Cardiac isoform of alpha 2 macroglobulin, an early diagnostic marker for cardiac manifestations in AIDS patients

This study investigated the possible role of the cardiac isoform of alpha 2-macroglobulin (CA2M) as an early diagnostic marker for HIV-associated cardiovascular manifestations. A total of 349 samples were analysed by Western blot and quantified by sandwich enzyme-linked immunosorbent assay. The levels of CA2M present in sera of HIV-associated cardiac diseases were significantly higher than those of HIV without cardiac involvement and healthy sera. CA2M may act as a novel diagnostic marker to identify cardiac manifestations in HIV/AIDS patients.     

Clinical significance of serum tumour M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma

Background/aimsTo investigate the clinical significance of serum Tu M2-PK and CA19-9 detection in the diagnosis of cholangiocarcinoma.MethodsThe tumour markers (Tu M2-PK and CA19-9) in 115 patients with cholangiocarcinoma, 85 patients with benign disease and 120 blood donors were detected by ELISA.ResultsThe levels of serum Tu M2-PK and CA19-9 were markedly higher in the patients with cholangiocarcinoma than in controls (P < 0.05). Tu M2-PK showed more sensitivity (84.2%) and specificity (90%) than CA19-9 (68.4%) and (75%).ConclusionsTu M2-PK may be used as a valuable diagnosis marker in cholangiocarcinoma.     

Tumor M2-Pyruvate Kinase, a New Metabolic Marker for Pancreatic Cancer

An isoenzyme of pyruvate kinase (Tu M2-PK) is overexpressed by tumor cells and can be measured in blood by a specific immunoenzymatic assay. Our objective was to investigate the diagnostic value of Tu M2-PK in comparison with that of CA 19-9 in pancreatic cancer. We studied 265 subjects: 60 with histologically confirmed pancreatic cancer, 43 with benign pancreatic diseases (acute and chronic pancreatitis), 5 with benign cystic neoplasms of the pancreas, 9 with neuroendocrine tumors, 77 with other abdominal malignancies, 47 with benign digestive diseases, and 24 healthy controls. Levels of plasma Tu M2-PK and serum CA 19-9 were determined by commercially available specific immunoassays. The diagnostic sensitivity and specificity of Tu M2-PK for pancreatic cancer were 85 and 41%, respectively, while those of CA 19-9 were 75 and 81%. The combination of the two tests significantly increased sensitivity (97%) but lowered specificity (38%). In discriminating between pancreatic cancer and acute or chronic pancreatitis, Tu M2-PK turned out to be less accurate than CA 19-9. In patients without pancreatic tumor, cholestasis appeared not to affect the values of Tu M2-PK, while CA 19-9 was found to be significantly higher. Tu M2-PK was also abnormally high in the majority of patients with other digestive malignancies or neuroendocrine tumors. The results demonstrate that Tu M2-PK has a satisfactory sensitivity but a poor specificity in the diagnosis of pancreatic cancer. Used together with CA 19-9, the sensitivity increases considerably.     

Combined detection tumor markers for diagnosis and prognosis of gallbladder cancer

AIM:To clarify the value of combined use of markers for the diagnosis of gallbladder cancer and prediction of its prognosis.METHODS:Serum cancer antigens(CA)199,CA242,carcinoembryonic antigen(CEA),and CA125 levels were measured in 78 patients with gallbladder cancer(GBC),78 patients with benign gallbladder diseases,and 78 healthy controls using electrochemiluminescence.CA199,CA242,CEA,and CA125 levels and positive rates were analyzed and evaluated pre-and postoperatively.Receiver operator characteristic curves were used to determine diagnostic sensitivity and specificity of GBC.Survival time analysis,including survival curves,and multivariate survival analysis of a Cox proportional hazards model was performed to evaluate independent prognostic factors.RESULTS:Serum CA242,CA125,and CA199 levels in the GBC group were significantly higher when compared with those in the benign gallbladder disease and healthy control groups(P<0.01).With a single tumor marker for GBC diagnosis,the sensitivity of CA199 was the highest(71.7%),with the highest specificity being in CA242(98.7%).Diagnostic accuracy was highest with a combination of CA199,CA242,and CA125(69.2%).CA242 could be regarded as a tumor marker of GBC infiltration in the early stage.The sensitivity of CA199 and CA242 increased with progression of GBC and advanced lymph node metastasis(P<0.05).The78 GBC patients were followed up for 6-12 mo(mean:8 mo),during which time serum CA199,CA125,and CA242 levels in the recurrence group were significantly higher than in patients without recurrence(P<0.01).The post-operative serum CA199,CA125,and CA242levels in the non-recurrence group were significantly lower than those in the GBC group(P<0.01).Multivariate survival analysis using a Cox proportional hazards model showed that cancer of the gallbladder neck and CA199 expression level were independent prognostic factors.CONCLUSION:CA242 is a marker of GBC infiltration in the early stage.CA199 and cancer of the gallbladder neck are therapeutic and prognostic markers.     

