Pretreatment Levels of Serum Vascular Endothelial Growth Factor do not Correlate with Outcome in Patients with Locally Advanced Cervical Cancer

Objective: To evaluate pretreatment levels of serum VEGF in locally advanced cervical cancer patients, andassess any association with clinocopathological parameters and response to radiotherapy. Methods: Patientswith histologically proven and diagnosed locally advanced cervical cancer or stages IIB-IVA were included inthis study. Blood serum was obtained by peripheral venous puncture about 24 hours before the beginning ofradiotherapy. All patients were followed up at one and three month intervals from the last day of the completetreatment for evaluating the responses to radiotherapy. Results: Mean age of the 40 patients was 52.8±11.1years. Sixty percent were in stage IIB and 90% had squamous cell carcinoma. The median pretreatment level ofserum VEGF was 611.3 pg/ml (0.00-4,067.20 pg/ml). The pretreatment levels of serum VEGF did not correlatewith stage (p=0.75), tumor histology (p=0.91), tumor size (p=0.46) or tumor characteristics (p=0.49). Almost allpatients received concurrent chemoradiation as a curative treatment, with a complete response found in 94.9%.Values for patients who were completed response was rather lower than patients with persistent disease, butwithout statistical significance (581.4 pg/ml vs 759.6 pg/ml, p=0.37). Conclusion: Pretreatment levels of serumVEGF do not correlate with clinicopathological factors or response to radiation therapy.     

Prognostic and predictive value of vascular endothelial growth factor and its soluble receptors, VEGFR-1 and VEGFR-2 levels in the sera of small cell lung cancer patients

OBJECTIVES: Small cell lung cancer (SCLC) has a rapid growth rate and is characterized by early metastases. Tumor growth is dependent on angiogenesis. Vascular endothelial growth factor (VEGF) is an important regulator of angiogenesis. Whether surveillance of pre- and post-treatment serum VEGF and especially its receptors VEGF-1 and VEGF-2 levels in SCLC patients have impact on clinical outcome is unknown. METHODS: From February 2001 to January 2003, 39 consecutive patients with histological proven SCLC were enrolled into the study. Pre-treatment (n: 39) and post-treatment (n: 25) samples of the same patients were collected at the time of their response evaluation. The levels of VEGF and its receptors VEGFR-1 and VEGFR-2 were measured in the serum by quantitative sandwich enzyme immunoassay technique. RESULTS: The median pre-treatment serum VEGF, VEGFR-1, and VEGFR-2 levels which were significantly higher than the normal controls were 1,200 pg/ml (range, 1,414.3 +/- 956.2 pg/ml), 85 pg/ml (range, 97.8 +/- 70.7 pg/ml), and 11,550 pg/ml (range, 14,481 +/- 6,267 pg/ml), respectively. We detected a poor but positive correlation between VEGF and VEGFR-2 (r: 0.46, p: 0.003). Pre-treatment low serum VEGF (<728.5 pg/ml) value (p: 0.02) and good response to treatment (p: 0.008) were found as good prognostic factors by multivariate analysis. CONCLUSIONS: Low serum VEGF concentration is a significant and independent prognostic factor in SCLC patients. Surveillance of VEGF and its receptors to predict chemotherapy response is not useful. Whether the levels of serum VEGF and its receptors VEGFR-1 and VEGFR-2 have value in detecting treatment modalities of SCLC need further studies.     

