Expression of the co-signaling molecules CD40-CD40L and their growth inhibitory effect on pancreatic cancer in vitro

We investigated the expression of the co-signalling molecule CD40 in pancreatic cancer and the growth inhibitory effect of the recombinant soluble human CD40 ligand (rshCD40L) in pancreatic cancer cell lines. Twenty-six cases of pancreatic cancer tissues and corresponding paratumoral normal tissues were immunohistochemically analyzed for CD40 expression. The association of CD40 expression with clinicopathological parameters, including clinical stage, pathological grade, invasion and metastasis, were statistically analyzed. The serum sCD40 levels in pancreatic cancer patients were examined by ELISA. The expression of CD40 in the pancreatic cancer cell lines Panc-1, Aspc-1 and Miapaca-2 was examined by RT-PCR and flow cytometry. The growth inhibitory activity of rshCD40L on pancreatic cancer cell lines was determined by MTT assay. Tumor cell apoptosis was detected by TUNEL and Annexin V/PI double staining method. CD40 was positive both on the membrane and in the cytoplasm of tumor cells, 69.2% (18/26) of the cases were positive for CD40. CD40 expression was significantly higher in pancreatic cancer tissues compared to adjacent normal tissues (P<0.05). High CD40 expression was associated with TNM stage and lymph node metastasis (both P<0.05). Patients with pancreatic cancer have higher serum sCD40L levels (3.53 ± 0.70 ng/ml) compared to healthy subjects (1.81 ± 0.48 ng/ml, P<0.05). rshCD40L significantly inhibited the proliferation of the pancreatic cancer cell lines and induced apoptosis in these cell lines. The co-signaling molecule CD40 is highly expressed in pancreatic cancer tissues and cell lines and rshCD40L is a potential tool for antitumor therapies.     

Identification of a circulating soluble form of CD80: levels in patients with hematological malignancies

The release of soluble forms of CD80 provides a potentially powerful mechanism for the modulation of anti-tumor responses. In this report we investigated whether a soluble form of CD80 (sCD80) circulates in vivo and whether levels are altered in patients with hematological malignancies. Circulating sCD80 was detected by ELISA in all normal donor (0.024-0.318 ng/ml) and patient (0.02-3.75 ng/ml) blood analyzed. The majority of acute myeloid leukemia (13/17) and multiple myeloma (11/12) patients had normal sCD80 levels. Significantly elevated levels were detected in chronic lymphocytic leukemia (CLL, P = 0.0001) and mantle cell lymphoma (MCL, P = 0.0002) patients. MCL patients had the highest levels with 8/9 having levels > 0.318 ng/ml. Increased sCD80 levels in CLL were significantly associated with poor prognosis markers such as low platelet (P = 0.01) and hemoglobin (P = 0.002) levels, elevated WBC counts (P = 0.03) and expression of CD38 (P = 0.048). The immunoreactivity of the sCD80 in both normal and patient plasma was inhibited by the presence of CTLA-4-Ig, suggesting sCD80 is functional. Comparison of sCD80 and soluble CD86 levels demonstrated that these molecules were independently elevated in 39% of patients. The finding that a proportion of CLL and the majority of MCL patients contain elevated levels of sCD80 and the demonstration that sCD80 can interact with CTLA-4-Ig suggests a potential role for sCD80 in modulating anti-tumor responses during the malignant process.     

Markers of coagulation and angiogenesis in cancer-associated venous thromboembolism.

