Research advances in tumor markers for the diagnosis of hepatocellular carcinoma

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YANG Guimin

2018-01-01

Full Text Available Hepatocellular carcinoma (HCC is a malignant tumor with a high fatality rate in the world, and alpha-fetoprotein (AFP is the most commonly used tumor marker for HCC diagnosis. However, AFP does not have a satisfactory sensitivity or specificity and may lead to missed diagnosis when the tumor is small in the early stage of HCC. This article summarizes the clinical value of new tumor markers in the diagnosis, treatment monitoring, and prognosis judgment of HCC and analyzes the future prospects of the measurement of tumor markers for HCC. It is pointed out that combined determination of several tumor markers helps to improve the sensitivity and specificity of HCC diagnosis, and the screening and optimization of combined determination of tumor markers, noninvasive and efficient tumor markers, and individualized treatment are research hotspots in future.

The discovery of putative urine markers for the specific detection of prostate tumor by integrative mining of public genomic profiles.

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Min Chen

Full Text Available Urine has emerged as an attractive biofluid for the noninvasive detection of prostate cancer (PCa. There is a strong imperative to discover candidate urinary markers for the clinical diagnosis and prognosis of PCa. The rising flood of various omics profiles presents immense opportunities for the identification of prospective biomarkers. Here we present a simple and efficient strategy to derive candidate urine markers for prostate tumor by mining cancer genomic profiles from public databases. Prostate, bladder and kidney are three major tissues from which cellular matters could be released into urine. To identify urinary markers specific for PCa, upregulated entities that might be shed in exosomes of bladder cancer and kidney cancer are first excluded. Through the ontology-based filtering and further assessment, a reduced list of 19 entities encoding urinary proteins was derived as putative PCa markers. Among them, we have found 10 entities closely associated with the process of tumor cell growth and development by pathway enrichment analysis. Further, using the 10 entities as seeds, we have constructed a protein-protein interaction (PPI subnetwork and suggested a few urine markers as preferred prognostic markers to monitor the invasion and progression of PCa. Our approach is amenable to discover and prioritize potential markers present in a variety of body fluids for a spectrum of human diseases.

Clinical application and research of tumor markers in colorectal cancer

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Chen Yumei

2005-01-01

Colorectal cancer is one of the most common malignant tumors. There are many tumor markers for detecting colorectal cancer, some of which have been widely used in clinical area. However, still lack an ideal tumor marker of colorectal cancer. In this review, we simply characterized some common tumor markers including carcinoembryonic antigen, CA19-9, CA50, CA242 etc and their dignostic value. And here we discussed some combined detecting procedures which improve diagnostic accuracy of colorectal cancer. In addition, with the development of the biomoleculer technique, some newly discovered tumor markers and genetic marekers have gained great progress in the research of colorectal cancer, and will become a promissing technique in the diagnosis of colorectal cancer. (authors)

Application of tumor markers in the immunodiagnosis of cancer

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Gelder, F.B.; Barr, L.H.; Goldman, L.I.

1983-01-01

Recently, research directed toward the detection of both tumor-specific and tumor-related products has intensified for several reasons. 1. The growing knowledge of tumor metabolism has lead some investigators to hypothesize that most, if not all, malignant tumors produce these substances. 2. The use of multiple tumor markers appears more valuable than application of single markers. 3. The availability of highly sensitive and specific immunological methods provides the tools to measure substances which previously could not be assayed. 4. As additional information evolves, the events associated with malignant transformation and tumor behaviour may become clear. Tumor-related products include immune markers, altered cell surface membranes, as well as fetal and/or ectopic proteins, to name but a few. The synthesis of fetal and/or ectopic proteins occurs in several cancers. These have served as the basis for most immunodiagnostic tests and comprise the major thrust of this review

Physical mapping of a commonly deleted region, the site of a candidate tumor suppressor gene, at 12q22 in human male germ cell tumors

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Murty, V.V.V.S.; Bosl, G.J.; Chaganti, R.S.K. [Memorial Sloan-Kettering Cancer Center, New York, NY (United States)] [and others

1996-08-01

A candidate tumor suppressor gene (TSG) site at 12q22 characterized by a high frequency of loss of heterozygosity (LOH) and a homozygous deletion has previously (LOH) and a homozygous deletion has previously been reported in human male germ cell tumors (GCTs). In a detailed deletion mapping analysis of 67 normal-tumor DNAs utilizing 20 polymorphic markers mapped to 12q22-q24, we identified the limits of the minimal region of deletion at 12q22 between D12S377 (priximal) and D12S296 (distal). We have constructed a YAC contig map of a 3-cM region of this band between the proximal marker D12S101 and the distal marker D12S346, which contained the minimal region of deletion in GCTs. The map is composed of 53 overlapping YACs and 3 cosmids onto which 25 polymorphic and nonpolymorphic sequence-tagged sites (STSs) were placed in a unique order. The size of the minimal region of deletion was approximately 2 Mb from overlapping, nonchimeric YACs that spanned the region. We also developed a radiation hybrid (RH) map of the region between D12S101 and D12S346 containing 17 loci. The consensus order developed by RH mapping is in good agreement with the YAC STS-content map order. The RH map estimated the distance between D12S101 and D12S346 to be 246 cR{sub 8000} and the minimal region of deletion to be 141 cR{sub 8000}. In addition, four genes that were previously mapped to 12q22 have been excluded as candidate genes. The leads gained from the deletion mapping and physical maps should expedite the isolation and characterization of the TSG at 12q22. 35 refs., 4 figs., 2 tabs.

Detection of Secondary Liver Tumors in Patients with Colorectal Carcinoma by Using Tumor Markers

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Holubec jr., L.; Topolčan, O.; Třeška, V.; Holubec sen., L.; Pecen, Ladislav; Pikner, R.; Finek, J.; Visokai, V.; Lipská, L.

2002-01-01

Roč. 17, č. 3 (2002), s. 134-135 ISSN 0886-3849. [International Conference on Human Tumor Markers /19./. 25.08.2002-29.08.2002, Velje] Institutional research plan: AV0Z1030915 Keywords : tumor markers * colorectal CA Subject RIV: BA - General Mathematics

Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells.

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Wang, Denong; Wu, Lisa; Liu, Xiaohe

2017-01-01

We present here an experimental approach for exploring a new class of tumor biomarkers that are overexpressed by circulating tumor cells (CTCs) and are likely targetable in immunotherapy against tumor metastasis. Using carbohydrate microarrays, anti-tumor monoclonal antibodies (mAbs) were scanned against a large panel of carbohydrate antigens to identify potential tumor glycan markers. Subsequently, flow cytometry and fiber-optic array scanning technology (FAST) were applied to determine whether the identified targets are tumor-specific cell-surface markers and are, therefore, likely suitable for targeted immunotherapy. Finally, the tumor glycan-specific antibodies identified were validated using cancer patients' blood samples for their performance in CTC-detection and immunotyping analysis. In this article, identifying breast CTC-specific glycan markers and targeting mAbs serve as examples to illustrate this tumor biomarker discovery strategy.

A system for tumor heterogeneity evaluation and diagnosis based on tumor markers measured routinely in the laboratory.

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Hui, Liu; Rixv, Liu; Xiuying, Zhou

2015-12-01

To develop an efficient and reliable approach to estimate tumor heterogeneity and improve tumor diagnosis using multiple tumor markers measured routinely in the clinical laboratory. A total of 161 patients with different cancers were recruited as the cancer group, and 91 patients with non-oncological conditions were required as the non-oncological disease group. The control group comprised 90 randomly selected healthy subjects. AFP, CEA, CYFRA, CA125, CA153, CA199, CA724, and NSE levels were measured in all these subjects with a chemiluminescent microparticle immunoassay. The tumor marker with the maximum S/CO value (sample test value:cutoff value for discriminating individuals with and without tumors) was considered as a specific tumor marker (STM) for an individual. Tumor heterogeneity index (THI)=N/P (N: number of STMs; P: percentage of individuals with STMs in a certain tumor population) was used to quantify tumor heterogeneity: high THI indicated high tumor heterogeneity. The tumor marker index (TMI), TMI = STM×(number of positive tumor markers+1), was used for diagnosis. The THIs of lung, gastric, and liver cancers were 8.33, 9.63, and 5.2, respectively, while the ROC-areas under the curve for TMI were 0.862, 0.809, and 0.966. In this study, we developed a novel index for tumor heterogeneity based on the expression of various routinely evaluated serum tumor markers. Development of an evaluation system for tumor heterogeneity on the basis of this index could provide an effective diagnostic tool for some cancers. Copyright © 2015 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Prognostic impact of normalization of serum tumor markers following neoadjuvant chemotherapy in patients with borderline resectable pancreatic carcinoma with arterial contact.

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Murakami, Yoshiaki; Uemura, Kenichiro; Sudo, Takeshi; Hashimoto, Yasushi; Kondo, Naru; Nakagawa, Naoya; Okada, Kenjiro; Takahashi, Shinya; Sueda, Taijiro

2017-04-01

The survival benefit of neoadjuvant therapy for patients with borderline resectable pancreatic carcinoma has been reported recently. However, prognostic factors for this strategy have not been clearly elucidated. The aim of this study was to clarify prognostic factors for patients with borderline resectable pancreatic carcinoma who received neoadjuvant chemotherapy. Medical records of 66 patients with pancreatic carcinoma with arterial contact who intended to undergo tumor resection following neoadjuvant chemotherapy were analyzed retrospectively. Prognostic factors were investigated by analyzing the clinicopathological factors with univariate and multivariate survival analyses. Gemcitabine plus S-1 was generally used as neoadjuvant chemotherapy. The objective response rate was 24%, and normalization of serum tumor markers following neoadjuvant chemotherapy was achieved in 29 patients (44%). Of the 66 patients, 60 patients underwent tumor resection and the remaining six patients did not due to distant metastases following neoadjuvant chemotherapy. For all 66 patients, overall 1-, 2-, and 5-year survival rates were 87.8, 54.5, and 20.5%, respectively (median survival time, 27.1 months) and multivariate analysis revealed that normalization of serum tumor markers was found to be an independent prognostic factor of better overall survival (P = 0.023). Moreover, for 60 patients who undergo tumor resection, normalization of serum tumor markers (P = 0.005) was independently associated with better overall survival by multivariate analysis. Patients with pancreatic carcinoma with arterial contact who undergo neoadjuvant chemotherapy and experience normalization of serum tumor markers thereafter may be good candidates for tumor resection.

Evaluation of tumor markers for the differential diagnosis of benign and malignant ascites.

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Liu, Fang; Kong, Xinjuan; Dou, Qian; Ye, Jin; Xu, Dong; Shang, Haitao; Xu, Keshu; Song, Yuhu

2014-01-01

The diagnosis of malignant ascites is a challenging problem in clinical practice, non-invasive techniques should be developed to improve diagnostic accuracy. The diagnostic performances of tumor markers in malignant ascites remained unsettled. Our aim was to evaluate diagnostic performance of tumor markers in differential diagnosis of benign and malignant ascites. A total of 437 patients were enrolled, and the relevant parameters of the patients were analyzed for the differentiation of benign ascites from malignant ascites. At the predetermined cutoff values of tumor makers, tumor markers in ascitic fluid showed better diagnostic performance than those in serum. Combined use of tumor markers and the cytology increased the diagnostic yield of the latter by 37%. In cytologically negative malignant ascites, tumor markers provided assistance in differentiating malignant ascites from benign ascites, and the combination of ascitic tumor markers yielded 86% sensitivity, 97% specificity. Use of a panel of tumor markers exhibited excellent diagnostic performance in diagnosing malignant ascites, which indicated the detection of tumor markers may represent a beneficial adjunct to cytology, thus guiding the selection of patients who might benefit from further invasive procedures.

The presence of tumor associated macrophages in tumor stroma as a prognostic marker for breast cancer patients

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Medrek, Catharina; Pontén, Fredrik; Jirström, Karin; Leandersson, Karin

2012-01-01

Tumor associated macrophages (TAMs) are alternatively activated macrophages that enhance tumor progression by promoting tumor cell invasion, migration and angiogenesis. TAMs have an anti-inflammatory function resembling M2 macrophages. CD163 is regarded as a highly specific monocyte/macrophage marker for M2 macrophages. In this study we evaluated the specificity of using the M2 macrophage marker CD163 as a TAM marker and compared its prognostic value with the more frequently used pan-macrophage marker CD68. We also analyzed the prognostic value of the localization of CD163 + and CD68 + myeloid cells in human breast cancer. The extent of infiltrating CD163 + or CD68 + myeloid cells in tumor nest versus tumor stroma was evaluated by immunohistochemistry in tissue microarrays with tumors from 144 breast cancer cases. Spearman’s Rho and χ 2 tests were used to examine the correlations between CD163 + or CD68 + myeloid cells and clinicopathological parameters. Kaplan Meier analysis and Cox proportional hazards modeling were used to assess the impact of CD163 + and CD68 + myeloid cells in tumor stroma and tumor nest, respectively, on recurrence free survival, breast cancer specific and overall survival. We found that infiltration of CD163 + and CD68 + macrophages into tumor stroma, but not into tumor nest, were of clinical relevance. CD163 + macrophages in tumor stroma positively correlated with higher grade, larger tumor size, Ki67 positivity, estrogen receptor negativity, progesterone receptor negativity, triple-negative/basal-like breast cancer and inversely correlated with luminal A breast cancer. Some CD163 + areas lacked CD68 expression, suggesting that CD163 could be used as a general anti-inflammatory myeloid marker with prognostic impact. CD68 + macrophages in tumor stroma positively correlated to tumor size and inversely correlated to luminal A breast cancer. More importantly, CD68 in tumor stroma was an independent prognostic factor for reduced breast cancer

Correlation of bone scintigraphy findings and tumor markers during follow-up prostate cancer

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Aizawa, Taku

1996-01-01

In the last 9 years, 217 patients with prostate cancer were treated at our department. Of these patients 153 cases treated by estrogen therapy were followed up by bone scintigraphy and tumor marker examinations (prostate specific antigen [PSA], prostate acid phosphatase [PAP], gamma-seminoprotein [γ-SM) . The correlation between changes on bone scintigrams and synchronous changes in tumor markers was evaluated retrospectively. In cases in which bone metastasis was not recognized on bone scintigrams before treatment, changes of tumor markers corresponded with subsequent changes on bone scintigrams in more than 90%. However, in cases with bone metastasis on bone scintigrams before treatment, changes of bone scintigrams and changes of tumor markers corresponded in only 55% of cases. Changes of bone scintigrams do not always correspond with changes of tumor markers. However, by taking into consideration physical examination parameters such as bone pain, in addition to changes of tumor markers, most changes on bone scintigrams can be anticipated. The reasons for lack of correspondence between changes of bone scintigrams and changes of tumor markers may be, changes of tumor markers are more rapid than the changes on bone scintigram, some poorly differentiated cancers do not have increased tumor marker levels and bone scintigrams do not demonstrate soft tissue involvement. In the follow-up of patients with prostate cancer, it is not necessary to perform bone scintigraphy regularly at 3-month intervals. Bone scintigraphy should only be performed when serum levels of tumor markers increase or bone pain appears. (author)

Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

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Vordermark, D.; Brown, J.M.

2003-01-01

Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1α (HIF-1α), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1α responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1α overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a benefit from specific hypoxia

Endogenous markers of tumor hypoxia. Predictors of clinical radiation resistance?

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Vordermark, D. [Dept. of Radiation Oncology, Univ. of Wuerzburg (Germany); Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States); Brown, J.M. [Dept. of Radiation Oncology, Stanford Univ. School of Medicine, Stanford, CA (United States)

2003-12-01

Background: Eppendorf electrode measurements of tumor oxygenation have defined an adverse effect of tumor hypoxia on prognosis after radiotherapy and other treatment modalities, in particular in head and neck and cervix carcinomas as well as soft tissue sarcomas. Recently, the immunohistochemical detection of proteins involved in the ''hypoxic response'' of tumor cells has been discussed as a method to estimate hypoxia in clinical tumor specimens. Material and Methods: This review focuses on clinical and experimental data, regarding prognostic impact and comparability with other methods of hypoxia detection, for three proteins suggested as endogenous markers of tumor hypoxia: hypoxia-inducible factor-1{alpha} (HIF-1{alpha}), carbonic anhydrase 9 (CA 9), and glucose transporter 1 (GLUT1). Results: None of the three potential hypoxia markers is exclusively hypoxia-specific, and in each case protein can be detected under normoxic conditions in vitro. HIF-1{alpha} responds rapidly to hypoxia but also to reoxygenation, making this marker quite unstable in the context of clinical sample collection. The perinecrotic labeling pattern typical of chronic hypoxia and a reasonable agreement with injectable hypoxia markers such as pimonidazole have most consistently been described for CA 9. All three markers showed correlation with Eppendorf electrode measurements of tumor oxygenation in carcinoma of the cervix. In nine of 13 reports, among them all three that refer to curative radiotherapy for head and neck cancer, HIF-1{alpha} overexpression was associated with poor outcome. CA 9 was an adverse prognostic factor in cervix, head and neck and lung cancer, but not in two other head and neck cancer reports. GLUT1 predicted for poor survival in colorectal, cervix and lung cancer. Conclusion: Endogenous markers have the potential to indicate therapeutically relevant levels of hypoxia within tumors. Clinical trials assessing a marker's ability to predict a

Systematic identification and validation of candidate genes for detection of circulating tumor cells in peripheral blood specimens of colorectal cancer patients.

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Findeisen, Peter; Röckel, Matthias; Nees, Matthias; Röder, Christian; Kienle, Peter; Von Knebel Doeberitz, Magnus; Kalthoff, Holger; Neumaier, Michael

2008-11-01

The presence of tumor cells in peripheral blood is being regarded increasingly as a clinically relevant prognostic factor for colorectal cancer patients. Current molecular methods are very sensitive but due to low specificity their diagnostic value is limited. This study was undertaken in order to systematically identify and validate new colorectal cancer (CRC) marker genes for improved detection of minimal residual disease in peripheral blood mononuclear cells of colorectal cancer patients. Marker genes with upregulated gene expression in colorectal cancer tissue and cell lines were identified using microarray experiments and publicly available gene expression data. A systematic iterative approach was used to reduce a set of 346 candidate genes, reportedly associated with CRC to a selection of candidate genes that were then further validated by relative quantitative real-time RT-PCR. Analytical sensitivity of RT-PCR assays was determined by spiking experiments with CRC cells. Diagnostic sensitivity as well as specificity was tested on a control group consisting of 18 CRC patients compared to 12 individuals without malignant disease. From a total of 346-screened genes only serine (or cysteine) proteinase inhibitor, clade B (ovalbumin), member 5 (SERPINB5) showed significantly elevated transcript levels in peripheral venous blood specimens of tumor patients when compared to the nonmalignant control group. These results were confirmed by analysis of an enlarged collective consisting of 63 CRC patients and 36 control individuals without malignant disease. In conclusion SERPINB5 seems to be a promising marker for detection of circulating tumor cells in peripheral blood of colorectal cancer patients.

The correlation between internal and external markers for abdominal tumors: Implications for respiratory gating

International Nuclear Information System (INIS)

Gierga, David P.; Brewer, Johanna; Sharp, Gregory C.; Betke, Margrit; Willett, Christopher G.; Chen, George T.Y.

2005-01-01

Purpose: The correlation of the respiratory motion of external patient markers and abdominal tumors was examined. Data of this type are important for image-guided therapy techniques, such as respiratory gating, that monitor the movement of external fiducials. Methods and Materials: Fluoroscopy sessions for 4 patients with internal, radiopaque tumor fiducial clips were analyzed by computer vision techniques. The motion of the internal clips and the external markers placed on the patient's abdominal skin surface were quantified and correlated. Results: In general, the motion of the tumor and external markers were well correlated. The maximum amount of peak-to-peak craniocaudal tumor motion was 2.5 cm. The ratio of tumor motion to external-marker motion ranged from 0.85 to 7.1. The variation in tumor position for a given external-marker position ranged from 2 to 9 mm. The period of the breathing cycle ranged from 2.7 to 4.5 seconds, and the frequency patterns for both the tumor and the external markers were similar. Conclusions: Although tumor motion generally correlated well with external fiducial marker motion, relatively large underlying tumor motion can occur compared with external-marker motion and variations in the tumor position for a given marker position. Treatment margins should be determined on the basis of a detailed understanding of tumor motion, as opposed to relying only on external-marker information

meta-analysis of Serum Tumor Markers in Lung Cancer

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Xianfeng LU

2010-12-01

Full Text Available Background and objective The detection of serum tumor markers is of great value for early diagnosis of lung cancer. The aim of this study is to summarize the clinic significance characteristics of serum markers contributing to the detection of lung cancer. Methods References about serum markers of lung cancer were estimated using meta-analysis method. 712 references which included more than 20 cases, 20 controls, the serum markers of 52 832 patients with malignancies and 32 037 patients as controls were evaluated. Results Overall the detection of 13 markers play a significant part in lung cancer diagnosis. The sensitivity of CEA, CA125, CYFRA21-1, TPA, SCCAg, DKK1, NSE, ProGRP in the patients’ serum with lung cancer were 47.50%, 50.11%, 57.00%, 50.93%, 49.00%, 69.50%, 39.73%, 51.48% and the specificity were 92.34%, 80.19%, 90.16%, 88.41%, 91.07%, 92.20%, 89.11%, 94.89%. In the combined analysis of tumor markers: the sensitivity, specificity of NSE+ProGRP were 88.90% and 72.82% in diagnosis of small cell lung cancer, respectively. In diagnosis of squamous corcinoma, the sensitivity and specificity of TSGF+SCCAg+CYFRA21-1 were 95.30% and 74.20%. The the sensitivity and specificity of CA153+Ferrtin+CEA were 91.90% and 44.00% in diagnosis of lung cancer. Conclusion Although the assay of tumor markers in serum is useful for diagnosis of early lung cancer, the sensitivity and specificity are low. Combined detection of these tumor markers could increase sensitivity and specificity.

Prognostic impact of cytological fluid tumor markers in non-small cell lung cancer.

