血清唾液酸检测对癌症诊断的临床价值

作者测定了５７７例正常人和２４１例恶性肿瘤患者血清总唾液酸（ＴＳＡ）和血清脂质结合唾液酸（ＬＳＡ）的含量。结果表明：ＴＳＡ和ＬＳＡ的含量变化与疗效一致，治疗有效者ＴＳＡ和ＬＳＡ与正常人相比，均无显著性差异（Ｐ＞０．０５）；治疗无效（包括未经治疗）者与正常人相比除原发性肝癌、乳腺癌外均有显著性差异（Ｐ＜０．０１）。血清ＴＳＡ和ＬＳＡ测定对肺癌、胃癌、大肠癌等有临床诊断价值（Ｐ＜０．０１），对鼻咽癌诊断效果更好（Ｐ＜０．００１）。对肝癌、乳腺癌的诊断价值有限（Ｐ＞０．０５）。恶性肿瘤患者ＴＳＡ与ＬＳＡ含量间无相关关系（ｒ＝０．０９；Ｐ＞０．０５；ｎ＝１１７）。ＬＳＡ检测不能代替ＴＳＡ检测，两者应该联合检测以提高其阳性率。     

Total and lipid-bound sialic acid in the cerebrospinal fluid of patients with brain tumors

Total sialic acid (TSA) and lipid-bound sialic acid (LSA) were determined in the cerebrospinal fluid (CSF) from 63 patients with various neurological diseases. Of these, 27 had brain tumors: 20 had glioma, and 7 pituitary adenoma. TSA levels were significantly increased in the CSF of 18 of the 20 glioma patients (p less than 0.001), while in the adenoma patients were indistinguishable from the controls; with a 90 and 0% test sensitivity respectively. Conversely, the LSA concentrations were significantly elevated, both, in the glioma and pituitary adenoma patients (p less than 0.001), with a 68 and 100% test sensitivity respectively. These preliminary data suggest that measurement of TSA and LSA in the CSF should prove useful for the diagnosis of brain tumors and, perhaps, in the follow-up of patients undergoing treatment for brain tumors.     

Evaluation of serum sialic acid, heat stable alkaline phosphatase and fucose as markers of breast carcinoma

Serum levels of total sialic acid (TSA), lipid bound sialic acid (LSA), heat stable alkaline phosphatase (HSAP) and fucose were measured in 39 patients with breast carcinoma, 14 patients with benign breast diseases and 35 healthy female individuals. Elevated levels of the four biomarkers in breast carcinoma were significant when compared with controls (p less than 0.001). Fucose levels were most sensitive (71.8%), while TSA levels were most specific (64.3%) for breast carcinoma. Sensitivity and specificity were 100% when combinations of LSA with fucose and TSA with HSAP were studied respectively. LSA was significantly elevated in infiltrating duct carcinoma patients compared with lobular carcinoma (p less than 0.001). TSA, HSAP and fucose also had lower mean values in lobular carcinoma as compared to infiltrating duct carcinoma. Increase in the levels of LSA and HSAP after surgical removal of the tumor in breast carcinoma occurred prior to the clinical evidence of the recurrence. The results indicate that the combination of the markers studied might be useful in breast cancer diagnosis and treatment monitoring.     

唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

唾液酸作为肺癌标志物的ROC分析

用受试者试验特征性曲线（ROC）建立了血清TSA与LSA对肺癌与非癌患者的最佳诊断分界值（Cut－off），TSA为76mg／dl，LSA为23mg／dl，肺癌组TSA与LSA的含量均明显高林非癌组，同时比较了TSA与LSA的诊断灵敏度，特异性，符合率，ROCAUC和信息量。血清唾液酸作为肺癌标志物时，TSA与LSA的ROCAUC无显著性差异（P＞O．05），二者间信息量的u值为0．91，P＞0．05。提示只要选一个最佳cut－off值，单测血清TSA就有可能达到筛选肺癌的目的。     

Five tumor markers in lung cancer: significance of total and "lipid"-bound sialic acid.

