Prognostic significance of elevated endothelin-1 levels in patients with colorectal cancer

BACKGROUND: Prognostic factors from clinical, laboratory and pathological data of patients with colorectal cancer are essential to identify high-risk groups to whom beneficial adjuvant therapy could be given. Endothelin-1, a growth factor, has been associated with the development and spread of solid tumours. This prospective study was performed to determine whether preoperative plasma big ET-1 levels might be useful as a prognostic indicator in patients with colorectal carcinoma. METHOD: Sixty-five consecutive patients with colorectal cancer confirmed by biopsy were included prospectively into this study over a 12-month period. Plasma samples from a peripheral vein were obtained prior to surgery. Univariate analysis of survival using age (< or > 70 years), sex, Dukes' stage (A&B versus C), tumour size (< or > 50 mm), vascular invasion and plasma big ET-1 levels was performed and significant factors were then analysed with the Cox regression model. RESULTS: Three variables, age, Dukes' tumour stage and plasma big ET-1 levels, were found to have prognostic significance (p<0.05). Factors associated with a poorer prognosis were age >70 years (p=0.02), Dukes' C tumours (p=0.04) and plasma big ET-1 levels >4.2 pg/mL (p=0.02). The Cox regression model identified the same three variables as having independent prognostic value for overall survival. CONCLUSION: Preoperative plasma big ET-1 levels may be useful in predicting overall survival in patients with colorectal cancer. Plasma big ET-1 levels may be useful in the selection of high-risk lymph node-negative patients with colorectal cancer for adjuvant therapy.     

Clinical significance of serum leptin level in patients with gastric cancer

Leptin may support the proliferation and hinder the apoptosis of tumor cells. Although leptin expression has been studied in several human tumors, its potential clinical significance remains uncertain in patients with gastric carcinoma. Furthermore, the majority of available findings have been determined from preclinical studies using stomach carcinoma tissue section and, to date, few studies have evaluated the clinical significance of leptin in the serum or plasma of gastric carcinoma patients. In the current study, the serum concentration of soluble leptin was assessed in gastric carcinoma patients, and its contributions to the clinical parameters and prognosis of patients were determined. A total of 63 pathologically confirmed gastric cancer patients and 30 healthy subjects were enrolled in the study and circulating leptin levels in the serum of all subjects were determined by ELISA. The serum leptin concentrations were significantly lower in the gastric cancer patients compared with the healthy control group (P = 0.009). In the gastric cancer patients, the clinical features of patient age, sex, lesion localization, histopathology, pathological grade, stage of disease, and serum tumor markers including lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 19–9 were not correlated with serum leptin concentration. Furthermore, no association was observed between serum leptin concentration and responsiveness to chemotherapy (P = 0.51), and leptin level had no apparent prognostic role in clinical outcome (P = 0.57). In conclusion, although it was not predictive or prognostic, serum leptin level may be a valuable diagnostic indicator in patients with gastric carcinoma.     

Clinical significance of serum epithelial cell adhesion molecule (EPCAM) levels in patients with lung cancer

Cellular adhesion molecules might be good markers in some types of malignant tumors, thus providing useful information in diagnosis and prognosis. The objective of this study was to determine the clinical significance of the serum levels of epithelial cell adhesion molecule (EPCAM) in lung cancer patients. One hundred and thirty lung cancer patients were enrolled in this study. Serum EPCAM levels were determined by the solid-phase sandwich ELISA method. Age- and sex-matched 34 healthy controls were included in the analysis. The median age was 58 years, ranging 35–80 years. The majority of the patients had NSCLC (83.8 %) and stage IV disease (60.8 %). There was no significant difference in the serum EPCAM levels between lung cancer patients and healthy controls (p = 0.16). Moreover, known clinical variables including age of patient, gender, histology, stage of disease, and response to chemotherapy were not found to be correlated with serum EPCAM concentrations (p > 0.05). Similarly, no prognostic role was found for outcome (1-year survival rate 62 vs. 65.1 %, p = 0.89). In conclusion, serum EPCAM concentrations have no diagnostic, predictive, and prognostic roles in lung cancer patients.     

