Cell loss and proliferation in non-small cell lung carcinoma: correlation with histological subtype

BACKGROUND: Cell kinetic data are important indicators of the aggressiveness of tumor and treatment response. The size of a neoplasm depends on the balance between cell proliferation and death. Thus, the analysis of the kinetics of cell proliferation and death may explain differences in the rates of tumour progression. METHODS: We studied apoptosis and proliferative indices in 95 cases of non-small cell lung carcinomas. The analysis was performed on paraffin-embedded tissue, by both MIB-1 immunocytochemical detection to establish the proliferation index and the in-situ end labelling method for the apoptosis index. The two indices were related. RESULTS: Our results showed a high proliferative index and cell loss rate in squamous cell carcinoma, and a low proliferative index and cell loss rate in adenocarcinoma, suggesting two different growth patterns. CONCLUSION: These findings could explain the different biological behaviour and treatment response of the tumours. The tendency of a cancer cell to undergo apoptosis may be especially important for the chemotherapy of malignant tumours with a low growth rate, which are typically resistant to cytostatic agents.     

孕酮，CA125及TNF-alpha水平与先兆流产的关系

目的：探讨孕酮,CA125 及TNF-alpha水平与先兆流产发生的关系。方法：选择2014 年2 月-2015 年2 月在我院诊断并接受治疗的先兆流产患者60 例,根据妊娠结局不同,将患者分为完成妊娠组和终止妊娠组。另选取同期顺利分娩的产妇作为对照组。比较三组研究对象血清孕酮,CA125 及TNF-琢水平。结果：先兆流产患者血清孕酮水平低于对照组,而CA125 及TNF-alpha水平高于对照组,差异具有统计学意义（P<0.05）;先兆流产终止妊娠组血清孕酮水平低于完成妊娠组,而CA125 及TNF-alpha水平高于完成妊娠组,差异具有统计学意义（P<0.05）。孕酮,CA125 及TNF-alpha水平是先兆流产发生的影响因素（P<0.05）。结论：孕酮水平低,CA125 及TNF-alpha水平高是先兆流产发生的危险因素。临床应给予高度重视,积极采取有效的保胎治疗,避免不良妊娠结局。     

Significance of CA72.4 in patients with colorectal cancer. Comparison with CEA and CA19.9.

CA72.4 is a new tumor-associated antigen identified by monoclonal antibodies cc49 and B72.3. Serum levels of CA72.4 were measured in patients with benign and malignant diseases. The cut-off used was 4 U/mL. CA72.4 is a highly specific marker since only 3% of 162 patients with benign diseases had elevated levels of antigen. Forty-four percent of 89 patients with colorectal cancer had elevated CA72.4 levels. Compared with CEA and CA19.9, we have found that CEA (75%) is the most sensitive marker (p less than 0.001). The simultaneous use of two or three markers did not further contribute to the evaluation of patients with colorectal cancer.     

An international proficiency study with the tumor marker CA 125

A strict and adequate quality assurance program is the only real guarantee of the reliability of laboratory test results. Such proficiency testing was carried out for the CA 125 test system in five university laboratories over a period of three years (1984-1987) using five different reference materials (BIOREF, FRG). A concentration-dependent performance profile could thus be established evaluating a total of 301 assays. Intra-assay precision of the test ranged between 4.8 and 11.5%, and interassay precision between 13.6 and 19.1%. Laboratory specific average values of the individual reference materials ranged between 26 and 32 U/ml for reference 1, 51 and 59 U/ml for reference 2, 109 and 121 U/ml and 193 to 240 U/ml for references 3 and 4, respectively. Mean values for reference 5 ranged between 401 and 458 U/ml. There was no significant difference between mean values for the laboratories. Considerable batch-dependent variations of values became evident during the study but these were not indicated by the kit control supplied by the manufacturer. During the whole investigation period no systematic drift in values could be observed using trend analysis, indicating excellent stability of the reference material if stored frozen (-20 degrees C).     