Total sialic acid (TSA) and "lipid-bound" sialic acid (LSA) were evaluated in comparison to carcinoembryonic antigen (CEA) and ferritin and neuron specific enolase (NSE) in 152 untreated patients with primary lung cancer, 107 benign pulmonary disease patients and 207 notmal controls. The mean concentrations of TSA, LSA and CEA in lung cancer patients, were significantly higher than in benign and normal controls (p less than 0.001), while the mean ferritin and NSE levels were significantly higher than in normal controls only (p less than 0.001). At the designated cut-off serum levels, sensitivities of the five markers for lung cancer were in decreasing order: TSA 86.5% (greater than 80 mg/dL), LSA 77% (greater than 20 mg/dL), CEA 46.4% (greater than 5 ng/mL), ferritin 36% (greater than 300 ng/mL) and NSE 34.5% (greater than 12.5 ng/mL). Using the benign pulmonary values as negative controls the specificity of each marker was as follows: CEA 88%, ferritin 72%, NSE 58%, TSA 44% and LSA 44%. In small cell lung cancer (SCLC) patients, NSE mean concentrations and sensitivity were significantly higher than in non-small lung cancer (NSCLC) patients (9.63 +/- 4.4 versus 23.54 +/- 16.9, p less than 0.001 and 74% versus 21.4% respectively). While in NSCLC patients only CEA levels correlated well with the stage of the disease, in SCLC patients concentrations of TSA, LSA and ferritin were significantly higher in extensive than in limited disease stages. These preliminary data suggest that, although TSA and LSA are highly sensitive markers in lung cancer, their specificity is low.     

Clinical evaluation of four tumor markers in malignant and benign pleural effusions.

Total sialic acid (TSA), lipid-bound sialic acid (LSA), ferritin and carcinoembryonic antigen (CEA) were evaluated in 55 patients with malignant pleural effusions and in 32 patients with benign (exudative) pleural effusions. No significant differences were found in the pleural fluid TSA, LSA and ferritin levels between malignant and benign conditions. CEA levels in malignant effusions were significantly higher than those in benign effusions (43.13 +/- 72.8 ng/ml versus 2.6 +/- 5.56 ng/ml, p less than 0.01). At a cut-off level of 5 ng/ml, 60% of the patients with cancer showed elevated pleural fluid CEA levels. The specificity and diagnostic accuracy of CEA in distinguishing malignant from benign pleural exudates were both very high (91% and 71% respectively). Therefore, of the four markers investigated, only CEA could be a valuable tool in the detection of pleural malignancy.     

颅内肿瘤患者血清总唾液酸测定的临床意义

作者对正常健康人73名、颅内良性肿瘤40例、恶性胶质瘤30例及脑转移瘤13例的血清TSA进行测定。结果显示：所有颅内肿瘤患者组血清TSA水平均显著高于正常对照组，其中，脑转移瘤组最高，恶性胶质瘤组次之，良性肿瘤组居第三位。所以，测定血清TSA水平对CT或MRL显示的颅内肿瘤的性质判定具有辅助诊断价值。     

Total and lipid-bound plasma sialic acid as diagnostic markers in colorectal cancer patients: correlation with cathepsin B expression in progression to Dukes stage