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Cho, Arthur; Hur, Jin; Hong, Yoo Jin; Lee, Hye-Jeong; Kim, Young Jin; Hong, Sae Rom; Suh, Young Joo; Im, Dong Jin; Kim, Yun Jung; Lee, Jae Seok; Shim, Hyo Sup; Choi, Byoung Wook

2016-03-01

The serum tumor markers CYFRA 21-1, carcinoembryonic antigen (CEA), and squamous cell carcinoma antigen (SCCA) are useful in diagnosis and prognosis of non-small cell lung cancer (NSCLC). Cytologic tumor markers obtained during needle aspiration biopsies (NAB) of lung lesions are useful for NSCLC diagnosis. This study investigated the incremental prognostic value of cytologic tumor markers compared to serum tumor markers. This prospective study included 253 patients diagnosed with NSCLC by NAB with cytologic tumor marker analysis. Levels of cytologic CYFRA 21-1, CEA, SCCA, and their serum counterparts were followed up for survival analysis. Optimal cutoff values for each tumor marker were obtained for overall survival (OS) and progression-free survival (PFS) analyses. All patients were followed up for a median of 22.8 months. Using cutoff values of 0.44 ng/ml for C-SCCA, 2.0 ng/ml for S-SCCA, and 3.3 ng/ml for S-CYFRA, a multivariate analysis revealed that high S-SCCA (hazard ratio, HR, 1.84) and high C-SCCA (HR, 1.63) were independent predictive factors of OS. The 3-year overall survival rate was 55 vs. 80 % for high and low C-SCCA, respectively. Cytologic tumor marker level detection is easily obtainable and provides prognostic information for NSCLC. Cytologic tumor markers provide comparable prognostic information relative to serum tumor markers, with C-SCCA acting as a strong prognostic factor of overall survival and PFS.

Pimonidazole: a novel hypoxia marker for complementary study of tumor hypoxia and tumor biology

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Varia, Mahesh A.; Kennedy, Andrew S.; Calkins-Adams, Dennise P.; Rinker, Lillian; Novotny, Debra; Fowler, Wesley C.; Raleigh, James A.

1997-01-01

Purpose/Objectives: Tumor hypoxia appears to be associated with treatment resistance and with gene expression that may lead to hypoxia-mediated selection of tumor cells as a source for cell growth and metastases. The objective of this study was to develop complementary techniques of hypoxia detection with molecular markers of cell proliferation and metastases in order to investigate the role of tumor hypoxia in tumor biology. Materials and Methods: Pimonidazole is a 2-nitroimidazole which is reductively-activated and becomes covalently bound to thiol-containing proteins only in hypoxic cells. These adducts can be detected using immunohistochemistry, enzyme linked immunosorbent assay or flow cytometry as a measure of hypoxia in tumors. Quantitative immunohistochemical analysis has been completed for five patients with squamous cell carcinoma of the cervix who were given pimonidazole hydrochloride (0.5 g/m 2 intravenously) followed by cervical biopsies 24 hours later. Informed consent was obtained according to a protocol approved by the Institutional Review Board. A minimum of 3 random biopsies were obtained from the tumors and at least four sections examined from each biopsy site. Formalin fixed, paraffin embedded tissue sections were immunostained for pimonidazole binding using a mouse monoclonal antibody. Commercially available monoclonal antibodies were used to detect cell proliferation markers MIB-1 (Ki-67) and to detect vascular endothelial growth factor (VEGF) in tumor cells in contiguous sections. The extent of immunostaining was expressed as the percent of immunostained to total tumor cells as determined by Chalkley point counting. Results: No clinical toxicities were associated with pimonidazole infusion. Immunostaining with pimonidazole antibody was observed in all patients indicating the presence of tumor hypoxia. Qualitatively there is little or no overlap between the areas of hypoxia and proliferation. Quantitative data tabulated below show the

Feline Coronavirus 3c Protein: A Candidate for a Virulence Marker?

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A. S. Hora

2016-01-01

Full Text Available Feline infectious peritonitis virus (FIPV is highly virulent and responsible for the highly fatal disease feline infectious peritonitis (FIP, whereas feline enteric coronavirus (FECV is widespread among the feline population and typically causes asymptomatic infections. Some candidates for genetic markers capable of differentiating these two pathotypes of a unique virus (feline coronavirus have been proposed by several studies. In the present survey, in order to search for markers that can differentiate FECV and FIPV, several clones of the 3a–c, E, and M genes were sequenced from samples obtained from cats with or without FIP. All genes showed genetic diversity and suggested the presence of FCoV mutant spectrum capable of producing a virulent pathotype in an individual-specific way. In addition, all the feline coronavirus FIPV strains demonstrated a truncated 3c protein, and the 3c gene was the only observed pathotypic marker for FCoVs, showing that 3c gene is a candidate marker for the distinction between the two pathotypes when the mutant spectrum is taken into account.

Prognostic values of tumor endothelial markers in patients with colorectal cancer

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Rmali, KA; Puntis, MCA; Jiang, WG

2005-01-01

AIM: Tumor endothelial markers (TEMs) are a newly discovered family of endothelial markers associated with tumor specific angiogenesis. This study sought to examine the levels of expression (qualitatively and quantitatively) for TEMs in human colon cancer.

Serum tumor markers in pediatric osteosarcoma: a summary review

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Savitskaya Yulia A

2012-03-01

Full Text Available Abstract Osteosarcoma is the most common primary high-grade bone tumor in both adolescents and children. Early tumor detection is key to ensuring effective treatment. Serum marker discovery and validation for pediatric osteosarcoma has accelerated in recent years, coincident with an evolving understanding of molecules and their complex interactions, and the compelling need for improved pediatric osteosarcoma outcome measures in clinical trials. This review gives a short overview of serological markers for pediatric osteosarcoma, and highlights advances in pediatric osteosarcoma-related marker research within the past year. Studies in the past year involving serum markers in patients with pediatric osteosarcoma can be assigned to one of four categories, i.e., new approaches and new markers, exploratory studies in specialized disease subsets, large cross-sectional validation studies, and longitudinal studies, with and without an intervention. Most of the studies have examined the association of a serum marker with some aspect of the natural history of pediatric osteosarcoma. As illustrated by the many studies reviewed, several serum markers are emerging that show a credible association with disease modification. The expanding pool of informative osteosarcoma-related markers is expected to impact development of therapeutics for pediatric osteosarcoma positively and, it is hoped, ultimately clinical care. Combinations of serum markers of natural immunity, thyroid hormone homeostasis, and bone tumorigenesis may be undertaken together in patients with pediatric osteosarcoma. These serum markers in combination may do better. The potential effect of an intrinsic dynamic balance of tumor angiogenesis residing within a single hormone (tri-iodothyronine is an attractive concept for regulation of vascularization in pediatric osteosarcoma.

Tumor microenvironment in head and neck squamous cell carcinomas: predictive value and clinical relevance of hypoxic markers. A review.

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Hoogsteen, Ilse J; Marres, Henri A M; Bussink, Johan; van der Kogel, Albert J; Kaanders, Johannes H A M

2007-06-01

Hypoxia and tumor cell proliferation are important factors determining the treatment response of squamous cell carcinomas of the head and neck. Successful approaches have been developed to counteract these resistance mechanisms although usually at the cost of increased short- and long-term side effects. To provide the best attainable quality of life for individual patients and the head and neck cancer patient population as a whole, it is of increasing importance that tools be developed that allow a better selection of patients for these intensified treatments. A literature review was performed with special focus on the predictive value and clinical relevance of endogenous hypoxia-related markers. New methods for qualitative and quantitative assessment of functional microenvironmental parameters such as hypoxia, proliferation, and vasculature have identified several candidate markers for future use in predictive assays. Hypoxia-related markers include hypoxia inducible factor (HIF)-1alpha, carbonic anhydrase IX, glucose transporters, erythropoietin receptor, osteopontin, and others. Although several of these markers and combinations of markers are associated with treatment outcome, their clinical value as predictive factors remains to be established. A number of markers and marker profiles have emerged that may have potential as a predictive assay. Validation of these candidate assays requires testing in prospective trials comparing standard treatment against experimental treatments targeting the related microregional constituent. (c) 2007 Wiley Periodicals, Inc. Head Neck, 2007.

Additional diagnostic value of tumor markers in cytological fluid for diagnosis of non-small-cell lung cancer

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Hur Jin

2012-09-01

Full Text Available Abstract Background Cytological fluid from a needle aspiration biopsy (NAB is obtained directly from tumor tissue, therefore many biomarker candidates will be present in high concentrations. The aim of this study was to prospectively assess and validate the tumor markers CYFRA 21–1, CEA, and SCC in cytological fluid obtained from NAB samples to determine if they improved the performance of NAB for diagnosing non-small cell lung cancer (NSCLC. Methods A total of 194 patients (M:F = 128:66, mean age 63.7 years with suspected malignant pulmonary lesions were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21–1, CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL in serum and 15.7 ng/mL in cytological fluid for CYFRA 21–1, 5 ng/mL and 0.6 ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC. Results Of 194 patients, 139 patients (71.6% had NSCLC and 55 (28.4% had benign lesions. Sensitivity increased significantly for NAB combined with cytological tumor markers compared with NAB alone (CYFRA 21–1: 95% versus 83.5%, p Conclusion Of the tested tumor markers, cytological fluid measurements of CYFRA 21–1 improved the diagnostic performance of NAB for NSCLC.

Tumor markers kits development for use in radioimmunometric assays

International Nuclear Information System (INIS)

Ahmed, B.

1997-01-01

The immunoassays such as RIA and IRMA are now widely used through the world for the quantitation of a variety of substances in the biological fluid for their high sensibility and specificity which required simple equipments. These techniques are also very used in Algeria for an effective amelioration of public heath The assays kits of RIA/IRMA of thyroid hormones are the most used, followed by peptidic hormones, steroids hormones and IRMA Tumor Markers (T.M) kits. In spite of the important demand, of tumor markers kits for the diagnosis and follow up of cancers their use are always insufficient due to the high cost. The research contract programme proposed by IAEA on the theme 'The Developments of IRMA Tumor Markers Kits' of prostate specific Antigen (PSA) and Tissue Polypeptide Specific Antigen (TPS) will allowed us to produce locally with best quality-price, the main reagents for PSA and TPS IRMA assays kits for diagnosis and follow up the prostate and breast cancers which are very spready in the country. This report include the following points: Generalities on the use of tumor markers in Algeria, programme for the Development of the PSA IRMA assay (schedule of protocols applied for each reagents; annual planning for assessing the programme activities) and conclusion

The accuracy of CT and tumor markers in the detection of a recurrent ovarian carcinoma

International Nuclear Information System (INIS)

Wakabayashi, Yukari; Ishida, Jiro; Kotake, Fumio; Hirose, Masahiro; Kawana, Koji; Abe, Kimihiko; Amino, Saburo; Negishi, Yoshiyuki; Akiya, Kiyoshi

1989-01-01

Twenty-three patients previously diagnosed as having ovarian cancer were examined with both serum tumor markers (CA 125, CA 19-9, TPA, IAP, AFP) and a pelvic CT scan. The tumor markers predict the clinical outcome more accurately than the CT scan. Further, the tumor markers showed a clear correlation with the clinical course. But in one case, however, the tumor markers were seen to reduce below the normal level from chemotherapy, while the CT scan showed a tumor mass. Thus, both, a CT scan and tumor marker assays are felt to be indispensable for detecting the recurrence of an ovarian cancer. (author)

Tumor markers in pancreatic cancer: a European Group on Tumor Markers (EGTM) status report.

LENUS (Irish Health Repository)

Duffy, M J

2012-02-01

Pancreatic ductal adenocarcinoma is one of the most difficult malignancies to diagnose and treat. The aim of this article is to review how tumor markers can aid the diagnosis and management of patients with this malignancy. The most widely used and best validated marker for pancreatic cancer is CA 19-9. Inadequate sensitivity and specificity limit the use of CA 19-9 in the early diagnosis of pancreatic cancer. In non-jaundiced patients, however, CA 19-9 may complement other diagnostic procedures. In patients with resectable pancreatic cancer, presurgical and postresection CA 19-9 levels correlate with overall survival. In advanced disease, elevated pretreatment levels of CA 19-9 are associated with adverse patient outcome and thus may be combined with other factors for risk stratification. Most, but not all, reports indicate that serial levels of CA 19-9 correlate with response to systemic therapy. Use of CA 19-9 kinetics in conjunction with imaging is therefore recommended in monitoring therapy. Although several potential serum and tissue markers for pancreatic cancer are currently undergoing evaluation, none are sufficiently validated for routine clinical use. CA 19-9 thus remains the serum pancreatic cancer marker against which new markers for this malignancy should be judged.

Significance of serum tumor markers monitoring in carcinomas of unknown primary site

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Pejčić Ivica

2010-01-01

Full Text Available Background/Aim. Unknown primary tumors represent a heterogeneous group of malignancies that are indicative of ominous prognosis. Cancer of unknown primary site (CUP is defined as the lack of any detectable primary site after full evaluation, and accounts for approximately 3-5% of all newly diagnosed patients with malignancies. The aim of this report was to present the prognostic and predictive value of 8 serum tumor markers in this group of patients. Methods. The study involved 63 patients. On histological examination, all the patients were presented with metastatic tumors whose primary site (origin could not be detected with noninvasive diagnostic techniques. Following the routine light microscopy, all histological findings were classified into one of the following three groups: plano-cellular carcinoma - 8 patients; adenocarcinoma - 33 patients; unclassifiable (undifferentiated carcinoma - 22 patients. In all the cases we evaluated 8 serum tumor markers: alpha-fetoproteins (AFP, chronic gonadotrophin beta submit, human (beta-HCG, neuron specific enolase (NSE, marker of malignant ovarian tumors (CA 125, prostate-specific antigene (PSA, marker of malignant brest tumor (CA 15-3, marker of malignant pancreas tumor and gastrointestinal tumor (Ca 19-9, carcinoembryonic antigen (CEA at the time of diagnosis. The patients on chemotherapy had the markers determined after the third and sixth chemocycle, i.e. at the time of illness progression observation, if present. The patients responding to chemotherapy with complete response (CR, partial response (PR or stable disease (SD had the markers determined after three-month periods until the time of relapse or progression. Chemotherapy was applied in 32 patients (20 females and 12 males, aged 29-70 years, who met the inclusion criteria. The following chemotherapy regimen was used: doxorubicin 50mg/m2 (day 1, cisplatin 60mg/m2 (day 1, and etoposide 120 mg/m2 (days 1-3. The period between two chemotherapy

SUVmax of 18F-FDG PET/CT correlates to expression of major chemotherapy-related tumor markers and serum tumor markers in gastric adenocarcinoma patients.

Science.gov (United States)

Bai, Lu; Guo, Chi-Hua; Zhao, Yan; Gao, Jun-Gang; Li, Miao; Shen, Cong; Guo, You-Min; Duan, Xiao-Yi

2017-06-01

The expression of P53 was previously found by us significantly correlated with maximal standardized uptake value (SUVmax) in non-small cell lung cancer (NSCLC) patients. Hence, the aim of this study was to clarify the relationship between SUVmax and the status of the chemotherapy-related tumor marker expression or serum tumor markers in gastric adenocarcinoma patients. Sixty-four gastric adenocarcinoma patients who underwent 18F-FDG PET/CT prior to treatment were enrolled in this study. Immunohistochemistry was performed to detect changes of Her-2, P53 and Survivin in lesions, and electrochemiluminescence (ECL) method was used to quantify expression of serum CA72-4, CA19-9 and CEA of these patients. Then, the relationships between these parameters above were assessed by Spearman correlation analysis. Also, receiver-operating characteristic (ROC) curve was performed to determine the best cut-off value of SUVmax for suggesting chemotherapy resistant tumor markers. Besides, we identified a linear correlation to estimate the equations between SUVmax and the serum tumor markers. Our results showed that higher SUVmax was detected in patients with positive expression of Her-2 and P53, compared with negative groups. The Spearman correlation analysis showed that SUVmax was associated with Her-2 or P53 with the moderate relevant Pearson correlation coefficient. ROC curve analysis showed that the sensitivity and specificity of SUVmax for suggesting Her-2 or P53-positive, when the cut-off value of SUVmax was set at 3.25 or 5.45, respectively. Moreover, the relationship between SUVmax and serum tumor markers were analyzed by linear correlation analysis, and serum CA72-4 and CA19-9 could be used as independent parameters to establish an equation for SUVmax by the linear regression models. These results suggested that SUVmax of 18F-FDG PET/CT could be used to predict and evaluate Her-2 or P53 related chemotherapy resistance of gastric adenocarcinoma patients. However, before PET

Limited utility of tissue micro-arrays in detecting intra-tumoral heterogeneity in stem cell characteristics and tumor progression markers in breast cancer.

Science.gov (United States)

Kündig, Pascale; Giesen, Charlotte; Jackson, Hartland; Bodenmiller, Bernd; Papassotirolopus, Bärbel; Freiberger, Sandra Nicole; Aquino, Catharine; Opitz, Lennart; Varga, Zsuzsanna

2018-05-08

Intra-tumoral heterogeneity has been recently addressed in different types of cancer, including breast cancer. A concept describing the origin of intra-tumoral heterogeneity is the cancer stem-cell hypothesis, proposing the existence of cancer stem cells that can self-renew limitlessly and therefore lead to tumor progression. Clonal evolution in accumulated single cell genomic alterations is a further possible explanation in carcinogenesis. In this study, we addressed the question whether intra-tumoral heterogeneity can be reliably detected in tissue-micro-arrays in breast cancer by comparing expression levels of conventional predictive/prognostic tumor markers, tumor progression markers and stem cell markers between central and peripheral tumor areas. We analyzed immunohistochemical expression and/or gene amplification status of conventional prognostic tumor markers (ER, PR, HER2, CK5/6), tumor progression markers (PTEN, PIK3CA, p53, Ki-67) and stem cell markers (mTOR, SOX2, SOX9, SOX10, SLUG, CD44, CD24, TWIST) in 372 tissue-micro-array samples from 72 breast cancer patients. Expression levels were compared between central and peripheral tumor tissue areas and were correlated to histopathological grading. 15 selected cases additionally underwent RNA sequencing for transcriptome analysis. No significant difference in any of the analyzed between central and peripheral tumor areas was seen with any of the analyzed methods/or results that showed difference. Except mTOR, PIK3CA and SOX9 (nuclear) protein expression, all markers correlated significantly (p < 0.05) with histopathological grading both in central and peripheral areas. Our results suggest that intra-tumoral heterogeneity of stem-cell and tumor-progression markers cannot be reliably addressed in tissue-micro-array samples in breast cancer. However, most markers correlated strongly with histopathological grading confirming prognostic information as expression profiles were independent on the site of the

Values of tumor markers (AFP, β-HCG and CEA) and gamma-camera scintigraphy in patients with testicular tumors

International Nuclear Information System (INIS)

Milkov, V.; Sultanov, S.; Tsvetkov, D.

1989-01-01

Complex gamma-camera and radioimmunologic study of the tumor markers AFP, β-HCG and CEA was performed in 7 patients with testicular tumors. In all tested patients gamma-camera scintigraphy of the testes clearly delineated the zone of the pathological process. Gamma-camera examination very well differentiates malignant from nonmalignant processes in the testes. The serum levels of the tumor markers AFP and β-HCG proved elevated in 3 of the tested patients during the preoperative period. The histological types of the tumors in these patients were: teratocarcinoma in one and embryonal carcinoma in the other two. It is believed that investigation of the three tumor markers may gain acceptance as additonal method in the complex diagnosis of these diseases

Clinical significance of determination of 3 tumor markers in bronchoalveolar lavage fluid

International Nuclear Information System (INIS)

Chen Rui; Hu Huacheng; Hu Yunzhu

2003-01-01

Objective: To investigate the value of 3 tumor markers in bronchoalveolar lavage fluid (BALF) for diagnosis and evaluation of disease extent in patients with lung cancer. Methods: The level of CEA, CYFRA21-1 and NSE in BALF was measured in 92 patients with lung cancer and 40 patients with benign lung diseases by using chemoluminescence, RIA and ELISA methods respectively. Results: The level of all 3 tumor markers measured in BALF was much higher in lung cancer group than that in benign lung disease group (P<0.01 or P<0.05), and it was higher in patients with advanced disease (stage III and IV) than that in stage I and II. These tumor markers increased in different degrees among the patients in various pathological classifications. It was also found the level of these tumor markers was higher and more sensitive in BALF than that in serum. Conclusion: The measurement of the tumor markers in BALF has more significant value than the measurement in serum, which contribute to the early diagnosis, pathological classification and prognosis evaluation of lung cancer

Stability of Markers Used for Real-Time Tumor Tracking After Percutaneous Intrapulmonary Placement

International Nuclear Information System (INIS)

Voort van Zyp, Noelle C. van der; Hoogeman, Mischa S.; Water, Steven van de; Levendag, Peter C.; Holt, Bronno van der; Heijmen, Ben J.M.; Nuyttens, Joost J.

2011-01-01

Purpose: To determine the stability of markers used for real-time tumor tracking after percutaneous intrapulmonary placement. Methods and Materials: A total of 42 patients with 44 lesions, 111 markers, and ≥2 repeat computed tomography (CT) scans were studied. The tumor on the repeat CT scans was registered with the tumor on the planning CT scan. Next, the three-dimensional marker coordinates were determined on the planning CT scan and repeat CT scans. Marker stability was analyzed by the displacement of the markers and the displacement of the center of mass (COM) of the marker configurations. In addition, we assessed the reliability of using the intermarker distance as a check for displacements in the COM of the marker configurations. Results: The median marker displacement was 1.3 mm (range, 0.1-53.6). The marker displacement was >5 mm in 12% of the markers and >10 mm in 5% of the markers. The causes of marker displacement >5 mm included marker migration (2 of 13) and target volume changes (5 of 13). Nonsynchronous tumor and marker movement during breathing might have been responsible for the displacements >5 mm in the other 6 of 13 markers. The median displacement in the COM of the marker configurations was 1.0 mm (range, 0.1-23.3). Displacements in the COM of the marker configurations of ≥2.0 mm were detected by changes in the intermarker distance of >1.5 mm in 96% of the treatment fractions. Conclusion: The median marker displacement was small (1.3 mm). Nevertheless, displacements >5 mm occurred in 12% of the markers. Therefore, we recommend the implantation of multiple markers because multiple markers will enable a quick and reliable check of marker displacement by determining the change in the intermarker distance. A displacement in the COM of the marker configuration of ≥2.0 mm was almost always detected (96%) by a change in the distance between the markers of >1.5 mm. This enabled the displaced marker to be disabled, such that tumor localization was

Diagnostic value of multi-tumor markers protein biochip detection for primary pulmonary cancer

International Nuclear Information System (INIS)

Xu Fengpo; Wu Yiwei; Li Qingru; Fa Yihua

2005-01-01

To evaluate the diagnostic value of multi-tumor markers protein biochip detection for primary pulmonary cancer, 12 tumor markers including AFP, CEA, NSE, CA125, CA15-3, CA242, CA19-9, PSA, f-PSA, FER, β-HCG and HGH were measured by the protein biochip in the serum of 45 primary pulmonary cancer patients. Positive rate of tumor markers was FER (42.2%), CEA (35.6%), CA125 (24.4%), CA15-3 (17.8%), CA242 (13.3%), CA19-9 (11.1%), β-HCG(8.9%), HGH(6.7%), NSE(4.4%), AFP (0), f-PSA (0) and PSA (0), respectively. The rate of patients with one abnorma indicator was 57.8% except FER. The positive rate using multi-tumor markers protein biochip detection was significantly higher than that of single tumor marker detective method, and this detection can be used for the diagnosis of patients with primary pulmonary cancer. (authors)

Radioimmunoassay of tumor markers in serum of patients with renal carcinoma

International Nuclear Information System (INIS)

Cordoni-Voutsas, M.; Glaubitt, D.; Wagner, W.; Lichtenberg, T.