晚期恶性肿瘤血清VEGF含量测定的临床意义

目的：探讨血清血管内皮生长因子（VEGF）浓度在晚期恶性肿瘤中的临床意义。方法：应用酶联免疫吸附试验（ELISA）测定40例晚期恶性肿瘤（非小细胞肺癌、鼻咽癌、食管癌）患者血清的VEGF浓度，10名健康成人作为对照。结果：40例晚期恶性肿瘤患者血清VEGF浓度为（477．07±374．10）pg／ml，显著高于健康成人（139．09±133．41）pg／ml，差异有统计学意义（P=0．016），其中治疗前血清VEGF浓度在非小细胞肺癌为（518．53±378．99）pg／ml，食管癌为（399．21±393．69）pg／ml，鼻咽癌为（500．68±348．48）pg／ml，与健康成人比较差异有统计学意义（P值分别为0．011、0．044和0．019）。化疗有效患者的血清VEGF浓度（400．41±332．84）pg／ml显著低于化疗前浓度（777．10±666．01）pg／ml，差异有统计学意义（P=0．034）。结论：血清VEGF可作为晚期恶性肿瘤监测病情、判断放疗和预后一个有用的指标。     

Evaluation of inflammatory cytokines in malignant and benign pleural effusions

We measured the levels of inflammatory cytokines interleukin-1alpha (IL-1alpha), interleukin-1beta (IL-1beta), interleukin-2 (IL-2), interleukin-6 (IL-6), interleukin-8 (IL-8), and tumor necrosis factor-alpha (TNF-alpha) in pleural effusions and serum in 65 consecutive patients: 32 with malignant pleural effusion (MPE) (group A), and 33 with inflammatory benign pleural effusion (BPE) (group B). Serum levels of 15 healthy individuals served as control. Concentrations of IL-1alpha were higher in serum compared to pleural fluid in both groups (47.1+/-33.9 vs. 25.9+/-1.7 fmol/ml, p<0.001, in group A; and 39.9+/-30.9 vs. 25.4+/-16.3 fmol/ml, p<0.02, in group B). Similarly, concentrations of IL-1beta and IL-2 were significantly higher in serum compared to pleural fluid in both groups. In contrast, IL-6, IL-8 and TNF-alpha were found at high concentration in MPE in comparison to serum IL-6: 171.8+/-60.4 vs. 7. 2+/-7 fmol/ml (p<0.001), IL-8: 1175.15+/-2385.6 vs. 285.2+/-187.2 pg/ml (p<0.05), TNF-alpha: 204.9+/-82.9 vs. 79.4+/-31.9 fmol/ml (p<0. 001). Similarly, pleural concentrations of IL-6, IL-8 and TNF-alpha were higher in BPE patients in comparison to serum IL-6: 124.3+/-56. 2 vs. 8.6+/-6.4 fmol/ml (p<0.001) IL-8: 2109.2+/-4121.5 vs. 291. 6+/-197.9 pg/ml (p<0.02), TNF-alpha: 183.8+/-28.2 vs. 86.2+/-23.9 fmol/ml (p<0.001). These data suggest that IL-6, IL-8 and TNF-alpha might be secreted locally at the site of active disease both in benign and malignant pleural effusions.     

Tnp-alpha determination in serum and pleural effusion in patients with lung-cancer

The relationship between Tumor Necrosis Factor-alpha (TNF-alpha) in the serum and pleural fluid of lung cancer patients and the extent and the histological cell type was studied. TNF-(a)lpha level was determined in the serum of 68 patients with lung cancer [51 non-small cell lung cancer (NSCLC) and 17 small cell lung cancer (SCLC)] and in pleural fluid of 30 patients with lung cancer (22 NSCLC, 11 of them positive for neoplastic cells and 8 SCLC, 7 of them positive). Sera of 31 healthy subjects and the pleural fluid of 15 non-malignant pleural effusions were tested as controls. TNF-alpha serum level was increased in patients with lung cancer (healthy subjects 7.8+/-3.3 pg/ml; lung cancer 16.2+/-9.1 pg/ml), in NSCLC as well as SCLC and a relationship with the extent of the disease was found in both the histological types. In pleural fluid, no differences of TNF-alpha level were observed between neoplastic and benign inflammatory effusion, between SCLC and NSCLC or between cases positive and negative for the presence of neoplastic cells. Serum TNF-alpha may be an indicator of tumour burden; conversely, TNF-alpha in pleural fluid, was unable to discriminate between neoplastic and benign effusion.     

