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.     

Diagnosis Value of Membrane Glycolipids Biochemistry Index in Intracranial and Gastrointestinal Tumors

The diagnostic value of membrane glycolipid biochemistry index, the lipid-bound sialic acid (LSA) and totalsialic acid (TSA) in cerebrospinal fluid (CSF) was evaluated in 30 intracranial and 65 gastrointestinal tumors.The plasma LSA, TSA and red cell membrane sialic acid (R-SA) in were determined according to the method ofSevenmerhulm. Our results showed that the levels of LSA and TSA in CSF of intracranial tumor patients washigher than that of normal group(p<0.01). The concentration of TSA and LSA in patients with malignant gliomawas higher than that of benign meningioma patients(P<0.01). No significance was found between intracranialhalmatoma patients and normal control group for levels of membrane glycolipids (p>0.05). Results also found thatthe plasma LSA, TSA and R-SA of gastric carcinoma were significantly higher than those of control group (p<0.05);while no significant difference was found in the plasma LSA, TSA and R-SA levels between chronic gastritis,gastrohelcoma and normal control group (p>0.05). Plasma LSA, TSA and R-SA levels of gastric carcinoma patientwere significantly higher than those of chronic gastritis patients and gastrohelcoma patients(p<0.05). It was alsofound that plasma LSA, TSA and R-SA contents were significantly higher in large intestine carcinoma patientsthan in benign in stestine tumor patients (p<0.05) while no significant difference was found between intestinebenign tumor and normal control group (p>0.05). The levels of LSA, TSA and R-SA were obviously higher inthe patients with metastasis than in the ones without (p<0.05.) The membrane glycolipid biochemistry indexLSA and TSA in CSF are sensive markers for diagnosing intracranial tumors. For gastrointestinal malignanttumors the plasma LSA TSA and red blood cell membrane SA may be considered as auxiliary indicators fordiagnosis. They can be used for distinguishing benign from malignant 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.     

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。     

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.     

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。     

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.     

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.     

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.     

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。     

Correlation of total (TSA) and lipid and bound (LSA) sialic acid levels with cytology of cyst or body fluids in cancer patients.

In this preliminary study, aiming at the early diagnosis or the confirmation of neoplastic spreading, the levels of sialic acid (TSA and LSA, total sialic acid and "lipid bound" sialic acid) were measured and correlated with the corresponding cytologic findings in 111 body or cystic fluid samples taken from patients with suspected or confirmed cancer. The samples were classified according to the body fluid origin: peritoneal (35), breast cyst (22), pleural (21), thyroid gland cyst (5), renal cyst (5), ovarian cyst (6), bronchial washing (3), douglasic cavity (3) and various other origins (11). It was found that 32.43% of the samples were TSA positive, 44.14% LSA positive, 20.75% cytologic and 8.49% cytology suspect (positive + suspect = 29.24%). Thus, the combination of a tumor biomarker with the corresponding cytology of the body fluid gives the best possible results, as regards both the confirmation of positive cytology and the detection of possible metastases, as well as the monitoring of the disease after treatment.     

Lipid bound sialic acid in cancer patients

Serum lipid-bound sialic acid (LSA) was measured with a recently described procedure in 108 healthy subjects and in 138 patients with a variety of solid tumors and hematologic malignancies. At the time of serum sampling, 128 patients had active disease and 10 patients had no evidence of disease. LSA was elevated in 104 of 128 (81.2%) patients with active disease, while carcinoembryonic antigen, analyzed in 74, was elevated only in 21 (28.4%) (P less than 0.05). Sensitivity of the serum LSA test ranged from 66% for breast and gastrointestinal cancer to 92% for lung cancer. In patients with lung cancer, ovarian cancer or Hodgkin's disease, LSA was correlated with the extent of disease and it also proved to be useful in following the course of disease. Our preliminary data indicate that this test can be used as a monitor of tumor burden.     