Clinical significance of preoperative serum sialic acid levels in colorectal cancer: utility in the detection of patients at high risk of tumor recurrence

This study was conducted to evaluate the significance of preoperative serum sialic acid levels in the diagnosis and prognosis of colorectal cancer (CRC). Total sialic acid (TSA) was determined by the thiobarbituric acid method and normalized to total protein (TP). A postoperative follow-up of CRC patients classified as Dukes' stages A, B or C was performed and survival analysis was carried out to evaluate the impact of sialic acid levels on tumor recurrence. Our diagnostic studies indicate that TSA/TP is a better marker than either TSA or carcinoembryonic antigen (CEA), especially for the detection of CRC patients at an early stage. At a cutoff of 30.90 nmol/mg of protein, TSA/TP showed a sensitivity of 85% with a specificity of 97% to discriminate CRC patients from healthy donors. In survival analysis, both TSA and TSA/TP were found to be significant prognostic factors for tumor recurrence in CRC. Furthermore, TSA/TP could distinguish patients at high risk of recurrence within Dukes' stage B and in multivariate analysis it was identified as the best independent prognostic factor. According to our results, preoperative serum TSA/TP content could supply additional information to that provided by Dukes' stage about the prognosis of CRC patients.     

Elevated serum endothelin-1 levels in patients with colorectal cancer; relevance for prognosis

BACKGROUND: It has been demonstrated that the Doppler Perfusion Index (DPI) is increased in patients who are at risk of developing liver metastases from colorectal cancer. It has been postulated that a circulating hormonal factor is involved in the relative vasoconstriction throughout the splanchnic bed. Endothelin-1 (ET-1), a potent vasoconstrictor which has been associated with tumor growth and is produced by colorectal tumors, may play an important role in this phenomenon. In this paper the prognostic value of serum ET-1 in colorectal cancer is discussed. METHODS: Preoperative serum levels of ET-1 were assessed in three groups of patients: group A underwent resection of the colorectal tumor and remained free of recurrence (n=20); group B developed metachronous liver metastases at least six months after colorectal resection (n=14); and group C presented with colorectal cancer and synchronous liver metastases (n=22). RESULTS: The mean (SD) serum ET-1 levels in groups A, B and C were 1.59 (0.41) pmol/L, 1.70 (0.32) pmol/L and 1.85 (0.47) pmol/L, respectively. These values were significantly different from those of healthy controls (1.22 (0.31), p<0.05). Kaplan-Meier analyses revealed no prognostic value of preoperative serum ET-1 levels. CONCLUSIONS: These preliminary results demonstrate that serum ET-1 levels are raised in patients with colorectal cancer. Serum ET-1 levels do not seem to be of prognostic value for survival.     

Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p?<?0.001). Both the NLR and PLR were shown to be good prognostic biomarkers of overall survival (OS) (p?=?0.002 and p?=?0.001, respectively). The PLR was an independent prognostic factor of OS based on multivariate analysis (hazard ratio, 1.971; 95% confidence interval, 1.102–3.335; p?=?0.021).     

Clinical significance of preoperative neutrophil-lymphocyte versus platelet-lymphocyte ratio in patients with operable colorectal cancer

The objective of this study was to clarify whether the neutrophil-lymphocyte ratio (NLR) and the platelet-lymphocyte ratio (PLR) are significant prognostic markers in patients with resectable colorectal cancer (CRC). A total of 200 patients who underwent curative resection for CRC were enrolled. The NLR and PLR were positively correlated (p?相似文献   

Coagulation factor levels in non-metastatic colorectal cancer patients

There is evidence that high plasma levels of factor (F) VIII, FIX, FXI and fibrinogen are independent risk factors for venous thromboembolism. AIM: To determine the plasma concentrations of several coagulation factors and C4b-binding protein (C4BP) in a group of patients with non-metastatic colorectal cancer in order to investigate some aspects of cancer-acquired thrombophilia. METHODS: Plasma fibrinogen, FII, FV, FVII, FVIII, FIX, FX, FXI and FXII activity levels and C4BP concentrations were determined in 73 patients with non-metastatic colorectal cancer (48 colon and 25 rectum) and in 67 matched control subjects. No one in either group had had previous thrombotic events. RESULTS: Mean plasma concentrations of fibrinogen (functional and antigen), FVIII, FIX, FV and C4BP were significantly higher in colorectal cancer patients than in control subjects, while FVII and FXII levels were significantly decreased. Several correlations were found between the increased coagulation factors and C4BP concentrations, while FVII was highly correlated with FXII. CONCLUSIONS: In colorectal cancer patients high plasma fibrinogen, FVIII and FIX levels might represent further risk factors for venous thrombotic complications in the immediate post-surgery period, while decreased FVII and FXII concentrations may be an index of intravascular coagulation activation, still in a subclinical phase.     