1984-01-01

Having noted an increased serum level of TPA and CEA in patients with renal carcinoma the authors extended these studies by using a larger number of tumor markers. In 15 patients (11 men and 4 women after menopause) aged 33 to 74 years who had renal carcinoma, among them 3 with tumor metastases, the serum concentration of TPA, CA 12-5, CEA, AFP, ferritin, prolactin, β-HCG, and β/sub 2/-microglobulin was measured by radioimmunoassay. Monoclonal antibodies were used in the determination of serum CA 12-5 and CEA. In all patients surgical treatment, irradiation, or cytostatic therapy had not been performed. In serum the normal range was exceeded by TPA in 7 patients, CA 12-5 in 3, CEA and AFP in one each, ferritin in 12, prolactin in 2, and β/sub 2/-microglobulin in 10 patients. In one man serum prolactin was reduced. Serum β-HCG was normal in all patients. According to these results serum ferritin, TPA, and β/sub 2/-microglobulin are of great value as tumor markers in patients with renal carcinoma. In several patients the increase of serum β/sub 2/-microglobulin may be ascribed partly to deterioration of renal function. As no consistent patterns of tumor markers in serum were observed it is recommended to determine several tumor markers and not only one of them during the follow-up of patients. Radioimmunoassays for measuring the serum level of tumor markers, especially ferritin, TPA, and β/sub 2/-microglobulin, may considerably assist in the management of patients with renal carcinoma by providing early information about tumor recurrence or metastases

Real-time tumor tracking using implanted positron emission markers: Concept and simulation study

International Nuclear Information System (INIS)

Xu Tong; Wong, Jerry T.; Shikhaliev, Polad M.; Ducote, Justin L.; Al-Ghazi, Muthana S.; Molloi, Sabee

2006-01-01

The delivery accuracy of radiation therapy for pulmonary and abdominal tumors suffers from tumor motion due to respiration. Respiratory gating should be applied to avoid the use of a large target volume margin that results in a substantial dose to the surrounding normal tissue. Precise respiratory gating requires the exact spatial position of the tumor to be determined in real time during treatment. Usually, fiducial markers are implanted inside or next to the tumor to provide both accurate patient setup and real-time tumor tracking. However, current tumor tracking systems require either substantial x-ray exposure to the patient or large fiducial markers that limit the value of their application for pulmonary tumors. We propose a real-time tumor tracking system using implanted positron emission markers (PeTrack). Each marker will be labeled with low activity positron emitting isotopes, such as 124 I, 74 As, or 84 Rb. These isotopes have half-lives comparable to the duration of radiation therapy (from a few days to a few weeks). The size of the proposed PeTrack marker will be 0.5-0.8 mm, which is approximately one-half the size of markers currently employed in other techniques. By detecting annihilation gammas using position-sensitive detectors, multiple positron emission markers can be tracked in real time. A multimarker localization algorithm was developed using an Expectation-Maximization clustering technique. A Monte Carlo simulation model was developed for the PeTrack system. Patient dose, detector sensitivity, and scatter fraction were evaluated. Depending on the isotope, the lifetime dose from a 3.7 MBq PeTrack marker was determined to be 0.7-5.0 Gy at 10 mm from the marker. At the center of the field of view (FOV), the sensitivity of the PeTrack system was 240-320 counts/s per 1 MBq marker activity within a 30 cm thick patient. The sensitivity was reduced by 45% when the marker was near the edge of the FOV. The scatter fraction ranged from 12% ( 124 I, 74 As

Tumor hypoxia at the micro-regional level: clinical relevance and predictive value of exogenous and endogenous hypoxic cell markers

International Nuclear Information System (INIS)

Bussink, Johan; Kaanders, Johannes H.A.M.; Kogel, Albert J. van der

2003-01-01

Background and purpose: Tumor oxygenation is recognized as an important determinant of the outcome of radiotherapy and possibly also of other treatment modalities in a number of tumor types and in particular in squamous cell carcinomas. The hypoxic status of various solid tumors has been related to a poor prognosis due to tumor progression towards a more malignant phenotype, with increased metastatic potential, and an increased resistance to treatment. It has been demonstrated in head and neck cancer that hypoxic radioresistance can be successfully counteracted by hypoxia modifying approaches. The microregional distribution and the level of tumor hypoxia depend on oxygen consumption and temporal and spatial variations in blood supply. It is unclear if severely hypoxic cells can resume clonogenicity when O 2 and nutrients become available again as a result of (treatment related) changes in the tumor microenvironment. Non-terminally differentiated hypoxic cells that are capable of proliferation are important for outcome because of their resistance to radiotherapy and possibly other cytotoxic treatments. Various exogenous and endogenous markers for hypoxia are currently available and can be studied in relation to each other, the tumor architecture and the tumor microenvironment. Use of nitroimidazole markers with immunohistochemical detection allows studying tumor cell hypoxia at the microscopic level. Co-registration with other microenvironmental parameters, such as vascular architecture (vascular density), blood perfusion, tumor cell proliferation and apoptosis, offers the possibility to obtain a comprehensive functional image of tumor patho-physiology and to study the effects of different modalities of cancer treatment. Conclusion: A number of functional microregional parameters have emerged that are good candidates for future use as indicators of tumor aggressiveness and treatment response. The key question is whether these parameters can be used as tools for

Carcinoembryonic antigen (CEA) as tumor marker in lung cancer

DEFF Research Database (Denmark)

Knudsen, Mie Grunnet; Sorensen, J B

2012-01-01

The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic...... significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those...... relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA...

Transferability of microsatellite markers located in candidate genes for wood properties between Eucalyptus species

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Cintia V. Acuña

2014-12-01

Full Text Available Aim of study:  To analyze the feasibility of extrapolating conclusions on wood quality genetic control between different Eucalyptus species, particularly from species with better genomic information, to those less characterized. For this purpose, the first step is to analyze the conservation and cross-transferability of microsatellites markers (SSRs located in candidate genes.Area of study: Eucalyptus species implanted in Argentina coming from different Australian origins.Materials and methods: Twelve validated and polymorphic SSRs in candidate genes (SSR-CGs for wood quality in E. globulus were selected for cross species amplification in six species: E. grandis, E. saligna, E. dunnii, E. viminalis, E. camaldulensis and E. tereticornis.Main results: High cross-species transferability (92% to 100% was found for the 12 polymorphic SSRs detected in E. globulus. These markers revealed allelic diversity in nine important candidate genes: cinnamoyl CoA reductase (CCR, cellulose synthase 3 (CesA3, the transcription factor LIM1, homocysteine S-methyltransferase (HMT, shikimate kinase (SK, xyloglucan endotransglycosylase 2 (XTH2, glutathione S-transferase (GST, glutamate decarboxylase (GAD and peroxidase (PER.Research highlights: The markers described are potentially suitable for comparative QTL mapping, molecular marker assisted breeding (MAB and for population genetic studies across different species within the subgenus Symphyomyrtus.Keywords: validation; cross-transferability; SSR; functional markers; eucalypts; Symphyomyrtus.

Tumor markers in finding recurrent disease in colorectal cancer: a diagnostic review

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Anneke Muller Kobold

2013-02-01

Full Text Available Aim: In the search for evidence-based follow-up of patients after resection for colorectal cancer, numerous tumor markers have been proposed. This review has evaluated these markers and comments on the diagnostic accuracy in finding recurrent disease in relation to Carcino-Embryonic Antigen (CEA. Methods: A comprehensive literature review (1985-2010 was performed by two independent reviewers. Sensitivity and specificity of markers mentioned in the articles were checked by recalculation. A validated quality score system was used to estimate study quality. Results: Seventeen studies focusing on eight different markers were included. Three markers were shown to have comparable or better accuracy than CEA: TPA, CA 242 and CA 72-4 in at least one study. These three markers, from four independent studies, showed a tumor marker sensitivity of > 60% in combination with an outperformance of CEA in follow-up. These results were not confirmed by six other studies investigating the same markers. Conclusion: This review revealed three tumor markers other than CEA that have been shown to adequately indicate recurrences in colorectal cancer. However, comparability of studies was difficult. Therefore a prospective study of these markers seems necessary to investigate their real value, and to overcome design and inclusion biases.

Serum tumor markers in chronic kidney disease: as clinical tool in diagnosis, treatment and prognosis of cancers.

Science.gov (United States)

Amiri, Fateme Shamekhi

2016-01-01

Cancer is singled out as the biggest cause of death in the world, predicted to reach 13.1 million cancer-related deaths by the year 2030. Although there are no specific tumor markers used in cancer screening, some markers can be used to assist in making a diagnosis and determining a prognosis. They can be used to follow in cases where the diagnosis is cancer through monitoring of the disease recurrence and/or evaluating the response to therapy. These markers are not specific as the number increases in multiple cases of cancer. Some markers are positive in a single type of cancer; others are detectable in more than one type. An ideal tumor marker should be highly sensitive, specific, and reliable with high prognostic value. Other characteristics of an ideal tumor marker are organ specificity and correlation of it with tumor stages. However, none of the tumor markers reported to date has all these characteristics. Influence of different stages of chronic kidney function on serum tumor markers is variable. Furthermore, hemodialysis, peritoneal dialysis, and kidney transplantation affect on tumor markers differently. Sometimes, no study has been found in the literature review. Combined serum tumor markers may also be valuable. This literature review points the role of serum tumor markers in screening, diagnosis, and follow-up of cancer patients in chronic kidney disease patients and renal allograft recipients. In addition, impact of chronic kidney disease and kidney transplantation on different serum tumor markers is briefly explored.

Carcinoembryonic antigen (CEA) as tumor marker in lung cancer.

Science.gov (United States)

Grunnet, M; Sorensen, J B

2012-05-01

The use of CEA as a prognostic and predictive marker in patients with lung cancer is widely debated. The aim of this review was to evaluate the results from studies made on this subject. Using the search words "CEA", "tumor markers in lung cancer", "prognostic significance", "diagnostic significance" and "predictive significance", a search was carried out on PubMed. Exclusion criteria was articles never published in English, articles before 1981 and articles evaluating tumor markers in lung cancer not involving CEA. Initially 217 articles were found, and 34 were left after selecting those relevant for the present study. Four of these included both Non-Small Cell Lung Cancer (NSCLC) and Small Cell Lung Cancer (SCLC) patients, and 31 dealt solely with NSCLC patients. Regarding SCLC no studies showed that serum level of CEA was a prognostic marker for overall survival (OS). The use of CEA serum level as a prognostic marker in NSCLC was investigated in 23 studies and the use of CEA plasma level in two. In 18 (17 serum, 1 plasma) of these studies CEA was found to be a useful prognostic marker for either OS, recurrence after surgery or/and progression free survival (PFS) in NSCLC patients. Interestingly, an overweight of low stage (stage I-II) disease and adenocarcinoma (AC) patients were observed in this group. The remaining 7 studies (6 serum, 1 plasma) contained an overweight of patients with squamous carcinoma (SQ). One study found evidence for that a tumor marker index (TMI), based on preoperative CEA and CYFRA21-1 serum levels, is useful as a prognostic marker for OS in NSCLC. Six studies evaluated the use of CEA as a predictive marker for risk of recurrence and risk of death in NSCLC patients. Four of these studies found, that CEA was useful as a predictive marker for risk of recurrence and risk of death measured over time. No studies found CEA levels useful as a diagnostic marker for lung cancer. With regard to NSCLC the level of CEA measured in tumor tissue in

Marker-based quantification of interfractional tumor position variation and the use of markers for setup verification in radiation therapy for esophageal cancer

NARCIS (Netherlands)

Jin, Peng; van der Horst, Astrid; de Jong, Rianne; van Hooft, Jeanin E.; Kamphuis, Martijn; van Wieringen, Niek; Machiels, Melanie; Bel, Arjan; Hulshof, Maarten C. C. M.; Alderliesten, Tanja

2015-01-01

The aim of this study was to quantify interfractional esophageal tumor position variation using markers and investigate the use of markers for setup verification. Sixty-five markers placed in the tumor volumes of 24 esophageal cancer patients were identified in computed tomography (CT) and follow-up

Lung tumor tracking during stereotactic radiotherapy treatment with the CyberKnife: Marker placement and early results

International Nuclear Information System (INIS)

Nuyttens, J.J.; Prevost, J.B.; Praag, J.; Hoogeman, M.; Levendag, P.C.; Klaveren, R.J. van; Pattynama, P.M.T.

2006-01-01

Lung tumor tracking during stereotactic radiotherapy with the CyberKnife requires the insertion of markers in or close to the tumor. To reduce the risk of pneumothorax, three methods of marker placement were used: 1) intravascular coil placement, 2) percutaneous intrathoracal, and 3) percutaneous extrathoracal placement. We investigated the toxicity of marker placement and the tumor response of the lung tumor tracking treatment. Markers were placed in 20 patients with 22 tumors: 13 patients received a curative treatment, seven a palliative. The median Charlson Comorbidity Score was 4 (range: 1-8). Platinum fiducials and intravascular embolisation coils were used as markers. In total, 78 markers were placed: 34 intrathoracal, 23 intravascular and 21 extrathoracal. The PTV equaled the GTV + 5 mm. A median dose of 45 Gy (range: 30-60 Gy, in 3 fractions) was prescribed to the 70-85% isodose. The response was evaluated with a CTscan performed 6-8 weeks after the last treatment and routinely thereafter. The median follow-up was 4 months (range: 2-11). No severe toxicity due to the marker placement was seen. Pneumothorax was not seen. The local control was 100%. Four tumors in four patients showed a complete response, 15 tumors in 14 patients a partial response, and three tumors in two patients with metastatic disease had stable disease. No severe toxicity of marker placement was seen due to the appropriate choice of one of the three methods. CyberKnife tumor tracking with markers is feasible and resulted in excellent tumor response. Longer follow-up is needed to validate the local control

Clinical Evaluation and Cost-Effectiveness Analysis of Serum Tumor Markers in Lung Cancer

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Rong Wang

2013-01-01

Full Text Available The detection of serum tumor markers is valuable for the early diagnosis of lung cancer. Tumor markers are frequently used for the management of cancer patients. However, single markers are less efficient but marker combinations increase the cost, which is troublesome for clinics. To find an optimal serum marker combination panel that benefits the patients and the medical management system as well, four routine lung cancer serum markers (SCCA, NSE, CEA, and CYFRA21-1 were evaluated individually and in combination. Meanwhile, the costs and effects of these markers in clinical practice in China were assessed by cost-effectiveness analysis. As expected, combinations of these tumor markers improved their sensitivity for lung cancer and different combination panels had their own usefulness. NSE + CEA + CYFRA21-1 was the optimal combination panel with highest Youden’s index (0.64, higher sensitivity (75.76%, and specificity (88.57%, which can aid the clinical diagnosis of lung cancer. Nevertheless, the most cost-effective combination was SCCA + CEA, which can be used to screen the high-risk group.

Clinical values of detection of multiple tumor markers in pleural fluid for diagnosis malignancy

International Nuclear Information System (INIS)

Xiao Chuangqing; Jiang Li; Zhou Guanghua; He Yunnan

2005-01-01

Objective: To improve the diagnostic accuracy for the differentiation of malignant from tuberculous pleural effusion with determination of multiple tumor markers in pleural fluid. Methods: With a multiple tumor markers combined protein chip diagnostic system, contents of twelve common tumor markers were detected in the chest fluid from 60 patients with malignant pleural effusion and 30 patients with tuberculous pleural effusion. Results: For pulmonary carcinoma related pleural effusion, the contents of four common tumor markers (CEA, NSE, SF, CA125) in chest fluid were significantly higher those in tuberculous related chest fluid. The diagnostic positive rate of combined test of these four marker for malignancy could be as high as 96.7%. Conclusion: Combined determination of chest fluid CEA, NSE, SF, CA125 contents was very sensitive and accurate for differentiation of malignant from tuberculous pleural effusion. (authors)

Age-stratified analysis of tumor markers and tumor characteristics in adolescents and young women with mature cystic teratoma

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Huseyin Yesilyurt

2018-06-01

Full Text Available Background: Serum tumor markers are widely used for the preoperative evaluation of an adnexal mass. Elevations of cancer antigen (CA 125 and CA 19-9 have been reported in patients with mature cystic teratoma (MCT. The aim of the study is to investigate the relation of serum tumor markers with tumor characteristics in young women with MCT. Methods: We conducted a retrospective review of 157 patients under the age of 35 who underwent laparoscopic surgery for ovarian MCT. Patients were divided into two age groups: Group I (n = 80: adolescents/young adults (aged 13–25 years and Group II (n = 77: women aged 26–35 years. Data were analyzed for serum tumor markers, tumor size, and bilaterality. Results: The rates of elevated CA 125 and CA 19-9 were 10.7% and 31.5%, respectively, for Group I, and 13.9% and 26.5%, respectively, for Group II. The bilaterality rate was higher in Group II compared to Group I (19.5% vs. 8.8%, respectively, p = 0.04. Serum CA 125 and CA 19-9 elevations were not related to tumor size in Group I. In Group II, elevated levels of CA 125 were also unrelated to tumor size. However, significant elevation in CA 19-9 levels was observed when tumor size was larger than 4 cm in this age group (p = 0.004. Elevated CA 125 and CA 19-9 levels were not significantly associated with the presence of bilateral MCT in either group. Conclusion: The results of our study indicate that elevations of CA 19-9 are associated with larger tumor size in women aged 26–35 years, but not in adolescents/young adults. However, elevated serum CA 125 levels are not related to tumor size in either age group. Keywords: Adolescents, Mature cystic teratoma, Tumor marker, Tumor size, Young women

The Combination of the Tumor Markers Suggests the Histological Diagnosis of Lung Cancer

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Linjie Liu

2017-01-01

Full Text Available Tumor markers are beneficial for the diagnosis and therapy monitoring of lung cancer. However, the value of tumor markers in lung cancer histological diagnosis is unknown. In this study, we analyzed the serum levels of six tumor markers (CEA, CYFRA21-1, SCC, NSE, ProGRP, and CA125 in 2097 suspected patients with lung cancer and determined whether the combination of the tumor markers was useful for histological diagnosis of lung cancer. We found that CYFRA21-1 was the most sensitive marker in NSCLC. ProGRP showed a better clinical performance than that of NSE in discriminating between SCLC and NSCLC. The serum level of CYFRA21-1 or SCC was significantly higher in squamous carcinoma (p<0.05, and the levels of ProGRP and NSE were significantly higher in SCLC (p<0.05. According to the criteria established, SCLC and NSCLC were discriminated with sensitivity of 87.12 and 62.63% and specificity of 64.61 and 99.5%, respectively. The sensitivity and specificity in the differentiation of adenocarcinoma and squamous carcinoma were 68.1 and 81.63% and 70.73 and 65.93%, with NPV of 46.03 and 68.97% and PPV of 85.82 and 79.47%, respectively. Our results suggested the combination of six tumor markers could discriminate the histological types of lung cancer.

Inflammatory markers in blood and serum tumor markers predict survival in patients with epithelial appendiceal neoplasms undergoing surgical cytoreduction and intraperitoneal chemotherapy.

Science.gov (United States)

Chua, Terence C; Chong, Chanel H; Liauw, Winston; Zhao, Jing; Morris, David L

2012-08-01

The study examines the role inflammatory and tumor markers as biomarkers to preoperatively predict outcome in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy. Associations between baseline variables, tumor markers [CEA (carcinoembyronic antigen], CA125, CA199), inflammatory markers including neutrophils-lymphocyte ratio (NLR), platelet-lymphocyte ratio (PLR), and C-reactive protein (CRP) with progression-free survival (PFS) and overall survival (OS) were examined in patients undergoing surgical cytoreduction and intraperitoneal chemotherapy for epithelial appendiceal neoplasm. A total of 174 patients with epithelial appendiceal neoplasm (low-grade pseudomyxoma, n = 117; appendiceal cancer, n = 57) underwent cytoreduction. On univariate analysis, all 3 inflammatory and tumor markers predicted for both PFS and OS, respectively; NLR ≤ 2.6 (P = 0.01, P = 0.002), PLR ≤ 166 (P = 0.006, P = 0.016), CRP ≤ 12.5 (P = 0.001, P = 0.008), CEA (P 37 (P = 0.003), and a CRP > 12.5 (P = 0.013). A higher peritoneal cancer index (PCI > 24) was associated with elevation in CEA > 12, CA125 > 39, CA199 > 37, PLR > 166 and CRP > 12. The tumor histologic subtype was associated with CA 199 levels. The results from this investigation suggest that preoperative inflammatory markers in blood and serologic tumor markers may predict outcomes and are associated with tumor biology in patients with epithelial appendiceal neoplasm undergoing cytoreduction and intraperitoneal chemotherapy treatment.

Changes in Values of Tumor Markers with Pregnant Women in their IInd Trimester

Czech Academy of Sciences Publication Activity Database

Topolčan, O.; Holubec jr., L.; Pecen, Ladislav; Pikner, R.; Svobodová, S.