Evaluation and limitations of the lipid-associated sialic acid test for the detection of human cancer

Previous studies and those of the authors have reported about raised levels of lipid-bound sialic acid (LSA) in sera of patients with various neoplasms. Most authors have used the method of Katopodis and Stock for isolating serum LSA. Because of the discrepancy of the amount of extracted LSA with the content of pure gangliosides in sera reported by other groups the authors analyzed the composition of the extracted LSA by immunochemical approaches. They were able to isolate considerable amounts of glycoproteins containing sialic acid as acid alpha-1-glycoprotein, antitrypsin, haptoglobin, antichymotrypsin, and immunoglobulins from the so-called "LSA" fraction. There is a very strong correlation between the raised LSA levels and the content of acid-alpha-1-glycoprotein in the sera of patients with malignancy. Therefore the term lipid-bound sialic acid applied to this test is misleading, since glycoproteins containing sialic acid are mostly responsible for the high "LSA" levels.     

The utility of lipid-associated sialic acid (LASA or LSA) as a serum marker for malignancy. A review of the literature.

The utility of the lipid-associated sialic acid (LASA or LSA) test as a serum marker for malignancy is reviewed. The name LASA or LSA test is confusing because it suggests that only or mainly lipid-bound sialic acid is measured. In reality, glycoprotein-bound sialic acid is determined predominantly. The assay appears to have a particularly high positivity rate in leukemia, Hodgkin's disease, melanoma, sarcoma, advanced ovarian carcinoma and oropharyngeal tumors, suggesting that LASA may serve as a valuable marker in these malignancies. As a consequence of the rise of sialic acid-rich acute-phase proteins, such as alpha 1-acid glycoprotein, in inflammatory diseases the specificity of LASA and therefore its diagnostic accuracy is low. LASA can be useful for monitoring cancer patients during treatment, especially in combination with other tumor markers.     

Serum sialic acid (TSA/LSA) and carcinoembryonic antigen (CEA) levels in cancer patients undergoing radiotherapy.

The main aim of this study was to evaluate the response of total Sialic Acid (TSA) and "Lipid-bound" Sialic Acid (LSA) compared to Carcinoembryonic Antigen (CEA), in 284 patients undergoing radiotherapy. Serial measurements of TSA by the enzymatic method (Boehringer-Mannheim Kit), LSA by the resorcinol-HC1 (Katopodis and Stock) and CEA by EIA (Abbott Kit) were performed in a total of 1017 blood sera. We statistically estimated the four greater groups of cancer patients [bladder (69), lung (58), uterus (31) and breast (29)]. Diagnostic marker sensitivities (% true positives) estimated from the 0-time-values--before initiation of radiotherapy--in relation to the established cut-off levels were in decreasing order: TSA 89.3% (80 mg/dL). LSA 88.8% (20 mg/dL) and CEA 26.75% (5 ng/mL). The overall tumor marker response to treatment, after its completion, estimated as % of patients with final blood serum levels of these markers, was in decreasing order: LSA 85.6%, TSA 81.3%, and CEA 65.8%. These data show that a) the diagnostic sensitivity of Sialic Acid (LSA/TSA) is more than 3 times higher than that of CEA and b) the response of Sialic Acid (LSA/TSA) to treatment is about 15% higher than that of CEA. In conclusion, this study confirms the high diagnostic sensitivity of Sialic Acid as a tumor marker and suggests that, with marginal superiority of Sialic Acid, all three markers are sufficiently responsive to be employed as adjunctive means in monitoring cancer patients underdoing radiotherapy.     

Personality traits,patient-centered health status and prognosis of brain tumor patients

Personality traits can be related to prognosis of cancer patients. The study aimed to evaluate the association of big-five personality dimensions with emotional and cognitive health status, and prognosis of brain tumor patients. A total of 178 patients admitted for brain tumor surgery were evaluated for personality traits (Tem item Personality Inventory), depressive/anxiety symptoms (Hospital Anxiety and Depression Scale or HADS) and cognitive functioning (Mini Mental State Examination or MMSE) on admission. One-hundred and forty-three patients were re-evaluated (HADS and MMSE scales) at hospital discharge. Follow-up continued until November, 2015. Thirty-five patients were diagnosed with high-grade glioma, 15 with low-grade glioma and 128 with benign brain tumors (meningioma, pituitary adenoma and vestibular schwannoma). In multivariate regression analyses adjusted for age, gender, past brain tumor treatment, psychiatric histories and medication use, and education, greater TIPI-Extroversion score was associated with greater admission MMSE score (β?=?0.159); TIPI-Emotional stability score, with lower HADS-Depression and HADS-Anxiety scores on admission (β?=???0.407 and β?=???0.404, respectively) and at discharge (β?=???0.404 and β?=???0.319, respectively); and greater TIPI-Openness score, with lower admission HADS-D score (β?=???0.255, p?=?0.001). In benign brain tumor patients, greater TIPI-Openness score was associated with reduced mortality risk [HR?=?0.554 95% CI (0.376–0.814) p?=?0.003)] independently from age, gender and histological diagnosis. Personality traits were not associated with survival of high-grade and low-grade glioma patients. Emotional stability and openness are associated with lower depressive/anxiety symptom severity, and extroversion with better cognitive functioning independently from demographic and clinical risk factors. Openness predicts lower mortality risk of low-grade/benign brain tumor patients.     