Clinical significance of plasma vascular endothelial growth factor in gastrointestinal cancer

Circulating vascular endothelial growth factor (VEGF) was measured in gastric and colorectal cancer patients using an enzyme-linked immunosorbent assay (ELISA). Firstly, serum and plasma samples were collected from 20 normal controls to compare the values of VEGF and to determine which specimen type was most suitable for detecting circulating VEGF. Seventeen of 20 normal controls had plasma VEGF levels under the limit of detection (15 pg/ml) and the levels of the remaining three controls were 21, 22 and 38 pg/ml. In contrast, all serum samples indicated high levels of VEGF (mean 238 pg/ml), ranging from 44 to 450 pg/ml. In a time-course test of two normal controls serum VEGF values increased markedly between 30 and 60 min and remained high, whilst plasma VEGF values were low up to 480 min. Thus, plasma samples are more suitable for the measurement of circulating VEGF. Next, plasma VEGF levels were examined in 44 patients with gastric cancer (8 early, 7 advanced without remote metastasis and 29 metastatic), 13 with colorectal adenoma (2 with focal cancer) and 26 with colorectal carcinoma (8 advanced without metastasis and 18 metastatic) before treatment. An extremely high plasma concentration of VEGF was seen in some cancer patients with metastasis. To discriminate these patients, a cut-off level was determined, considering both the distribution of the sample concentration and the upper limit of 95% confidence area of VEGF in the cancer patients without metastasis. The cut-off value was 108 pg/ml and most cancer patients without metastases had VEGF levels below the cut-off value. In 11 of 29 metastatic gastric cancer patients (38%) and 9 of 18 metastatic colorectal cancer patients (50%), plasma VEGF levels were higher than the cut-off value. Survival was also analysed in the patients with metastasis. It was significantly longer in the patients with low VEGF levels (below the cut-off) than in those with high VEGF levels (logrank test, P = 0.042). 34 patients with metastasis (19 gastric cancer and 15 colorectal cancer) were treated with systemic chemotherapy, and their pretreatment levels of plasma VEGF and conventional tumour markers (CEA and CA19-9) were evaluated in relation to response. The response to chemotherapy was significantly higher in patients with low VEGF levels (< or = 108 pg/ml) than in those with high VEGF levels (P = 0.047). Such a difference was not observed with CEA/CA19-9. In conclusion, plasma VEGF is a useful marker for tumour metastasis and patient survival, and a possible predictive factor for the response of patients with gastrointestinal cancer to chemotherapy.     

Tumor necrosis factor-alfa production by monocytes from lung and colorectal cancer patients

Tumour necrosis factor-alpha (TNF-alpha) is a monocyte (MO)-derived cytokine that plays an essential role in the immunological system. In the present study our aim was to evaluate the levels of TNF-alpha secreted by MO from cancer patients. Blood MO were obtained from 10 lung cancer patients (LCP), 10 colorectal cancer patients (CCP) and 10 healthy donors (HD). TNF-alpha levels in MO culture supernatants spontaneously (sp) secreted or after stimulation with LPS treatment were evaluated using a commercial ELISA kit (sensibility: 10-1000 pg/ml). Mean values, expressed as pg/ml were: LCP: sp= 452.6+/-107.2, LPS= 589.5+/-126.7); CCP: sp= 84.1+/-25.0, LPS= 437.3+/-93.2; HD: sp= 74.2+/-21.5, LPS= 573.5+/-87.1. We concluded that MO from LCP secrete high levels of TNF-alpha spontaneously (p< 0.003 versus HD) and it was also observed an absence of response to LPS treatment in the 33% of the cases in these patients.     