PURPOSE: Serum cathepsin B (CB), Total Sialic acid (TSA), total sialic acid (TSA) and lipid bound sialic acid (TSA) concentrations more useful than the other markers investigated for detecting different malignancies. Our aim was to investigate the possible correlation between serum CB with TSA, LSA in colorectal carcinoma with pathological stages progressed of the disease. METHODS: The study was performed on 177 patients (109 patients with colon and 68 patients with rectal) and 50 healthy individuals comprised the control group. Serum CB activity was determined using fluorogenic substrate. Serum TSA and LSA Concentrations were measured according to the method described by Katopodis. RESULTS: Plasma CB and TSA levels in the tumor group were significantly increased in comparison with the controls group (P < or = 0.0001). No significant differences were observed in LSA level between the tumor group and the controls group. T/N ratios for CB, TSA elevated 2.3-fold, 2.5-fold respectively). LSA 1.8-fold. Serum CB activity, TSA concentrations values in plasma samples of patients were increased significantly with pathological stages progressed (P < or = 0.0001). CB is seen to correlate more strongly with TSA in tumor group (P < or = 0.0001, r= 0.7277) in comparison with controls group. These correlations became more significant as the stage of the disease progressed. CONCLUSION: The present investigations indicate that CB activity, serum TSA, concentrations are sensitive markers for detecting and earliest diagnosis of colorectal cancer. These markers with other clinical and biochemical criteria may play important metabolic roles in cancer progression.     

Usefulness of serum glycoconjugates in precancerous and cancerous diseases of the oral cavity

Sera from 47 healthy controls, 18 normal individuals with the habit of tobacco chewing, 43 patients with oral precancerous (PC) conditions, and 40 patients with oral cancer (OC) were studied for the levels of total sialic acid (TSA), lipid-bound sialic acid (LSA), mucoid proteins, and protein-bound hexoses (PBH) (galactose and mannose). The changes in the glycoconjugate levels were insignificant between the controls and the normal tobacco chewers. All four parameters were significantly elevated in oral PC patients compared with controls. The levels of PBH and LSA showed significant increase in the oral PC patients compared with the normal tobacco chewers. A significant increase was observed in the levels of TSA, LSA, mucoid proteins, and PBH in OC patients compared with controls, normal tobacco chewers, and patients with oral PC. Increasing levels of all the biomarkers were found with progression of the malignant disease. Elevations in the levels of TSA and LSA were statistically significant in Stage IV patients compared with Stage III patients. The patients with metastases had higher levels of the biomarkers than the patients with primary OC. However, elevations only in LSA levels were statistically significant. These results suggest that evaluations of the serum glycoconjugate levels may be useful in diagnosis of the patients with oral PC or OC. In addition to their value in early detection, they can also help in staging of the disease.     

Serum glycoconjugates in patients with anemia and myeloid leukemia

Because of carbohydrate alterations in malignant cells, serum glycoproteins have drawn considerable attention. In the current investigation we determined total sialic acid (TSA), lipid bound sialic acid (LSA), protein bound hexoses (galactose + mannose), fucose, hexosamines (galactosamine + glucosamine) and mucoid protein concentrations in the serum of patients with anemia and myeloid leukemia. The results were compared with those obtained in healthy individuals. In the leukemia patients we observed significant increases in glycoconjugates compared with the controls (P less than 0.001), and in TSA and fucose levels compared with the anemia patients (P less than 0.001). LSA and hexosamine levels were significantly lower in anemia patients with respect to the leukemia patients (P less than 0.01 and P less than 0.05 respectively), whereas levels of mucoid proteins and hexoses did not show significant differences. Except for hexosamines, all the markers tested were significantly elevated in the anemia patients compared with the controls. The present study suggests that the glycoconjugates investigated might be useful biochemical markers for differentiating anemic from leukemic conditions.     