PURPOSE: We sought to determine whether venous thromboembolism in cancer patients is associated with aberrant plasma levels of hemostatic and angiogenic factors. PATIENTS AND METHODS: Peripheral blood was collected before anticoagulant therapy from cancer patients with acute deep venous thrombosis (DVT; DVT + cancer group, n = 32), those without DVT (cancer control group, n = 36), and patients with acute DVT but no cancer (DVT control group, n = 58). Plasma assays of activation and inhibition of coagulation and fibrinolysis, as well as angiogenesis activation, were then performed. RESULTS: Median levels of thrombin-antithrombin complex, prothrombin fragments 1 + 2, and von Willebrand factor antigen were significantly greater in the DVT + cancer group than in the cancer control and DVT control groups (17.8 ng/mL v 4.6 ng/mL and 9.8 ng/mL, P =.0001 and P =.003, respectively; 3.65 nmol/L v 1.60 nmol/L and 2.71 nmol/L, P <.0001 and P =.011, respectively; and 4.04 U/mL v 2.26 U/mL and 2.06 U/mL, P <.0001, respectively). Median levels of tissue-type plasminogen activator were also significantly higher, while protein C activity was lower in the DVT + cancer group than in the DVT control group (14.6 ng/mL v 9.50 ng/mL, respectively, P =.0005; 0.89 U/mL v 1.11 U/mL, respectively, P =.0008). CONCLUSION: These data not only support prior observations of coagulation activation in patients with malignancy, but also provide new evidence for enhanced coagulation activation in the setting of acute venous thromboembolism in cancer. Future prospective studies are warranted to determine whether these and other potential markers of hypercoagulability may help to identify cancer patients at highest risk for venous thromboembolism.     

Soluble CD44 variant 6 as a prognostic indicator in patients with colorectal cancer

The expression of CD44v6 is well known as a useful marker of tumor progression and prognosis in colorectal cancer. In this study, we evaluated the serum levels of soluble CD44 splice variants containing exon v6 (sCD44v6) and examined the histological expression of CD44v6 in patients with colorectal cancer. Serum samples were obtained from 44 primary colorectal cancer patients before surgery. We used enzyme-linked immunosorbent assay to determine the serum levels of sCD44v6. The expression of CD44v6 was examined by immunohistochemical staining of the primary tumors obtained from the same patients. Both the serum concentration of sCD44v6 and the expression of CD44v6 were significantly associated with lymph node metastasis (p < 0.05). Furthermore, the serum level of sCD44v6 was higher in those patients with CD44v6-positive tumor tissues (154.4 +/- 34.8 ng/ml) than in those with CD44v6-negative ones (130.7 +/- 32.3 ng/ml; p < 0.05). The 5-year survival rate was significantly lower in patients with high serum levels of sCD44v6 (52.4%) than in those with low levels of sCD44v6 (78.0%; p < 0.05), and it was also significantly lower in patients with CD44v6-positive cancer (42.1%) than in those with CD44v6-negative cancer (84%; p < 0. 01). We concluded that preoperative elevation in the serum levels of sCD44v6 might be a prognostic indicator for patients with colorectal cancer.     

Combined effects of klotho and soluble CD40 ligand on A549 lung cancer cells

Although the roles of soluble CD40 ligand (sCD40L) or the klotho gene in lung cancer cells have been studied, little is known about the functions of klotho combined with sCD40L in lung cancer. The present study was designed to investigate the biological effects of klotho combined with sCD40L on the A549 lung cancer cell line (CD40 positive) and their possible mechanisms. Lung cancer A549 cells were chosen as target cells and CD40 signals were stimulated by soluble CD40 ligand (sCD40L). In this study, we found that klotho, soluble CD40 ligand and their combination can increase cell proliferation inhibition and the apoptosis rate in A549 cells by inhibiting the cell cycle, up-regulating Bax gene expression and (or) down-regulating Bcl-2 gene expression; and their combination has a stronger effect on A549 cell apoptosis and proliferation inhibition compared to klotho or sCD40L alone. These data suggest that the combination of klotho and sCD40L may provide an efficient method to treat non-small cell lung cancer.     

Evaluation of soluble CD44 in patients with breast and colorectal carcinomas and non-Hodgkin's lymphoma.