慢性肾小球肾炎患者治疗前后血清CRP和VEGF浓度变化及临床意义

目的：研究慢性肾小球肾炎（CNG）中血清C反应蛋白（CRP）和血管内皮生长因子（VEGF）的浓度变化及其临床意义。方法：采用ELISA法测定35例正常对照组与41例慢性肾小球肾炎患者治疗前后血清IL-6和VEGF的浓度,同时放射免疫分析法测定血清TNF-α浓度,免疫比浊法测定血清CRP与尿Alb浓度。结果：①治疗前后CNG患者血清中IL-6、TNF-α和CRP较正常对照组均显著升高（P〈0.05或P〈0.01）,但治疗后IL-6、TNF-α和CRP水平显著低于治疗前（P〈0.01）,且血清CRP与IL-6和TNF-α呈正相关（P〈0.01）。②治疗后,CNG患者血清VEGF水平与尿Alb含量较治疗前明显降低（P〈0.05或P〈0.01）,仍显著高于正常对照组（P〈0.05或P〈0.01）,且血清VEGF与尿Alb水平呈正相关（P〈0.01）。结论：CRP、IL-6和TNF-α参与了CNG患者慢性炎症反应,VEGF则与蛋白尿的产生密切相关,治疗前后血清CRP和VEGF检测对于慢性肾小球肾炎的病情了解及临床疗效评估均具有重要的临床价值。     

Changes and significance of serum angiopoietin-2 levels in patients with coronary heart disease

Coronary heart disease (CHD) is characterized by inflammatory process and endothelial dysfunction. To investigate angiopoietin-2 (Ang-2) profiles, we evaluated serum Ang-2 levels in different types of CHD in 166 subjects. Ang-2 was measured by enzyme-linked immunosorbent assay. Serum Ang-2 levels were significantly elevated in patients with CHD and gradually increased with advance of CHD. Ang-2 was positively correlated with Gensini scores and hs-CRP. Ang-2 might have potential implication in detecting and monitoring the progression of CHD.     

Preoperative carbohydrate antigen 195 (CA195) and CEA serum levels as prognostic factors in patients with colorectal cancer

We evaluated in 214 patients with primary colorectal cancer the prognostic value of the preoperative serum levels of CEA and CA195. For CEA these levels were above the cutoff of 6 ng/ml in 31.3% of patients, whereas for CA195 they were higher than 12 U/ml in 35.9% of patients. The simultaneous use of both antigens increased the sensitivity to 49%, which was significantly higher than that of CEA (p < 0.001) and CA195 (p < 0.01) taken singly. The mean preoperative CEA levels were significantly (p < 0.001) correlated with Dukes' stage only, while there was a significant correlation between preoperative serum levels of CA195 and Dukes' stage (p < 0.001), grade of differentiation (p < 0.01) and tumor location (p < 0.05). The results indicated that high preoperative serum levels of CEA and CA195 were associated with a shorter overall survival (p < 0.0001). In addition, separate Cox multivariate analysis showed that preoperative CA195 was, after Dukes' stage, the strongest factor to predict overall survival (p < 0.0001).     

Cryptosporidiosis in patients with colorectal cancer

Parasitological examination of feces was carried out for 55 patients with diagnosed colorectal cancer before chemotherapy. Except for Cryptosporidium sp., no other intestinal parasites were found in the specimens; moreover, only the patients with watery diarrhea were Cryptosporidium sp.-positive by enzyme immunoassay. Prevalence of infection in the group of patients with diarrhea (23 persons) was 43.5%, whereas it was 18% for the entire group of patients under study. Coproantigens of this parasite were detected primarily in the patients with tumors located on the left side (in the sigmoid and descending colon).     