Clinical utility of vascular endothelial growth factor in diagnosing malignant pleural effusions

While the early diagnosis of cancer has been fully respected, it is still however often difficult for clinicians to confirm malignant pleural effusions (PE), which essentially indicate the end-stage cancer. It has now been demonstrated that vascular endothelial growth factor (VEGF) is a pivotal angiogenesis factor and associated with tumor growth and metastasis. The aim of this study was then to assess the diagnostic performance of VEGF in malignant PE. In this controlled and blinded prospective study, 113 consecutive patients with PE were recruited. For each eligible case, the VEGF levels of pleural fluid (PF) and serum were examined simultaneously using enzyme immunoassay. The reference standard for malignant PE was clinical evaluation and PF cytology with pleural biopsy, other examination and follow-up added as needed. According to the final diagnoses, 81 qualified cases were grouped as malignant (n=32) and benign (n=49) PE. For PF VEGF level, the mean in malignant group was higher than that in benign group (1358+/-1493 pg/mL vs. 422+/-317 pg/mL, p=0.001). As did for serum VEGF level (650+/-533 pg/mL vs. 137+/-189 pg/mL, p<0.001). Using receiver operating characteristic analysis, the determined diagnostic cut-off points of VEGF levels of PF and serum for malignant PE were 959.25 pg/mL and 212.36 pg/mL, with sensitivities of 47%, 69% and specificities of 96%, 88%, respectively. For cascade connection and parallel operation of PF VEGF and serum VEGF, the sensitivities were 34%, 81% at specificities of 98%, 86%, respectively. These findings suggest that VEGF could be used in diagnosing malignant PE as a useful adjunct of conventional algorithm. Different VEGF test strategies, including test on PF, serum and both, may be selected according to practical needs.     

Pet birds and risk of lung cancer in North-Western Germany

The relationship between non-small cell lung cancer and platelet counts, serum levels of vascular endothelial growth factor (VEGF) and endostatin, is unclear. Platelet counts and serum VEGF and endostatin levels were measured preoperatively in 99 patients with non-small cell lung cancer, and the relationship between these factors and clinicopathological features, including prognosis, was examined. Mean serum VEGF level was slightly higher in patients than in healthy subjects (P=0.23). Mean serum endostatin level was 42.4+/-40.4 ng/ml in patients compared to 16.3+/-10.3 ng/ml in healthy subjects (P=0.0003). Serum endostatin levels were significantly higher in patients with involvement greater than T2 or stage IB, compared to other patients. Platelet count and serum endostatin level greater than the median were associated with poor prognosis. Our results suggested that platelet count and serum endostatin level may be useful markers for non-small cell lung cancer.     

幽门螺杆菌相关性胃疾病血清IL-8和NO含量的检测及意义

目的　检测幽门螺杆菌 (HP)相关性胃疾病患者血清白细胞介素 8(IL 8)和NO浓度 ,探讨其与HP感染的关系 ,以及HP感染引起胃上皮细胞增殖与凋亡失衡 ,导致胃癌形成的可能分子机制。方法　以ELISA法检测血清IL 8浓度 ,镀铜镉粒还原法检测血清NO浓度。结果　IL 8浓度在正常组织 (2 2 .5 0± 1.87pg ml)、浅表性胃炎 (34.99± 7.89pg ml)、萎缩性胃炎 (6 5 .2 7± 10 .6 0pg ml)及胃癌 (94 .84± 11.0 9pg ml)组间差异有显著性 (P <0 .0 1) ;萎缩性胃炎组NO浓度 (39.93± 5 .4 3μmol L)明显高于胃癌组 (37.0 2± 4 .13μmol L ,P <0 .0 5 ) ,其余各组间差异无显著性。HP(+)组IL 8和NO浓度显著高于HP(- )组 (77.30± 2 0 .92pg ml,39.16± 14 .4 0pg ml,P <0 .0 1;39.77± 5 .5 7μmol L ,35 .35±5 .2 4 μmol L ,P <0 .0 1) ;CagA(+)HP组IL 8和NO浓度显著高于HP(- )组 (83.4 5± 16 .92pg ml,6 6 .2 4± 2 3.2 1pg ml,P <0 .0 1;4 0 .97± 4 .5 9μmol L ,37.6 2± 6 .5 8μmol L ,P <0 .0 5 )。浅表性胃炎及萎缩性胃炎组的IL 8与NO呈正相关 (r分别为 0 .881和 0 .995 ) ,正常组和胃癌组无相关性。结论　血清IL 8和NO浓度与CagA(+)HP菌株感染密切相关 ;血清IL 8和NO浓度测定与HP菌株CagA分型联合检测将有助     

