Hyperhomocysteinemia is a risk factor for cancer and a new potential tumor marker

Plasma homocysteine (Hcy), a well-known independent risk factor for coronary heart disease, is also a risk factor for cancer. Results from our studies indicate that Hcy could be used as a tumor marker. We found elevated circulating total homocysteine (tHcy) in cancer patients even though they were not treated with anti-folate drugs. In serial specimens from cancer patients undergoing treatment, the change of tHcy coincided with the concentration of tumor markers. The rapid proliferation of tumor cells contributed to the much higher concentrations of circulating tHcy. Both concentrations of tHcy and tumor marker would increase in parallel during the growth of tumor cell, but only the Hcy concentration would decline in response to tumor cell death. Several biochemical changes, including folate deficiency, oxidative stress, aberrant DNA methylation, and production of homocysteine thiolactone have been identified in association with hyperhomocysteinemia, which explained why elevated homocysteine eventually led to carcinogenesis. Conceivably, tHcy may be used as a more accurate tumor marker for monitoring cancer patients during treatment, and hyperhomocysteinemia as a risk factor for carcinogenesis.     

The fractal dimension of chromatin - a potential molecular marker for carcinogenesis,tumor progression and prognosis

Introduction: Fractality is omnipresent in medicine and life sciences. In particular, the fractal principle is found simultaneously at different organization levels of the cell nucleus. The aim of this review is to show whether fractal characteristics of chromatin could be related to tumor pathology and pathophysiology.

Areas covered: This review provides an overview of the application of fractal measurements of chromatin or DNA for the characterization of physiological or pathological processes, in particular for the detection of preneoplastic changes, the characterization of tumor progression, the differential diagnosis between neoplasms and for prognosis. We used a network-based literature research strategy, i.e. after a systematic investigation by key-words, we looked for all citations (and the citations to these citations) of the selected papers in Scopus and Webofscience.

Expert opinion: The fractal dimension (FD) increases during carcinogenesis, thus permitting the diagnosis of malignancy. In various malignant tumors, a higher FD or diminished goodness-of-fit of its regression line indicates a more aggressive behavior and worse prognosis. Applying new spectral techniques, the chromatin FD can be estimated at scales below the light microscopic resolution. The latter also permits the examination of live cells and studies on field carcinogenesis and chemoprophylaxis.     

CA-549: A new tumor marker for patients with advanced breast cancer

A murine monoclonal antibody, BC4E 549, an IgG₁ adapted as tracer antibody in a sandwich immunoradiometric assay, was used to detect a circulating breast cancer-associated antigen, CA-549, in patients with advanced breast cancer. The study was designed to examine the specificity and sensitivity of CA-549 measurements as a specific circulating marker for breast cancer. In a population of 100 normal pre-and postmenopausal women, serum levels ranged from 1–10 μ/ml. In contrast, 38 of 46 patients (83%) with active, advanced-stage breast cancer had circulating levels in excess of 10 μ/ml, and levels in several patients exceeded 100 μ/ml. Patients on adjuvant therapy with breast cancer in remission, patients with benign breast disease, and patients with cancers of other sites such as colorectal, ovarian, and lung cancer did not show significant elevations (>10 μ/ml, P > 0.001) of this circulating antigen. Measurement of this breast cancer associated antigen may be of use in the evaluation of treatment for patients with advanced stage breast cancer.     

肿瘤化疗病人医院感染调查及防治对策

[目的 ]了解肿瘤化疗病人医院感染情况。 [方法 ]回顾性调查 2 0 0 3年 1月— 2 0 0 3年 12月我科出院 714例肿瘤化疗病人的临床资料。 [结果 ]发生医院感染 15 2例 ,感染率为 2 1.2 9% ,感染部位依次是呼吸道、胃肠道、口腔黏膜 ;易感因素以化疗为主 ( 10 2例 ,占 67.1% )。 [结论 ]肿瘤化疗病人必须重点进行监控和采取有效的预防措施 ,降低医院感染。     

