-alpha is initially synthesized as a high-molecular-weight, glycosylated, membrane-associated precursor of approximately 160 amino acids. The low-molecular-weight TGF-alpha peptide as well as the precursor are biologically active in a number of systems and can function as transforming proteins when overexpressed. TGF-alpha binds to and activates the EGF receptor, and TGF-alpha and the EGF receptor are coexpressed in a number of human and rodent tumors and tumor cell lines--which suggests that TGF-alpha can function as an autocrine or paracrine growth factor. TGF-alpha is transiently expressed in some fetal and adjacent maternal tissues during development and is also expressed in a number of adult tissues; this pattern of expression suggests that the growth factor is involved in several distinct physiological functions.     

The growth promoting effect of transforming growth factor-alpha in human breast cancer cell lines

Two human breast cancer cell lines, BT-20 and ZR-75-1, were examined with the aim of the elucidating the pathological roles of human transforming growth factor (TGF)-alpha in breast cancers. The TGF-alpha receptor was found to be present in both cell lines. A clonogenic assay revealed that concentrations of TGF-alpha greater than 10(10) M induced a significant increase in colony formation, indicating TGF-alpha to be a breast cancer cell growth factor. Northern blot analysis revealed, moreover, that both cell lines expressed TGF-alpha mRNA. Taking these observations together, it is reasonably possible to assume that TGF-alpha is an autocrine growth factor for breast cancer cells. Although it has been proposed that TGF-alpha could be an epidermal growth factor (EGF) superagonist with regard to its colony formation stimulating activity, the present study demonstrated the colony formation stimulating activities of TGF-alpha and EGF not to be all that much different in the two breast cancer cell lines.     

Transforming growth factor-alpha secretion by epidermal growth factor-dependent human tumor cell lines

Pairs of cell lines from spontaneous human tumors (cervical adenocarcinoma, melanoma, and synovial sarcoma) were established using serum-free culture conditions with and without exogenous epidermal growth factor (EGF). EGF-adapted cultures of melanoma and cervical adenocarcinoma origin secreted higher levels of bioactive transforming growth factor alpha (TGF-alpha) when compared to cultures maintained in the absence of EGF. Depletion of EGF for these EGF-adapted cultures resulted in growth arrest. In contrast, the sarcoma cell lines did not secrete TGF-alpha regardless of the culture conditions but EGF significantly stimulated proliferation of these cells in short-term assays. We show that exogenous EGF induces TGF-alpha production and supports proliferation of tumor cells of various tissue origin but is not essential for in vitro growth factor-deprived conditions.     

Overexpression of transforming growth factor-alpha and epidermal growth factor-receptor in idiopathic pulmonary fibrosis

BACKGROUND AND AIM: A recent transgenic mouse model overexpressing transforming growth factor alpha (TGF-alpha) led to a phenotype of pulmonary fibrosis. In order to validate this mouse as a model for idiopathic pulmonary fibrosis in humans, we studied the expression of TGF-alpha in lung tissue of patients with idiopathic pulmonary fibrosis compared to control lung tissue. METHODS: Tissue from both groups was obtained from operative specimens and immediately formalin-fixed and paraffin embedded. Contiguous four micron sections were prepared for conventional histochemical staining and staining with antibodies to either TGF-alpha or the epidermal growth factor-receptor (EGF-R). Immunostaining was performed using the Ventana ES automated immunohistochemistry system. Four cell types were examined (vascular endothelium, bronchial epithelium, type 2 pneumocytes, and fibroblasts) and stain activity was scored on a six point scale. RESULTS: Eleven patients with IPF were compared to seven control subjects. TGF-alpha immunoreactivity was significantly higher in the IPF patients than in controls in the vascular endothelium, type 2 pneumocytes, and fibroblasts (P < 0.005). [IPF (4(2-4) Median (Range)) than the controls (0.5(0-2), p < 0.0005).] The differences in EGF-R, one of the receptors for TGF-alpha, between these two patient populations were not as striking. There was a small but significantly greater expression of EGF-R in the bronchial epithelium and type 2 pneumocytes of the IPF patients. CONCLUSIONS: TGF-alpha is overexpressed in patients with IPF, especially in the vascular endothelial cells.     