CD44 is a transmembrane glycoprotein involved in cell-cell and cell-substrate interactions. As a cell surface molecule, CD44 may be shed or released into the circulation by proteolytic enzymatic mechanisms. Therefore, soluble CD44 can be found in cell culture supernatants as well as in plasma. In this study we evaluated the levels of soluble total CD44 (sCD44) in serum samples of patients with breast and colorectal carcinoma as well as non-Hodgkin's lymphoma in order to correlate prognosis with sCD44 expression. Besides, we evaluated other clinical tumour markers routinely used, Cancer Antigen (CA) 15.3 and CA 19.9. We investigated 132 serological samples from breast cancer patients, 48 sera from colorectal tumours, 48 samples from stage IV non-Hodgkin's lymphoma and sera from 80 individuals without evidence of cancer or autoimmune disease. Breast cancer patients were divided into three groups: a) patients with no clinical evidence of positive nodules and no metastatic disease; b) patients with positive nodules; and c) patients with metastasis. sCD44 mean serum levels in these groups were 198+/-54 ng/ml, 221+/-78 ng/ml and 242+/-119 ng/ml, respectively, while the marker CA 15.3 values were 15.6+/-6.6 U/ml, 14.0+/-5.8 U/ml and 211.5+/-358.9 U/ml, respectively. sCD44 levels for colorectal tumour were 243+/-72 ng/ml, while CA 19.9 serum levels were 230+/-270 U/ml. Stage IV non-Hodgkin's lymphoma sCD44 levels were 398+/-160 ng/ml. sCD44, CA 15.3 and CA 19.9 values for healthy individuals without evidence of any cancer pathology were 223+/-58 ng/ml, 16.4+/-6.2 U/ml and 33+/-14 U/ml, respectively. From these results we conclude that sCD44 might be used as a reliable marker for patients with non-Hodgkin's lymphoma. However, sCD44 levels failed to correlate with prognosis, tumour burden or metastasis in breast and colorectal cancer patients. Neither was any correlation found between high CA 15.3 or CA 19.9 levels and soluble CD44 serum level.     

肺癌患者外周血血小板活化标志物水平及其临床意义

背景与目的 中、晚期肿瘤患者的血小板往往处于活化状态,其血小板黏附分子的表达和释放增加.本研究的目的是探讨肺癌患者手术前、后外周血血小板活化标志物的动态变化规律及其与肺癌的关系.方法 采用流式细胞术(flow cytometry,FCM)检测120例肺癌患者手术前、后外周血血小板活化标志物(CD62P和CD63)水平,以60例健康体检者作为对照.结果 肺癌患者手术前外周血CD62P、CD63水平均显著高于正常对照组(P＜0.01).肺癌患者术后第7天外周血CD62P、CD63水平显著低于术前和术后第1天(P＜0.01).肺癌患者术前外周血CD62P、CD63水平与肺癌原发肿瘤大小、有无淋巴结转移和分期有密切关系(P＜0.01),与肺癌细胞分化程度、组织学类型、患者性别和年龄无明显关系(P＞0.05).结论 肺癌患者外周血血小板活化标志物水平升高,且与肺癌的发生、发展和淋巴结转移有一定关系,因而有可能作为动态监测肺癌患者病情进展、判断预后的参考指标.     

Serological Evaluation of Soluble CD44 in Renal Cancer

In this study, we examined the feasibility of using elevated serum CD44 concentration as an indicator in renal cancer. We performed enzyme-linked immunosorbent assays using 63 sera obtained from 47 patients with renal cancer and 16 healthy controls and evaluated the clinico-pathological parameters. The concentration of soluble CD44 standard (sCD44std), indicating the concentration of all circulating CD44 isoforms, was significantly higher in renal cancer patients than in normal individuals (745±170 ng/ml vs. 563±159 ng/ml, P =0.001). The concentration of soluble CD44 splice isoforms sharing exon v6 (sCD44v6) was also higher in the same patients (287±121 vs. 220±59, P =0.056). However, there were no correlations between the concentrations of sCD44std or sCD44v6 and clinico-pathological parameters such as grade, stage, histological type, tumor size and growth type. The ratio of sCD44std/sCD44v6 was higher in the rapid growth-type cancers than in the slow growth-type cancers (3.95±2.12 vs. 2.63±0.82, P =0.014). These findings suggested that the serum concentration of unknown soluble CD44 isoforms not sharing exon v6, which are present in sCD44std, increases in patients with rapid growth-type cancers. These findings indicated that sCD44std and sCD44v6 are not useful indicators of tumor burden and metastasis in patients with renal cancer, but that an unknown sCD44 isoform(s) plays a role in the biological behavior of the rapid growth-type cancers.     