Significance of serum receptor-binding cancer antigen (RCAS1) in pancreatic cancer and benign pancreatobiliary diseases.

BACKGROUND/AIMS: RCAS1 is a novel tumor marker, and there are no sufficient data about the utility of this antigen as a serum tumor marker and about its tumor specificity. We aimed at measuring the serum levels of RCAS1 in patients with pancreatic cancer and at determining its diagnostic efficacy. METHODS: Sera collected from patients with pancreas adenocarcinomas (39 cases) and benign biliary and pancreatic diseases (19 cases) and from healthy volunteers (13 cases) were analyzed for RCAS1 and the results compared with CA19-9. The relation between serum RCAS1 and tumor stage was also evaluated. RESULTS: The serum RCAS1 levels exceeded the normal limit in 92.3, 26.3, and 23.0% of the patients with pancreatic cancer and benign biliary and pancreatic diseases and healthy volunteers, respectively. RCAS1 had a specificity similar to that of CA19-9 in pancreatic cancer, whereas RCAS1 had a higher sensitivity (p < 0.05). Both tumor markers had similar predictive values of positive and negative tests for pancreatic cancer. The RCAS1 level was less influenced than the CA19-9 level by biliary stenoses. The median serum levels of RCAS1 increased, as the tumor stage increased. CONCLUSIONS: RCAS1 is a valuable serum marker for the diagnosis of pancreatic cancer. The RCAS1 and CA19-9 levels increase the diagnostic efficiency of each other in pancreatic cancer.     

Tumour markers CA 19-9 and CA 50 in digestive tract malignancies.

CA 19-9 and CA 50 are tumour marker tests measuring the same carbohydrate structure, sialosyl-fucosyl-lactotetraose--that is, the sialylated Lewis blood group antigen. In addition, the C50 antibody reacts with sialosyl-lactotetraose, which may be expressed in small amounts in some carcinomas. In this study we compared these tests in sera from patients with benign and malignant digestive tract diseases. The sensitivity of the markers for different cancers was also compared at several specificity levels with patients with benign diseases as reference groups. Both markers showed a high sensitivity for pancreatic cancer (77% for CA 19-9; 69% for CA 50) and biliary cancer (88%). The figures in colorectal cancer were almost as high as those reported for CEA; 16-21% elevated values in Dukes A and B tumours and 44-47% in Dukes C and D tumours. The sensitivity for gastric cancer was 48% for both markers. CA 50 had a higher sensitivity for liver cancer (55%) than CA 19-9 (9%), but the proportion of elevated values in benign liver diseases was also higher (33% versus 15%, respectively). Overall, there was good correlation between the CA 19-9 and CA 50 levels, and the difference in sensitivity and specificity was marginal. In clinical practice the greatest value of CA 19-9 and CA 50 is in the diagnosis of pancreatic cancer.     

Islet amyloid polypeptide is not a satisfactory marker for detecting pancreatic cancer

BACKGROUND & AIMS: Islet amyloid polypeptide (IAPP) levels are elevated in pancreatic cancer and may be a useful marker of pancreatic cancer-associated diabetes. The aim of this study was to compare the sensitivity and specificity for pancreatic cancer of IAPP with that of CA19-9, examine clinical characteristics of diabetes in pancreatic cancer, and define the relationship of IAPP to diabetes of pancreatic cancer. METHODS: Fasting serum glucose, IAPP, and CA 19-9 were measured in 130 subjects with pancreatic cancer, 250 subjects with other pancreatic and peripancreatic diseases, and 116 controls. In pancreatic cancer patients, we noted tumor stage and the presence and duration of diabetes. RESULTS: IAPP was markedly elevated in pancreatic cancer, especially in patients with diabetes. However, the sensitivity of IAPP for pancreatic cancer was less than that of CA 19-9 (40% vs. 75%; P < 0.001). Diabetes was present in 46% of pancreatic cancers and 55% of resectable tumors. In pancreatic cancer with diabetes, the sensitivity of IAPP was only 50%. In resectable cancer it was 27%. CONCLUSIONS: IAPP is elevated in pancreatic cancer but is not sensitive enough to replace or complement existing tests. Diabetes occurs early and frequently in pancreatic cancer. Development of a sensitive and specific marker for pancreatic-associated diabetes might lead to diagnosis of resectable pancreatic cancer.     