Regulation of CA 125 expression in cultured human carcinoma cells

CA 125 shedding is not a constitutive and stable process but may be affected by cell cycle and cell proliferation as well as by various growth factors and cytokines. Interferons, interleukin-1 beta, tumor necrosis factor-alpha and transforming growth factor-alpha have been shown to induce while glucocorticoids and transforming growth factor-beta have been shown to suppress the release of the tumor marker CA 125 from ovarian carcinoma cells. Several endogenous as well as exogenous factors may affect CA 125 biosynthesis; however, a major question remains whether this observed modulation of CA 125 expression in vitro is of clinical importance.     

Discovery of differentially expressed genes related to histological subtype of hepatocellular carcinoma

Hepatocellular carcinoma (HCC) is one of the most common human malignancies in the world. To identify the histological subtype-specific genes of HCC, we analyzed the gene expression profile of 10 HCC patients by means of cDNA microarray. We proposed a systematic approach for determining the discriminatory genes and revealing the biological phenomena of HCC with cDNA microarray data. First, normalization of cDNA microarray data was performed to reduce or minimize systematic variations. On the basis of the suitably normalized data, we identified specific genes involved in histological subtype of HCC. Two classification methods, Fisher's discriminant analysis (FDA) and support vector machine (SVM), were used to evaluate the reliability of the selected genes and discriminate the histological subtypes of HCC. This study may provide a clue for the needs of different chemotherapy and the reason for heterogeneity of the clinical responses according to histological subtypes.     

胃癌患者血清CA125、CA724、CEA、CA199水平的表达及与临床病理特征的关系研究

目的:研究胃癌患者血清糖链抗原125(CA125)、糖链抗原724(CA724)、癌胚抗原(CEA)、糖链抗原199(CA199)水平的表达及与临床病理特征的关系。方法:选取2016年5月-2017年8月我院收治的胃癌患者94例记为胃癌组,胃部良性病变患者82例记为良性病变组,另取同期于我院接受体检的健康志愿者80例记为对照组。分别测定三组受试者血清CA125、CA724、CEA、CA199水平,并分析上述指标与胃癌患者临床病理特征的关系,并观察胃癌患者各指标单独检测和联合检测的阳性率。结果:三组受试者血清CA125、CA724、CEA、CA199水平整体比较差异有统计学意义(P0.05),胃癌组、良性病变组、对照组的血清CA125、CA724、CEA、CA199水平呈逐渐降低趋势,两两对比差异有统计学意义(P0.05)。不同性别的胃癌患者CA125、CA724、CEA、CA199水平比较差异无统计学意义(P0.05),年龄60岁、TNM分期为Ⅲ-Ⅳ期、肿瘤大小≥5 cm2的胃癌患者CA125、CA724、CEA、CA199水平均高于年龄≤60岁、TNM分期为Ⅰ-Ⅱ期、肿瘤大小5 cm2的胃癌患者,差异有统计学意义(P0.05)。联合检测的胃癌阳性率高于CA125、CA724、CEA、CA199单独检测,且CA724单独检测高于CA125、CEA、CA199单独检测,差异有统计学意义(P0.05)。结论:胃癌患者血清CA125、CA724、CEA、CA199水平较高,与患者的年龄、TNM分期、肿瘤大小等因素有关,且联合检测的胃癌检出率较高,可为胃癌的早期诊断提供指导作用。     