2002-01-01

Roč. 17, č. 3 (2002), s. 121-123 ISSN 0886-3849. [International Conference on Human Tumor Markers /19./. 25.08.2002-29.08.2002, Velje] Institutional research plan: AV0Z1030915 Keywords : tumor markers * pregrancy Subject RIV: BA - General Mathematics

Neuropathological biomarker candidates in brain tumors: key issues for translational efficiency.

Science.gov (United States)

Hainfellner, J A; Heinzl, H

2010-01-01

Brain tumors comprise a large spectrum of rare malignancies in children and adults that are often associated with severe neurological symptoms and fatal outcome. Neuropathological tumor typing provides both prognostic and predictive tissue information which is the basis for optimal postoperative patient management and therapy. Molecular biomarkers may extend and refine prognostic and predictive information in a brain tumor case, providing more individualized and optimized treatment options. In the recent past a few neuropathological brain tumor biomarkers have translated smoothly into clinical use whereas many candidates show protracted translation. We investigated the causes of protracted translation of candidate brain tumor biomarkers. Considering the research environment from personal, social and systemic perspectives we identified eight determinants of translational success: methodology, funding, statistics, organization, phases of research, cooperation, self-reflection, and scientific progeny. Smoothly translating biomarkers are associated with low degrees of translational complexity whereas biomarkers with protracted translation are associated with high degrees. Key issues for translational efficiency of neuropathological brain tumor biomarker research seem to be related to (i) the strict orientation to the mission of medical research, that is the improval of medical practice as primordial purpose of research, (ii) definition of research priorities according to clinical needs, and (iii) absorption of translational complexities by means of operatively beneficial standards. To this end, concrete actions should comprise adequate scientific education of young investigators, and shaping of integrative diagnostics and therapy research both on the local level and the level of influential international brain tumor research platforms.

Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

Energy Technology Data Exchange (ETDEWEB)

Ohta, Kengo, E-mail: yesterday.is.yesterday@gmail.com; Shimohira, Masashi, E-mail: mshimohira@gmail.com [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan); Sasaki, Shigeru, E-mail: ssasaki916@yahoo.co.jp; Iwata, Hiromitsu, E-mail: h-iwa-ncu@nifty.com; Nishikawa, Hiroko, E-mail: piroko1018@gmail.com; Ogino, Hiroyuki, E-mail: oginogio@gmail.com; Hara, Masaki, E-mail: mhara@med.nagoya-cu.ac.jp [Nagoya City West Medical Center, Department of Radiation Oncology, Nagoya Proton Therapy Center (Japan); Hashizume, Takuya, E-mail: tky300@gmail.com; Shibamoto, Yuta, E-mail: yshiba@med.nagoya-cu.ac.jp [Nagoya City University Graduate School of Medical Sciences, Department of Radiology (Japan)

2015-10-15

PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors.

Transarterial Fiducial Marker Placement for Image-guided Proton Therapy for Malignant Liver Tumors

International Nuclear Information System (INIS)

Ohta, Kengo; Shimohira, Masashi; Sasaki, Shigeru; Iwata, Hiromitsu; Nishikawa, Hiroko; Ogino, Hiroyuki; Hara, Masaki; Hashizume, Takuya; Shibamoto, Yuta

2015-01-01

PurposeThe aim of this study is to analyze the technical and clinical success rates and safety of transarterial fiducial marker placement for image-guided proton therapy for malignant liver tumors.Methods and MaterialsFifty-five patients underwent this procedure as an interventional treatment. Five patients had 2 tumors, and 4 tumors required 2 markers each, so the total number of procedures was 64. The 60 tumors consisted of 46 hepatocellular carcinomas and 14 liver metastases. Five-mm-long straight microcoils of 0.018 inches in diameter were used as fiducial markers and placed in appropriate positions for each tumor. We assessed the technical and clinical success rates of transarterial fiducial marker placement, as well as the complications associated with it. Technical success was defined as the successful delivery and placement of the fiducial coil, and clinical success was defined as the completion of proton therapy.ResultsAll 64 fiducial coils were successfully installed, so the technical success rate was 100 % (64/64). Fifty-four patients underwent proton therapy without coil migration. In one patient, proton therapy was not performed because of obstructive jaundice due to bile duct invasion by hepatocellular carcinoma. Thus, the clinical success rate was 98 % (54/55). Slight bleeding was observed in one case, but it was stopped immediately and then observed. None of the patients developed hepatic infarctions due to fiducial marker migration.ConclusionTransarterial fiducial marker placement appears to be a useful and safe procedure for proton therapy for malignant liver tumors

Biochemical Markers for Osteoarthritis: Is There any Promising Candidate?

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Elif Aydın

2016-04-01

Full Text Available Osteoarthritis (OA is the most common degenerative joint disease. OA affects millions of individuals each year and becoming the most important cause of pain in geriatric population. Progressive destruction of articular cartilage is one of the prominent features of the disease. The diagnosis of OA is generally based on clinical and radiographical findings, which are insufficient to determine early-stage OA and predict disease course. There is a need for biomarkers that help clinicians early diagnose, assess disease activity, predict prognosis and monitor response to therapy. There are a growing number of publications regarding candidate markers in this field. The aim of this paper was to review recent studies on biochemical markers that reflect cartilage, synovial and bone turnover and their clinical use in patients with OA.

Design of tumor biomarker-monitoring trials: a proposal by the European Group on Tumor Markers

NARCIS (Netherlands)

Sölétormos, György; Duffy, Michael J.; Hayes, Daniel F.; Sturgeon, Catharine M.; Barak, Vivian; Bossuyt, Patrick M.; Diamandis, Eleftherios P.; Gion, Massimo; Hyltoft-Petersen, Per; Lamerz, Rolf M.; Nielsen, Dorte L.; Sibley, Paul; Tholander, Bengt; Tuxen, Malgorzata K.; Bonfrer, Johannes M. G.

2013-01-01

A major application of tumor biomarkers is in serial monitoring of cancer patients, but there are no published guidelines on how to evaluate biomarkers for this purpose. The European Group on Tumor Markers has convened a multidisciplinary panel of scientists to develop guidance on the design of such

Additional diagnostic value of tumor markers in cytological fluid for diagnosis of non-small-cell lung cancer

International Nuclear Information System (INIS)

Hur, Jin; Chung, Kyung Young; Lee, Hye Sun; Choi, Byoung Wook; Lee, Hye-Jeong; Nam, Ji Eun; Kim, Young Jin; Hong, Yoo Jin; Kim, Hee Yeong; Kim, Se Kyu; Chang, Joon; Kim, Joo-Hang

2012-01-01

Cytological fluid from a needle aspiration biopsy (NAB) is obtained directly from tumor tissue, therefore many biomarker candidates will be present in high concentrations. The aim of this study was to prospectively assess and validate the tumor markers CYFRA 21–1, CEA, and SCC in cytological fluid obtained from NAB samples to determine if they improved the performance of NAB for diagnosing non-small cell lung cancer (NSCLC). A total of 194 patients (M:F = 128:66, mean age 63.7 years) with suspected malignant pulmonary lesions were prospectively enrolled and underwent percutaneous NAB. Levels of CYFRA 21–1, CEA, and SCC were measured by immunoassay in serum and cytological fluid obtained during aspiration biopsy. Cut-off values to determined malignancy were 3.3 ng/mL in serum and 15.7 ng/mL in cytological fluid for CYFRA 21–1, 5 ng/mL and 0.6 ng/mL for CEA, and 2 ng/mL and 0.86 ng/mL for SCC. Of 194 patients, 139 patients (71.6%) had NSCLC and 55 (28.4%) had benign lesions. Sensitivity increased significantly for NAB combined with cytological tumor markers compared with NAB alone (CYFRA 21–1: 95% versus 83.5%, p < 0.001, CEA: 92.1% versus 83.5%, p = 0.002, SCC: 91.4% versus 83.5%, p = 0.003). Accuracy improved significantly for NAB combined with cytological CYFRA 21–1 compared with NAB alone (95.9% versus 88.1%, p < 0.001). The area under curve (AUC) of NAB with cytological CYFRA 21–1 was significantly larger than for NAB alone (0.966 versus 0.917, p = 0.009). Of the tested tumor markers, cytological fluid measurements of CYFRA 21–1 improved the diagnostic performance of NAB for NSCLC

In vitro and in vivo applications of tumor markers

International Nuclear Information System (INIS)

Chatal, J.F.; Ricolleau, G.; Fumoleau, P.; Vuillez, J.P.H.; Chetanneau, A.; Peltier, P.; Lacroix, H.

1988-01-01

In vitro and in vivo applications of tumor markers are reviewed. Concerning in vitro applications, the following topics are developed: ideal marker criterion; present availability of markers; immunoassay methodology; clinical applications; future prospects (oncogenes). In vivo applications deal with immunoscintigraphy a new imaging technique, different from conventional morphological methods, based on specific recognition of antigenic target and involving many immunologic, hemodynamic and methodologic parameters. These various parameters are presented and clinical applications and future prospects of immunoscintigraphy are evaluated [fr

Gold markers for tumor localization and target volume delineation in radiotherapy for rectal cancer

International Nuclear Information System (INIS)

Vorwerk, Hilke; Christiansen, Hans; Hess, Clemens Friedrich; Hermann, Robert Michael; Liersch, Thorsten; Ghadimi, Michael; Rothe, Hilka

2009-01-01

In locally advanced rectal cancer, neoadjuvant radiochemotherapy is indicated. To improve target volume definition for radiotherapy planning, the potential of implanted gold markers in the tumor region was evaluated. In nine consecutive patients, two to three gold markers were implanted in the tumor region during rigid rectoscopy. Computed tomography scans were performed during treatment planning. All electronic portal imaging devices (EPIDs) recorded during treatment series were analyzed. All patients underwent complete tumor resection with meticulous histopathologic examination. The gold markers could easily be implanted into the mesorectal tissue at the caudal tumor border without any complications. They were helpful in identifying the inferior border of the planning target volume in order to spare normal tissue (in particular anal structures). No significant shift of the markers was found during the course of therapy. Marker matching of the EPIDs did not improve patient positioning in comparison to bone structure matching. The former position of at least one marker could be identified in all patients during histopathologic examination. The use of gold marker enables a more precise definition of the target volume for radiotherapy in patients with rectal cancer. This could eventually allow a better protection of anal structures of patients with a tumor localization = 5 cm cranial of the anal sphincter. The implantation of the gold markers improved communication between the surgeon, the radiooncologist and the pathologist resulting in intensified exchange of relevant informations. (orig.)

Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

Science.gov (United States)

2017-08-01

AWARD NUMBER: W81XWH-15-1-0243 TITLE: Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution PRINCIPAL...SUBTITLE 5a. CONTRACT NUMBER Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution 5b. GRANT NUMBER 5c. PROGRAM...derive a prognostic classifier. 15. SUBJECT TERMS NSCLC; tumor evolution ; whole exome sequencing 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF

Combining PET/CT with serum tumor markers to improve the evaluation of histological type of suspicious lung cancers.

Science.gov (United States)

Jiang, Rifeng; Dong, Ximin; Zhu, Wenzhen; Duan, Qing; Xue, Yunjing; Shen, Yanxia; Zhang, Guopeng

2017-01-01

Histological type is important for determining the management of patients with suspicious lung cancers. In this study, PET/CT combined with serum tumor markers were used to evaluate the histological type of lung lesions. Patients with suspicious lung cancers underwent 18F-FDG PET/CT and serum tumor markers detection. SUVmax of the tumor and serum levels of tumor markers were acquired. Differences in SUVmax and serum levels of tumor markers among different histological types of lung cancers and between EGFR mutation statues of adenocarcinoma were compared. The diagnostic efficiencies of SUVmax alone, each serum tumor marker alone, combined tumor markers and the combination of both methods were further assessed and compared. SCC had the highest level of SUVmax, followed by SCLC and adenocarcinoma, and benign lesions had a lowest level. CYFRA21-1 and SCC-Ag were significantly higher in SCC, NSE was significantly higher in SCLC (Ptumor marker or SUVmax alone. When combined, the AUC, sensitivity and specificity increased significantly (Ptumor markers (P>0.05 for all). SUVmax and serum tumor markers show values in evaluating the histological types of suspicious lung cancers. When properly combined, the diagnostic efficiency can increase significantly.

Molecular analysis of childhood primitive neuroectodermal tumors defines markers associated with poor outcome

DEFF Research Database (Denmark)

Scheurlen, W G; Schwabe, G C; Joos, S

1998-01-01

PURPOSE: The diagnostic and prognostic significance of well-defined molecular markers was investigated in childhood primitive neuroectodermal tumors (PNET). MATERIALS AND METHODS: Using microsatellite analysis, Southern blot analysis, and fluorescence in situ hybridization (FISH), 30 primary tumors......: In our study, amplification of c-myc was a poor-prognosis marker in PNET. LOH of chromosome 17p was associated with metastatic disease. Molecular analysis of primary tumors using these markers may be useful for stratification of children with PNET in future prospective studies. The other aberrations...... investigated were not of significant prognostic value, but may provide an entry point for future large-scale molecular studies....

Diagnostic value of multiple tumor markers for patients with esophageal carcinoma.

Science.gov (United States)

Zhang, Jun; Zhu, Zhenli; Liu, Yan; Jin, Xueyuan; Xu, Zhiwei; Yu, Qiuyan; Li, Ke

2015-01-01

Various studies assessing the diagnostic value of serum tumor markers in patients with esophageal cancer remain controversial. This study aims to comprehensively and quantitatively summarize the potential diagnostic value of 5 serum tumour markers in esophageal cancer. We systematically searched PubMed, Embase, Chinese National Knowledge Infrastructure (CNKI) and Chinese Biomedical Database (CBM), through February 28, 2013, without language restriction. Studies were assessed for quality using QUADAS (quality assessment of studies of diagnostic accuracy). The positive likelihood ratio (PLR) and negative likelihood ratio (NLR) were pooled separately and compared with overall accuracy measures using diagnostic odds ratios (DORs) and symmetric summary receiver operating characteristic (SROC) curves. Of 4391 studies initially identified, 44 eligible studies including five tumor markers met the inclusion criteria for the meta-analysis, while meta-analysis could not be conducted for 12 other tumor markers. Approximately 79.55% (35/44) of the included studies were of relatively high quality (QUADAS score≥7). The summary estimates of the positive likelihood ratio (PLR), negative likelihood ratio (NLR) and diagnostic odds ratio (DOR) for diagnosing EC were as follows: CEA, 5.94/0.76/9.26; Cyfra21-1, 12.110.59/22.27; p53 antibody, 6.71/0.75/9.60; SCC-Ag, 7.66/0.68/12.41; and VEGF-C, 0.74/0.37/8.12. The estimated summary receiver operating characteristic curves showed that the performance of all five tumor markers was reasonable. The current evidence suggests that CEA, Cyfra21-1, p53, SCC-Ag and VEGF-C have a potential diagnostic value for esophageal carcinoma.

Clinical performance of LOCI™-based tumor marker assays for tumor markers CA 15-3, CA 125, CEA, CA 19-9 and AFP in gynecological cancers.

Science.gov (United States)

Dolscheid-Pommerich, Ramona C; Keyver-Paik, Mignon; Hecking, Thomas; Kuhn, Walther; Hartmann, Gunther; Stoffel-Wagner, Birgit; Holdenrieder, Stefan

2017-10-01

Evidence is sparse regarding the clinical performance of luminescent oxygen channeling immunoassays-based tumor marker assays in gynecological cancer. Analyzing serum samples of 336 patients with Dimension™Vista1500, we investigated the diagnostic power of carbohydrate antigen 15-3, carbohydrate antigen 125, carcinoembryonic antigen, carbohydrate antigen 19-9, and alpha-fetoprotein in patients suffering from different types of gynecological cancer and precancerous gynecological diseases and compared findings to appropriate control groups. The cohort comprised 177 female patients with gynecological cancers (73 breast, 22 cervical, 16 endometrial, 17 vulva, and 49 ovarian cancers), 26 patients with precancerous gynecological diseases (11 vulva, 4 cervical, and 10 breast), 109 patients with benign gynecological diseases, and 24 healthy controls. Discriminative power was assessed by areas under the curve in receiver operating characteristic curves, and sensitivities were determined at a fixed specificity of 95%. Levels of biomarkers in healthy controls were in the expected ranges and a discriminative power between gynecological cancers and healthy controls was observed for several tumor markers. Established tumor type-associated markers were elevated in specific gynecological cancers and benign controls as well as within precancerous gynecological diseases and healthy control group. In ovarian cancer, carbohydrate antigen 125 and carbohydrate antigen 15-3 were significantly elevated compared to the respective benign diseases. Carbohydrate antigen 125 was the most conclusive marker (area under the curve = 0.86% and 77.6% sensitivity at 95% specificity). In breast cancer, carcinoembryonic antigen and carbohydrate antigen 15-3 were significantly higher than in the respective benign diseases. Carcinoembryonic antigen achieved the most conclusive area under the curve (0.65) with 31.5% sensitivity at 95% specificity. None of the investigated markers was found to be of

FOXP3 Transcription Factor: A Candidate Marker for Susceptibility and Prognosis in Triple Negative Breast Cancer

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Leandra Fiori Lopes

2014-01-01

Full Text Available Triple negative breast cancer (TNBC is a relevant subgroup of neoplasia which presents negative phenotype of estrogen and progesterone receptors and has no overexpression of the human epidermal growth factor 2 (HER2. FOXP3 (forkhead transcription factor 3 is a marker of regulatory T cells (Tregs, whose expression may be increased in tumor cells. This study aimed to investigate a polymorphism (rs3761548 and the protein expression of FOXP3 for a possible involvement in TNBC susceptibility and prognosis. Genetic polymorphism was evaluated in 50 patients and in 115 controls by allele-specific PCR (polymerase chain reaction. Protein expression was evaluated in 38 patients by immunohistochemistry. It was observed a positive association for homozygous AA (OR = 3.78; 95% CI = 1.02–14.06 in relation to TNBC susceptibility. Most of the patients (83% showed a strong staining for FOXP3 protein in the tumor cells. In relation to FOXP3-positive infiltrate, 47% and 58% of patients had a moderate or intense intratumoral and peritumoral mononuclear infiltrate cells, respectively. Tumor size was positively correlated to intratumoral FOXP3-positive infiltrate (P=0.026. In conclusion, since FOXP3 was positively associated with TNBC susceptibility and prognosis, it seems to be a promising candidate for further investigation in larger TNBC samples.

INHIBIN AS A MARKER FOR GRANULOSA-CELL TUMOR

NARCIS (Netherlands)

LAPPOHN, RE; BURGER, HG; BOUMA, J; BANGAH, M; KRANS, M

1992-01-01

In order to determine whether serum-immunoreactive inhibin could constitute a biochemical marker for the presence and progression of ovarian granulosa cell tumors and their metastases, we measured immunoreactive inhibin concentrations in series of serum samples obtained from 8 patients with

Use of Tumor Markers in Gastrointestinal Cancers: Surgeon Perceptions and Cost-Benefit Trade-Off Analysis.

Science.gov (United States)

Acharya, Amish; Markar, Sheraz R; Matar, Michael; Ni, Melody; Hanna, George B

2017-05-01

Gastrointestinal cancers constitute the third most common cancers worldwide. Tumor markers have long since been used in the postoperative surveillance of these malignancies; however, the true value in clinical practice remains undetermined. This study aimed to evaluate the clinical utility of three tumor markers in colorectal and esophagogastric cancer. A systematic review of the literature was undertaken to elicit the sensitivity, specificity, statistical heterogeneity and ability to predict recurrence and metastases for carcinoembryonic antigen (CEA), cancer antigen (CA) 19-9 and CA125. European surgeons were surveyed to assess their current practice and the characteristics of tumor markers they most valued. Data from the included studies and survey were combined in a cost-benefit trade-off analysis to assess which tumor markers are of most use in clinical practice. Diagnostic sensitivity and specificity were ranked the most desirable characteristics of a tumor marker by those surveyed. Overall, 156 studies were included to inform the cost-benefit trade-off. The cost-benefit trade-off showed that CEA outperformed both CA19-9 and CA125, with lower financial cost and a higher sensitivity, and diagnostic accuracy for metastases at presentation (area under the curve [AUC] 0.70 vs. 0.61 vs. 0.46), as well as similar diagnostic accuracy for recurrence (AUC 0.46 vs. 0.48). Cost-benefit trade-off analysis identified CEA to be the best performing tumor marker. Further studies should seek to evaluate new tumor markers, with investigation tailored to factors that meet the requirements of practicing clinicians.

Translating epithelial mesenchymal transition markers into the clinic: Novel insights from proteomics

Directory of Open Access Journals (Sweden)

Vergara Daniele

2016-03-01

Full Text Available The growing understanding of the molecular mechanisms underlying epithelial-to-mesenchymal transition (EMT may represent a potential source of clinical markers. Despite EMT drivers have not yet emerged as candidate markers in the clinical setting, their association with established clinical markers may improve their specificity and sensitivity. Mass spectrometry-based platforms allow analyzing multiple samples for the expression of EMT candidate markers, and may help to diagnose diseases or monitor treatment efficiently. This review highlights proteomic approaches applied to elucidate the differences between epithelial and mesenchymal tumors and describes how these can be used for target discovery and validation.

Criteria for the Selection of Reference Groups in the Statistical Evaluation of Tumor Markers

Czech Academy of Sciences Publication Activity Database

Holubec jr., L.; Topolčan, O.; Pikner, R.; Pecen, Ladislav; Holubec sen., L.

2002-01-01

Roč. 22, 1B (2002), s. 531 ISSN 0250-7005. [International Hamburg Symposium on Tumor Markers /11./. 27.01.2002-29.01.2002, Hamburg] Institutional research plan: AV0Z1030915 Keywords : reference groups * tumor markers Subject RIV: BA - General Mathematics

[Utility of Multiple Increased Lung Cancer Tumor Markers in Treatment of Patients with Advanced Lung Adenocarcinoma].