血清与脑脊液唾液酸含量测定对脑瘤与脊髓瘤诊断价值的比较

检测脑瘤与脊髓肿瘤患者血清和脑脊液中唾液酸的含量，比较两者对脑瘤与脊髓瘤的诊断价值。方法应用ＳＡ快速比色测定盒对１１３例脑肿瘤和２４例脊髓肿瘤患者血清及ＣＳＦ唾认酸含量进行测定，分别进行组间比较。结论血清和ＣＳＦ中ＳＡ含量可和为脑瘤与脊髓瘤的诊断指标之一，而ＣＳＦ中ＳＡ含量的测定对脑瘤与脊髓瘤的诊断更具临床价值。     

SERUM LIPID-BOUND SIALIC ACID IN LUNG CANCER PATIENTS

ＳＥＲＵＭＬＩＰＩＤ－ＢＯＵＮＤＳＩＡＬＩＣＡＣＩＤＩＮＬＵＮＧＣＡＮＣＥＲＰＡＴＩＥＮＴＳＬｉｎｇＸｉａｏｐｉｎｇ；林小萍；ＺｈａｎｇＸｉｚｅｎｇ；张熙曾；ＷａｎｇＱｉｎｇｓｈｅｎｇ；王庆生（ＤｅｐａｒｔｍｅｎｔｏｆＳｉｎｏ－ＪａｐｅｎＥｓｏｐｈａ...     

Elevated levels of MIC‐1/GDF15 in the cerebrospinal fluid of patients are associated with glioblastoma and worse outcome

For patients with brain tumors identification of diagnostic and prognostic markers in easy accessible biological material, such as plasma or cerebrospinal fluid (CSF), would greatly facilitate patient management. MIC‐1/GDF15 (growth differentiation factor 15) is a secreted protein of the TGF‐beta superfamily and emerged as a candidate marker exhibiting increasing mRNA expression during malignant progression of glioma. Determination of MIC‐1/GDF15 protein levels by ELISA in the CSF of a cohort of 94 patients with intracranial tumors including gliomas, meningioma and metastasis revealed significantly increased concentrations in glioblastoma patients (median, 229 pg/ml) when compared with control cohort of patients treated for non‐neoplastic diseases (median below limit of detection of 156 pg/ml, p < 0.0001, Mann–Whitney test). However, plasma MIC‐1/GDF15 levels were not elevated in the matching plasma samples from these patients. Most interestingly, patients with glioblastoma and increased CSF MIC‐1/GDF15 had a shorter survival (p = 0.007, log‐rank test). In conclusion, MIC‐1/GDF15 protein measured in the CSF may have diagnostic and prognostic value in patients with intracranial tumors. © 2009 UICC     

Measurements of CSF biochemical tumor markers in patients with meningeal carcinomatosis and brain tumors

Summary CSF beta-glucuronidase, polyamines and carcinoembryonic antigen (CEA) were analyzed in 16 patients with meningeal carcinomatosis from solid tumor in systemic organs, 27 with benign brain lesions, 18 with primary brain tumors, 14 with metastatic brain tumors and 5 with leptomeningeal dissemination of other malignant diseases. Beta-glucuronidase levels in all cases of meningeal carcinomatosis, meningeal gliomatosis and meningeal lymphoma were higher than 100 g/dl/hr; on the other hand, levels in all cases of benign brain lesions were below 100 g/dl/hr. Levels of beta-glucuronidase and polyamines were not high in the cases with positive cytology after tumor resection. Polyamine levels were below 0.05 nmol/ml in all cases after resection of the metastatic brain tumor.Cystic fluid of malignant tumors showed high levels of beta-glucuronidase and polyamines. On the other hand, the levels of polyamines in the cystic fluid of benign tumor were low, although the levels of beta-glucuronidase were high. Some cases of meningeal carcinomatosis with high levels of serum CEA did not show high levels of CSF CEA. For metastatic brain tumors, the cases with intraparenchymal tumors, especially with dural attachment showed high levels of beta-glucuronidase and CEA preoperatively, but they returned to normal after surgery. In cases of meningeal carcinomatosis treated by intrathecal chemotherapy with methotrexate (MTX) and cytosine arabinoside (Ara-C), CSF beta-glucuronidase reflected the neurological status better than the cell count decreased rapidly following chemotherapy and beta-glucuronidase was considered as a useful CSF marker in cases of meningeal carcinomatosis to monitor the course of the disease. The same situation was observed in CSF CEA and CEA was also considered as a useful marker when CEA levels in CSF are higher than those in serum.     