Serum erythropoietin and thrombopoietin levels in patients with essential thrombocythaemia

In 40 patients with essential thrombocythaemia (ET) serum erythropoietin (EPO) and thrombopoietin (TPO) concentrations were determined and compared with the EPO and TPO values of a healthy control group. The mean EPO serum concentration for 24 control patients was 9.4 mU/ml +/- 3.7 (range 2-17.9), for 32 untreated ET patients at diagnosis 6.6 mU/ml +/- 7.6 (range 0.5-44.3) and for 8 ET patients treated with cytoreduction 14.1 mU/ml +/- 8.0 (range 4.5-26.1). Serum EPO levels in untreated ET patients at diagnosis were significantly lower compared with serum EPO levels in healthy control patients (p=0.002). Serum EPO levels in treated ET patients were not different from serum EPO levels in healthy controls (p=0.13) but were significantly higher compared with untreated ET patients (p=0.003). Serum TPO levels were determined in 18 of 40 ET patients, the mean TPO serum concentration was 211 pg/ml +/- 109 (range 62,5-345). The mean TPO serum concentration for 10 untreated ET patients at diagnosis was 162 pg/ml +/- 87 (range 62,5-302) and for 8 ET patients who had received cytoreductive treatment 272 pg/ml +/- 106 (range 96-345), respectively (p=0.04). Both serum TPO levels for treated and untreated ET patients were significantly higher (p<0.001) compared with serum TPO levels for healthy controls. The results of our study suggest a difference in the regulation of serum EPO and TPO in patients with ET. While the mean serum EPO level is decreased in untreated ET patients, the corresponding mean serum TPO level is increased. Treatment with cytoreduction, results in normalisation of the mean serum EPO level, whereas the mean TPO serum level remains elevated.     

Correlation between tumor necrosis factor-alpha and D-dimer levels in non-small cell lung cancer patients

The present study was designed to investigate whether a correlation exists between IL-6, TNF-alpha and coagulation (Thrombin-antithrombin, TATc) or fibrinolysis (D-dimer) activation in non-small cell lung cancer (NSCLC) patients. One hundred thirty patients with NSCLC (n=65, 53 males, mean age 65 +/- 8, adenocarcinoma n=32, squamous cancer n=33) or chronic obstructive pulmonary disease (COPD) (n=65, 51 males, mean age 67 +/- 9) were studied. As control group 65 healthy donors (51 males, mean age 61 +/- 14) were also evaluated. The results obtained showed that median D-dimer levels were higher in NSCLC patients (3.0 microg/ml) compared either to COPD patients (1.1 microg/ml, P<0.05) or controls (0.3 microg/ml, P<0.0001). Positive TNF-alpha levels (>10 pg/ml) were found in 26% of NSCLC compared to 3% of COPD (P<0.002) and 5% of controls (P<0.0005). On the other hand, positive (>8.5 pg/ml) IL-6 levels were found in 53% of NSCLC and 21% of COPD patients, compared to 5% of control subjects (P<0.001). Median TATc levels were elevated in either NSCLC (6.9 microg/l) or COPD (5.7 microg/l) patients compared to controls (1.8 microg/l, P<0.0001). Elevated D-dimer levels were significantly associated to positive TNF-alpha levels in patients without distant metastasis (F=4.3, P<0.05). Moreover, TNF-alpha levels (P<0.01) were independently related to the presence of positive D-dimer levels in patients with non-metastatic NSCLC. These results suggest that increased levels of TNF-alpha might be responsible for an activation of fibrinolysis in patients with NSCLC.     