非小细胞肺癌患者血清中HPA及VEGF检测临床意义

目的:探讨非小细胞肺癌(non-small cell lung cancer,NSCLC)患者血清中乙酰肝素酶(heparanase,HPA)和血管内皮生长因子(vascular endothelial growth factor,VEOF)水平检测的意义.方法:56例NSCLC患者纳入研究,以21例健康志愿者为正常对照组,比较分析两组受试者血清中乙酰肝素酶、VEGF水平的差异,并与临床病理特征进行比较分析.结果:在NSCLC患者血清乙酰肝素酶和VEGF水平显著高于正常对照组.在NSCLC患者中,血清乙酰肝素酶和VEGF水平在低分化、临床Ⅲ+Ⅳ期和淋巴结转移阳性患者中较高,与患者性别、年龄、病理类型无关.血清乙酰肝素酶与VEGF水平显著正相关.结论:NSCLC患者血清乙酰肝素酶及VEGF水平显著高于正常水平,与NSCLC的生长、浸润和转移有关,可作为判断NSCLC预后及指导治疗的指标.     

Functional significance of gastrin gene expression in human cancer cells

The gastrointestinal peptide, gastrin, stimulates the growth of human pancreatic cancer. A receptor for gastrin activity, the cholecystokinin-C (CCK-C) receptor, has been identified in binding assays, cloned and sequenced, and is a splice variant of the CCK-B receptor. The relationship of gastrin and the CCK-C receptor to the growth of cancer cells was examined in vitro and in vivo. Stable transfection of the sense cDNA of gastrin into human MDA Amp-7 ampullary cancer cells, which normally lack gastrin gene expression but possess CCK-C receptors, increased cell growth up to 10-fold over wild type (WT) and vector-transfected (VT) cells. MDA Amp-7 tumors of gastrin-transfected cells reduced latency time for a visible tumor by 35%, decreased the timetable of tumor incidence, and increased tumor size by at least 2-fold in comparison to WT and VT groups. Transfection of human BxPC-3 pancreatic cancer cells, which normally express gastrin and possess CCK-C receptors, with the antisense cDNA to human gastrin decreased cell number by 30% in culture and tumor size by 53% compared to the WT and VT groups. Transfection of sense gastrin cDNA to monkey COS-1 cells, which normally lack both the gastrin and the CCK-C receptor genes, had no effect on growth. These studies demonstrate that gastrin and the CCK-C receptor form an autocrine loop in human pancreatic cancer that plays a role in regulating growth.     

Investigation of the relationship between GSTM1 gene variations and serum trace elements,plasma malondialdehyde levels in patients with colorectal cancer

Background

The aim of this study is to investigate of the relationship between GSTM1 gene variations and serum trace elements, plasma malondialdehyde levels in patient with colorectal cancer.

Mateials and Methods.

Genotype distributions of GSTM1 gene variations were determined using real-time polymerase chain reaction method. Serum trace element levels were determined using atomic absorption spectrophotometer method and plasma MDA levels were measurement by spectrophotometric method.

Results

Serum Cu levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GA heterozygous genotype of the GSTM1 (rs 112,778,559) gene variation compared to healthy controls (p?<?0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in patients carrying GG homozygous genotype of the GSTM1 (rs 112778559) gene variation compared to healthy controls carrying same genotype (p?<?0.05). Serum Cu, Zn levels, plasma MDA levels and Cu/Zn ratio were determined significantly higher in the group of CRC patient carrying the GG homozygous genotype of the GSTM1 (rs 12068997) gene variation compared to healthy controls (p?<?0.05). On the other hand, serum Se levels were detected significantly lower in CRC patients carrying GA heterozygous and GG homozygous genotypes for GSTM1 (rs 112,778,559) and (rs 12,068,997) gene variations compared to healthy controls (p?<?0.05).

Conclusion

In our study, the evaluation of serum Cu, Zn and Se trace element levels and plasma MDA levels according to GSTM1 gene variations genotype distributions were enabled to obtain important biomarkers in terms of CRC development and progression.