食管癌血清和尿液中血管内皮生长因子水平的变化及其意义

目的检测食管癌患者术前血清和尿液中血管内皮生长因子(VEGF)水平,探讨VEGV与食管癌的关系及其临床意义.方法应用酶联免疫吸附法(ELISA)对82例食管癌患者术前血清和尿液中VEGF水平进行测定,并对其进行对照分析.结果食管癌患者术前血清和尿液VEGF水平分别为(92.81±5.86)ng/L和(277.92±22.71)ng/L,明显高于正常人组(P＜0.01).食管癌组术前尿液VEGF水平与肿瘤的分化程度、侵袭程度、临床分期及淋巴结转移等密切相关(P＜0.05);且术前尿液组的VEGF水平明显高于术前血清组(P＜0.01).结论VEGF可能参与食管癌的发生、发展和转移过程的调控,尿液VEGF含量的增强,预示食管癌的转移和预后不良.     

Tumor necrosis factor-alpha and interferon-gamma in serum of multiple myeloma patients

The levels of TNF-alpha and IFN-gamma were examined in serum from 32 patients with multiple myeloma and 33 healthy controls using sensitive enzyme-linked immunosorbent assays (ELISA). The detection limits for TNF-alpha and IFN-gamma were 80 pg/ml and 200 pg/ml, respectively. All samples were obtained at the time of diagnosis, before treatment. In sera from 8 of the myeloma patients the TNF-alpha concentrations were above the detection limit with a maximum value of 1.0 ng/ml. Overall, the TNF-alpha levels of the myeloma patients did not differ from the levels of the control group. Detectable amounts of IFN-gamma were found in 17 of the patient sera with 10.7 ng/ml as the top value. In contrast, the control group showed significantly lower s-IFN-gamma levels without detectable amounts in any of the samples (p less than 0.01). High IFN-alpha levels in 4 patients coincided with intercurrent infections but were not accompanied by a parallel increase of the TNF-alpha levels. The TNF-alpha and IFN-gamma values were compared with the serum levels of beta 2-microglobulin, calcium and creatinine, the M-component, the erythrocyte sedimentation rate, the degree of plasma cell infiltration of the bone marrow, the degree of skeletal destructions and with patients survival. No significant correlations could be observed between TNF-alpha or IFN-gamma and these variables of myeloma activity. We conclude that detection of serum TNF-alpha and IFN-gamma levels in multiple myeloma appears to be without any clinical value.     

Epidermal growth-factor and transforming growth factor-alpha in human meningiomas

Recently we have shown that human meningiomas overexpress epidermal growth factor receptor (EGFR) (Torp SH et al APMIS 100: 797-802, 1992). We therefore wanted to examine these tumours for the expression of the EGFR ligands epidermal growth factor (EGF) and transforming growth factor-alpha (TGF-alpha). Normal human meningeal tissues were used as controls. Immunohistochemistry (IH) and radioimmunoassay (RIA) demonstrated the presence of EGF and/or TGF-alpha. immunoreactivity in sixteen of nineteen meningiomas. By means of RIA detectable amount of TGF-alpha was also recorded in normal leptomeninges. Discrepancies between IH and RIA were noted and are discussed. Our findings suggest that EGFR/EGF/TGF-alpha play a role in growth regulatory mechanisms in human meningiomas.     

Production of transforming growth factor-alpha in human tumour cell lines

Forty-one human tumour cell lines were examined for the production of epidermal growth factor (EGF)/transforming growth factor (TGF)-alpha-like activity (EGF/TGF-alpha-LA), immunoreactive (IR-) EGF and IR-TGF-alpha. EGF/TGF-alpha-LA was determined by radioreceptor assay, in which the factors with capacity to bind to EGF receptor could be detected. IR-EGF and IR-TGF-alpha were determined by the respective radioimmunoassays. Both EGF/TGF-alpha-LA and IR-TGF-alpha were detected in 11 tumour cell lines. The levels of EGF/TGF-alpha-LA correlated well with those of IR-TGF-alpha. A small amount of IR-TGF-alpha was detected in five other lines. In contrast, IR-EGF was not detectable in any of the 41. Consequently, it can be concluded that EGF/TGF-alpha-LA produced by human tumour cells is mainly TGF-alpha rather than EGF. It was also revealed that melanoma cell lines produce a large amount of TGF-alpha frequently. Gel filtration studies revealed that TGF-alpha produced by melanoma cell lines was identical to human (h) TGF-alpha(1-50), except for one line, in which IR-TGF-alpha with a different molecular size was detected. Northern blot analysis revealed that bands corresponding to hTGF-alpha mRNA were present in melanoma cell lines producing a large amount of IR-TGF-alpha, indicating that the TGF-alpha produced is the product of hTGF-alpha gene. Further studies are required to discover the actual biological roles of TGF-alpha produced by melanoma cells as well as other types of cancer cells.