非小细胞肺癌患者血清sCD44v6检测的临床意义

目的：探讨检测血清sCD44v6在非小细胞肺癌（NSCLC）诊断中的价值。方法：以酶联免疫吸附测定（ELISA）法检测50例NSCLC患者血清中sCD44v6的浓度，观察其与NSCLC的诊断、预后的相关性。结果：肺鳞癌组sCD44v6的水平[（307．47±79．00）ng／ml]，肺腺癌组sCD44v6水平[（369．53±114．19）ng／m1]，明显高于正常对照组[（95．60±17．50）ng／m1]，差异有显著性P〈0．001，NSCLCⅢ＋Ⅳ期患者sCD44v6的水平[（412．60±68．02）ng／m1]明显高于正常对照组[（95．60±17．50）ng／ml]，差异有显著性P〈0．001；结论：sCD44v6水平与NSCLC及其转移有明显关联，可作为判断NSCLC组织类型和分期的辅助指标，对早期诊断的价值不大。     

肺癌患者血清CA125检测的临床应用

目的:探讨CA125对肺癌鉴别诊断和观察疗效的临床意义。方法:采用免疫放射分析法测定健康人和按组织学分类的各类肺癌患者血清CA125水平及阳性率,同时检测各样品的血清CEA水平,进行统计分析。结果:患者组较健康对照组CA125水平显著增高(P<0.01)。肺鳞癌组CA125阳性率为84％,腺癌为65％,腺鳞癌为56％,小细胞肺癌为40％;1例大细胞肺癌CA125检测值为230U/ml、CEA值为18ng/mL。肺鳞癌阳性率较其它组x~2检验有显著意义(p<0.01),CA125与CEA呈正相关(R=0.852)。结论:血清CA125可作为对肺癌早期诊断、鉴别诊断及观察疗效的较好参考指标。     

Increased plasma levels of insulin-like growth factor 2 and insulin-like growth factor binding protein 3 are associated with endometrial cancer risk.

Circulating insulin-like growth factors (IGFs) and their binding proteins have been associated with increased risk of breast, prostate, colon, and lung cancer. To examine the association of IGFs and endometrial cancer risk, we measured the plasma levels of IGF-1, IGF-2, and IGF binding protein 3 (IGFBP-3) by ELISA in 80 women with endometrial cancer and 80 age-matched control subjects with no history of cancer. Mean plasma levels of IGF-2 were significantly higher in women with cancer versus controls (670 ng/ml versus 380 ng/ml, P < 0.001). In contrast, significantly lower mean plasma levels of IGF-1 (155 mg/ml versus 185 ng/ml, P < 0.01) and IGFBP-3 (1703 ng/ml versus 2170 ng/ml, P < 0.001) were observed among cases compared to the control group. Women in the highest quartile of IGF-2 were found to have 9.67 (95% confidence interval 3.29-28.43) times the risk of endometrial cancer than women in the lowest quartiles. Women in the highest quartile of IGFBP-3 were associated with a significantly decreased risk for developing endometrial cancer (odds ratio = 0.23, 95% confidence interval 0.09-0.60). These data suggest that increased plasma levels of IGF-2 and decreased levels of IGFBP-3 are associated with an increased risk of endometrial cancer. Further validation of these results is needed to determine the potential usefulness of risk assessment.     

Soluble CD40 ligand (sCD40L) provides a new delivery system for targeted treatment

BACKGROUND:

A wide range of hematologic malignancies arises from numerous cell types. In an attempt to offer a new target for treating B‐cell malignancies, in this study, the authors tested the possibility of using the CD40/CD40L system as a common targeting system for the various malignancies in this group.