Overlapping humoral autoimmunity links rheumatic fever and the antiphospholipid syndrome

OBJECTIVE: Rheumatic fever (RF) and the antiphospholipid syndrome (APS) are autoimmune diseases that share similar cardiac and neurological pathologies. We assessed the presence of shared epitopes between M protein, N-acetyl-beta-D-glucosamine (GlcNAc) and beta2 glycoprotein-I (beta2GPI), the pathogenic molecules engaged in these autoimmune conditions. METHODS: Sera from the APS patients were affinity-purified on beta2GPI and beta2GPI-related peptide columns. Sera from RF patients were affinity-purified on protein G column. The beta2GPI and M protein-related peptides were prepared by conventional solid-phase peptide synthesis. The enzyme-linked immunosorbent assay direct binding and inhibition studies were performed on the RF and APS sera for the presence, and cross-reactivity, of antibodies against beta2GPI, beta2GPI-related peptides, streptococcal M protein, M-derived peptides and GlcNAc. RESULTS: Antibodies (Abs) to beta2GPI were found in 24.4% of 90 RF patients. Antibodies against various beta2GPI-related peptides were found in 1.1-36.7% of the patients. The immunoglobulin G sera from RF patients possessed significant anti-beta2GPI activity, while sera from APS patients contained a considerable anti-streptococcal M protein as well as anti-GlcNAc activity. Furthermore, affinity-purified anti-beta2GPI and anti-beta2GPI-related peptide Abs from APS patients cross-reacted with streptococcal M protein and M5 peptide, while beta2GPI and beta2GPI-related peptides inhibited anti-streptococcal M protein activity from RF patients. The results were confirmed by immunoblot analyses. The beta2GPI also inhibited anti-GlcNAc activity from APS patients with chorea. CONCLUSIONS: The results of our study, showing a considerable overlap of humoral immunity in RF and APS, support a hypothesis that common pathogenic mechanisms underlie the development of cardiac valve lesions and Central Nervous System abnormalities in both diseases.     

Fecal M2-pyruvate kinase (M2-PK): a novel marker of intestinal inflammation

BACKGROUND: Surrogate markers of bowel inflammation are increasingly being recognized as important, not only as markers of disease activity in inflammatory bowel disease (IBD) but also to differentiate irritable bowel syndrome (IBS) from IBD. The dimeric M2-isoform of pyruvate kinase (M2-PK) has been reported to be elevated in fecal specimens from colorectal cancer (CA) patients, but its role in IBD is unknown. This study investigated the usefulness of fecal M2-PK in cohorts of patients with IBD, IBS, and CA. METHODS: Stool samples were obtained for calprotectin and M2-PK measurements in patients with previously diagnosed IBD or new patients being investigated for lower gastrointestinal (GI) symptoms in a UK university hospital. Other investigations were performed as directed by the investigating physician and patients with known IBD were assessed for disease activity by a physician global assessment, Harvey-Bradshaw index (HBI), or endoscopic grading. RESULTS: Fecal M2-PK and calprotectin measurements were obtained for 148 patients: 50 with ulcerative colitis (UC); 31 with Crohn's disease (CD), 43 with irritable bowel syndrome/functional bowel disorders (IBS); 7 with colorectal CA, and 17 with miscellaneous conditions (excluded from the analysis). Median M2-PK values (U/mL) were significantly elevated in UC: 20.0 (95% confidence interval [CI] 5.4-69.0, P < 0.0001), CD: 24.3 (95% CI 6.4-44.0, P < 0.0001), and CA: 7.0 (95% CI 4.3-88.0, P < 0.0006) compared to IBS: 0.1 (95% CI 0.0-3.2). There was a strong linear correlation of M2-PK with calprotectin levels. A predetermined cutoff level of 3.7 U/mL for a normal M2-PK test produced a sensitivity, specificity, and positive predictive value (PPV) of 73%, 74%, and 89%, respectively, for organic disease. Furthermore, M2-PK levels were significantly elevated in active, compared to inactive, disease for CD (30 versus 0.55 U/mL, P < 0.005) and UC (40 versus 1.2 U/mL, P = 0.006), respectively. CONCLUSIONS: Fecal M2-PK is elevated in IBD as well as in CA patients and is a sensitive and relatively specific marker for organic GI pathology, with a PPV of 89%. Furthermore, it appears to be a potentially valuable, noninvasive marker of disease activity in IBD.     