     

Diagnostic significance of serum HMGB1 in colorectal carcinomas

High mobility group box 1 protein (HMGB1), a nuclear protein, can be translocated to the cytoplasm and secreted in colon cancer cells. However, the diagnostic significance of HMGB1 has not been evaluated in colorectal carcinomas. For this purpose, we have screened the expression and secretion of HMGB1 in 10 colon cancer cell lines and 1 control cell line and found that HMGB1 was detected in the culture medium. To evaluate the diagnostic value of HMGB1, we performed an enzyme-linked immunosorbent assay to measure HMGB1 levels and compared them to carcinoembryonic antigen (CEA) levels in the serum samples of 219 colorectal carcinoma patients and 75 healthy control subjects. We found that the serum HMGB1 level was increased by 1.5-fold in patients with colorectal carcinoma compared to those in healthy controls. When HMGB1 and CEA levels were compared, HMGB1 had similar efficacy as CEA regarding cancer detection (the sensitivity was 20.1% for HMGB1 vs. 25.6% for CEA, and the specificity was 96% for HMGB1 vs. 90.7% for CEA). Moreover, the diagnostic accuracy of HMGB1 for stage I cancer was significantly higher than that of CEA (sensitivity: 41.2% vs. 5.9%; specificity: 96% vs. 90.7). When we combined HMGB1 and CEA, the overall diagnostic sensitivity was higher than that of CEA alone (42% vs. 25.6%), and the diagnostic sensitivity for stage I was also elevated (47% vs. 5.9%). However, the prognosis of patients was not related with serum HMGB1 concentrations. Our findings indicate that serum HMGB1 levels are increased in a subset of colorectal carcinomas, suggesting their potential utility as a supportive diagnostic marker for colorectal carcinomas.     

妊娠高血压综合征患者血清瘦素、TNF-α水平测定及其临床意义

目的检测妊娠高血压综合征患者血清中瘦素、TNF-α的水平,并探讨其与妊高征发病的关系。方法用放射免疫法测定35例妊高征患者外周血中瘦素及TNF-α的水平,并以21例正常晚期妊娠妇女(正常妊娠组)作比较。结果(1)妊高征组血清瘦素水平为(32.9±11.5)ng/ml,明显高于正常妊娠组的(18.9±3.0)ng/ml,P<0.05;轻度妊高征组血清瘦素水平为(22.0±4.8)ng/ml,与正常妊娠组比较,差异无显著性,P>0.05;中、重度妊高征组血清瘦素水平分别为(31.1±5.2)、(41.8±10.9)ng/ml,与轻度妊高征组及正常妊娠组比较,差异有显著性,P均<0.05;轻、中、重妊高征组之间血清瘦素水平差异有显著性(P均<0.05)。(2)妊高征组血清TNF-α水平为(22.7±11.5)fmol/ml,明显高于正常妊娠组的(9.2±2.1)fmol/ml,P<0.05,轻度妊高征组血清TNF-α水平为(11.5±4.1)fmol/ml,与正常妊娠组比较,差异无显著性,P>0.05;中、重度妊高征组血清TNF-α水平分别为(19.5±7.4)、(32.9±8.3)fmol/ml,与轻度妊高征组及正常妊娠组比较,差异有显著性(P均<0.05);轻、中、重妊高征组之间血清TNF-α水平差异有显著性(P均<0.05)。(3)妊高征组血清瘦素水平与TNF-α水平呈正相关(分别为r=0.56,P<0.01)。结论妊高征患者血清TNF-α水平增高可能是导致血清瘦素水平升高的原因之一。     

Platelet activation in patients with colorectal cancer

Aspirin may reduce the risk of colorectal neoplasia at doses similar to those recommended for the prevention of cardiovascular disease. Thus, we aimed to address whether enhanced platelet activation, as assessed by the measurement of the urinary excretion of 11-dehydro-TXB(2) (a major enzymatic metabolite of TXB(2)), occurs in patients with colorectal cancer. In 10 patients with colorectal cancer, the urinary excretion of 11-dehydro-TXB(2) was significantly higher than in 10 controls, matched for sex, age and cardiovascular risk factors [1001(205-5571) versus 409(113-984) pg/mg creatinine, respectively, median (range), P<0.05]. The administration of aspirin 50 mg daily for 5 consecutive days to colorectal cancer patients caused a cumulative inhibition of platelet cyclooxygenase (COX)-1 activity either ex vivo, as assessed by the measurement of serum TXB(2) levels, or in vivo, as assessed by urinary 11-dehydro-TXB(2) excretion. In conclusion, enhanced platelet activation occurs in colorectal cancer patients. Permanent inactivation of platelet COX-1 by low-dose aspirin might restore anti-tumor reactivity.