肺癌患者血清中新型肿瘤标志物CK18-3A9检测的临床意义

目的评价一种新型的血清肿瘤标志物CK18-3A9在肺癌辅助诊断和疗效评估中的临床应用价值。方法应用化学发光法检测100例肺部良性疾病患者和100名正常人血清中CK18-3A9的水平以及165例肺癌患者化疗前和化疗后1个周期血清中CK18-3A9的水平。结果肺癌患者血清中CK18-3A9的水平均明显高于肺部良性疾病组和正常人组(P<0.01);CK18-3A9在腺癌中的水平和敏感性明显高于其他类型的肺癌(P<0.05);CK18-3A9在Ⅲ期+Ⅳ期中的水平明显高于Ⅰ期+Ⅱ期(P<0.05)。疾病进展患者化疗1个周期后CK18-3A9的水平明显升高(P<0.01);疾病稳定和部分缓解患者化疗1个周期后CK18-3A9的水平明显下降(P<0.01)。结论新型肿瘤标志物CK18-3A9的检测对于肺癌的辅助诊断和鉴别诊断有一定的临床应用价值,CK18-3A9可作为一种肺癌化疗疗效评价参考指标,值得在临床上推广使用。     

Physiological monitoring for critically ill patients: testing a predictive model for the early detection of sepsis.

OBJECTIVE: To assess the predictive value for the early detection of sepsis of the physiological monitoring parameters currently recommended by the Surviving Sepsis Campaign. METHODS: The Project IMPACT data set was used to assess whether the physiological parameters of heart rate, mean arterial pressure, body temperature, and respiratory rate can be used to distinguish between critically ill adult patients with and without sepsis in the first 24 hours of admission to an intensive care unit. RESULTS: All predictor variables used in the analyses differed significantly between patients with sepsis and patients without sepsis. However, only 2 of the predictor variables, mean arterial pressure and high temperature, were independently associated with sepsis. In addition, the temperature mean for hypothermia was significantly lower in patients without sepsis. The odds ratio for having sepsis was 2.126 for patients with a temperature of 38 degrees C or higher, 3.874 for patients with a mean arterial blood pressure of less than 70 mm Hg, and 4.63 times greater for patients who had both of these conditions. CONCLUSIONS: The results support the use of some of the guidelines of the Surviving Sepsis Campaign. However, the lowest mean temperature was significantly less for patients without sepsis than for patients with sepsis, a finding that calls into question the clinical usefulness of using hypothermia as an early predictor of sepsis. Alone the group of variables used is not sufficient for discriminating between critically ill patients with and without sepsis.     

AFP-L3: a new generation of tumor marker for hepatocellular carcinoma.

BACKGROUND: Alpha-fetoprotein (AFP) from hepatocellular carcinoma (HCC) displays differential affinity to lectin Lens culinaris agglutinin (LCA) compared to that from chronic hepatitis/liver cirrhosis. According to their binding capability to LCA, total AFP can be separated into three different glycoforms, AFP-L1, AFP-L2, and AFP-L3. AFP-L1 is the non-LCA-bound fraction, which constitutes the major glycoform of AFP in serum of chronic hepatitis and liver cirrhosis. AFP-L3 is the LCA-bound fraction of AFP. It has been reported that malignant liver cells produce AFP-L3, even when HCC is at its early stages, and especially when the tumor mass is supplied by the hepatic artery. Clinical research has determined that AFP-L3 is a highly specific marker for HCC. The AFP-L3 can be detected in the serum of approximately 35% of the patients with small HCC (<2 cm). The AFP-L3-positive HCC has potential for rapid growth and early metastasis. Compared to imaging techniques, it has been shown to have 9-12 months of lead-time in early HCC recognition. Combined sensitivity of AFP-L3 for HCC is 56%, with a specificity of >95%. METHODS: Automated assay for measuring AFP-L3 has been developed and introduced in clinical use. The new automated method for measurement of ALP-L3 is based on liquid phase binding of the AFP-L3 glycoform with LCA and two specific monoclonal antibodies labeled with peroxidase and polysulfated tyrosine peptide, respectively. CONCLUSION: AFP-L3 is a new generation of tumor marker for HCC and yields useful information on HCC for clinical decision making.     