表面增强激光解析电离飞行时间质谱法筛选肺癌患者血清和肺泡灌洗液中标志蛋白的研究

目的 应用表面增强激光解析电离飞行时间质谱(SELDI-TOF-MS)技术筛选肺癌患者血清和BALF中的差异性表达蛋白,探讨是否可作为诊断肺癌的肿瘤标志物.方法 应用SELDI-TOF-MS技术通过弱阳离子交换蛋白芯片(WCX-2芯片)分别检测35例肺癌和18例肺部良性病变患者血清和BALF中的蛋白质质谱图,用Biomarker Pattern软件分析肺癌的差异蛋白并初步建立诊断模型,通过盲筛进一步验证诊断模型.结果 在肺癌患者血清中发现5个高表达的蛋白质波峰,选用其中质荷比为5639的差异蛋白波峰建立分类树模型,其诊断的敏感度为80%(28/35),特异度为78%(14/18).盲法验证的敏感度为85%(17/20),特异度为90%(9/10),粗符合率为87%(26/30),Youden指数为0.7.在肺癌患者BALF中发现8个高表达蛋白质波峰,选用其中质荷比为7976和11 809的差异蛋白波峰建立分类树模型,其诊断的敏感度为86%(30/35),特异度为72%(13/18).盲法验证的敏感度为90%(18/20),特异度为90%(9/1O),粗符合率为90%(27/30),Youden指数为0.8.平行试验结果显示两者联合应用时诊断肺癌的敏感度、准确率及特异度均为100%,具有互补作用.结论SELDI-TOF-MS技术可筛选出肺癌患者血清和BALF中差异性表达蛋白,作为一种肿瘤标志物,其诊断敏感度高,特异度好,尤其是BALF中差异性表达蛋白的测定可能具有较好的临床应用前景.

Abstract：

Objective To detect the protein markers in serum and bronchoalveolar lavage fluid (BALF) of the patients with lung cancer by surface-enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) technology, and to explore if they can be used as markers for the diagnosis of lung cancer.Methods SELDI-TOF-MS technology and protein chips weak cation exchange (WCX-2 chip) were used to detect the protein mass spectrum in serum and BALF of 35 patients with lung cancer and 18 cases of benign pulmonary diseases.The different protein markers were analyzed by Biomarker Pattern Software and the initial diagnosis models were set up.The diagnosis models were verified further by blind screen to confirm the efficacy of diagnosis.Results Five protein peaks in the sera of the patients with lung cancer were significantly higher (P ＜ 0.05 ).The protein peak with a mass/charge ratio (M/Z)of 5639 was selected to establish the classification tree model.The sensitivity of diagnosis was 80% (28/35) and the specificity was 78% (14/18).The results verified by blind screen showed a sensitivity of 85% (17/20),a specificity of 90% (9/10), a crude accuracy (CA) of 87% ( 26/30 ) and Youden' s index (γ) of 0.7.Eight protein peaks in the BALF of the patients with lung cancer were significantly higher ( P ＜ 0.05).The different protein peaks with M/Z of 7976 and 11 809 respectively were selected to establish the classification tree model.The sensitivity of diagnosis was 86% (30/35) and the specificity was 72% (13/18).The results verified by blind screen showed a sensitivity of 90% (18/20), a specificity of 90% (9/10), a CA of 90% (27/30) and γof 0.8.There was a complementary role in combination of differential proteins in serum and BALF and the sensitivity, specificity and accuracy of diagnosis for lung cancer were 100% by parallel test.Conclusions The SELDI-TOF-MS technology can screen out the differential protein markers in serum and BALF of the patients with lung cancer, which show high sensitivity and specificity as tumor markers.The differential proteins in the BALF may be more promising for clinical application.     