METHODS:

Two chimeric proteins, soluble CD40 ligand (sCD40L)‐caspase 3 (sCD40L‐l‐Caspase3) and sCD40L‐pseudomonas exotoxin 38 (PE38) (sCD40L‐l‐PE38), were constructed, expressed, and partially purified. The ability of the chimeric proteins to kill tumor cells that expressed CD40 was tested by using proliferation assays. In addition, the induction of apoptosis in treated cells was followed by measuring expression levels of apoptotic proteins using real‐time polymerases chain reaction analysis, caspase 3 enzymatic activity, and tracking changes in the cell cycle with fluorescence‐activated cell‐sorting analysis.

RESULTS:

The chimeric proteins exhibited concentration‐dependent and time‐dependent killing ability. The new chimeric proteins had no effect in several carcinoma cell lines that did not express the CD40 receptor. Treating tumor cells with sCD40L‐based chimeric proteins led to internalization of the fusion proteins into the cell cytoplasm of B cells. Shortly after treatment, a sharp rise in B‐cell chronic lymphocytic leukemia/lymphoma 2 (Bcl2) expression levels occurred. Approximately 36 hours after the initiation of treatment, Bcl2 levels dropped, whereas Bcl2‐associated X protein (Bax) expression levels rose, pushing the cells toward apoptosis. Concomitantly, caspase 3 RNA levels rose.

CONCLUSIONS:

sCD40L‐based chimeric proteins were able to bind and internalize into B cells that expressed the CD40 receptor and specifically and efficiently induced apoptotic death. Moreover, the current results validated for the first time the ability of sCD40L to serve as a direct delivery system for targeted molecules. sCD40L‐based chimeric cytotoxic proteins offer a new weapon in the everlasting war against cancer. Cancer 2012. © 2012 American Cancer Society.     

不能手术的非小细胞肺癌同步放化疗对血清CD44v6 和VEGF表达水平的影响及其临床意义*

目的:检测不能手术的非小细胞肺癌（NSCLC ）患者同步放化疗前、后血清CD44v6 和VEGF（sCD 44v6,sVEGF ）表达水平,探讨其动态变化规律与不能手术NSCLC 病理生理特征、疗效及预后的相关性。方法:采用生物素- 亲和素系统ELISA 双抗体夹心法定量检测50例不能手术NSCLC 患者同步放化疗前、后血清CD44v6 和VEGF的表达水平。结果:1）治疗前CD44v6 水平（570.89± 63.30）ng/L 和VEGF水平（241.09± 85.96）ng/L 均显著高于对照组（356.32± 97.68）ng/L（P<0.01）与（103.72± 39.22）ng/L（P<0.05）。 2）治疗前VEGF表达水平与原发肿瘤大小、远处转移、细胞分化及临床分期等有显著相关性（P<0.05）,与原发部位、淋巴结转移和组织学类型等无明显相关性（P>0.05）。 而CD44v6 表达水平与原发肿瘤大小、远处转移、细胞分化、临床分期、淋巴结转移及组织学类型等有显著相关性（P<0.05）,与原发部位、性别和年龄无明显相关性（P>0.05）。 3）治疗前CD44v6 水平（570.89±63.30）ng/L 和VEGF 水平（241.09± 85.96）ng/L 均分别高于治疗后的水平（281.44± 74.28）ng/L（P<0.01）和（133.64± 67.69）ng/L（P<0.01）。 4）治疗后CD44v6 和VEGF平均水平与治疗前比较,CR组显著降低（P<0.01）,PD组降低不明显（P>0.05）,而PR组和SD组降低介于两者之间（P<0.05）。 5）治疗前、后CD44v6 和VEGF 水平呈正相关（r=0.291,P<0.05）。 结论:同步放化疗前后CD44v6/VEGF水平与不能手术NSCLC 的多项临床病理特征密切相关。它们的水平变化是预测不能手术NSCLC 生物学行为的有用指标,可为临床判断疗效及预后提供依据。      