血管内皮生长因子在肝细胞癌血清中的表达意义

目的研究血管内皮生长因子(vascularendothelialgrowthfactor,VEGF)在肝细胞癌(HCC)患者周围血血清中的表达水平与肝癌临床病理特征及肝癌转移复发之间的关系.方法运用sandwich酶联免疫吸附测定法定量检测115例HCC、40例肝脏良性疾病患者和30例健康人血清中VEGF的含量.结果HCC组血清VEGF表达水平[(465.62±336.24)pg/ml]与肝脏良性疾病组[(159.54±120.58)pg/ml]、与健康人组[(123.53±51.84)pg/ml]比较,差异均有显著性(P值均=0.0001);VEGF表达阳性率分别为77.4%、25.0%和3.3%.HCC转移组患者血清VEGF表达水平与未转移组相比,差异有显著性(P=0.001).血清VEGF表达水平还与HCC合并门静脉瘤栓、肿瘤大小和TNM分期密切相关,VEGF含量随TNM分期升高而逐步升高.结论疗前HCC患者的血清VEGF表达水平,是反映HCC侵袭生长及转移潜能的有效生物学指标.     

Serum interleukin-2 (IL-2), soluble IL-2 receptors and tumor necrosis factor-alfa levels are significantly increased in acute myeloid leukemia patients

Serum interleukin-2 (IL-2), soluble IL-2 receptors (sIL-2R) and tumor necrosis factor-alfa (TNF-alpha) levels were determined in 66 previously untreated consecutive patients with acute myeloid leukemia (AML) and in 22 normal volunteers. The following mean (+/- SE) values were observed in patients and controls, respectively: 35 +/- 14.7 (range 0.5-500) and 0.7 +/- 0.02 (0.5-0.8 U/ml for IL-2 (p = 0.001); 1622 +/- 289 (110-10,600) and 422 +/- 30 (207-666) U/ml for sIL-2R (p = 0.0001); 1247 +/- 196 (218-4672) and 152 +/- 11 (75-308) pg/ml for TNF-alpha (p = 0.0001). With respect to the FAB classification system, we found a significantly different distribution of serum IL-2 mean values in distinct subcategories, i.e. 3.4 +/- 1.9 U/ml in M1-M2-M3 and 42.4 +/- 20.4 U/ml in M4-M5 subgroups, respectively (p = 0.01), whereas sIL-2R and TNF-alpha levels were 1144 +/- 322 U/ml and 1120 +/- 317 pg/ml in M1-M2-M3 patients and 1945 +/- 317 U/ml and 1270 +/- 259 pg/ml in the M4-M5 group. A significantly positive correlation between TNF-alpha and sIL-2R (r = 0.53; p = 0.002) was also detected in the M4-M5 group. Sixty-three out of 66 patients received an intensive chemotherapy program. Univariate analysis showed that age and sIL-2R greater than 2000 U/ml significantly affected both complete remission rate and overall survival, whereas by multivariate analysis, age was the only independent variable significantly influencing survival. These data confirm recent in vitro evidence suggesting the role of IL-2, sIL-2R, and TNF-alpha in the control of normal hematopoiesis and leukemogenesis. Since the availability of recombinant cytokines for clinical use in AML, it is crucial to understand their spectrum of interaction in order to select the appropriate combination for in vivo administration.     

Pretreatment serum endostatin as a prognostic indicator in metastatic gastric carcinoma