Lymphocyte subsets in patients with brain tumors

Summary T lymphocyte subsets of peripheral blood were studied in preoperative patients with various types of intracranial neoplasms. The subsets were analysed using monoclonal antibodies against lymphocyte membrane markers, and flow cytometry was used to quantitate percent positive cells with the antibodies. Twenty-seven patients were selected for this study, including twelve patients with malignant primary intrinsic tumors histologically consistent with a diagnosis of malignant astrocytoma or glioblastoma multiforme, and fifteen patients with extrinsic tumors diagnosed as meningioma, pituitary adenoma, craniopharygnioma and neurinoma. Twenty-five age and sex-matched individuals without evidence of either local or systemic disorders served as control subjects.The results revealed that the OKT4/8 cell ratio was 1.4±0.4 in the malignant group, 1.8±0.4 in the benign group and 2.1±0.8 in the control group. The ratio was significantly lower in the malignant group than in the control group (p<0.05). Leu-11⁺ cells were found to be 9.7±4.7 in the malignant group, 9.0±3.4 in the benign and 7.8±2.7 in the control group. These results showed that Leu-11⁺ cells in the patients with malignant tumors were significantly increased in comparison with the control group (p < 0.05). The alteration of the lymphocyte subsets is considered to be an effect of neurohormones in balance through the transmission function of the brain-endocrine axis to lymphocytes in immunomodulation.     

Levels of soluble intercellular adhesion molecule-1 and total sialic acid in serum of patients with colorectal cancer

BACKGROUND AND OBJECTIVES: Serum soluble intercellular adhesion molecule-1 (sICAM-1) and total sialic acid (TSA) are related to the metastatic potential of cancer cells. The purpose of the present investigation was to determine sICAM-1 and TSA levels in colorectal carcinoma and correlate their levels with the cancer stage. METHODS: The sera from 65 patients with colorectal cancer (18 at Dukes' B, 24 at Dukes' C, 23 at Dukes' D) were extracted before treatment. The concentrations of sICAM-1 and TSA were measured by enzyme-linked immunoassay and the thiobarbituric acid method, respectively, and compared with those from a healthy control group (n = 42). RESULTS: Mean serum sICAM-1 and TSA levels were found to be higher in the total patient group than in the control group (P < 0.0001). The concentrations of sICAM-1 and TSA were significantly higher in patients with Dukes' C and Dukes' D. The correlations between sICAM-1 and TSA became more significant as the stage of the disease increased (r = 0.58, P < 0.05 in Dukes' B, r = 0.88, P < 0.01 in Dukes' C and r = 0.81, P < 0.01 in Dukes' D). CONCLUSIONS: The results of this investigation indicate that sICAM-1 and TSA are the best of the tested markers. These markers should prove useful for monitoring malignant disease stage and for evaluating the effectiveness of various therapeutic approaches for colorectal carcinomas.     

CA125和TSGF联合检测在妇科肿瘤诊断中的应用价值

目的 探讨联合检测血清CA125和肿瘤相关物质群（TSGF）的含量对妇科恶性肿瘤的诊断及疗效监测的应用价值。方法 妇科恶性肿瘤患者223例、妇科良性肿瘤患者90例及正常对照98人的血清样品，分别用电化学发光免疫测定法和化学比色定量法测定CA125和TSGF含量，然后进行分析。结果 与良性肿瘤组和健康体检组相比，妇科恶性肿瘤患者血清CA125和TSGF的含量明显升高（P〈0.01），CA125和TSGF测定对妇科恶性肿瘤的敏感度分别是58.3%和72.2% ，特异度分别是91.0%和90.4%。二者联合检测的敏感度和特异度分别为79.4%和82.4%。妇科恶性肿瘤患者血清CA125和TSGF含量在治疗后与治疗前相比,有显著差异（P〈0.05）。 结论 血清CA125和TSGF检测对妇科肿瘤良恶性的辅助诊断及鉴别诊断具有一定应用价值，联合检测不仅可以提高妇科恶性肿瘤的阳性诊断率，对妇科恶性肿瘤的疗效观察和术后监测也具有一定价值。     