乳腺癌患者血清中sCD44v6检测的临床意义

目的：探讨乳腺癌患者血清中可溶性CD44v6（sCD44v6）蛋白的含量及其临床意义。方法：采用酶联免疫吸附实验（ELISA）检测48例乳腺癌患者手术前后及10例健康对照组血清中sCD44v6蛋白的含量。结果：48例乳腺癌患者血清中sCD44v6蛋白的含量为（546.45±63.79）ng/ml,显著高于健康对照组（167.32±50.06ng/ml,P〈0.01。乳腺癌患者行根治性手术后sCD44 v6蛋白的含量明显下降,有统计学意义,P〈0.05。并与淋巴结转移、组织学分级、TNM分期及低龄（≤35岁）密切相关。结论：sCD44v6水平可作为诊断、治疗乳腺癌及预测乳腺癌患者转移复发风险及预后的辅助指标。     

开胸手术对非小细胞肺癌患者血清VEGF、MMP-9水平变化的影响分析

目的 分析开胸手术对非小细胞肺癌(non-small cell lung cancer)患者血清VEGF、MMP-9水平变化的影响.方法 将非小细胞肺癌患者79例作为观察组;良性肺部疾病患者56例和健康志愿者25例作为对照组.观察组患者和良性肺部疾病患者均进行了开胸肺切除手术,然后按照病理类型和TNM分期对观察组患者治疗前的VEGF、MMP-9水平进行检测统计,并与健康对照组比较分析,并对治疗前后观察组和良性对照组患者的VEGF、MMP-9水平进行统计分析.结果 按照患者病理类型检测VEGF水平为:腺癌(332.3±82.3)pg/ml,鳞癌(364.5±81.8)pg/ml,其他病理类型(375.8±88.6)pg/ml;所有患者的MMP-9水平分别为腺癌(199.4±82.2)ng/ml,鳞癌(183.2±102.6)ng/ml,其他病理类型(185.1±112.9)ng/ml,所有肺癌患者的VEGF水平和MMP-9水平均显著高于健康对照组(P<0.05).Ⅰ期患者的VEGF水平和MMP-9水平分别为(245.4±54.3)pg/ml和(141.2±58.2)ng/ml,明显低于其他分期患者VEGF水平和MMP-9水平(P<0.05).观察组患者治疗前后VEGF水平和MMP-9水平均显著高于良性对照组患者(P<0.05).结论开胸手术治疗非小细胞肺癌患者,术后患者的VEGF水平和MMP-9水平明显升高,但没有明显的相关性.患者术前VEGF水平和MMP-9水平也明显高于良性肺部疾病患者,且与患者的分化程度相关.     

可溶性CD40配体对肺癌细胞 A549的生物学作用及其机制研究

背景与目的:尽管对 CD40分子在 B细胞中的功能已有深入的研究,但 CD40在肺癌细胞中的功能目前知之甚少.本研究旨在探讨可溶性 CD40配体(solublE-CD40 ligand, sCD40L)对肺癌细胞株 A549(CD40表达阳性细胞株)的生物学作用及其相关机制.方法:采用四氮唑盐(MTT)比色、 3H标记胸腺脱氧嘧啶核苷( 3H-TdR)掺入法检测 sCD40L对 A549细胞增殖的影响,免疫荧光标记和流式细胞术测定细胞表型及细胞周期的改变,流式细胞术、逆转录聚合酶链式反应( RT-PCR)及 Western blot分析测定 sCD40L对 A549细胞凋亡的影响及 Bcl-2、 Bax基因表达的变化.结果:(1) sCD40L可抑制 A549细胞的增殖(与对照组比较 P< 0.05).(2) sCD40L作用 72 h后, A549细胞表面 CD49e、 CD54、 TNFRⅠ及 CD95L的表达 [分别为( 61.2± 4.8)%,( 31.2± 6.1)%,( 42.7± 5.9)%,( 38.2± 3.4)% ]较对照组 [分别为 (34.7± 2.1)%, (7.1± 1.6)%, (15.2± 4.1)%, (10.1± 2.3)% ]明显升高,而 TNFRⅡ的表达 [( 8.7± 0.8)% ]较对照组 [( 58.1± 3.6)% ]下降.( 3) sCD40L作用 72h后, A549细胞 G1 期细胞比例 [(76.0± 9.1)% ]较对照组 [(56.7± 6.9)% ]增加, S期细胞比例 [(10.3± 5.7)% ]较对照组 [(32.7± 5.5)% ]减少. ( 4) sCD40L在短期( 72 h)内并不引起 A549细胞明显凋亡,但可上调 Bax的表达.结论: sCD40L可引起肺癌细胞 A549生长抑制,细胞周期和表型改变,并可引起凋亡相关基因表达的改变.     