CA 125: the past and the future

Over the last 15 years, substantial progress has been made in understanding the potential and the limitations of the CA 125 assay. More than 2000 papers have been published concerning laboratory and clinical studies of CA 125. The original CA 125 assay utilized the OC 125 antibody that recognizes the CA 125 epitope on a high molecular weight glycoprotein. Despite repeated attempts, the gene encoding the peptide component has not yet been cloned. Monoclonal antibodies have been raised against other epitopes expressed by this molecule, leading to the development of the CA 125-II assay that exhibits less day-to-day variation. Using either assay, elevated levels of CA 125 are detected in a number of benign conditions, including endometriosis. CA 125 is most consistently elevated in epithelial ovarian cancer, but can be expressed in a number of gynecologic (endometrial, fallopian tube) and non-gynecologic (pancreatic, breast, colon and lung) cancers. The best established application of the CA 125 assay is in monitoring ovarian cancer. The rate of decline in CA 125 during primary chemotherapy has been an important independent prognostic factor in several multivariate analyses. Persistent elevation of CA 125 at the time of a second look surgical surveillance procedure predicts residual disease with > 95% specificity. Rising CA 125 values have preceded clinical detection of recurrent disease by at least 3 months in most, but not all studies. Given the modest activity of salvage chemotherapy, this information has not yet impacted on survival. Rising CA 125 during subsequent chemotherapy has been associated with progressive disease in more than 90% of cases. CA 125 may serve as an effective surrogate marker for clinical response in phase II trials of new drugs. CA 125 levels can aid in distinguishing malignant from benign pelvic masses, permitting effective triage of patients for primary surgery. Early detection of ovarian cancer remains the most promising application of CA 125. An algorithm has been developed that estimates the risk of ovarian cancer (ROC) based upon the level and trend of CA 125 values. A major trial has been initiated that uses the ROC algorithm to trigger transvaginal sonography and/or subsequent laparotomy. Such a trial could demonstrate improvement in survival through early detection. This strategy should provide adequate specificity, but sensitivity for early stage disease may not be optimal. In the future, improved sensitivity may be attained using multiple markers and neural network analysis. Most serum tumor markers have been proteins or carbohydrates, but lipid markers such as lysophosphatidic acid deserve evaluation. Genomic and proteonomic technologies should identify additional novel markers.     

血清CA125在胃癌腹膜转移诊断中的临床评价

目的:检测癌相关抗原125(A125)在胃癌腹膜转移病人血清中的表达状况并探讨其在胃癌腹膜转移中的诊断意义.方法:选择经病理证实的70例胃癌患者为研究对象,其中胃癌腹膜转移者和无腹膜转移者各35例.手术前一周用放射免疫法检测其血清中CAl25含量,同时测定肿瘤相关抗原CA19-9和CEA作参照,术前常规行腹部B超或CT检查.剖腹探查时观察腹膜转移的部位、范围、数目及大小等.健康对照30例.结果:胃癌组血清CA125水平明显高于对照组(P＜0.05).在35例出现腹膜转移的胃癌患者中,血清CA125水平超过正常值(35 U/ml)者有28例(80%),范围从87 U/ml～480 U/ml,其数值与腹膜转移的程度成正比;而无腹膜转移组的35例患者,只有1例血清CA125水平略有升高(47U/ml),两组间存在显著差异(P＜0.01).结论:血清CA125水平可作为胃癌腹膜转移有效的预测指标,CA125水平在出现腹膜转移的胃癌患者血清中显著升高,并提示预后不良.     

Detection of tumor marker CA125 in ovarian carcinoma using quantum dots

The fluorescent labeling of biological materials usingsmall-molecule organic dyes is widely employed in bio-logical imaging and clinical diagnosis. Organic fluoro-phores, however, have certain characteristics that limittheir advantages in some applications. These limitationsinclude narrow excitation bands and broad emissionbands with red spectral tails, which make the simultaneousevaluation of several light-emitting probes difficult due tospectral overlap. Also, many organic dyes exhibit highp…     

Immunosuppressive acidic protein (IAP) and CA 125 assays in detection of human ovarian cancer: preliminary results

Serum levels of the immunosuppressive acidic protein (IAP) and CA-125 were measured in 45 patients with ovarian tumors (30 malignant and 15 benign) before surgery. Concentrations of both markers were slightly increased in benign forms but still within the upper limit for controls. The sensitivity of IAP in detecting ovarian cancer was higher than CA-125 (83.4% versus 76.7%). Five false negatives were observed in IAP assay and seven for CA-125. Parallel determination of both markers, however, improved the diagnostic accuracy up to 90.0% of the total malignant cases. Combined measurements of circulating IAP and CA-125 are therefore recommended in the detection of ovarian cancers.     