Verification of the effectiveness of fucosylated haptoglobin as a pancreatic cancer marker in clinical diagnosis

BackgroundFucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL) that had specificity for fucose α1-6 was reported as an effective biomarker for several gastrointestinal diseases. The aim of this study was to verify Fucosylated haptoglobin detected by Pholiota squarrosa lectin (PhoSL-HP) as a pancreatic cancer (PC) marker using a new method of PhoSL-ELISA.MethodsPhoSL-HP in sera from 98 PC patients and 158 non-PC samples including 32 intraductal papillary mucinous neoplasm (IPMN) patients, 21 chronic pancreatitis (CP) patients and 105 non-pancreatic disease controls (NPDC) were measured. We compared sensitivities, specificities and areas under the curves (AUC) of PhoSL-HP, CA19-9 and CEA as single markers. We also evaluated PhoSL-HP as combination marker by comparing AUC of CA19-9 combined with PhoSL-HP or CEA.ResultsThe sensitivities of PhoSL-HP, CA19-9 and CEA for PC were 58%, 76% and 42%, respectively. Although the specificity of PhoSL-HP for NPDC was inferior to both of CA19-9 and CEA, that for pancreatic diseases was higher than both of CA19-9 and CEA. Combined CA19-9 with PhoSL-HP, the AUC was significantly higher at 0.880 than single use of CA19-9 at 0.825 in case of distinguishing PC from other pancreatic diseases. In contrast, the AUC of CA19-9 was not elevated significantly when combined with CEA.ConclusionPhoSL-HP would be a useful marker for PC and have sufficient complementarity for CA19-9.     

Utility of serum CA19-9 in diagnosis of cholangiocarcinoma： In comparison with CEA

AIM:The diagnosis of cholangiocarcinoma is often difficult,making management approaches problematic. A reliable serum marker for cholangiocarcinoma would be a useful diagnostic test. The aims of our study were to evaluate the usefulness of a serum CA19-9 determination in the diagnosis of cholangiocarcinoma.METHODS: We prospectively measured serum CA19-9 and CEA concentrations in patients with cholangiocarcinoma (n=35), benign biliary diseases (n=92), and healthy individuals (n=15). Serum CA19-9 and CEA concentrations were measured by an immunoradiometric assay without knowledge of the clinical diagnosis.RESULTS:The sensitivity of a CA19-9 value&gt;37KU&#183;L^-1 and a CEA value &gt;22μg&#183;L^-1 in diagnosing cholangiocarcinoma were 77.14% and 68.57%, respectively. When compared with the benign biliary diseases group,the true negative rates of serum CA19-9 and CEA were 84.78% and 81.52%,respectively. The false positive rates of serum CA19-9 and CEA were 15.22% and 18.48%, whereas the accuracy of serum CA19-9 and CEA were 82.68% and 77.95%,respectively. Serum CA19-9 and CEA concentrations were significantly elevated (P&lt;0.001 and P&lt;0.05) in patients with cholangiocarcinoma (290.31&#177;5.34KU&#183;L^-1 and 36.46&#177;18.03μg&#183;L^-1) compared with patients with benign biliary diseases (13.38&#177;2.59KU&#183;L^-1 and 13.84&#177;3.85μg&#183;L^-1) and healthy individuals (12.78&#177;3.69KU&#183;L^-1 and 11.48&#177;3.37μg&#183;L^-1). In 15 patients undergoing curative resection of cholangiocarcinoma,the mean serum CA19-9 concentration was decreased from a preoperative level of 286.41&#177;4.36KU&#183;L^-1 to a postoperative level of 62.01&#177;17.43KU&#183;L^-1 (P&lt;0.001), and the mean serum CEA concentration from 39.41&#177;24.35μg&#183;L^-1 to 28.69&#177;11.03μg&#183;L6-1(P&lt;0.05). In patients with cholangiocarcinoma,however, no correlation was found between serum CEA and CA19-9 concentrations (r=-0.036).CONCLUSION:These data suggest that the serum CA19-9 determination is a useful addition to the available tests for the differential diagnosis of cholangiocarcinoma. Serum CA19-9 is an effective tumor marker in diagnosing cholangiocarcinoma,deciding whether the tumor has been radically resected and monitoring effect of treatment.     

Utility of serum ratio of heart-type fatty acid-binding protein to myoglobin for cardiac damage regardless of renal dysfunction.