Decreased expression of BTG3 was linked to carcinogenesis, aggressiveness, and prognosis of ovarian carcinoma

B-cell translocation gene 3 (BTG3) is a member of the BTG family which inhibits cell proliferation, metastasis, and angiogenesis, and also regulates cell-cycle progression and differentiation in a variety of cell types. However, there is no study to analyze BTG3 expression in epithelial ovarian carcinoma (EOC). Here, we investigated the expression of BTG3 in EOC carcinogenesis and subsequent progression. BTG3 mRNA expression was detected by real-time RT–PCR in ovarian benign and malignant tumors. The expression of BTG3 protein was examined by immunohistochemistry on tissue microarrays containing ovarian normal tissue, benign and borderline epithelial ovarian tumors, and EOCs. Relationships of BTG3 with both EOC clinicopathology and prognosis were analyzed statistically. The expression of BTG3 protein was also evaluated in ovarian normal tissue, benign tumors, and EOCs by western blot. The BTG3 mRNA expression level was higher in ovarian normal tissue and benign tumors than that in borderline, primary, and metastatic carcinoma (p?<?0.05), and was negatively correlated with dedifferentiation and FIGO staging of EOC (p?<?0.05). Using western blot, BTG3 protein was found lower in EOCs compared to the normal and benign tumors (p?<?0.05), and poorly differentiated EOCs showed lower BTG3 expression than well-differentiated and moderately differentiated EOCs (p?<?0.05). Immunohistochemically, BTG3 protein expression was statistically lower in EOCs than normal tissue and benign tumors (p?<?0.05). EOC patients with low BTG3 protein expression showed a higher incidence of metastasis (p?=?0.020), poor differentiation (p?=?0.030), and shorter disease-free time and overall survival time (p?<?0.05). By using Cox’s proportional hazard model, BTG3 protein expression and FIGO staging were independent prognostic factors for both disease-free time and overall survival time of EOCs (p?<?0.05). It was suggested that down-regulated BTG3 expression might play roles in the pathogenesis and aggressiveness of EOC. BTG3 protein expression may be considered as a good marker to indicate the favorable prognosis of EOCs.     

血浆纤溶酶原激活物抑制剂－1及其抑制剂活性与卵巢恶性肿瘤的相关性研究

目的:研究血浆纤溶酶原激活物抑制剂－1（PAI-1）及其抑制剂活性（PAI-1:A）与卵巢恶性肿瘤的相关性。方法:选择来我院就诊的卵巢肿瘤患者88例,分成二组:卵巢良性肿瘤组40例,卵巢恶性肿瘤组48 例,正常对照组40例。分别进行血浆纤溶酶原激活物抑制剂－1（PAI-1）及其抑制剂活性（PAI-1:A）的测定,分析比较正常组与患者组PAI-1/PAI-1:A水平的变化。结果:正常组与卵巢良性肿瘤组间比较差异无显著性（P＞0.05);正常组、卵巢良性肿瘤组与卵巢恶性肿瘤(Ⅰ期)组间比较差异无显著性（P＞0.05）;正常组、卵巢良性肿瘤组与卵巢恶性肿瘤(Ⅱ期、Ⅲ期、Ⅳ期)组间比较差异有显著性（P＜0.01）。结论:随着卵巢肿瘤恶性程度的增加,血浆纤溶酶原激活物抑制剂－1（PAI-1）含量减少,其抑制剂（PAI-1:A）活性降低,而血浆组织型纤溶酶原激活物（t-PA）含量及其活性（t-PA:A）增加。