经单鼻孔-蝶窦入路切除垂体瘤35例分析

目的:探讨经单鼻孔-蝶窦入路显微手术切除垂体瘤的临床效果、手术方法及术后处理。方法:回顾性分析采用经单鼻孔-蝶窦入路显微手术治疗的35例垂体瘤患者的临床资料。结果:35例垂体瘤患者中,泌乳素腺瘤22例,生长激素腺瘤4例,非分泌性腺瘤9例。肿瘤全切27例,次全切除6例,大部分切除2例。术后发生电解质紊乱2例,暂时性尿崩症5例,脑脊液鼻漏1例,持续1周。没有发生视力恶化、颅神经损伤、感染、长期脑脊液漏等严重并发症,无死亡。结论:经单鼻孔-蝶窦入路显微手术切除垂体瘤具有创伤小,手术时间短,安全性高,并发症少,术后康复快,垂体功能保存率高等优点。严格把握好手术适应证和禁忌症,能使需要手术治疗的垂体瘤患者取得满意的治疗效果。     

Plasma specific miRNAs as predictive biomarkers for diagnosis and prognosis of glioma

Objective

Glioblastoma multiforme (GBM) is a highly malignant brain tumor with a poor prognosis. MicroRNAs (miRNAs) are a class of small non-coding RNAs, approximately 21–25 nucleotides in length. Recently, some researchers have demonstrated that plasma miRNAs are sensitive and specific biomarkers of various cancers. The primary aim of the study is to investigate whether miRNAs present in the plasma of GBM patients can be used as diagnostic biomarkers and are associated with glioma classification and clinical treatment.

Materials and Methods

Plasma samples were attained by venipuncture from 50 patients and 10 healthy donors. Plasma levels of miRNAs were determined by real-time quantitative polymerase chain reaction.

Results

The plasma levels of miR-21, miR-128 and miR-342-3p were significantly altered in GBM patients compared to normal controls and could discriminate glioma from healthy controls with high specificity and sensitivity. However, these three miRNAs were not significantly changed in patients with other brain tumors such as meningioma or pituitary adenoma. Furthermore, the plasma levels of these three miRNAs in GBM patients treated by operation and chemo-radiation almost revived to normal levels. Finally, we also demonstrated that miR-128 and miR-342-3p were positively correlated with histopathological grades of glioma.

Conclusions

These findings suggest that plasma specific miRNAs have potential use as novel biomarkers of glioma and may be useful in clinical management for glioma patients.     

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

BACKGROUND: Adhesion molecules have been implicated in tumor progression. In this study, we aimed to investigate serum soluble intercellular adhesion molecule-1 (sICAM-1) and total sialic acid (TSA) levels in laryngeal carcinoma and correlate their levels with the cancer stage. METHOD: The sera from 35 patients with laryngeal cancer (10 at stage II, 12 at stage III and 13 at stage IV) 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 = 34). RESULTS: Mean serum sICAM-1 and TSA levels were found to be higher in the total patient group (the lowest level belonging to stage II) than in the control group (p < 0.001, control versus total patient group). As the stage of the disease increased, higher levels of sICAM-1 and TSA were determined. The correlations between TSA and sICAM-1 became more significant as the stage of the disease increased (r= 0.67, p < 0.05 in stage II, r= 0.86, p < 0.001 in stage III and r = 0.90, p < 0.001 in stage IV). CONCLUSION: These data reveal that the significant correlations between sICAM-1 and TSA in laryngeal cancer, more prominent at advanced stage, might reflect the similar nature of these molecules, which function as adhesion molecules.