BACKGROUND: The serum ratio of heart-type fatty acid-binding protein to myoglobin (F/M) has been shown to be a new marker for cardiac damage and volume overload in hemodialysis patients. We evaluated the utility of F/M in hemodialysis patients compared to control subjects. METHODS AND RESULTS: Twenty-one hemodialysis patients and 17 control subjects with normal renal function were investigated. Using a cutoff point of mean + 2SD of the F/M in the controls (value: 0.147), the hemodialysis patients were divided into 2 groups. The concentrations of atrial natriuretic peptide (ANP) and brain natriuretic peptide after hemodialysis in the high F/M group were higher than those in the low F/M group. The mean level of ANP in the low F/M group was almost the upper limit of normal range. The values of left ventricular end-diastolic dimension and left ventricular mass index in the high F/M group were higher than those in the low F/M group, and the mean levels of those in the low F/M group were almost the same as those in the controls. CONCLUSIONS: The F/M can be evaluated by the absolute value regardless of renal dysfunction, and the value of 0.147 might be useful for determining the cutoff level of cardiac involvement.     

ERCP联合胆汁肿瘤标志物测定对可疑胰胆管疾病的诊断价值研究

目的探讨胆汁肿瘤标志物测定在ERCP对可疑胰胆管疾病诊断中的辅助作用。方法对经B超、MRCP、生化、血清肿瘤标志物等常规检查未能明确诊断的可疑胰胆管疾病患者,进行ERCP检查或对症治疗,同时行胆汁肿瘤标志物测定,选取29例明确诊断的病例分为良性和恶性组,比较2组在生化、肿瘤标志物上的差别,同时评估和比较B超、EUS、MRCP、ERCP、ERCP＋胆汁肿瘤标志物对可疑胰胆管疾病的诊断价值。结果生化、血清癌胚抗原（CEA）、血清CA19-9、胆汁CA19—9,在2组间差异无统计学意义,而胆汁CEA在恶性组中平均值高于良性组,且差异有统计学意义（P〈0．001）,ERCP联合胆汁CEA测定对可疑胰胆管疾病诊断准确率为69．0％（20／29）,高于单纯的B超6．9％（2／29）、EUS60．0％（6／10）、MRCP37．9％（11／D）和ERCP41．4％（12／29）。结论ERCP联合胆汁的CEA测定能进一步提高可疑胰胆管疾病诊断的准确性,对良恶性疾病的鉴别诊断有着辅助作用。     

Rotational mechanics of the left ventricle in AL amyloidosis

Aims: The aim of this study was to investigate whether alterations in left ventricular (LV) twisting and untwisting motion could be induced by cardiac involvement in patients with immunoglobulin light‐chain (AL) systemic amyloidosis. Methods and Results: Forty‐five patients with AL amyloidosis and 26 control subjects were evaluated. After standard echocardiographic measurement and two‐dimensional (2D) speckle tracking echocardiography, LV rotation at both basal and apical planes, twisting, twisting rate, and longitudinal strain were measured. Tissue Doppler imaging (TDI) derived early diastolic peak velocity at septal mitral annulus (E′) was also evaluated. Twenty‐six of 45 patients with systemic amyloidosis were classified as having cardiac amyloidosis (CA) if the mean value of the LV wall thickness was ≥ 12 mm or not (NCA) if this value was not reached. In NCA patients, both LV twist and untwisting rate were increased while they were decreased in CA patients making them similar to the control group. Longitudinal strain was reduced only in CA patients. Impaired relaxation as indicated by E′ values was progressively reduced in the course of the disease. Conclusions: Both twisting and untwisting motions are increased in patients with AL systemic amyloidosis with no evidence of cardiac involvement while they are reduced in patients with evident amyloidosis cardiac involvement. This finding suggests that impaired LV relaxation induces a compensatory mechanism in the early phase of the disease, which fails in more advanced stage when both twisting and untwisting rates are reduced. The increase in LV rotational mechanics could be a marker of subclinical cardiac involvement. (Echocardiography 2010;27:1061‐1068)     