危重病患者血浆可溶性肿瘤坏死因子受体与蛋白质分解代谢的关系及其预后价值

目的　探讨肿瘤坏死因子 α (TNF α)及其可溶性受体I (sTNFRⅠ )、应激激素与危重病蛋白质高分解代谢的关系及其在预后判断中的价值。方法　危重病组 (n =5 0 )按随访结果分为存活组和死亡组 ,同时设立正常对照组 (n =15 )。检测研究对象血中TNF α、sTNFRⅠ、应激激素及营养指标水平 ,并进行相关性分析。结果　⑴危重病患者sTNFRⅠ、TNF α、皮质醇、胰高血糖素均显著高于正常对照组 (P值均小于 0 0 1) ,而前白蛋白 (PA)、转铁蛋白 (TF)、白蛋白 (ALB)均显著低于正常对照组 (P值均小于0 0 0 1)。 (2 )危重病死亡组APACHEⅡ评分、sTNFRⅠ、皮质醇、胰高血糖素均高于存活组 (P <0 0 5 ) ,但TNF α、PA、TF、ALB水平 ,两组间差异无显著性。⑶各指标的相关性分析结果 :①APACHEⅡ评分与sTNFRⅠ、TNF α、皮质醇、胰高血糖素水平相关 (P <0 0 5 ) ,而与营养指标无关。②sTNFRⅠ与PA、TF、ALB水平均相关 (P <0 0 5 ) ,TNF α仅与PA水平相关 (P <0 0 5 ) ,皮质醇、胰高血糖素与上述蛋白水平均无相关性。③sTNFRⅠ、TNF α均与皮质醇、胰高血糖素水平相关 (P <0 0 5 )⑷以危重病预后为因变量的Logistic回归分析示仅APACHEⅡ评分和sTNFRⅠ仍独立与危重病预后相关。结论　TNF α、sTNFRⅠ介导了危重病蛋     

Serum total homocysteine increases with the rapid proliferation rate of tumor cells and decline upon cell death: a potential new tumor marker

BACKGROUND: We were interested to know why cancer patients are frequently associated with elevated circulating total homocysteine (tHcy) even though they are not treated with anti-folate drugs. METHODS: We employed tissue cultures to compare both the homocysteine (Hcy)-released and production of tumor markers between tumor and normal cell lines. RESULTS: We detected much higher concentrations of homocysteine (Hcy) released by the tumor cells. However, much less difference was found between normal and tumor cell lines when Hcy concentration was expressed per the same number of cells. During the cell culture, the increase of Hcy and the increase of tumor marker concentration paralleled each other for the first 7 days. After the seventh day of the culture when cells started dying, tumor markers continued to rise, whereas levels of Hcy and cell numbers leveled off. We found that the serum concentration of Hcy fluctuated in circulation coinciding with that of tumor marker in individual cancer patients unless taking anti-neoplastic drug. CONCLUSIONS: The elevation of tHcy concentration may be caused by the rapid tumor cell proliferation and reflect only the number of live cells. Serum Hcy may be a potentially useful tumor marker to monitor tumor activity.     

Tumor M2 pyruvate kinase: a tumor marker and its clinical application in gastrointestinal malignancy

Proliferating cells, in particular tumor cells, express a dimeric isoenzyme of pyruvate kinase, termed Tumor M2 pyruvate kinase. In the last few years, much attention has been paid to this novel tumor marker that can be determined in EDTA-plasma and in the feces. It has been used in diagnosis and surveillance of a variety of malignant diseases. As compared with the established tumor markers, Tumor M2-PK in EDTA-plasma proves to have at least equal sensitivity in pancreatic, gastric, esophageal, colorectal and cholangiocellular cancer. In combination with established tumor markers, EDTA-plasma M2-PK is a useful tool in diagnosis and surveillance of gastrointestinal tumors. In colorectal cancer, M2-PK in EDTA-plasma even proves superiority as compared with CEA. Fecal Tumor M2-PK testing resembles a good noninvasive screening parameter for colorectal cancer with a reported sensitivity of 68.8-91.0% and a specificity of 71.9-100%. It is superior to fecal occult blood testing in colorectal cancer screening. Since it is effective, easy to handle and bears rather low costs, fecal Tumor M2-PK testing is recommended for large-scale CRC screening.     