Science.gov (United States)

Peng, Yan; Wang, Yan; Hao, Xuezhi; Li, Junling; Liu, Yutao; Wang, Hongyu

2017-10-20

Among frequently-used tumor markers in lung cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 125 (CA125), cytokeratin 19 (CYFRA21-1) and squamous carcinoma antigen (SCC), neuron specific enolase (NSE) and pro-gastrin-releasing peptide (ProGRP) are respectively expressed highly in lung adenocarcinoma, lung squamous carcinoma and small cell lung cancer. By comparing patients with multiple increased tumor markers (group A) and patients with increase of CEA and/or CA125 (group B), this study aims to investigate the utility of multiple increased tumor markers in therapeutic evaluation and prediction of disease relapsing in patients with advanced lung adenocarcinoma. Patients with stage IV lung adenocarcinoma who receiving the first line chemotherapy in Cancer Hospital, Chinese Academy of Medical Sciences were enrolled and retrospectively analyzed. Clinical characteristic, serum tumor markers before chemotherapy, efficacy evaluation, progression-free survival (PFS) were analyzed. Except CEA and CA125, the highest ratio of increased tumor markersin group A was CYFRA21-1 (93%), then was NSE (36%), SCC (13%) and ProGRP (12%). Patients with multiple increased tumor markers tend to have more distant metastasis (Ptumor markers have high risk of relapse, and maintenance therapy can reduce relapse risk.

Investigating the KLF4 Gene Expression as a New Molecular Marker in Breast Tumors

Directory of Open Access Journals (Sweden)

MA Hosseinpour Feizi

2013-12-01

Results: The results showed that: 1 KLF4 is over expressed in Breast tumors rather than adjacent normal tissues. 2 KLF4 is an oncogene in breast tumors (at least in IDC type. 3 The KLF4 expression levels are related significantly with nature of malignant breast tumors. Conclusion: Findings do not confirm KLF4 as a diagnostic marker in classification and identification of tumoral tissues from non-tumoral ones in breast, but we can use this marker to identify at least 50% of invasive Ductal Carcinoma in breast and utilize it as a potential predictive factor to demonstrate severity degree in various tumors.

Splenomegaly and tumor marker response following selective internal radiation therapy for non-resectable liver metastases from neuroendocrine tumor

International Nuclear Information System (INIS)

Shehata, M.; Yan, K.; Itoh, Seiji; King, J.; Glenn, D.; Quinn, R.; Morris, D.L.

2009-01-01

The aim of this study was to investigate changes in spleen size, the level of chromogranin A as a tumor marker, and the relationship between these two parameters before and 3 months after selective internal radiation therapy (SIRT) for non-resectable liver metastases from neuroendocrine tumor (NET). Our first serious adverse event with this relatively new treatment is also discussed. A retrospective review of a prospective database identified patients with non-resectable liver metastases from NET who underwent SIRT between 2003 and 2007. Patients who underwent CT scans before and 3 months after treatment were included. The patients were divided into two groups: those with and without a 20% or more increase in splenic volume on the CT scans. The percentages of patients showing a tumor marker response in the two groups were then compared. Fourteen patients were included in the present analysis. A tumor marker response was seen in 6 of 7 patients (85.7%) who showed an increase in splenic volume of >20%, and in 3 of 7 patients (42.9%) without an increase in splenic volume (p=0.266). There was one death as a result of oesophageal variceal bleeding due to portal hypertension at 9 months after treatment. Splenic enlargement after SIRT may be associated with tumor marker response, although this could not be confirmed statistically in this study due to the small number of patients. Long-term splenomegaly and portal hypertension may be important complications of SIRT. This issue needs to be investigated further using a larger number of patients and longer follow-up. (author)

Histopathologic Consideration of Fiducial Gold Markers Inserted for Real-Time Tumor-Tracking Radiotherapy Against Lung Cancer

International Nuclear Information System (INIS)

Imura, Mikado; Yamazaki, Koichi; Kubota, Kanako C.; Itoh, Tomoo; Onimaru, Rikiya; Cho, Yasushi; Hida, Yasuhiro; Kaga, Kichizo; Onodera, Yuya; Ogura, Shigeaki; Dosaka-Akita, Hirotoshi; Shirato, Hiroki; Nishimura, Masaharu

2008-01-01

Purpose: Internal fiducial gold markers, safely inserted with bronchoscopy, have been used in real-time tumor-tracking radiotherapy for lung cancer. We investigated the histopathologic findings at several points after the insertion of the gold markers. Methods and Materials: Sixteen gold markers were inserted for preoperative marking in 7 patients who subsequently underwent partial resection of tumors by video-assisted thoracoscopic surgery within 7 days. Results: Fibrotic changes and hyperplasia of type 2 pneumocytes around the markers were seen 5 or 7 days after insertion, and fibrin exudation without fibrosis was detected 1 or 2 days after insertion. Conclusions: Because fibroblastic changes start approximately 5 days after gold marker insertion, real-time tumor-tracking radiotherapy should be started >5 days after gold marker insertion

Low accuracy of tumor markers for diagnosing pancreatic neuroendocrine tumors in multiple endocrine neoplasia type 1 patients

NARCIS (Netherlands)

de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

2013-01-01

Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

Low Accuracy of Tumor Markers for Diagnosing Pancreatic Neuroendocrine Tumors in Multiple Endocrine Neoplasia Type 1 Patients

NARCIS (Netherlands)

de Laat, Joanne M.; Pieterman, Carolina R. C.; Weijmans, Maaike; Hermus, Ad R.; Dekkers, Olaf M.; de Herder, Wouter W.; van der Horst-Schrivers, Anouk N. A.; Drent, Madeleine L.; Bisschop, Peter H.; Havekes, Bas; Vriens, Menno R.; Valk, Gerlof D.

2013-01-01

Context: The assessment of tumor markers for diagnosing pancreatic neuroendocrine tumors (pNET) in multiple endocrine neoplasia type 1 (MEN1) patients is advised in the current guidelines but has never been validated for this purpose. Objective: The objective of the study was to assess the

Utility of CEA and CA 19-9 tumor markers in diagnosis and prognostic assessment of mucinous epithelial cancers of the appendix.

Science.gov (United States)

Carmignani, C Pablo; Hampton, Regina; Sugarbaker, Christina E; Chang, David; Sugarbaker, Paul H

2004-09-15

Tumor markers are a clinical tool frequently used in oncology in association with other clinical and radiologic information. For gastrointestinal cancer, carcinoembryonic antigen (CEA) and carbohydrate antigen 19-9 (CA 19-9) tumor markers have found selected clinical application. The use of these tumor markers in mucinous epithelial tumors of the appendix has not been previously determined. In patients with peritoneal dissemination of a mucinous epithelial malignancy of the appendix, tumor markers CEA and CA 19-9 were prospectively recorded preoperatively within 1 week prior to definitive treatment. Also, if the appendiceal tumor recurred, the tumor marker was determined. The accuracy of these two tumor markers in the management of this disease was determined for these two specific clinical situations. CEA was elevated in 56% of 532 patients and CA 19-9 was elevated in 67.1% of these patients. Although the absolute level of tumor marker did not correlate with prognosis, a normal value indicated an improved survival. CEA was elevated in 35.2% of 110 patients determined to have recurrent disease; CA 19-9 was elevated in 62.9% and at least one of the tumor markers was elevated in 68.2% of patients. An elevated CEA tumor marker at the time of recurrence indicated a reduced prognosis. Both CEA and CA 19-9 tumor markers were elevated in a majority of these patients and should be a valuable diagnostic tool previously underutilized in this group of patients. These tumor markers were also of benefit in the assessment of prognosis in that a normal level indicated an improved prognosis. At the time of a reoperative procedure, CEA and CA 19-9 tumor markers gave information regarding the progression of disease. These tumor markers have practical value in the management of epithelial appendiceal malignancy with peritoneal dissemination. Copyright 2004 Wiley-Liss, Inc.

Diagnostic and prognostic yield of tumor markers in cancer of unknown primary site

International Nuclear Information System (INIS)

Pervez, T.; Ibraheim, M.I.

2006-01-01

A case of metastatic carcinoma of unknown primary is reported that had widely disseminated disease from the very outset. Every effort was made to find out the primary by integrating all results and specially tumor markers. It was assumed that lung was the most possible site for primary. Tumor markers did not show their diagnostic value even in combined panel, they only showed their prognostic value. (author)

Immunoperoxidase staining and radioimmunobinding of human tumor markers separated by direct tissue agarose isoelectric focusing

International Nuclear Information System (INIS)

Saravis, C.A.; Cunningham, C.G.; Marasco, P.V.; Cook, R.B.; Zamcheck, N.; FMC Corp., Rockland, ME

1980-01-01

The new technique of agarose isoelectric focusing is used to identify, quantitate, and characterize specific tumor markers. After fixation of the isoelectric focusing patterns these are reacted with specific anti-tumor marker antisera, then with second antibody either peroxidase conjugated or radiolabellad (radioiodine). (RB) [de

Validation of candidate gene markers for marker-assisted selection of potato cultivars with improved tuber quality.

Science.gov (United States)

Li, Li; Tacke, Eckhard; Hofferbert, Hans-Reinhardt; Lübeck, Jens; Strahwald, Josef; Draffehn, Astrid M; Walkemeier, Birgit; Gebhardt, Christiane

2013-04-01

Tuber yield, starch content, starch yield and chip color are complex traits that are important for industrial uses and food processing of potato. Chip color depends on the quantity of reducing sugars glucose and fructose in the tubers, which are generated by starch degradation. Reducing sugars accumulate when tubers are stored at low temperatures. Early and efficient selection of cultivars with superior yield, starch yield and chip color is hampered by the fact that reliable phenotypic selection requires multiple year and location trials. Application of DNA-based markers early in the breeding cycle, which are diagnostic for superior alleles of genes that control natural variation of tuber quality, will reduce the number of clones to be evaluated in field trials. Association mapping using genes functional in carbohydrate metabolism as markers has discovered alleles of invertases and starch phosphorylases that are associated with tuber quality traits. Here, we report on new DNA variants at loci encoding ADP-glucose pyrophosphorylase and the invertase Pain-1, which are associated with positive or negative effect with chip color, tuber starch content and starch yield. Marker-assisted selection (MAS) and marker validation were performed in tetraploid breeding populations, using various combinations of 11 allele-specific markers associated with tuber quality traits. To facilitate MAS, user-friendly PCR assays were developed for specific candidate gene alleles. In a multi-parental population of advanced breeding clones, genotypes were selected for having different combinations of five positive and the corresponding negative marker alleles. Genotypes combining five positive marker alleles performed on average better than genotypes with four negative alleles and one positive allele. When tested individually, seven of eight markers showed an effect on at least one quality trait. The direction of effect was as expected. Combinations of two to three marker alleles were

[Markers of angiogenesis in tumor growth].

Science.gov (United States)

Nefedova, N A; Kharlova, O A; Danilova, N V; Malkov, P G; Gaifullin, N M

2016-01-01

Angiogenesis is a process of new blood vessels formation. The role of angiogenesis in growth, invasion and metastasis of malignant tumours is nowdays universally recognized. Though, investigation of mechanisms of blood vessels formation and elaboration methods for assessment of tumour angiogenesis are still up-dated. Another important concern are different aspects of usage of immunohistochemical markers of blood vessels endothelium (CD31 and CD34) for assessment of tumour aggressiveness and prognosis. The problems of malignant lymphangiogenesis are also up-to-date. The focus is on methods of immunohistochemical visualization of forming lymphatic vessels, role of podoplanin, the most reliable marker of lymphatic vessels, in their identification, and formulization of the main criteria for lymphangiogenesis estimation, its correlation with metastatic activity and prognostic potential. Studying of angiogenesis and lymph angiogenesis in malignant tumors is important and challenging direction for researching tumour progression and invention of antiangiogenic therapy.

Linkage study of nonsyndromic cleft lip with or without cleft palate using candidate genes and mapped polymorphic markers

Energy Technology Data Exchange (ETDEWEB)

Stein, J.D.; Nelson, L.D.; Conner, B.J. [Univ. of Texas, Houston (United States)] [and others

1994-09-01

Nonsyndromic cleft lip with or without cleft palate (CL(P)) involves fusion or growth failure of facial primordia during development. Complex segregation analysis of clefting populations suggest that an autosomal dominant gene may play a role in this common craniofacial disorder. We have ascertained 16 multigenerational families with CL(P) and tested linkage to 29 candidate genes and 139 mapped short tandem repeat markers. The candidate genes were selected based on their expression in craniofacial development or were identified through murine models. These include: TGF{alpha}, TGF{beta}1, TGF{beta}2, TGF{beta}3, EGF, EGFR, GRAS, cMyc, FGFR, Jun, JunB, PDFG{alpha}, PDGF{beta}, IGF2R, GCR Hox7, Hox8, Hox2B, twirler, 5 collagen and 3 extracellular matrix genes. Linkage was tested assuming an autosomal dominant model with sex-specific decreased penetrance. Linkage to all of the candidate loci was excluded in 11 families. RARA was tested and was not informative. However, haplotype analysis of markers flanking RARA on 17q allowed exclusion of this candidate locus. We have previously excluded linkage to 61 STR markers in 11 families. Seventy-eight mapped short tandem repeat markers have recently been tested in 16 families and 30 have been excluded. The remaining are being analyzed and an exclusion map is being developed based on the entire study results.

Effect of surgical resection combined with transcatheter arterial chemoembolization on postoperative serum tumor marker levels and stem cell characteristics during tumor recurrence

Directory of Open Access Journals (Sweden)

Sen Yang

2017-05-01

Full Text Available Objective: To study the effect of surgical resection combined with transcatheter arterial chemoembolization (TACE on postoperative serum tumor marker levels and stem cell characteristics during tumor recurrence. Methods: A total of 98 patients with liver cancer who received radical resection in our hospital between May 2013 and July 2015 were reviewed and divided into TACE group and control group according to whether they received TACE within two months after surgical resection. Serum levels of tumor markers were detected 4 weeks after operation; the tumor recurrence was followed up within 3 years after operation, and the expression of stem cell marker molecules and cell proliferation molecules in recurrent lesions were detected. Results: 4 weeks after radical hepatectomy, serum AFP, AFP-L3, GP73 and GPC3 levels in TACE group were significantly lower than those in control group; Nanog, CD133, EpCAM, PICK1, CyclinD1, C-myc and Survivin expression in surgically removed lesions of TACE group were not different from those of control group while Nanog, CD133, EpCAM, PICK1, CyclinD1, C-myc and Survivin expression in recurrent lesions were significantly lower than those of control group. Conclusion: Surgical resection combined with TACE can more effectively remove liver cancer lesions, reduce the tumor marker levels and inhibit the tumor stem cell characteristics and cell proliferation activity in recurrent lesions.

CA19-9: A promising tumor marker for pancreatic carcinoma

International Nuclear Information System (INIS)

Sakahara, H.; Endo, K.; Nakajima, K.; Hidaka, A.; Nakashima, T.; Ohta, H.; Torizuka, K.; Naito, A.; Suzuki, T.

1984-01-01

In order to evaluate CA19-9 as a tumor marker for pancreatic carcinoma (PC), serum levels of CA19-9 were compared with those of CEA and elastase-1 in 56 patients, consisted of 43 cases with histologically proven adenocarcinomas and 13 cases with chronic pancreatitis. Serum levels were determined by using RIA kit obtained from CIS, France (CA19-9 and CEA) and Abbot (elastase-1). CA19-9 gave the highest accuracy among tumor markers the authors have studied and serum levels were markedly elevated over 100U/ml in 30 (70%) cases with PC, whereas none in chronic pancreatitis. CA19-9 values were closely related to the tumor size and the presence or absence of metastsis on CT findings. Small tumors of less than 3cm in diameter, although the site of tumor was limited to the head of the pancreas, showed positive results in 2 out of 5 cases. Furthermore, CA19-9 was at a level of less than 22U/ml in 98 normal controls and was found to be elevated in only 4 (3%) out of 124 patients with benign diseases, including liver diseases, gastric ulcer, cholelithiasis, and so on. These results indicate that CA19-9 is much better in diagnosis and management of PC than is CEA

Tumor markers in finding recurrent disease iin colorectal cancer: a diagnostic review

DEFF Research Database (Denmark)

Verberne, Charlotte; de Jong, W.H.; Grossmann, Irene

2013-01-01

Aim: In the search for evidence-based follow-up of patients after resection for colorectal cancer, numerous tumor markers have been proposed. This review has evaluated these markers and comments on the diagnostic accuracy in finding recurrent disease in relation to Carcino-Embryonic Antigen (CEA...

TIMP-1 as a tumor marker in breast cancer - an update

DEFF Research Database (Denmark)

Würtz, Sidse Ørnbjerg; Rasmussen, Anne-Sofie Schrohl; Mouridsen, Henning

2008-01-01

. This review gives an update on the ongoing investigation of the potential role of TIMP-1 as a tumor marker in breast cancer. Furthermore, we link the clinical findings with studies of the molecular actions of the TIMP-1 protein, raising hypotheses that may explain why TIMP-1 could play an important role...... opportunities emerge in the future this need will continue to grow. Thus, the search for molecular markers of prognosis and prediction is ongoing. Tissue Inhibitor of Metalloproteinases-1 (TIMP-1) has been suggested as a marker of both prognosis and response to treatment. Several studies have demonstrated...... the association between TIMP-1 and prognosis in breast cancer and new studies within this area have focused on the possibility of using blood samples or paraffin embedded tissue instead of tumor tissue extracts for measurements of TIMP-1. Interestingly, recent studies have investigated the association between...

Frequent loss of heterozygosity and altered expression of the candidate tumor suppressor gene 'FAT' in human astrocytic tumors

International Nuclear Information System (INIS)

Chosdol, Kunzang; Misra, Anjan; Puri, Sachin; Srivastava, Tapasya; Chattopadhyay, Parthaprasad; Sarkar, Chitra; Mahapatra, Ashok K; Sinha, Subrata

2009-01-01

We had earlier used the comparison of RAPD (Random Amplification of Polymorphic DNA) DNA fingerprinting profiles of tumor and corresponding normal DNA to identify genetic alterations in primary human glial tumors. This has the advantage that DNA fingerprinting identifies the genetic alterations in a manner not biased for locus. In this study we used RAPD-PCR to identify novel genomic alterations in the astrocytic tumors of WHO grade II (Low Grade Diffuse Astrocytoma) and WHO Grade IV (Glioblastoma Multiforme). Loss of heterozygosity (LOH) of the altered region was studied by microsatellite and Single Nucleotide Polymorphism (SNP) markers. Expression study of the gene identified at the altered locus was done by semi-quantitative reverse-transcriptase-PCR (RT-PCR). Bands consistently altered in the RAPD profile of tumor DNA in a significant proportion of tumors were identified. One such 500 bp band, that was absent in the RAPD profile of 33% (4/12) of the grade II astrocytic tumors, was selected for further study. Its sequence corresponded with a region of FAT, a putative tumor suppressor gene initially identified in Drosophila. Fifty percent of a set of 40 tumors, both grade II and IV, were shown to have Loss of Heterozygosity (LOH) at this locus by microsatellite (intragenic) and by SNP markers. Semi-quantitative RT-PCR showed low FAT mRNA levels in a major subset of tumors. These results point to a role of the FAT in astrocytic tumorigenesis and demonstrate the use of RAPD analysis in identifying specific alterations in astrocytic tumors

Value of 18F-FDG PET/CT Combined With Tumor Markers in the Evaluation of Ascites.

Science.gov (United States)

Han, Na; Sun, Xun; Qin, Chunxia; Hassan Bakari, Khamis; Wu, Zhijian; Zhang, Yongxue; Lan, Xiaoli

2018-05-01

The purpose of this study is to investigate the value of 18 F-FDG PET/CT combined with assessment of tumor markers in serum or ascites for the diagnosing and determining the prognosis of benign and malignant ascites. Patients with ascites of unknown cause who underwent evaluation with FDG PET/CT were included in this retrospective study. The maximum standardized uptake value (SUV max ) and levels of the tumor markers carbohydrate antigen-125 (CA-125) and carcinoembryonic antigen (CEA) in serum and ascites were recorded. The diagnostic values of FDG PET/CT, CEA and CA-125 levels in serum or ascites, and the combination of imaging plus tumor marker assessment were evaluated. Factors that were predictive of survival were also analyzed. A total of 177 patients were included. Malignant ascites was eventually diagnosed in 104 patients, and benign ascites was diagnosed in the remaining 73 patients. With the use of FDG PET/CT, 44 patients (42.3%) were found to have primary tumors. The sensitivity, specificity, and accuracy of FDG PET/CT were 92.3%, 83.6%, and 88.7%, respectively. CA-125 levels in serum and ascites showed much better sensitivity than did CEA levels, but they showed significantly lower specificity. If the combination of tumor markers and FDG PET/CT was analyzed, the sensitivity, specificity, and accuracy of tumor markers in serum were 96.6%, 78.1%, and 88.7%, and those of tumor markers in ascites were 97.7%, 80.0%, and 90.4%, respectively. Sex may be an important factor affecting survival time (hazard ratio, 0.471; p = 0.004), but age, CEA level, and FDG PET/CT findings could not predict survival. FDG PET/CT combined with assessment of tumor markers, especially CEA, increased the efficacy of diagnosis of ascites of unknown causes. Male sex conferred a poorer prognosis, whereas age, CEA level, and FDG uptake had no predictive significance in patients with malignant ascites.

A minimally invasive multiple marker approach allows highly efficient detection of meningioma tumors

Directory of Open Access Journals (Sweden)

Meese Eckart

2006-12-01

Full Text Available Abstract Background The development of effective frameworks that permit an accurate diagnosis of tumors, especially in their early stages, remains a grand challenge in the field of bioinformatics. Our approach uses statistical learning techniques applied to multiple antigen tumor antigen markers utilizing the immune system as a very sensitive marker of molecular pathological processes. For validation purposes we choose the intracranial meningioma tumors as model system since they occur very frequently, are mostly benign, and are genetically stable. Results A total of 183 blood samples from 93 meningioma patients (WHO stages I-III and 90 healthy controls were screened for seroreactivity with a set of 57 meningioma-associated antigens. We tested several established statistical learning methods on the resulting reactivity patterns using 10-fold cross validation. The best performance was achieved by Naïve Bayes Classifiers. With this classification method, our framework, called Minimally Invasive Multiple Marker (MIMM approach, yielded a specificity of 96.2%, a sensitivity of 84.5%, and an accuracy of 90.3%, the respective area under the ROC curve was 0.957. Detailed analysis revealed that prediction performs particularly well on low-grade (WHO I tumors, consistent with our goal of early stage tumor detection. For these tumors the best classification result with a specificity of 97.5%, a sensitivity of 91.3%, an accuracy of 95.6%, and an area under the ROC curve of 0.971 was achieved using a set of 12 antigen markers only. This antigen set was detected by a subset selection method based on Mutual Information. Remarkably, our study proves that the inclusion of non-specific antigens, detected not only in tumor but also in normal sera, increases the performance significantly, since non-specific antigens contribute additional diagnostic information. Conclusion Our approach offers the possibility to screen members of risk groups as a matter of routine

Serum level of tumor marker CA-125 in ovarian pathology

International Nuclear Information System (INIS)

Bagni, B.; Feggi, L.M.; Prandini, N.; Pasini, S.; Mollica, G.