Endostatin is the C-terminal antiangiogenic fragment of the extracellular matrix protein collagen XVIII, and is generated by tumor-derived proteases. The presence of serum endostatin in patients with gastric cancer has not been reported. The authors assessed the serum levels of endostatin in patients with gastric carcinoma and evaluated their association with the levels of vascular endothelial growth factor (VEGF) and the clinical outcome. A total of 107 patients with gastric cancer were included in the study. Pretherapeutic serum levels of endostatin and VEGF were measured using an ELISA, and compared with those in 23 healthy controls. The serum levels of endostatin and VEGF were higher in gastric cancer patients than in healthy controls (endostatin, 70.1 +/- 16.6 vs. 52.2 +/- 6.2 ng/mL [p < 0.001]; VEGF, 55.1 +/- 7.6 vs. 32.1 +/- 2.4 ng/mL [p < 0.001]; mean +/- SD). Serum endostatin levels were significantly associated with the presence of distant metastases (r = 0.556, p < 0.001) and VEGF levels (r = 0.335, p < 0.001), but not with the depth of tumor invasion, differentiation, or regional lymph node status. A serum endostatin level above the 75th percentile of the distribution for the patients (79.2 ng/mL) was associated with a poor outcome (last follow-up at 42 months; median survival time, 9 vs. 20 months [log-rank, p = 0.017]; median time to progression, 5 vs. 10 months [log-rank, p = 0.022]) in the patients with metastatic gastric cancer. The results suggest for the first time that an elevated serum level of endostatin at the diagnosis of metastatic gastric cancer could be predictive of a poor outcome.     

Pro-gastrin-releasing peptide in patients with benign and malignant diseases.

The specificity and sensitivity of pro-gastrin-releasing peptide (ProGRP) was evaluated in 37 healthy subjects, 197 patients with benign diseases and 310 patients with malignant diseases of different origins. Abnormal ProGRP serum levels (>50 pg/ml) were found in 10% of the patients with benign diseases and in 26.1% of the patients with active cancer. None of the healthy subjects had abnormal ProGRP levels. The benign disease with the highest ProGRP concentration was renal failure, with abnormal values in 51.6% of the patients studied. Excluding patients with renal failure or patients with creatinine levels greater than 1.5 mg/dl, raised ProGRP values (<80 ng/ml) were found in 2.5% (4/160) of patients with benign diseases and in 4.9% of patients with active malignancies other than lung cancer or neuroendocrine tumors (<110 ng/ml). Abnormal ProGRP serum levels were found in 26.2% of patients with non-small cell lung cancer (NSCLC) (mean 40.5 +/- 35.4 pg/ml) and in 76.8% of patients with small cell lung cancer (SCLC) (mean 694 +/- 1,776 pg/ml) (p < 0.001). ProGRP serum levels >300 pg/ml were only found in SCLC patients (41.4%). ProGRP results were related to tumor extension in SCLC (sensitivity in limited disease 58.3%, in extensive disease 95.5%) but not in NSCLC. In summary, renal failure is the most frequent source of false-positive results with ProGRP, and this marker is useful in the histological differential diagnosis of lung cancer.     

In vivo release of vascular endothelial growth factor from colorectal carcinomas

The formation of new blood vessels is essential for the growth of malignant tumors and their hematogenic spread. Tumor-induced neoangiogenesis occurs through sprouting of preexisting vessels. An alternative mechanism might be the recruitment of bone marrow-derived endothelial cells, or their precursors, to the tumor site by the release of vascular endothelial growth factor (VEGF) from cancer cells, i.e., tumor-induced postnatal vasculogenesis. To investigate if a significant amount of VEGF is released from malignant tumors in vivo, thus potentially mobilizing endothelial precursor cells (EPC) from the bone marrow, we measured plasma levels of soluble VEGF obtained from tumor-draining mesenteric veins (VEGF-M) during surgery and, simultaneously, in venous blood obtained distant from the tumor (VEGF-P). This analysis was performed in 29 patients with colorectal carcinoma. VEGF-M levels were substantially higher in patients with distant metastases (208 +/- 61 pg/ml) compared to patients with nonmetastatic disease (99 +/- 72 pg/ml, p = 0.003). Also, in patients with aggressive disease, i.e., histologically undifferentiated (G3) tumors, higher levels of VEGF-M were measured than in patients with tumors of lower histologic grading (196 +/- 46 vs. 107 +/- 80 pg/ml, p = 0.01). In conclusion, the release of significant amounts of soluble VEGF in vivo from clinically and/or histologically aggressive tumors might reflect their high angiogenic or vasculogenic potential, probably leading to the recruitment of EPC from the bone marrow.     