血清肿瘤标记物在肺癌诊断中的意义

目的　明确癌胚抗原 (CEA)、大分子糖蛋白抗原 (CA1 2 5)、细胞角蛋白 (Cyfra2 1 - 1 )在肺癌诊断中的意义。方法　收集血清标本 74份 ,其中肺部良性病变组 2 8例 ,肺腺癌组 19例 ,肺鳞癌组 16例 ,小细胞肺癌组 11例。CEA、CA1 2 5、Cyfra2 1 - 1 均用电化学发光分析技术检测 ,结果以均值±标准差和特异度及灵敏度两种方式评价。结果　 CEA的水平 ,良性病变组在正常参考范围内 ;腺癌、鳞癌、小细胞癌组均明显高于正常值上限 ,而各肺癌组间比较无显著差异 ,各肺癌组与肺部良性病变相比 ,均有显著性差异 (P<0 .0 0 1)。 CA1 2 5各组病变中均高于正常参考值 ,各组比较 ,只有肺腺癌组与良性病变组有显著性差异。 Cyfra2 1 - 1 在肺腺癌组、鳞癌组明显高于正常值 ,统计学上有显著性差异 ,良性病变组和小细胞癌组其值均在正常参考值范围内 ,但两组之间有显著性差异。 CEA的特异性高达 82 .14 % ,灵敏度为 5 8.6 9% ;CA1 2 5的灵敏度较高 ,但特异性很低 ,仅 4 2 % ;Cyfra2 1 - 1 的特异性近 90 % ,但灵敏度仅 4 5 %。对不同病理类型各肿瘤标记物的灵敏度亦不同 ,CEA、CA1 2 5在各型间无差别 ;Cyfra2 1 - 1 在非小细胞肺癌和小细胞肺癌间差别有统计学意义。结论　 CEA在肺部恶性病变中的特异性较高 ,灵敏度亦可     

Construction and expression of a humanized M2 autoantigen trimer and its application in the diagnosis of primary biliary cirrhosis

AIM: To construct and express a humanized M2 autoantigen trimer designated as BPO and to apply it in the diagnosis of primary biliary cirrhosis (PBC).METHODS: cDNA fragments encoding M2-reactive epitopes of pyruvate dehydrogenase complex E2 (PDC-E2), branched chain 2-oxo-acid dehydrogenase complex E2 (BCOADC-E2) and 2-oxo-glutarate dehydrogenase complex E2 (OGDC-E2) were amplified with PCR using total RNA extracted from human peripheral mononuclear blood cells. The fragments were cloned into the plasmid vector pQE-30 and then transferred into E. Coli M15 (pREP4) for expression, which was induced by isopropylthio-β-D-galactoside. The expressed recombinant BPO protein was demonstrated by SDS-PAGE, Western-blotting and Immunoabsorption test, its antigenic reactivity and specificity were identified with seven M2-positive sera confirmed at Euroimmun Research Center (Germany).Using the purified BPO, M2 antibodies in sera from patients with PBC and other liver related diseases were detected with ELISA.RESULTS: The expressed BPO was observed with both antigenic reactivity and specificity of M2 autoantigens. The determinaUon of M2 antibodies by BPO with EIISA was more sensitive than using the Euroimmun‘s kit with the coefficients of variation less than 10 % in both interassay and intraassay.With the newly established method, M2 antibodies werefound in 100 % (20/20) of patients with PBC. Six cases of liver disease with unknown etiology and 1 patient with drug induced liver injury had detectable levels of serum M2 antibodies. There were also 2 patients with autoimmune cholangitis and 1 with autoimmune hepatitis showing M2-antibody positive.CONCLUSION: Compared with the routine immunofluoresoenoe assay and commercially available assay kit using porcine heart mitochondrial protein as the antigen, the detection system established in the present study shows higher sensitivity and specificity and may be used as a powerful tool for the diagnosis of PBC.     

Calcific arteriolopathy (Calciphylaxis)

PURPOSE: Calcific arteriolopathy (CA), also known as " Calciphylaxis " describes a phenomenon of necrosis, mainly cutaneous and sometimes systemic, due to the obliteration of the arteriole's lumen. Initially there are under-intimal calcium deposits, and then the thrombosis occurs leading to the necrosis. CA affects mainly the renal insufficient hemodialysed patient, but not exclusively. We present 4 cases which illustrate well the etiologic spectrum of CA: terminal renal insufficiency, neoplasia, primary hyperparathyroidism, proteinuria, vitamin K inhibitors. We describe the AC's epidemiology, its cutaneous and systemic clinical presentations, its treatment. We make the hypothesis that CA is a strong risk marker in matter of cardiac mortality and we discuss this point. CURRENT KNOWLEDGE AND KEY POINTS: In this article we describe the numerous breakthroughs that have been made in matter of research about calcification over the past few years: inhibitors of calcium phosphate deposition, vitamin D and PTH1R, protein-calcium complexes, cell death, induction of bone formation. These data are analysed from a clinical point of view with practical purposes. We present CA not only as a cutaneous disease but as a systemic pathology. FUTURE PROSPECTS AND PROJECTS: The CA epidemiology is an incentive to more diagnosis suspicion in front of organ infarct involving a patient likely to be concerned by CA. The scientific and therapeutic breakthroughs in matter of calcification enable a better prevention of the disease. Nevertheless it remains very difficult to cure when installed.     