两种方法联合检测对早期先天性梅毒的监控和诊治价值

目的 探讨甲苯胺红不加热血清反应素试验(TRUST) 和明胶颗粒凝集试验(TPPA)联合检测对早期先天性梅毒的监控和诊治价值,为临床诊治早期先天性梅毒提供更有价值的实验依据.方法 采用TRUST测定梅毒血清非特异类脂质抗原,采用TPPA测定梅毒血清特异性螺旋体抗体.结果 2007～2010 年受检的1 846人次中,TPPA确证的梅毒特异性螺旋体抗体阳性94 例,检出率为5.09%(94/1 846),而TPPA和TRUST同时阳性仅28例,占总受检人数的1.52%(28/1 846),提示TPPA阳性而TRUST阴性的新生儿仍要定期观察和检查,以便得到及时的诊断和治疗.94 例确证的梅毒特异性螺旋体抗体阳性标本中,TRUST阳性28例,敏感性29.79%,TRUST检出33例阳性标本中,5例经TPPA确证为阴性,特异性为84.85%,TPPA检出梅毒的阳性率明显高于TRUST,差异有统计学意义(χ2=52.41,P＜0.01).2007 年检出新生儿血清特异性螺旋体抗体阳性20例,2008年29例,较2007年增长40.0%,2009年38例,较2008年增长31.0%.由此提示新生儿先天性梅毒其发病率呈逐年上升趋势,已经成为一个不容忽视的公共卫生问题,应该引起大家重视.结论 新生儿胎传梅毒的早期诊断、早期治疗是减少甚至杜绝对患者侵害的最有效方法.母亲在妊娠期内和新生儿出生后在临床监控中同时进行TRUST和TPPA检测,既能提高梅毒血清学的阳性检出率,减少漏检和误判,也可作为观察病程和疗效的指标,以便梅毒患者能得到及时有效的诊治.TRUST 和 TPPA联合检测为临床诊治早期先天性梅毒提供更有价值的实验室依据,更有利于梅毒的监控和诊治.     

Telomerase as a potential marker for inflammation and cancer detection in bronchial washing: A prospective study

ObjectivesThe diagnosis of lung cancer remains difficult especially in peripheral tumors, given the absence of relevant markers and of sensitive imaging techniques. Telomerase is a ribonucleotide enzyme responsible for the immortalization of cancerous cells and seems to increase in bronchial aspirates of lung cancer patients. The purpose of our study is to further investigate the value of telomerase measurement in bronchial aspirates as a diagnostic tool for lung cancer.Design and methodsRandom 82 bronchial aspirates were obtained from patients undergoing bronchoscopy to diagnose any lung illness including inflammation and cancer. Cytology examination, quantification of proteins by Bradford method, and telomerase activity measurement by quantitative Real-time PCR were performed. Out of 82 specimens, 11 were excluded because of hemolysis, absence of elements or lack of final diagnosis. ROC curve analysis was done.ResultsA significant difference in telomerase activity average was noted between normal patients and those with inflammation and cancer. Discriminatory capacity of telomerase activity was: for cancer vs. non cancer, AUC = 0.74 (95% CI: 0.62–0.84), sensitivity = 78%, specificity = 72%, Negative Predictive Value = 87%, at cut-off > 0.46 atmol/mg protein/20 min; for cancer vs. normal, AUC = 0.87 (95% CI: 0.72–0.96), se = 78%, sp = 92%, NPV = 71%, at cut-off > 0.46; for cancer vs. inflammation, AUC = 0.69 (95% CI: 0.55–0.80), se = 74%, sp = 70%, NPV = 79%, at cut-off > 1.03, and for inflammation vs. normal, AUC = 0.76 (95% CI: 0.62–0.88), se = 79%, sp = 77%, NPV = 59%, at cut-off > 0.ConclusionTelomerase activity in bronchial aspirates is a promising diagnostic marker for lung cancer and inflammation detection.     

Atrial fibrillation in patients of a medical clinic--a marker for multi-morbidity and unfavorable prognosis

Out of 724 patients admitted to the medical department of a community teaching hospital during three months 110 (14.5%) had electrocardiographically documented atrial fibrillation (AF). 56% had chronic and 44% intermittent AF. Only 66% of patients with AF suffered from diseases generally accepted as cause of AF, 29% had cardiovascular and pulmonary risk factors, 5% had lone AF. AF was already known in 66% of patients, in 21% AF was documented at the first time, only 14% were admitted because of AF, although AF was clearly the cause of symptoms in an additional 11%. The mean age of patients with AF (72 years) was higher than that of patients without AF. 95% of patients with AF suffered from more than one cardiovascular or pulmonary disease or risk factor (mean index of diseases of 3.2). Hospital mortality of patients with AF was much higher than mean total hospital mortality (19 vs 7.7) except in patients with lone AF. We conclude that AF is a marker of multimorbidity and bad prognosis in patients of general internal medicine.     