1987-01-01

The tumor marker CA-125 is an embrional glycoprotein detectable in tissues derived from celomatic epitelium. Serum Ca-125 was determined by RIA in 66 patients with various ovarian pathologies (16 malignant at stage III-IV and 50 benign). Six patients with ovarian carcinoma were monitored during the first week after surgery and chemiotherapy for a total of 150 days of treatment. It has been observed that CA-125 serum level is consistently above the normal range (>35 U/ml) in all malignant diseases. In benign pathology, levels above the normal were found to be represented almost exclusively by ovarian endometriosis. Furthermore, the results demonstrate that chemiotherapy alone is capable of lowering CA-125 serum levels. This tumor marker may be of great advantage in diagnosis and follow-up of ovarian malignancy

GeMprospector--online design of cross-species genetic marker candidates in legumes and grasses.

Science.gov (United States)

Fredslund, Jakob; Madsen, Lene H; Hougaard, Birgit K; Sandal, Niels; Stougaard, Jens; Bertioli, David; Schauser, Leif

2006-07-01

The web program GeMprospector (URL: http://cgi-www.daimi.au.dk/cgi-chili/GeMprospector/main) allows users to automatically design large sets of cross-species genetic marker candidates targeting either legumes or grasses. The user uploads a collection of ESTs from one or more legume or grass species, and they are compared with a database of clusters of homologous EST and genomic sequences from other legumes or grasses, respectively. Multiple sequence alignments between submitted ESTs and their homologues in the appropriate database form the basis of automated PCR primer design in conserved exons such that each primer set amplifies an intron. The only user input is a collection of ESTs, not necessarily from more than one species, and GeMprospector can boost the potential of such an EST collection by combining it with a large database to produce cross-species genetic marker candidates for legumes or grasses.

Gene expression markers in circulating tumor cells may predict bone metastasis and response to hormonal treatment in breast cancer.

Science.gov (United States)

Wang, Haiying; Molina, Julian; Jiang, John; Ferber, Matthew; Pruthi, Sandhya; Jatkoe, Timothy; Derecho, Carlo; Rajpurohit, Yashoda; Zheng, Jian; Wang, Yixin

2013-11-01

Circulating tumor cells (CTCs) have recently attracted attention due to their potential as prognostic and predictive markers for the clinical management of metastatic breast cancer patients. The isolation of CTCs from patients may enable the molecular characterization of these cells, which may help establish a minimally invasive assay for the prediction of metastasis and further optimization of treatment. Molecular markers of proven clinical value may therefore be useful in predicting disease aggressiveness and response to treatment. In our earlier study, we identified a gene signature in breast cancer that appears to be significantly associated with bone metastasis. Among the genes that constitute this signature, trefoil factor 1 (TFF1) was identified as the most differentially expressed gene associated with bone metastasis. In this study, we investigated 25 candidate gene markers in the CTCs of metastatic breast cancer patients with different metastatic sites. The panel of the 25 markers was investigated in 80 baseline samples (first blood draw of CTCs) and 30 follow-up samples. In addition, 40 healthy blood donors (HBDs) were analyzed as controls. The assay was performed using quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) with RNA extracted from CTCs captured by the CellSearch system. Our study indicated that 12 of the genes were uniquely expressed in CTCs and 10 were highly expressed in the CTCs obtained from patients compared to those obtained from HBDs. Among these genes, the expression of keratin 19 was highly correlated with the CTC count. The TFF1 expression in CTCs was a strong predictor of bone metastasis and the patients with a high expression of estrogen receptor β in CTCs exhibited a better response to hormonal treatment. Molecular characterization of these genes in CTCs may provide a better understanding of the mechanism underlying tumor metastasis and identify gene markers in CTCs for predicting disease progression and

Diagnostic value of combined detection of serum tumor markers for lung cancer

International Nuclear Information System (INIS)

Li Yanping; Wang Qun; Zhao Zihong; Zhou Shan

2013-01-01

Objective: To investigate the diagnostic value of combined detection of serum tumor markers, including CEA, CA125, neuron-specific enolase (NSE) and cytokeratin fragment antigen 21-1 (CYFRA21-1) for lung cancer patients. Methods: The subjects involved 138 diagnosed lung cancer patients (82 males, 56 females, average age 58.6 years, from October 2010 to March 2012), 96 patients with benign lung diseases (56 males, 40 females, average age 51.3 years) and 45 healthy adults (30 males, 15 females, average age 43.9 years). The pathological types of lung cancer consisted of 66 squamous cell carcinoma (SCC), 52 adenocarcinoma and 20 small cell lung cancer (SCLC). The serum levels of CEA, CA125, NSE and CYFRA21-1 were measured with electrochemiluminescence immunoassay. The diagnostic efficacy for different pathological types was compared among each single tumor marker and combination of tumor markers. One-way analysis of variance q test were used for statistical analysis. Results: The serum levels of CEA, CA125, NSE and CYFRA21-1 in patients with lung cancer were higher than those in patients with benign lung diseases and in healthy subjects (CEA: (19.99±30.99), (10.78±19.77), (3.25±3.42) μg/L; CA125: (79.70±95.98), (44.96±44.97), (20.66±7.13) μg/L; NSE: (35.23±40.22), (15.31±8.42), (13.30±5.65) μg/L; CYFRA21-1: (18.07±43.71), (8.30±8.83), (3.13±1.60) μg/L; F=4.481, 5.436, 4.776, 6.002, all P<0.05). The highest level of CEA, NSE or CYFRA21-1 were found in adenocarcinoma (F=4.932, P<0.05), SCLC (F=5.119, P<0.05) or SCC (F=5.378, P<0.05), respectively. The highest sensitivity tumor markers for SCC, SCLC and adenocarcinoma were CYFRA21-1 (78.8%, 52/66), NSE (75.0%, 15/20) and CEA (57.7%, 30/52), respectively. In combined detection, the highest sensitivity combinations for SCC, SCLC and adenocarcinoma were CEA + CYFRA21-1 + NSE (89.4%, 59/66), CEA + CYFRA21-1 + NSE (80.0%, 16/20) and CEA + CA125 + NSE (78.8%, 41/52), respectively. Conclusions: Combined detection

Dosimetric impact of gold markers implanted closely to lung tumors: a Monte Carlo simulation.

Science.gov (United States)

Shiinoki, Takehiro; Sawada, Akira; Ishihara, Yoshitomo; Miyabe, Yuki; Matsuo, Yukinori; Mizowaki, Takashi; Kokubo, Masaki; Hiraoka, Masahiro

2014-05-08

We are developing an innovative dynamic tumor tracking irradiation technique using gold markers implanted around a tumor as a surrogate signal, a real-time marker detection system, and a gimbaled X-ray head in the Vero4DRT. The gold markers implanted in a normal organ will produce uncertainty in the dose calculation during treatment planning because the photon mass attenuation coefficient of a gold marker is much larger than that of normal tissue. The purpose of this study was to simulate the dose variation near the gold markers in a lung irradiated by a photon beam using the Monte Carlo method. First, the single-beam and the opposing-beam geometries were simulated using both water and lung phantoms. Subsequently, the relative dose profiles were calculated using a stereotactic body radiotherapy (SBRT) treatment plan for a lung cancer patient having gold markers along the anterior-posterior (AP) and right-left (RL) directions. For the single beam, the dose at the gold marker-phantom interface laterally along the perpendicular to the beam axis increased by a factor of 1.35 in the water phantom and 1.58 in the lung phantom, respectively. Furthermore, the entrance dose at the interface along the beam axis increased by a factor of 1.63 in the water phantom and 1.91 in the lung phantom, while the exit dose increased by a factor of 1.00 in the water phantom and 1.12 in the lung phantom, respectively. On the other hand, both dose escalations and dose de-escalations were canceled by each beam for opposing portal beams with the same beam weight. For SBRT patient data, the dose at the gold marker edge located in the tumor increased by a factor of 1.30 in both AP and RL directions. In clinical cases, dose escalations were observed at the small area where the distance between a gold marker and the lung tumor was ≤ 5 mm, and it would be clinically negligible in multibeam treatments, although further investigation may be required.

Percutaneous fiducial marker placement prior to stereotactic body radiotherapy for malignant liver tumors: an initial experience

International Nuclear Information System (INIS)

Ohta, Kengo; Shimohira, Masashi; Murai, Taro; Nishimura, Junichi; Iwata, Hiromitsu; Ogino, Hiroyuki; Hashizume, Takuya; Shibamoto, Yuta

2016-01-01

The aim of this study was to describe our initial experience with a gold flexible linear fiducial marker and to evaluate the safety and technical and clinical efficacy of stereotactic body radiotherapy using this marker for malignant liver tumors. Between July 2012 and February 2015, 18 patients underwent percutaneous fiducial marker placement before stereotactic body radiotherapy for malignant liver tumors. We evaluated the technical and clinical success rates of the procedure and the associated complications. Technical success was defined as successful placement of the fiducial marker at the target site, and clinical success was defined as the completion of stereotactic body radiotherapy without the marker dropping out of position. All 18 fiducial markers were placed successfully, so the technical success rate was 100% (18/18). All 18 patients were able to undergo stereotactic body radiotherapy without marker migration. Thus, the clinical success rate was 100% (18/18). Slight pneumothorax occurred as a minor complication in one case. No major complications such as coil migration or bleeding were observed. The examined percutaneous fiducial marker was safely placed in the liver and appeared to be useful for stereotactic body radiotherapy for malignant liver tumors

Quantitative analysis of TEM-8 and CEA tumor markers indicating free tumor cells in the peripheral blood of colorectal cancer patients.

Science.gov (United States)

Raeisossadati, Reza; Farshchian, Moein; Ganji, Azita; Tavassoli, Alieza; Velayati, Arash; Dadkhah, Ezzat; Chavoshi, Somaye; Mehrabi Bahar, Mostafa; Memar, Bahram; Rajabi Mashhadi, Mohammad Taghi; Naseh, Hossein; Forghanifard, Mohammad Mahdi; Moghbeli, Meysam; Moaven, Omeed; Abbaszadegan, Mohammad Reza

2011-10-01

Colorectal cancer (CRC) remains the third most common cancer in the world. Approximately in 50 percent of patients, metastatic disease is a major cause of death. Therefore, early diagnosis of CRC is crucial for a successful outcome. For the detection of circulating cancer cells, this study applied a sensitive method that employed specific tumor markers for early detection. A total of 80 blood samples from 40 CRC patients and 40 age-matched healthy controls were collected for the study. The circulating mRNA levels of two CRC tumor markers, tumor endothelial marker 8 (TEM-8) and carcinoembryogenic antigen (CEA) were evaluated using an absolute quantitative real-time PCR assay in a Stratagene Mx-3000P real-time PCR system. GAPDH was used as the endogenous control. TEM-8 and CEA were primarily detected more in the CRC patients rather than in the controls: 22/40 vs 9/40, p=0.009 and 30/40 vs 11/40, p=0.00054, respectively. In the CRC patients, the mRNA level of these markers was significantly higher in comparison to the normal controls (p=0.018 and 0.01). The overall sensitivity of this panel was 65% with a specificity of 75%. Statistical analysis for demographic variants did not reach significant values. TEM-8 and CEA markers were detected more frequently and in significantly higher levels in the blood samples of patients compared with samples from age-matched healthy controls. The copy number of CEA and TEM-8 mRNA, as detected by a real-time quantitative PCR, appears to be a promising marker for evaluating the risk of tumor spread.

Insertion and fixation of fiducial markers for setup and tracking of lung tumors in radiotherapy

International Nuclear Information System (INIS)

Imura, Mikado; Yamazaki, Koichi; Shirato, Hiroki; Onimaru, Rikiya; Fujino, Masaharu; Shimizu, Shinichi; Harada, Toshiyuki; Ogura, Shigeaki; Dosaka-Akita, Hirotoshi; Miyasaka, Kazuo; Nishimura, Masaharu

2005-01-01

Purpose: Internal 1.5-mm fiducial markers were used in real-time tumor-tracking radiotherapy (RT) for lung cancer. The fixation rate of the markers using the bronchial insertion technique, reliability of the setup using markers around the target volume, dislocation of the markers after real-time tumor-tracking RT, and long-term toxicity of marker insertion were investigated. Methods and Materials: Between July 2000 and April 2004, 154 gold markers were inserted into 57 patients with peripheral lung cancer. The distances between the implanted markers in 198 measurements in 71 setups in 11 patients were measured using two sets of orthogonal diagnostic X-ray images of the real-time tumor-tracking RT system. The distance between the markers and the chest wall was also measured in a transaxial CT image on 186 occasions in 48 patients during treatment planning and during follow-up. The median treatment time was 6 days (range, 4-14 days). Results: In 115 (75%) of the 154 inserted markers, the gold marker was detected throughout the treatment period. In 122 markers detected at CT planning, 115 (94%) were detected until the end of treatment. The variation in the distances between the implanted markers was within ±2 mm in 95% and ±1 mm in 80% during treatment. The variation in the distances between the implanted markers was >2 mm in at least one direction in 9% of the setups for which reexamination with a CT scan was indicated. The fixation rate in the left upper lobe was lower than in the other lobes. A statistically significant relationship was found between a shorter distance between the markers and the chest wall and the fixation rate, suggesting that the markers in the smaller bronchial lumens fixed better than those in the larger lumens. A learning curve among the endoscopists was suggested in the fixation rate. The distance between the markers and the chest wall changed significantly within a median of 44 days (range, 16-181 days) after treatment. Conclusion: The

NDRG2 is a candidate tumor-suppressor for oral squamous-cell carcinoma

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Furuta, Hiroshi; Kondo, Yuudai [Division of Oral and Maxillofacial Surgery, Medicine of Sensory and Motor Organs, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Nakahata, Shingo; Hamasaki, Makoto [Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Sakoda, Sumio [Division of Oral and Maxillofacial Surgery, Medicine of Sensory and Motor Organs, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan); Morishita, Kazuhiro, E-mail: kmorishi@med.miyazaki-u.ac.jp [Division of Tumor and Cellular Biochemistry, Department of Medical Sciences, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki-gun, Miyazaki 889-1692 (Japan)

2010-01-22

Oral cancer is one of the most common cancers worldwide, and squamous-cell carcinoma (OSCC) is the most common phenotype of oral cancer. Although patients with OSCC have poor survival rates and a high incidence of metastasis, the molecular mechanisms of OSCC development have not yet been elucidated. This study investigated whether N-myc downstream-regulated gene 2 (NDRG2) contributes to the carcinogenesis of OSCC, as NDRG2 is reported to be a candidate tumor-suppressor gene in a wide variety of cancers. The down-regulation of NDRG2 mRNA, which was dependent on promoter methylation, was seen in the majority of OSCC cases and in several cases of precancerous leukoplakia with dysplasia. Induction of NDRG2 expression in an HSC-3/OSCC cell line significantly inhibited cell proliferation and decreased colony formation ability on soft agar. The majority of OSCC cell lines showed an activation of PI3K/Akt signaling, and enforced expression of NDRG2 in HSC-3 cells decreased the level of phosphorylated Akt at Serine 473 (p-Akt). Immunohistochemical p-Akt staining was detected in 56.5% of the OSCC tumors, and 80.4% of the tumors were negative for NDRG2 staining. Moreover, positive p-Akt staining was inversely correlated with decreased NDRG2 expression in OSCC tumors with moderate to poor differentiation (p < 0.005). Therefore, NDRG2 is a candidate tumor-suppressor gene for OSCC development and probably contributes to the tumorigenesis of OSCC partly via the modulation of Akt signaling.

Google goes cancer: improving outcome prediction for cancer patients by network-based ranking of marker genes.

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Christof Winter

Full Text Available Predicting the clinical outcome of cancer patients based on the expression of marker genes in their tumors has received increasing interest in the past decade. Accurate predictors of outcome and response to therapy could be used to personalize and thereby improve therapy. However, state of the art methods used so far often found marker genes with limited prediction accuracy, limited reproducibility, and unclear biological relevance. To address this problem, we developed a novel computational approach to identify genes prognostic for outcome that couples gene expression measurements from primary tumor samples with a network of known relationships between the genes. Our approach ranks genes according to their prognostic relevance using both expression and network information in a manner similar to Google's PageRank. We applied this method to gene expression profiles which we obtained from 30 patients with pancreatic cancer, and identified seven candidate marker genes prognostic for outcome. Compared to genes found with state of the art methods, such as Pearson correlation of gene expression with survival time, we improve the prediction accuracy by up to 7%. Accuracies were assessed using support vector machine classifiers and Monte Carlo cross-validation. We then validated the prognostic value of our seven candidate markers using immunohistochemistry on an independent set of 412 pancreatic cancer samples. Notably, signatures derived from our candidate markers were independently predictive of outcome and superior to established clinical prognostic factors such as grade, tumor size, and nodal status. As the amount of genomic data of individual tumors grows rapidly, our algorithm meets the need for powerful computational approaches that are key to exploit these data for personalized cancer therapies in clinical practice.

Immunohistochemical study of hepatocyte, cholangiocyte and stem cell markers of hepatocellular carcinoma: the second report: relationship with tumor size and cell differentiation.

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Kumagai, Arisa; Kondo, Fukuo; Sano, Keiji; Inoue, Masafumi; Fujii, Takeshi; Hashimoto, Masaji; Watanabe, Masato; Soejima, Yurie; Ishida, Tsuyoshi; Tokairin, Takuo; Saito, Koji; Sasajima, Yuko; Takahashi, Yoshihisa; Uozaki, Hiroshi; Fukusato, Toshio

2016-07-01

The purpose of this study is to investigate whether ordinary hepatocellular carcinomas (HCCs) show positivity of stem/progenitor cell markers and cholangiocyte markers during the process of tumor progression. Ninety-four HCC lesions no larger than 8 cm from 94 patients were immuno-histochemically studied using two hepatocyte markers (Hep par 1 and α-fetoprotein), five cholangiocyte markers (cytokeratin CK7, CK19, Muc1, epithelial membrane antigen and carcinoembryonic antigen) and three hepatic stem/progenitor cell markers (CD56, c-Kit and EpCAM). The tumors were classified into three groups by tumor size: S1, tumors were also classified according to tumor differentiation: well, moderately and poorly differentiated. The relationship between the positive ratios of these markers, tumor size and tumor differentiation was examined. The positive ratios of cholangiocyte markers tended to be higher in larger sized and more poorly differentiated tumors (except for CK7). The positive ratios of stem/progenitor cell markers tended to be higher in larger sized and more poorly differentiated tumors (except for c-Kit). Ordinary HCC can acquire the characteristic of positivity of cholangiocyte and stem/progenitor cell markers during the process of tumor progression. © 2016 The Authors. Journal of Hepato-Biliary-Pancreatic Sciences published by John Wiley & Sons Australia, Ltd on behalf of Japanese Society of Hepato-Biliary-Pancreatic Surgery.

AZU-1: A Candidate Breast Tumor Suppressor and Biomarker for Tumor Progression

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Chen, Huei-Mei; Schmeichel, Karen L; Mian, I. Saira; Lelie`vre, Sophie; Petersen, Ole W; Bissell, Mina J

2000-02-04

To identify genes misregulated in the final stages of breast carcinogenesis, we performed differential display to compare the gene expression patterns of the human tumorigenic mammary epithelial cells, HMT-3522-T4-2, with those of their immediate premalignant progenitors, HMT-3522-S2. We identified a novel gene, called anti-zuai-1 (AZU-1), that was abundantly expressed in non- and premalignant cells and tissues but was appreciably reduced in breast tumor cell types and in primary tumors. The AZU-1 gene encodes an acidic 571-amino-acid protein containing at least two structurally distinct domains with potential protein-binding functions: an N-terminal serine and proline-rich domain with a predicted immunoglobulin-like fold and a C-terminal coiled-coil domain. In HMT-3522 cells, the bulk of AZU-1 protein resided in a detergent-extractable cytoplasmic pool and was present at much lower levels in tumorigenic T4-2 cells than in their nonmalignant counterparts. Reversion of the tumorigenic phenotype of T4-2 cells, by means described previously, was accompanied by the up-regulation of AZU-1. In addition, reexpression of AZU-1 in T4-2 cells, using viral vectors, was sufficient to reduce their malignant phenotype substantially, both in culture and in vivo. These results indicate that AZU-1 is a candidate breast tumor suppressor that may exert its effects by promoting correct tissue morphogenesis.