Utility of the serum tumor markers: CYFRA 21.1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCC) in squamous cell lung cancer

The aim of this study is to assess the clinical usefulness of serum assays of carcinoembryonic antigen (CEA), squamous cell carcinoma antigen (SCC), and CYFRA 21.1 in the diagnosis of squamous cell lung cancer. Sixty patients with squamous cell, and twenty-four patients with nonsquamous cell histology of nonsmall cell lung cancer were enrolled in this study. Serum CEA, SCC, and CYFRA 21.1 levels were obtained by commercially available kits. Upper cutoff levels were 10 ng/ml, 3.5 ng/ml, and 3.5 ng/ml, respectively. In squamous cell lung cancer, percentages and 95% confidence interval (CI) of the patients with elevated levels were as follows: for CEA 23.3% (13-36), for SCC 20.0% (10-32), and for CYFRA 21.1 85.0% (73-93). The positivity rate of CYFRA 21.1 was more significant than CEA and SCC in both squamous and nonsquamous cell lung cancer. None of the markers were significant in differentiating squamous/nonsquamous histology. Only tumor marker CEA was significantly elevated in metastatic squamous cell lung cancer (p=0.004). A novel tumor marker CYFRA 21.1 can be used as a reliable tumor marker in diagnosing squamous cell lung cancer. In addition, CEA has an important role in determining metastatic disease.     

内皮抑素在肺癌患者外周血清及支气管肺泡灌洗液中的表达研究

 目的 探讨内皮抑素（Endostatin）在肺癌患者外周血清及支气管肺泡灌洗液（Bronchoalveolar lavage fluid，BALF）中的表达以及与肺癌临床病理生理特征的关系。方法 采用酶联免疫吸附法（Enzyme-linked immunosorbent assay，ELISA）检测初诊肺癌47例及肺良性病变18例患者外周血清及BALF中Endostatin的表达水平。结果 肺癌患者外周血清及BALF中Endostatin分别为（131．71±50．32）ng／ml和（502．56±302．00）ng／ml，显著高于肺良性病变者（P〈0．01）；肺癌晚期、有淋巴结及远处转移、肺腺癌患者外周血清及BALF中Endostatin高表达；肺癌患者Endostatin在外周血清及灌洗液中的表达呈线性正相关（P=0．000）。结论 检测外周血清及支气管肺泡灌洗液中Endostatin均有助于肺癌的诊断及较好提示其生物学行为。     

血清CD44v6表达在结直肠癌中的临床应用价值

目的 探讨血清可溶性细胞表面黏附分子sCD44v6在结、直肠癌中的临床应用价值.方法 96例不同Duke分期结、直肠癌患者和24例健康者,分别采用酶联免疫吸附法(ELISA)定量检测其血清sCD44v浓度,化学发光免疫法检测血清CEA浓度;并结合临床资料进行分析.结果 结、直肠癌患者sCD44v6浓度为275.3±115.8 ng/ml,明显高于健康对照组(61.3±7.8 ng/ml)(P＜0.05),若以健康对照组的(-x)+2s(76.9 ng/ml)作为正常上限值,其阳性率为73.96%;sCD44v6水平随癌肿Duke分期的升级和肿瘤细胞的转移而呈现递增趋势,各组之间比较差异有统计学意义(P＜0.05).与CEA相比,sCD44v6水平在反映癌组织浸润和转移程度上更直接、敏感.结论 结、直肠癌患者sCD44v6水平和阳性率均显著增高,并与肿瘤的分期和扩散转移程度密切相关;术前sCD44v6水平检测可作为结、直肠癌患者病程和转移预测的一个重要指标.