晚期卵巢高级别浆液性腺癌术后血CA125下降情况与残余病灶大小关系的研究

目的:探讨血清CA125测定对评估卵巢高级别浆液性腺癌术后血CA125下降情况与残余病灶大小关系的价值.方法:回顾性研究卵巢高级别浆液性腺癌Ⅱc-Ⅳ期患者62例,按照瘤体减灭术后残余病灶大小分为3组,A组为术后残余病灶＞1cm,B组为≤ 1cm者,C组为肉眼未见病灶者,查阅术前、术后第1次化疗后血CA125值.结果:C组下降百分比与B组、A组相比有统计学差异(分别为P=0.024,P=0.002).结论:术后残余病灶大小不同的患者血CA125下降情况不同,在关于肿瘤标志物的研究中将肉眼未见病灶组单独列出研究有很大的必要性.     

Relationship of tumoral hyaluronic acid and cathepsin D contents with histological type of gastric carcinoma

The aim of this work was to evaluate the cytosolic contents of hyaluronic acid (HA) and cathepsin D (CatD) in gastric carcinomas and their possible relationships with the clinicopathological parameters of the tumors. Our study demonstrated a wide variability in the cytosolic levels of HA (mean +/- SEM: 3748 +/- 411 ng/mg protein) and cathepsin D (52 +/- 4 pmol/mg protein) in the tumors of 78 gastric cancer patients. In addition, the tumoral contents of HA and CatD were significantly higher (p<0.005) in diffuse type (HA: 6027 +/- 1099 ng/mg protein; CatD: 75 +/- 13 pmol/mg protein) than in intestinal type (HA: 2735 +/- 242 ng/mg protein; CatD: 42 +/- 3 pmol/mg protein) carcinomas. These data suggest that both markers may contribute to the biological characterization of gastric carcinomas.     

Proteomic analysis distinguishes basaloid carcinoma as a distinct subtype of nonsmall cell lung carcinoma

The histopathologic type of lung cancer is known to be correlated with tumor behavior and prognosis. However, this classification is subjective and no specific molecular markers have been identified. The aim of this study was to identify protein markers in different types of nonsmall cell lung cancers. Two-dimensional polyacrylamide gel electrophoresis analysis was performed with paired samples of three squamous cell carcinomas, three adenocarcinomas, four large cell carcinomas, and four basaloid carcinomas. We found that 25 proteins in 14 cases of lung cancer were differentially expressed compared to matched nontumorous lung tissues. Among these 25 proteins, 11 proteins were down-regulated and 14 were up-regulated in these four types of lung cancer. Alloalbumin venezia, selenium-binding protein 1, carbonic dehydratase, heat shock 20KD-like protein, and SM22 alpha protein were down-regulated in all 14 cases of lung cancer examined, whereas alpha enolase was consistently up-regulated. Supervised hierarchical cluster analysis based on the 25 differentially expressed proteins showed that basaloid carcinoma formed one independent group, whereas the other three cancer types were not uniquely classifiable. Our findings suggest that basaloid carcinoma is a unique subtype of nonsmall cell lung carcinoma.     

Preoperative and longitudinal serum levels of CA 125 and CA 15.3 in patients with breast cancer

Serum levels of ovarian carcinoma antigen (CA 125) and breast carcinoma antigen (CA 15.3) were determined in 237 patients with breast carcinoma, 121 before any therapy and 116 after initial treatment, during uneventful follow-up or at the time of relapse. The aim was to assess how often the CA 125 test failed, i.e., was false-negative in patients in whom the CA 15.3 test was true-positive and, more important, whether it gave diagnostic information in patients in whom the CA 15.3 test failed. Before surgery or other initial therapy, serum CA 125 and CA 15.3 gave similar information in 85.1 percent of the patients: true-positive in 4.1 percent and false negative in 81.0 percent: CA 125 gave less information in 13.2 percent; and more information in only 1.7 percent. During follow-up, serum CA 125 and CA 15.3 gave similar information in 73.3 percent of the patients: true-positive (i.e., rising persistently from a nadir or elevated above 65 U/ml) in 23.3 percent, true-negative in 36.2 percent, and false-negative in 13.8 percent; CA 125 gave less information in 25.0 percent: false negative in 22.4 percent and false-positive in 2.6 percent; and more information in only 1.7 percent. Therefore, the CA 125 test appears useless for staging and is redundant when the CA 15.3 test is employed, for management of patients with breast cancer.     