Markers of fibrosis and epithelial to mesenchymal transition demonstrate field cancerization in histologically normal tissue adjacent to breast tumors

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Trujillo, Kristina A.; Heaphy, Christopher M.; Mai, Minh; Vargas, Keith M.; Jones, Anna C.; Vo, Phung; Butler, Kimberly S.; Joste, Nancy E.; Bisoffi, Marco; Griffith, Jeffrey K

2011-01-01

Previous studies have shown that a field of genetically altered but histologically normal tissue extends 1 cm or more from the margins of human breast tumors. The extent, composition and biological significance of this field are only partially understood, but the molecular alterations in affected cells could provide mechanisms for limitless replicative capacity, genomic instability and a microenvironment that supports tumor initiation and progression. We demonstrate by microarray, qRT-PCR and immunohistochemistry a signature of differential gene expression that discriminates between patient-matched, tumor-adjacent histologically normal breast tissues located 1 cm and 5 cm from the margins of breast adenocarcinomas (TAHN-1 and TAHN-5, respectively). The signature includes genes involved in extracellular matrix remodeling, wound healing, fibrosis and epithelial to mesenchymal transition (EMT). Myofibroblasts, which are mediators of wound healing and fibrosis, and intra-lobular fibroblasts expressing MMP2, SPARC, TGF-β3, which are inducers of EMT, were both prevalent in TAHN-1 tissues, sparse in TAHN-5 tissues, and absent in normal tissues from reduction mammoplasty. Accordingly, EMT markers S100A4 and vimentin were elevated in both luminal and myoepithelial cells, and EMT markers α-smooth muscle actin and SNAIL were elevated in luminal epithelial cells of TAHN-1 tissues. These results identify cellular processes that are differentially activated between TAHN-1 and TAHN-5 breast tissues, implicate myofibroblasts as likely mediators of these processes, provide evidence that EMT is occurring in histologically normal tissues within the affected field and identify candidate biomarkers to investigate whether or how field cancerization contributes to the development of primary or recurrent breast tumors. PMID:21105047

Inhibin as a tumor marker of ovarian cancer in postmenopausal women

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Modarres Gilani M

2010-05-01

Full Text Available "n Normal 0 false false false EN-US X-NONE AR-SA MicrosoftInternetExplorer4 /* Style Definitions */ table.MsoNormalTable {mso-style-name:"Table Normal"; mso-tstyle-rowband-size:0; mso-tstyle-colband-size:0; mso-style-noshow:yes; mso-style-priority:99; mso-style-qformat:yes; mso-style-parent:""; mso-padding-alt:0cm 5.4pt 0cm 5.4pt; mso-para-margin:0cm; mso-para-margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:11.0pt; font-family:"Calibri","sans-serif"; mso-ascii-font-family:Calibri; mso-ascii-theme-font:minor-latin; mso-fareast-font-family:"Times New Roman"; mso-fareast-theme-font:minor-fareast; mso-hansi-font-family:Calibri; mso-hansi-theme-font:minor-latin; mso-bidi-font-family:Arial; mso-bidi-theme-font:minor-bidi;} Background: Inhibin is a dimeric glycoprotein that has a depressive effect on the anterior hypophys secretion. The level of this tumor marker is undetectable in menopause women. In patients with gynecological cancer, especially granulosa and epidermal-type (mucinous, ovarian cancers considerable increase in the serum level of inhibin has been reported. The increased level of inhibin has been reported in patients with recurrent ovarian cancer."n"nMethods: We measured total serum inhibin and CA125 tumor marker level in 38 postmenopausal women with pathologically confirmed ovarian cancer before and after surgery out of 51 suspected women. Our control group were postmenopausal women that attended to our clinic for routine gynecologic check up. Both tumor markers were measured in these patients too."n"nResults: Among 38 women with ovarian cancer, 13(34.2% had elevated serum levels of total inhibin. Among the 16 women with serous adenocarcinoma, 3 patients (18.8% had elevated serum levels of inhibin. All the three women with granulosa cell tumor had elevated serum levels of inhibin (100% and 3 of 4(75% women with mucinous ovarian cancer had the same result. three out of 38 women in control group had elevated serum levels of

Systematic review on the role of serum tumor markers in the detection of recurrent pancreatic cancer.

Science.gov (United States)

Daamen, Lois A; Groot, Vincent P; Heerkens, Hanne D; Intven, Martijn P W; van Santvoort, Hjalmar C; Molenaar, I Quintus

2018-04-01

Biomarker testing can be helpful to monitor disease progression after resection of pancreatic cancer. This systematic review aims to give an overview of the literature on the diagnostic value of serum tumor markers for the detection of recurrent pancreatic cancer during follow-up. A systematic search was performed to 2 October 2017. All studies reporting on the diagnostic value of postoperatively measured serum biomarkers for the detection of pancreatic cancer recurrence were included. Data on diagnostic accuracy of tumor markers were extracted. Forest plots and pooled values of sensitivity and specificity were calculated. Four articles described test results of CA 19-9. A pooled sensitivity and specificity of respectively 0.73 (95% CI 0.66-0.80) and 0.83 (95% CI 0.73-0.91) were calculated. One article reported on CEA, showing a sensitivity of 50% and specificity of 65%. No other serum tumor markers were discussed for surveillance purposes in the current literature. Although testing of serum CA 19-9 has considerable limitations, CA 19-9 remains the most used serum tumor marker for surveillance after surgical resection of pancreatic cancer. Further studies are needed to assess the role of serum tumor marker testing in the detection of recurrent pancreatic cancer and to optimize surveillance strategies. Copyright © 2017 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.

Next-generation sequencing to identify candidate genes and develop diagnostic markers for a novel Phytophthora resistance gene, RpsHC18, in soybean.

Science.gov (United States)

Zhong, Chao; Sun, Suli; Li, Yinping; Duan, Canxing; Zhu, Zhendong

2018-03-01

A novel Phytophthora sojae resistance gene RpsHC18 was identified and finely mapped on soybean chromosome 3. Two NBS-LRR candidate genes were identified and two diagnostic markers of RpsHC18 were developed. Phytophthora root rot caused by Phytophthora sojae is a destructive disease of soybean. The most effective disease-control strategy is to deploy resistant cultivars carrying Phytophthora-resistant Rps genes. The soybean cultivar Huachun 18 has a broad and distinct resistance spectrum to 12 P. sojae isolates. Quantitative trait loci sequencing (QTL-seq), based on the whole-genome resequencing (WGRS) of two extreme resistant and susceptible phenotype bulks from an F 2:3 population, was performed, and one 767-kb genomic region with ΔSNP-index ≥ 0.9 on chromosome 3 was identified as the RpsHC18 candidate region in Huachun 18. The candidate region was reduced to a 146-kb region by fine mapping. Nonsynonymous SNP and haplotype analyses were carried out in the 146-kb region among ten soybean genotypes using WGRS. Four specific nonsynonymous SNPs were identified in two nucleotide-binding sites-leucine-rich repeat (NBS-LRR) genes, RpsHC18-NBL1 and RpsHC18-NBL2, which were considered to be the candidate genes. Finally, one specific SNP marker in each candidate gene was successfully developed using a tetra-primer ARMS-PCR assay, and the two markers were verified to be specific for RpsHC18 and to effectively distinguish other known Rps genes. In this study, we applied an integrated genomic-based strategy combining WGRS with traditional genetic mapping to identify RpsHC18 candidate genes and develop diagnostic markers. These results suggest that next-generation sequencing is a precise, rapid and cost-effective way to identify candidate genes and develop diagnostic markers, and it can accelerate Rps gene cloning and marker-assisted selection for breeding of P. sojae-resistant soybean cultivars.

Biological markers as predictors of radiosensitivity in syngeneic murine tumors

International Nuclear Information System (INIS)

Chang, Sei Kyung; Shin, Hyun Soo; Seong, Jin Sil; Kim, Sung Hee

2006-01-01

We investigated whether a relationship exists between tumor control dose 50 (TCD 50 ) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD 50 , TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 ∼ 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD 50 , TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21 WAF1/CIP1 , BAX, Bcl-2, Bcl-x L , Bcl-x S , and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD 50 or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD 50 , TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, ρ = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD 50 (ρ = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21 WAF1/CIP1 and p34 showed a significant correlation either with TCD 50 (R = 0.893, ρ = 0.041 and R = 0.904, ρ = 0.035) or with TGD (R = -0.922, ρ 0.026 and R = -0.890, ρ = 0.043). The tumors with high constitutive expression levels of p21 WAF1/CIP1 or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The constitutive expression levels of p21 WAF1/CIP1 or p34 can be used as biological

Biological markers as predictors of radiosensitivity in syngeneic murine tumors

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Chang, Sei Kyung; Shin, Hyun Soo [Bundang CHA General Hospital, Seongnam (Korea, Republic of); Seong, Jin Sil; Kim, Sung Hee [Yonsei Cancer Center, Yonsei University College of Medicine, Seoul (Korea, Republic of)

2006-06-15

We investigated whether a relationship exists between tumor control dose 50 (TCD{sub 50}) or tumor growth delay (TGD) and radiation induced apoptosis (RIA) in syngeneic murine tumors. Also we investigated the biological markers that can predict radiosensitivity in murine tumor system through analysis of relationship between TCD{sub 50}, TGD, RIA and constitutive expression levels of the genetic products regulating RIA. Syngeneic murine tumors such as ovarian adenocarcinoma, mammary carcinoma, squamous cell carcinoma, fibrosarcoma, hepatocarcinoma were used in this study. C3H/HeJ mice were bred and maintained in our specific pathogen free mouse colony and were 8 {approx} 12 weeks old when used for the experiments. The tumors, growing in the right hind legs of mice, were analyzed for TCD{sub 50}, TGD, and RIA at 8 mm in diameter. The tumors were also analyzed for the constitutive expression levels of p53, p21{sup WAF1/CIP1}, BAX, Bcl-2, Bcl-x{sub L}, Bcl-x{sub S}, and p34. Correlation analysis was performed whether the level of RIA were correlated with TCD{sub 50} or TGD, and the constitutive expression levels of genetic products regulating RIA were correlated with TCD{sub 50}, TGD, RIA. The level of RIA showed a significant positive correlation (R = 0.922, {rho} = 0.026) with TGD, and showed a trend to correlation (R = -0.848), marginally significant correlation with TCD{sub 50} ({rho} = 0.070). It indicates that tumors that respond to radiation with high percentage of apoptosis were more radiosensitive. The constitutive expression levels of p21{sup WAF1/CIP1} and p34 showed a significant correlation either with TCD{sub 50} (R = 0.893, {rho} = 0.041 and R = 0.904, {rho} = 0.035) or with TGD (R = -0.922, {rho} 0.026 and R = -0.890, {rho} = 0.043). The tumors with high constitutive expression levels of p21{sup WAF1/CIP1} or p34 were less radiosensitive than those with low expression. Radiosensitivity may be predicted with the level of RIA in murine tumors. The

Analysis of relationship between tumor markers and quantification of free DNA in serum of lung cancer patients

International Nuclear Information System (INIS)

Yang Shunfang; Zhang Peiling; Cao Jie; Zeng Jun; Dong Qianggang

2006-01-01

To evaluate the diagnostic value and relationship between five tumor markers (CA19- 9,CA125,CYFRA21-1 ,CEA,NSE) and free DNA in serum for lung cancer detection and try to find a new and more efficient tumor marker, the amounts of CA19-9, CA125, CYFRA21-1, CEA, NSE were determined by RIA and free DNA was determined by the use of quantitative real time PCR amplification of the human epidermal growth factor receptor (EGFR) in 52 lung cancer patients and 8 cases of benign pulmonary disease and 10 healthy controls. The resulls showed that average concentration of free DNA in serum of lung cancer patients, benign pulmo- nary disease and healthy controls was 107.6ng/mL, 76.86ng/mL and 18.8ng/mL, respective- ly. The diagnostic sensitivity, specificity and accuracy of free DNA for lung cancer were 71. 2%, 50% and 68.3%, same as the diagnostic value of combined detection of five tumor markers. The sensitivity, specificity and accuracy of the five tumor markers and free DNA combinend detection for lung cancer were 94.2%, 25% and 85%, respectively. The free DNA in the serum of lung cancer patients may be a new and better tumor marker. (authors)

Detection of multiple tumor markers using ultra-long carbon nanotube devices

Science.gov (United States)

So, Hye-Mi; Park, Dong-Won; Kim, Beom Soo; Kong, Ki-Jeong; Buh, Gyoung-Ho; Chang, Hyunju; Lee, Jeong-O.; Kong, Jing

2008-03-01

For the simultaneous detection of multiple tumor markers, we have fabricated ultra-long carbon nanotube sensors that can detect carcinoembryonic antigen (CEA) and prostate specific antigen (PSA), simultaneously. Ultra-long carbon nanotubes, several millimeters long, were grown by ethanol CVD, and fabricated as FET sensors by using conventional photolithography. To functionalize each segment of a single ultra-long nanotube device with multiple-tumor markers, we first functionalize the entire device with CDI-Tween 20 linking molecules, and then immobilized CEA and PSA antibodies using the microfluidic channel. The electrical conductance from CEA-antibody functionalized and PSA-antibody functionalized segment of a ultra-long carbon nanotube device was monitored simultaneously with Ag/AgCl reference electrode as a liquid gate. We will discuss the advantages of long-nanotube device in detail.

Detection of five tumor markers in lung cancer by trypsin digestion of sputum method

International Nuclear Information System (INIS)

Lin Min; Nong Tianlei; Liu Daying

2011-01-01

To explore the detection of five tumor markers by trypsin digestion of sputum in the diagnosis of lung cancer, the samples of sputum in patients with lung cancer and benign lung disease were digested by trypsin and used to measure five tumor markers. The results showed that the sputum were well digested by 6% trypsin at pH8 and no affect on the determination of tumor markers. The CEA, CA125, CA153, CA211 and NSE levels in lung cancer group were significantly higher than that of in benign group (P<0.05). The sputum CEA and CA125 levels were significantly higher than that of the serum levels (P<0.05). The detection of sputum CEA, CA125, CA153, CA211 and NSE levels have clinical value in the diagnosis of lung cancer. When combined with other diagnostic methods,it might be helpful for further diagnosis in non confirmed lung cancer patients. (authors)

Growth Factors and Breast Tumors, Comparison of Selected Growth Factors with Traditional Tumor Markers

Czech Academy of Sciences Publication Activity Database

Kučera, R.; Černá, M.; Ňaršanská, A.; Svobodová, Š.; Straková, M.; Vrzalová, J.; Fuchsová, R.; Třešková, I.; Kydlíček, T.; Třeška, V.; Pecen, Ladislav; Topolčan, O.; Padziora, P.

2011-01-01

Roč. 31, č. 12 (2011), s. 4653-4656 ISSN 0250-7005 Grant - others:GA MZd(CZ) NS9727; GA MZd(CZ) NS10238; GA MZd(CZ) NS10253 Institutional research plan: CEZ:AV0Z10300504 Keywords : growth factor * breast cancer * tumor markers * CA 15-3 * CEA * IGF1 * EGF * HGF Subject RIV: FD - Oncology ; Hematology Impact factor: 1.725, year: 2011

Radioimmunoassay of CA 19-9 tumor marker in the diagnosis of thyroid cancer

International Nuclear Information System (INIS)

Markov, V.V.; Slavnov, V.N.; Komissarenko, I.V.; Kovpak, N.A.; Kovalenko, A.E.; Guda, B.B.

1999-01-01

Applicability of determining carbohydrate antigen CA 19-9 content in blood serum, tissue extracts, and thyroid tumor aspiration biopsy samples to the differential diagnosis of benign and malignant tumors of thyroid is studied. Radioimmunoassay was used for measurements. It is shown that determination of marker CA 19-9 in blood serum is not informationally capable for the differential diagnosis of thyroid tumors. Considerable increase in CA 19-9 concentration was found in tumor aspiration biopsy samples from patients with malignant tumors this fact can be used for preoperative diagnosis of thyroid cancer [ru

Significance of serum and bile tumor markers in the diagnostic approach of patients with malignant pancreatobiliary disease.

Science.gov (United States)

Natsios, Athanasios; Vezakis, Antonios; Kaparos, Georgios; Fragulidis, Georgios; Karakostas, Nikolaos; Kouskouni, Evangelia; Logothetis, Emmanouil; Polydorou, Andreas

2015-01-01

Serum and bile tumor markers are under intense scrutiny for the diagnosis of malignant disease. The purpose of our study was to report the usefulness of serum and bile tumor markers for the discrimination between benign and malignant pancreatobiliary diseases. Between March 2010 and May 2013, 95 patients with obstructive jaundice or history of biliary obstruction, were included in the study. During ERCP, bile samples were obtained for measurement of tumor markers CEA, CA19- 9, CA125, CA72-4 and CA242. Serum samples were taken before ERCP for the same measurements. The patients were divided into two groups: patients with malignant disease and patients with benign disease. Serum tumor marker levels were significantly higher in patients with malignant disease. Serum CA242 and CA19-9 exhibited the highest diagnostic accuracy (76.8% and 73.7%, respectively). CA125 and CA72-4 levels in bile samples were significantly higher in patients with malignant disease. Bile CA125, CEA and CA72-4 achieved the best diagnostic accuracy (69, 65 and 65), respectively). The combined detection of CA19-9, CA242 in serum and CA125, CA72-4 in bile along with total bilirubin levels, showed the best diagnostic accuracy (81%). Serum and bile tumor markers, when studied alone, lack the diagnostic yield to discriminate benign from malignant pancreatobiliary diseases. In cases of diagnostic dilemmas the combination of serum and bile markers might be helpful.

Microsatellite instability as prognostic marker in bladder tumors: a clinical significance

Directory of Open Access Journals (Sweden)

Mittal RD

2005-01-01

Full Text Available Abstract Background Carcinoma of urinary bladder is one of the leading causes of death in India. Successful treatment of bladder cancer depends on the early detection & specific diagnostic approaches. In the present study, microsatellite instability (MSI has been evaluated as a prognostic marker in patients with superficial urinary bladder cancer in lower urinary tract for determining risk of recurrence. Methods A total of 44 patients with bladder tumors diagnosed with Transitional Cell Carcinomas [TCC] from lower urinary tract were selected for the study. Tumors were staged and graded according to AJCC-UICC (1997 classification and patients were followed with cystoscopy as per the protocol. Polymerase chain reaction (PCR was done to amplify microsatellite sequences at mononucleotide BAT – 26, BAT – 40, TGFβ RII, IGFIIR, hMSH3, BAX and dinucleotide D2S123, D9S283, D9S1851 and D18S58 loci in blood (control and tumor DNA. PCR products were separated on 8% denaturing polyacrylamide gel and visualized by autoradiography. Results MSI was observed in 72.7% of tumors at BAT – 26, BAT – 40, D2S123, D9S283, D9S1851 and D18S58 loci. Good association of MSI was seen with tumor stage and grade. MSI – High (instability at > 30% of loci was frequently observed in high stage (40.6% and high grade (59.4% tumors. Of 24 tumors of Ta-T1 stage with different grades, 11 (9/18 high grade and 2/6 low grade tumors recurred in the mean duration of 36 months. MSI positivity was significantly high in patients who had one or more recurrences (p = 0.02 for high grade and 0.04 for low grade tumors. Conclusions MSI may be an independent prognostic marker for assessing risk of recurrence in superficial tumors irrespective of the grade. Further studies on progression would help in stratifying the patients of T1G3 for early cystectomy vs bladder preservation protocol.

Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

Energy Technology Data Exchange (ETDEWEB)

Roman, Nicholas O., E-mail: nroman@mcvh-vcu.edu [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States); Shepherd, Wes [Department of Pulmonology, Virginia Commonwealth University, Richmond, VA (United States); Mukhopadhyay, Nitai [Department of Biostatistics, Virginia Commonwealth University, Richmond, VA (United States); Hugo, Geoffrey D.; Weiss, Elisabeth [Department of Radiation Oncology, Virginia Commonwealth University, Richmond, VA (United States)

2012-08-01

Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior-posterior), and z (superior-inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy-based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

Interfractional Positional Variability of Fiducial Markers and Primary Tumors in Locally Advanced Non-Small-Cell Lung Cancer During Audiovisual Biofeedback Radiotherapy

International Nuclear Information System (INIS)

Roman, Nicholas O.; Shepherd, Wes; Mukhopadhyay, Nitai; Hugo, Geoffrey D.; Weiss, Elisabeth

2012-01-01

Purpose: To evaluate implanted markers as a surrogate for tumor-based setup during image-guided lung cancer radiotherapy with audiovisual biofeedback. Methods and Materials: Seven patients with locally advanced non-small-cell lung cancer were implanted bronchoscopically with gold coils. Markers, tumor, and a reference bony structure (vertebra) were contoured for all 10 phases of the four-dimensional respiration-correlated fan-beam computed tomography and weekly four-dimensional cone-beam computed tomography. Results: The systematic/random interfractional marker-to-tumor centroid displacements were 2/3, 2/2, and 3/3 mm in the x (lateral), y (anterior–posterior), and z (superior–inferior) directions, respectively. The systematic/random interfractional marker-to-bone displacements were 2/3, 2/3, and 2/3 mm in the x, y, and z directions, respectively. The systematic/random tumor-to-bone displacements were 2/3, 2/4, and 4/4 mm in the x, y, and z directions, respectively. All displacements changed significantly over time (p < 0.0001). Conclusions: Although marker-based image guidance may decrease the risk for geometric miss compared with bony anatomy–based positioning, the observed displacements between markers and tumor centroids indicate the need for repeated soft tissue imaging, particularly in situations with large tumor volume change and large initial marker-to-tumor centroid distance.

The correlation between pre-operative serum tumor markers and lymph node metastasis in gastric cancer patients undergoing curative treatment.

Science.gov (United States)

Li, Fangxuan; Li, Shixia; Wei, Lijuan; Liang, Xiaofeng; Zhang, Huan; Liu, Juntian

2013-11-01

There was few study concentrated on the correlation between the evaluated tumor markers and lymph node metastasis. In this study, we aimed to evaluate the correlation between the CA724, CA242, CA199, CEA and the lymph node metastasis of gastric cancer and assess the prognostic value of them in different N stage patients. We analyzed the correlation between serum level of CA724, CA242, CA199, CEA and lymph node metastasis in 1501 gastric cancer patients. Lymph node metastasis of gastric cancer was related with tumor location, Bormann type, tumor size, histological type, depth of invasion and TNM stage (p CEA were positively correlated with the metastatic lymph node counts and the N stage (p tumor markers were higher (p tumor markers, the positive rates of tumor markers combination were higher. The combination of CA724 + CA242 + CA199 + CEA had highest positive rate. The higher CEA level related to N1 stage patients while higher CA199 was related with poor prognosis for N1 stage patients. For N0 and N2 stage patients, evaluation of CA724 indicated poorer prognosis. For N1 and N2 stage gastric patients, the patients with increased CA242 inclined to have shorter survival time. The tumor makers CA724, CA242, CA199 and CEA were evaluated significantly in the gastric patients with later N stage. The combination of these four tumor markers maybe prefer diagnostic index of gastric cancer and its lymph node metastasis. These tumor markers can be a possible indicator of poorer prognosis in different N stage patients.