A novel ultra-sensitive enzyme immunoassay for soluble human insulin receptor ectodomain and its measurement in urine from healthy subjects and patients with diabetes mellitus

ObjectiveFor the early identification of patients at risk of developing diabetes mellitus, and to prevent the onset of diabetes by performing dietary counseling and exercise guidance, we have developed an ultra-sensitive immune complex transfer enzyme immunoassay (ICT-EIA) to measure soluble human insulin receptor ectodomain (sIRα) in urine which is collected non-invasively.Design and methodsWe developed ICT-EIA for sIRα and measured urinary sIRα from 106 healthy volunteers, 35 obese volunteers and 42 patients with diabetes.ResultsThe detection limit of ICT-EIA (0.04 pg/mL), using a urine sample of as little as 100 μL, was a few hundred-fold higher than that of conventional ELISA. Using ICT-EIA, the urinary sIRα level in patients with diabetes (9.7 ± 20.1 pg/mg creatinine) was significantly higher than those in healthy volunteers (1.4 ± 0.9; P < 0.001).ConclusionICT-EIA for sIRα may be useful as a good marker for evaluating diabetes risk.     

NH2 terminal pro-brain natriuretic peptide plasma level as an early marker of prognosis and cardiac dysfunction in septic shock patients

OBJECTIVE: To investigate N-terminal pro-brain natriuretic peptide (NT-proBNP) level as a prognostic factor and a marker of myocardial dysfunction in patients with septic shock. DESIGN: Prospective observational study. SETTING: Intensive care unit. SUBJECTS: A total of 39 patients diagnosed with septic shock and requiring mechanical ventilation. MEASUREMENTS AND MAIN RESULTS: Demographic, hemodynamic, respiratory, and biological data (notably NT-proBNP, lactate, and cardiac troponin I) were collected at inclusion and every 12 hrs. The independent factors for death were higher Sequential Organ Failure Assessment score in the 24-hr period after inclusion (odds ratio, 4.7; 95% confidence interval, 1.15-19.3) and the highest NT-proBNP level in the 24-hr period after inclusion (odds ratio, 1.12 per 1000 pg/mL increase; 95% confidence interval, 1.05-1.26). An NT-proBNP of >13,600 pg/mL predicted intensive care unit mortality with an accuracy of 77%. Area under the receiver operating characteristic curve was 0.8 (p = .002; 95% confidence interval, 0.66-0.93). NT-proBNP levels were over the accepted normal range in all patients. Values were highest between 24 and 36 hrs after onset of septic shock and were significantly higher in nonsurvivors at each time between inclusion and day 7. The lowest left ventricular stroke work index of the first 24-hr period after inclusion was the only factor that independently influenced higher NT-proBNP levels at the same time (odds ratio, 0.91; 95% confidence interval, 0.84-0.98). CONCLUSION: NT-proBNP seems to be an early factor of prognosis and myocardial dysfunction in patients with septic shock.     

肺结核患者血清肿瘤标志物水平的变化及其临床意义

目的探究肺结核患者血清肿瘤标志物水平变化及其临床价值。方法收集2010年5月至2014年10月的80例活动性肺结核患者、50例健康体检者、50例肺癌患者,三组患者一般资料无统计学差异,采用化学发光免疫技术测定活动性肺结核患者治疗前后、健康体检者、肺癌患者血清CA125、CA199、CEA、SCC、NSE水平,比较肺结核患者、健康体检者、肺癌患者的血清肿瘤标志物水平及肺结核患者治疗前后血清肿瘤标志物水平变化。结果肺癌组患者血清CA125、CA199、CEA、SCC、NSE水平明显高于肺结核组与正常组,肺结核患者治疗前血清CA125、NSE水平明显高于正常组,肺结核组治疗2月后、治疗6月后血清CA125、NSE水平较治疗前明显降低,差异均具有统计学意义(P0.05),肺结核组治疗2月后、治疗6月后血清CA125、CA199、CEA、SCC、NSE水平与正常组无明显差异(P0.05)。结论肺结核患者血清CA125与NSE明显高于正常人,低于肺癌患者,可作为肺结核的重要鉴别诊断指标、治疗效果及预后评估指标。