Diagnostic and Prognostic Impact of Circulating YKL-40, IL-6, and CA 19.9 in Patients with Pancreatic Cancer

Purpose

We tested the hypothesis that high plasma YKL-40 and IL-6 associate with pancreatic cancer and short overall survival.

Patients and Methods

In all, 559 patients with pancreatic cancer from prospective biomarker studies from Denmark (n = 448) and Germany (n = 111) were studied. Plasma YKL-40 and IL-6 were determined by ELISAs and serum CA 19.9 by chemiluminescent immunometric assay.

Results

Odds ratios (ORs) for prediction of pancreatic cancer were significant for all biomarkers, with CA 19.9 having the highest AUC (CA 19.9: OR = 2.28, 95% CI 1.97 to 2.68, p<0.0001, AUC = 0.94; YKL-40: OR = 4.50, 3.99 to 5.08, p<0.0001, AUC = 0.87; IL-6: OR = 3.68, 3.08 to 4.44, p<0.0001, AUC = 0.87). Multivariate Cox analysis (YKL-40, IL-6, CA 19.9, age, stage, gender) in patients operated on showed that high preoperative IL-6 and CA 19.9 (dichotomized according to normal values) were independently associated with short overall survival (CA 19.9: HR = 2.51, 1.22–5.15, p = 0.013; IL-6: HR = 2.03, 1.11 to 3.70, p = 0.021). Multivariate Cox analysis of non-operable patients (Stage IIB-IV) showed that high pre-treatment levels of each biomarker were independently associated with short overall survival (YKL-40: HR = 1.30, 1.03 to 1.64, p = 0.029; IL-6: HR = 1.71, 1.33 to 2.20, p<0.0001; CA 19.9: HR = 1.54, 1.06 to 2.24, p = 0.022). Patients with preoperative elevation of both IL-6 and CA 19.9 had shorter overall survival (p<0.005) compared to patients with normal levels of both biomarkers (45% vs. 92% alive after 12 months).

Conclusions

Plasma YKL-40 and IL-6 had less diagnostic impact than CA 19.9. Combination of pretreatment YKL-40, IL-6, and CA 19.9 may have clinical value to identify pancreatic cancer patients with the poorest prognosis.     

Tumor antigen NB/70K and CA 125 levels in the blood of preoperative ovarian cancer patients and controls: a preliminary report of the use of the NB12123 and CA 125 radioimmunoassays alone and in combination

The NB12123 and CA125 radioimmunoassays, murine monoclonal antibody assays for measuring circulating levels of human ovarian tumor associated antigens NB/70K and CA 125, respectively, have been previously described. In the present study, preoperative serum samples were obtained from patients undergoing laparotomy for benign neoplastic ovarian tumors (N = 16), cancer of the cervix (N = 22), cancer of the uterus (N = 20), and cancer of the ovary (N = 47). Controls (N = 50) were obtained from healthy blood bank donors. No correlation was observed between the levels of NB/70K and CA 125 in these samples (r2 = .079, linear regression analysis). In general, increasing levels of both antigens were present with increasing tumor burden and higher histological grade. In addition, both markers were most elevated in the serum of ovarian cancer patients with serous and unclassified adenocarcinomas. Using 40 AU and 35 unit cut-offs for the NB/70K and CA 125 assay, respectively, overall specificity for healthy controls and patients with benign diseases approaches 100%. The combined sensitivity of the assays for ovarian cancer patient sera in this study indicates that the assays may be helpful in establishing a pre operative diagnosis of ovarian cancer. Complementarity of the NB/70K and CA 125 assays has been demonstrated, indicating that one or both assays may be used to monitor as many as 85% of ovarian cancer patients.