Persistent elevation of serum CA 19-9 with no evidence of malignant disease

BackgroundSerum CA 19-9 is the mainstay marker for the diagnosis of biliopancreatic malignancies, though a persistent elevation can also be observed in various benign diseases.AimsIn this study, a marked increase of serum CA 19-9 was seen in 10 patients who had no evidence of malignant disease. The possible causes of this finding are discussed.PatientsNine women and one man were studied, whose admitting diagnoses were as follows: pulmonary fibrosis in two, diabetes in two, non-ulcer dyspepsia in two, obesity in one, acute diarrhoea in one, colon diverticula in one and gastric ulcer in one.MethodsRoutine blood tests, tumour marker determinations, imaging studies and endoscopy were carried out at admission.ResultsSerum CA 19-9 levels ranged from 112 to 1338 IU/ml (mean 517 IU/ml). Abdominal ultrasonography, CT-scan, upper gastrointestinal X-ray series and gastrointestinal endoscopies were negative for malignancy. During the follow-up period (range 2–7 years) serum CA 19-9 values were persistently elevated in all patients.ConclusionsOur study shows that persistent and significant elevation of serum CA 19-9 can be found in non-malignant and non-cholestatic disease.     

Tumour M2-pyruvate kinase: a gastrointestinal cancer marker

BACKGROUND: Gastrointestinal cancer tumour markers are valuable in the detection of recurrence following resection or in monitoring response to chemotherapy. CEA, CA19-9, CA-50 and CA72-4 are currently available but are nonspecific and have a low sensitivity. 'Tumour M2-pyruvate kinase' was described by Eigenbrodt around 1985. In cancers the active tetrameric form of the M2 isoenzyme of pyruvate kinase converted to an inactive dimeric form by direct interaction with oncoproteins to channel glucose carbons into DNA synthesis. This review summarizes the current knowledge of this unique tumour marker with regard to its biochemistry, assay and potential use as a diagnostic and screening tool in gastrointestinal cancer. METHODS: A literature search was conducted for entries from 1980 to 2005 using PubMed and NeLH databases using tumour M2-pyruvate kinase, faecal tumour M2-pyruvate kinase, tumour metabolism, tumour markers and carcinoembryonic antigen as keywords. A total of 56 references relevant to tumour M2-pyruvate kinase were retrieved. Eighteen references were clinical studies involving plasma/faecal tumour M2-pyruvate kinase and gastrointestinal cancer. The remaining 38 references were clinical/nonclinical trials and reviews on tumour metabolism and plasma/faecal tumour M2-pyruvate kinase assay. Seven of the 18 clinical studies involved faecal M2-pyruvate kinase. Three of the 11 plasma tumour M2-pyruvate kinase studies were non-English language and were excluded. The sensitivity, specificity, positive predictive and negative predictive value for plasma/serum tumour M2-pyruvate kinase in the detection of gastrointestinal cancer was determined for each of the remaining eight studies. Data for gastrointestinal cancer M2-pyruvate kinase were compared with other gastrointestinal cancer markers. Data from three of the eight studies using a diagnostic cut-off value of 15 U/ml for ethylenediaminetetraacetic acid (EDTA) plasma tumour M2-pyruvate kinase were analysed together as a small meta-analysis. RESULTS: At a diagnostic cut-off value of 15 U/ml for tumour M2-pyruvate kinase in EDTA plasma the sensitivity, specificity, positive predictive and negative predictive value was 57.3, 89, 85.7 and 64.8%, respectively, for colorectal cancers, 62.1, 89, 88 and 64%, respectively, for gastric/oesophageal cancers and 72.5, 89, 58 and 94%, respectively, for pancreatic cancers. As a faecal marker for colorectal cancers, faecal tumour M2-pyruvate kinase has a sensitivity of 73-92% at a cut-off value of 4 U/ml as against 50% sensitivity for Guaiac faecal test. CONCLUSION: Circulating tumour M2-pyruvate kinase is more commonly elevated in oesophageal, gastric and colorectal cancer patients than conventional tumour markers. Faecal M2-pyruvate kinase is a sensitive marker of colorectal cancer. The clinical role of tumour M2-pyruvate kinase in gastrointestinal cancer management should be investigated in large-scale clinical trials.