晚期恶性肿瘤血清VEGF含量测定的临床意义

Objective: To elucidate the clinical significance of serum vascular endothelial growth factor (VEGF) level in patients with advanced cancer. Methods: Enzyme linked immunosorbent assay (ELISA) was used to determine the serum VEGF concentration in 40 patients with advanced cancer [non-small cell lung cancer (NSCLC), esophageal cancer (EC) and nasopharyngeal carcinoma (NPC)] before and after chemotherapy and 10 healthy volunteers as control group. Results: The serum VEGF concentrations in 40 cases of advanced cancer patients were significantly higher than those of 10 healthy control cases [(477.07 ± 374.10 ) pg/mL vs (139.09 ± 133.41 ) pg/mL; P = 0.016]. The serum VEGF concentrations in patients with NSCLC, EC and NPC were (518.53 ± 378.99) pg/mL, (399.21 ± 393.69) pg/mL and (500.68 ± 348.48) pg/mL, respectively. The differences were all statistically significant as compared with healthy control group (P values were 0.011,0.044 and 0.019, respectively). The serum VEGF concentrations of the patients in response to chemotherapy was significantly lower than those of the same patients before they undergoing chemotherapy [(400.41 332.84) pg/mL vs (777.10 ± 666.01) pg/mL; P = 0.034]. Conclusion: The serum VEGF level might be a novel and promising tumor marker of advanced malignancies and a predictor of disease progression, prognosis and therapeutic efficacy.     

NSCLC微波消融前后血清VEGF、Arg-1、iNOS水平变化及其相关性

目的 探讨微波消融治疗非小细胞肺癌(NSCLC)的疗效,分析微波消融前后NSCLC患者血清血管内皮生长因子(VEGF)、精氨酸酶-1(Arg-1)、诱导型一氧化氮合酶(iNOS)浓度的变化及三者之间的关系.方法 选取30例健康体检者作为对照组,30例晚期NSCLC患者为试验组,用酶联免疫吸附试验(ELISA)法检测健康体检者、晚期NSCLC患者微波消融术前及术后第1天、第3天、1个月血清VEGF、Arg-1、iNOS浓度.结果 微波消融治疗晚期NSCLC的有效率为33.3％ (10/30),疾病控制率为70.0％(21/30).微波消融术前NSCLC患者血清VEGF、Arg-1、iNOS浓度分别为(816.56±13.26)pg/ml、(5.17±0.20) ng/ml、(544.18±13.93) pg/ml,明显高于对照组的(93.43±9.93) pg/ml、(1.08±0.05) ng/ml、(8.08-±0.33) pg/ml,差异均有统计学意义(t=239.093,P＜0.001;t=110.359,P＜0.001;t=210.792,P＜0.001).晚期NSCLC患者微波消融术后第1天、第3天、1个月血清VEGF浓度分别为(708.41±10.49)pg/ml、(592.63±7.25) pg/ml、(521.91±8.32) pg/ml,均较治疗前明显降低(均P ＜0.05);Arg-1浓度分别为(5.95±0.10) ng/ml、(7.02±0.13) ng/ml、(7.67±0.92) ng/ml,均较治疗前明显升高(均P ＜0.05);iNOS浓度分别为(453.01±9.48)pg/ml、(393.21±9.42) pg/ml、(352.60±8.31)pg/ml,均较治疗前明显降低(均P＜0.05).NSCLC患者治疗前血清iNOS与VEGF表达呈正相关(r =0.379,P=0.039),Arg-1与VEGF表达呈负相关(r=-0.556,P=0.001),iNOS与Arg-1表达无关(r=-0.238,P=0.205).结论 微波消融是一种有效的NSCLC局部治疗手段,除可直接杀灭癌细胞外,亦可影响VEGF、Arg-1、iNOS表达水平,VEGF与iNOS和Arg-1有一定相关性,而iNOS与Arg-1无关.微波消融可在一定程度上改变肿瘤微环境,刺激机体产生抗肿瘤免疫.