Measurement of tumor volumes of hepatocellular carcinoma (HCC) by computed tomography (CT). Correlation with several tumor markers

Energy Technology Data Exchange (ETDEWEB)

Yoneshima, Manabu; Sawabu, Norio; Toya, Daishu

1984-09-01

Tumor volumes of HCC were measured by CT using planimeter and the clinical value of this measurement was evaluated by comparing several tumor markers. Tumor volumes measured by CT roughly agreed with those measured by angiography. In some cases, volumes from ultrasonography were smaller than those from CT and angiography. Tumor volumes measured by CT correlated significantly with the levels of ..cap alpha..-fetoprotein (AFP) but didn't relate to the presence of hepatoma specific ..gamma..-GTP isoenzyme (novel ..gamma..-GTP) nor to the values and positivities of LAI assay. In small HCCs (<=30 cm/sup 3/), the presence of novel ..gamma..-GTP and the levels of AFP were significantly lower than for larger tumors of HCC, but LAI assay wasn't lower. The non-tumorous volumes and the ratio of the non-tumorous volume to the whole liver volume didn't relate to the tests of liver function except for the presence of ascites.

Correlation of elvated tumor markers and hepatic and nodal metastases on CT in postgastrectomy patients for gastric cancer

International Nuclear Information System (INIS)

Lee, Hwa Jin; Park, Won Kyu; Seong, Ki Ho; Cho, Hyun Chul; Chang, Jae Chun; Park, Bok Hwan; Song, Sun Kyo

1997-01-01

The evaluation of tumor recurrence or metastasis in postgastrectomy cancer patients usually depends on a serum tumor marker test or radiologic study, but in both cases, accuracy is difficult to determine. The purpose of this study was to evaluate the relationship between abdominal CT and serum tumor markers. In 337cases involving 226 patients who had undergone curative surgery for gastric cancer, we compared serum tumor markers and CT for the evaluation of metastasis. Amoong these 337 cases, CEA level was measured in 317, CA 19-9 level in 166,and both of these in 146. The cutoff level for serum carcinoembryonic antigen (CEA) and CA19-9 were 10ng/ml and 33U/ml, respectively. CEA level was elevated in 59 of 317 cases(18.6%) and that of CA 19-9 in 58 of 166(34.9%). Slightly higher overall senstivity and specificity was observed for CEA than for CA19-9 (72.9% vs 67.2%, 83.3% vs 70.4%, respectively). Among the total of 337 cases, liver or lymph node metastases were detected in 91 cases (27.0%) on CT. Negative predictive value was significantly higher in CEA than in CA19-9 (93.1% vs 80%, respectively)(p<0.01), but positive predictive value was lower (50% vs 54.9%, respectively). On CT scan, there was a significant relationship between serum tumor marker level and hepatic and nodal metastasis ; specificity and positivity of serum tumor markers were both higher than senstivity and negativity. Follow-up CT less useful when tumor markers levels are not elevated, but when these are elevated in postgastrectomy cancer patients, meticulous radiologic evaluation is necessary for the early detection of residual or recurrent tumors

Investigations for a multi-marker RT-PCR to improve sensitivity of disseminated tumor cell detection.

NARCIS (Netherlands)

Vlems, F.A.; Diepstra, J.H.S.; Cornelissen, I.M.; Ligtenberg, M.J.L.; Wobbes, Th.; Punt, C.J.A.; Krieken, J.H.J.M. van; Ruers, T.J.M.; Muijen, G.N.P. van

2003-01-01

BACKGROUND: In order to develop a multi-marker RT-PCR, which as such may be more sensitive than a single marker assay for the detection of disseminated tumor cells, we evaluated six RT-PCR markers: cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), guanylyl cyclase C (GCC), epidermal growth

Investigations for a multi-marker RT-PCR to improve sensitivity of disseminated tumor cell detection

NARCIS (Netherlands)

Vlems, F. A.; Diepstra, J. H. S.; Cornelissen, I. M. H. A.; Ligtenberg, M. J. L.; Wobbes, Th; Punt, C. J. A.; van Krieken, J. H. J. M.; Ruers, T. J. M.; van Muijen, G. N. P.

2003-01-01

In order to develop a multi-marker RT-PCR, which as such may be more sensitive than a single marker assay for the detection of disseminated tumor cells, we evaluated six RT-PCR markers: cytokeratin 20 (CK20), carcinoembryonic antigen (CEA), guanylyl cyclase C (GCC), epidermal growth factor receptor

Clinical analysis of four serum tumor markers in 458 patients with ovarian tumors: diagnostic value of the combined use of HE4, CA125, CA19-9, and CEA in ovarian tumors

Directory of Open Access Journals (Sweden)

Chen F

2018-05-01

Full Text Available Fawen Chen,1,2 Jing Shen,3 Jianwei Wang,1 Pengwei Cai,1 Yi Huang3 1Department of Clinical Laboratory, Fujian Provincial Hospital South Branch, 2Department of Blood Transfusion, 3Department of Clinical Laboratory, Fujian Provincial Hospital, Provincial Clinical College of Fujian Medical University, Fuzhou, People’s Republic of China Purpose: To investigate the diagnostic values of human epididymis protein 4 (HE4, carbohydrate antigen 125 (CA125, carbohydrate antigen 19-9 (CA19-9, and carcinoembryonic antigen (CEA for ovarian tumors. Methods: The participants were divided into three groups: 386 healthy women (control group, 262 patients with benign ovarian tumors (the benign group, and 196 patients with malignant pelvic tumors (the malignant group. The serum levels of HE4, CA125, CA19-9, and CEA were analyzed by electrochemiluminescent immunoassay. Results: It showed that serum levels of HE4, CA125, CA19-9, and CEA of patients with ­malignant ovarian tumors were significantly higher than those in the control group and benign group (P<0.01. HE4 had a high specificity (96.56% in malignant ovarian tumors. The tumor markers HE4, CA125, CA19-9, and CEA had a sensitivity of 63.78%, 62.75%, 35.71%, and 38.78%, respectively. The combined use of two or more tumor markers (parallel test had a higher diagnostic sensitivity but lower specificity than a single tumor marker. The combined efficiency of HE4 and CA125 was the highest, with a sensitivity and specificity of 80.10% and 69.08%, respectively. HE4 and CA125 combined with the Risk of Ovarian Malignancy Algorithm provided an efficient means of screening and diagnosis of ovarian malignancies. The diagnostic sensitivity increased to 88.52% when three or four tumor markers were used but showed no significant difference compared with the combination of HE4 and CA125 (P>0.05. Conclusion: The combination of three or four tumor markers did not improve the diagnostic efficacy when compared with the combination

Prognostic DNA Methylation Markers for Prostate Cancer

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Siri H. Strand

2014-09-01

Full Text Available Prostate cancer (PC is the most commonly diagnosed neoplasm and the third most common cause of cancer-related death amongst men in the Western world. PC is a clinically highly heterogeneous disease, and distinction between aggressive and indolent disease is a major challenge for the management of PC. Currently, no biomarkers or prognostic tools are able to accurately predict tumor progression at the time of diagnosis. Thus, improved biomarkers for PC prognosis are urgently needed. This review focuses on the prognostic potential of DNA methylation biomarkers for PC. Epigenetic changes are hallmarks of PC and associated with malignant initiation as well as tumor progression. Moreover, DNA methylation is the most frequently studied epigenetic alteration in PC, and the prognostic potential of DNA methylation markers for PC has been demonstrated in multiple studies. The most promising methylation marker candidates identified so far include PITX2, C1orf114 (CCDC181 and the GABRE~miR-452~miR-224 locus, in addition to the three-gene signature AOX1/C1orf114/HAPLN3. Several other biomarker candidates have also been investigated, but with less stringent clinical validation and/or conflicting evidence regarding their possible prognostic value available at this time. Here, we review the current evidence for the prognostic potential of DNA methylation markers in PC.

An accurate algorithm to match imperfectly matched images for lung tumor detection without markers.

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Rozario, Timothy; Bereg, Sergey; Yan, Yulong; Chiu, Tsuicheng; Liu, Honghuan; Kearney, Vasant; Jiang, Lan; Mao, Weihua

2015-05-08

In order to locate lung tumors on kV projection images without internal markers, digitally reconstructed radiographs (DRRs) are created and compared with projection images. However, lung tumors always move due to respiration and their locations change on projection images while they are static on DRRs. In addition, global image intensity discrepancies exist between DRRs and projections due to their different image orientations, scattering, and noises. This adversely affects comparison accuracy. A simple but efficient comparison algorithm is reported to match imperfectly matched projection images and DRRs. The kV projection images were matched with different DRRs in two steps. Preprocessing was performed in advance to generate two sets of DRRs. The tumors were removed from the planning 3D CT for a single phase of planning 4D CT images using planning contours of tumors. DRRs of background and DRRs of tumors were generated separately for every projection angle. The first step was to match projection images with DRRs of background signals. This method divided global images into a matrix of small tiles and similarities were evaluated by calculating normalized cross-correlation (NCC) between corresponding tiles on projections and DRRs. The tile configuration (tile locations) was automatically optimized to keep the tumor within a single projection tile that had a bad matching with the corresponding DRR tile. A pixel-based linear transformation was determined by linear interpolations of tile transformation results obtained during tile matching. The background DRRs were transformed to the projection image level and subtracted from it. The resulting subtracted image now contained only the tumor. The second step was to register DRRs of tumors to the subtracted image to locate the tumor. This method was successfully applied to kV fluoro images (about 1000 images) acquired on a Vero (BrainLAB) for dynamic tumor tracking on phantom studies. Radiation opaque markers were

A novel method for monitoring high-risk breast cancer with tumor markers

DEFF Research Database (Denmark)

Sölétormos, G; Nielsen, D; Schiøler, V

1993-01-01

cancer. METHODS: Ninety females with high-risk breast cancer were included in the study. Response evaluation was based upon clinical examination, x-rays or histology and elaborated marker criteria. RESULTS: During the marker monitoring period, metastases in four patients were confined to skin or lymph......BACKGROUND: An early and reliable diagnosis of metastatic spread has increased interest in serum tumor markers. This study investigated the ability of CA 15.3, CEA, and TPA to identify, predict, and exclude metastases in bone/viscera during adjuvant treatment and follow-up of high-risk breast...

Clinical value of combined detection of tumor markers in effusion fluid for diagnosis of malignant pleural effusion and ascites

International Nuclear Information System (INIS)

Li Jiangang; Ji Zhigu; Cui Xuejun; Zhu Zili

2010-01-01

Objective: To study the clinical usefulness of combined detection of tumor markers in effusion fluid in patients with malignant pleural effusion or ascites. Methods: Combined detection of six tumor markers (CA125, CA50, CA15-3, CYFRA21-1, βHCG, HCG) in effusion fluid was performed in 92 patients with malignant pleural effusion and 78 patients with malignant ascites as well as 100 control benign specimens. These tumor markers were examined with CLIA, except CA50, which was examined with RIA. Exfoliative cytology was also examined in the malignant specimens. Results: The positive rate of these markers was highest with CA125, followed by CA50, CA15-3, CYFRA21-1, βHCG and HCG in order. βHCG and HCG, though with quite low positive rate, were still useful markers due to the almost zero false-positive rate, i.e. very high specificity. For combined determination of two markers, CA15 + CYFRA21-1 or CA125 + CA50 would result in the highest positive rate. For highly suspected but undetermined cases, the following criteria for malignancy would be helpful: (1) two or more positive among CA125, CA50, CA15-3, CYFRA21-1 (2) One of the four CAs positive + either βHCG or HCG (3) Both βHCG and HCG positive. Tumor markers positiveness would be supplementary to doubtful cytological studies. Conclusion: Combined detection of tumor markers in effusion fluid would be very helpful for diagnosis of malignancy. (authors)

Serum CA 125, carcinoembryonic antigen, and CA 19-9 as tumor markers in borderline ovarian tumors

NARCIS (Netherlands)

Engelen, MJA; de Bruijn, HWA; Hollema, H; ten Koor, KA; Willemse, PHB; Aalders, JG; van der Zee, AGJ

Objectives. The goals of this study were to analyze preoperative serum levels of CA 125, carcinoembryonic antigen (CEA), and CA 19-9 in patients with borderline ovarian tumors and to investigate if routine assessment of these markers in follow-up may lead to earlier detection of recurrence. Methods.

Nectin-4 is a new histological and serological tumor associated marker for breast cancer

International Nuclear Information System (INIS)

Fabre-Lafay, Stéphanie; Geneix, Jeannine; Lecocq, Eric; Popovici, Cornel; Dubreuil, Patrice; Viens, Patrice; Gonçalves, Anthony; Charafe-Jauffret, Emmanuelle; Jacquemier, Jocelyne; Birnbaum, Daniel; Lopez, Marc; Monville, Florence; Garrido-Urbani, Sarah; Berruyer-Pouyet, Carole; Ginestier, Christophe; Reymond, Nicolas; Finetti, Pascal; Sauvan, Richard; Adélaïde, José

2007-01-01

Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research. Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma. Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC), respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC) at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test. Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels correlate with the number of metastases (P = 0.038). Serum

Nectin-4 is a new histological and serological tumor associated marker for breast cancer

Directory of Open Access Journals (Sweden)

Sauvan Richard

2007-05-01

Full Text Available Abstract Introduction Breast cancer is a complex and heterogeneous disease at the molecular level. Evolution is difficult to predict according to classical histoclinical prognostic factors. Different studies highlight the importance of large-scale molecular expression analyses to improve taxonomy of breast cancer and prognostic classification. Identification of new molecular markers that refine this taxonomy and improve patient management is a priority in the field of breast cancer research. Nectins are cell adhesion molecules involved in the regulation of epithelial physiology. We present here Nectin-4/PVRL4 as a new histological and serological tumor associated marker for breast carcinoma. Methods Expression of Nectin-4 protein was measured on a panel of 78 primary cells and cell lines from different origins and 57 breast tumors by FACS analysis and immunohistochemistry (IHC, respectively. mRNA expression was measured by quantitative PCR. Serum Nectin-4 was detected by ELISA and compared with CEA and CA15.3 markers, on panels of 45 sera from healthy donors, 53 sera from patients with non-metastatic breast carcinoma (MBC at diagnosis, and 182 sera from patients with MBC. Distribution of histological/serological molecular markers and histoclinical parameters were compared using the standard Chi-2 test. Results Nectin-4 was not detected in normal breast epithelium. By contrast, Nectin-4 was expressed in 61% of ductal breast carcinoma vs 6% in lobular type. Expression of Nectin-4 strongly correlated with the basal-like markers EGFR, P53, and P-cadherin, and negatively correlated with the luminal-like markers ER, PR and GATA3. All but one ER/PR-negative tumors expressed Nectin-4. The detection of Nectin-4 in serum improves the follow-up of patients with MBC: the association CEA/CA15.3/Nectin-4 allowed to monitor 74% of these patients compared to 67% with the association CEA/CA15.3. Serum Nectin-4 is a marker of disease progression, and levels

Comparison of LUMIPULSE(®) G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers.

Science.gov (United States)

Marlet, Julien; Bernard, Maguy

2016-01-01

Tumor marker measurements are becoming essential for prognosis and follow-up of patients in oncology. In this context, we aimed to compare a new analyzer, Lumipulse(®) G1200 (Fujirebio group, distributed in Europe by the Innogenetics group) with Kryptor(®) (Thermo Fisher Scientific B.R.A.H.M.S, Asnières, France) and Modular(®) Elecsys E170 (Roche Diagnostics, Meylan, France) for the measurement of seven tumor markers: PSA, AFP, CEA, CA 15-3, CA 125, CA 19-9, and Cyfra 21-1. A total of 471 serum samples from patients with elevated tumor markers and 100 serum from healthy patients were analyzed with Lumipulse(®) G1200 and either Kryptor(®) (for AFP) or Modular(®) (for the six other markers). The good precision of Lumipulse(®) G1200 assays was confirmed with CVs Lumipulse results were well correlated with Modular or Kryptor results (r ≥ 0.94). Concordance of results interpretation was > 95% and tumor marker kinetics were all similar. We confirmed the analytical performances of Lumipulse(®) tumor marker assays except for the CYFRA 21-1 assay for which performances were poor in this study. We noticed a few discrepancies for the CEA assay. Besides, values obtained for CA 19-9 were higher with Lumipulse leading to a bias (slope = 1.5). But for the four other tumor markers assays (PSA, AFP, CA 125, CA 15-3), the results were directly transferable between Lumipulse and Kryptor or Modular, thus facilitating an eventual substitution of one system by another. © 2014 Wiley Periodicals, Inc.

Proteomic analysis of cerebrospinal fluid from children with central nervous system tumors identifies candidate proteins relating to tumor metastatic spread.

Science.gov (United States)

Spreafico, Filippo; Bongarzone, Italia; Pizzamiglio, Sara; Magni, Ruben; Taverna, Elena; De Bortoli, Maida; Ciniselli, Chiara M; Barzanò, Elena; Biassoni, Veronica; Luchini, Alessandra; Liotta, Lance A; Zhou, Weidong; Signore, Michele; Verderio, Paolo; Massimino, Maura

2017-07-11

Central nervous system (CNS) tumors are the most common solid tumors in childhood. Since the sensitivity of combined cerebrospinal fluid (CSF) cytology and radiological neuroimaging in detecting meningeal metastases remains relatively low, we sought to characterize the CSF proteome of patients with CSF tumors to identify biomarkers predictive of metastatic spread. CSF samples from 27 children with brain tumors and 13 controls (extra-CNS non-Hodgkin lymphoma) were processed using core-shell hydrogel nanoparticles, and analyzed with reverse-phase liquid chromatography/electrospray tandem mass spectrometry (LC-MS/MS). Candidate proteins were identified with Fisher's exact test and/or a univariate logistic regression model. Reverse phase protein array (RPPA), Western blot (WB), and ELISA were used in the training set and in an independent set of CFS samples (60 cases, 14 controls) to validate our discovery findings. Among the 558 non-redundant proteins identified by LC-MS/MS, 147 were missing from the CSF database at http://www.biosino.org. Fourteen of the 26 final top-candidate proteins were chosen for validation with WB, RPPA and ELISA methods. Six proteins (type 1 collagen, insulin-like growth factor binding protein 4, procollagen C-endopeptidase enhancer 1, glial cell-line derived neurotrophic factor receptor α2, inter-alpha-trypsin inhibitor heavy chain 4, neural proliferation and differentiation control protein-1) revealed the ability to discriminate metastatic cases from controls. Combining a unique dataset of CSFs from pediatric CNS tumors with a novel enabling nanotechnology led us to identify CSF proteins potentially related to metastatic status.

Evaluation of Tumor Shape Variability in Head-and-Neck Cancer Patients Over the Course of Radiation Therapy Using Implanted Gold Markers

International Nuclear Information System (INIS)

Hamming-Vrieze, Olga; Kranen, Simon Robert van; Beek, Suzanne van; Heemsbergen, Wilma; Herk, Marcel van; Brekel, Michiel Wilhelmus Maria van den; Sonke, Jan-Jakob; Rasch, Coenraad Robert Nico

2012-01-01

Purpose: This study quantifies tumor shape variability in head-and-neck cancer patients during radiation therapy using implanted markers. Methods and Materials: Twenty-seven patients with oropharyngeal tumors treated with (chemo)radiation were included. Helical gold markers (0.35 × 2 mm, 3-10/patient, average 6) were implanted around the tumor. Markers were identified on planning computed tomography (CT) and daily cone beam CT (CBCT). After bony anatomy registration, the daily vector length on CBCT in reference to the planning CT and daily marker movement perpendicular to the gross tumor volume (GTV) surface at planning CT (d normal ) of each marker were analyzed. Time trends were assessed with linear regression of the normal > markers . In 2 patients, 2 markers were implanted in normal tissue to evaluate migration by measuring intermarker distances. Results: Marker implantation was feasible without complications. Three-dimensional vectors (4827 measurements, mean 0.23 cm, interquartile ratio 0.24 cm) were highest in base of tongue sublocalization (P<.001) and bulky tumors (vectors exceeded 0.5 cm in 5.7% [0-20 mL], 12.0% [21-40 mL], and 21.7% [≥41 mL], respectively [P<.001] of measurements). The measured inward time trend in 11/27 patients correlated with the visual observed marker pattern. In patients with an outward trend (5/27) or no trend (11/27), visual observation showed predominantly an inhomogeneous pattern. Remarkably, in 6 patients, outward marker movement was observed in the posterior pharyngeal wall. The difference in distance between normal tissue markers (1 SD) was 0.05-0.06 cm without time trend, indicating that implanted markers did not migrate. Conclusions: During head-and-neck radiation therapy, normal tissue markers remained stable. Changes in position of tumor markers depended on sublocalization and tumor volume. Large differences in marker patterns between patients as well as within patients were observed. Based on our study, the cranial

Tumor endothelial markers define novel subsets of cancer-specific circulating endothelial cells associated with antitumor efficacy

Science.gov (United States)

Mehran, Reza; Nilsson, Monique; Khajavi, Mehrdad; Du, Zhiqiang; Cascone, Tina; Wu, Hua Kang; Cortes, Andrea; Xu, Li; Zurita, Amado; Schier, Robert; Riedel, Bernhard; El-Zein, Randa; Heymach, John V.

2014-01-01

Circulating endothelial cells (CEC) are derived from multiple sources including bone marrow (circulating endothelial progenitors [CEP]) and established vasculature (mature CEC). Although CEC have shown promise as a biomarker for cancer patients, their utility has been limited in part by the lack of specificity for tumor vasculature and the different non-malignant causes that can impact CEC. Tumor endothelial markers (TEM) are antigens enriched in tumor vs non-malignant endothelia. We hypothesized that TEMs may be detectable on CEC and that these circulating TEM+ endothelial cells (CTEC) may be a more specific marker for cancer and tumor response than standard CEC. We found that tumor-bearing mice had a relative increase in numbers of circulating CTEC, specifically with increased levels of TEM7 and TEM8 expression. Following treatment with various vascular targeting agents, we observed a decrease in CTEC that correlated with the reductions in tumor growth. We extended these findings to human clinical samples and observed that CTEC were present in esophageal cancer and non-small cell lung cancer (NSCLC) patients (N=40) and their levels decreased after surgical resection. These results demonstrate that CTEC are detectable in preclinical cancer models and cancer patients. Further, they suggest that CTEC offer a novel cancer-associated marker that may be useful as a blood-based surrogate for assessing the presence of tumor vasculature and antiangiogenic drug activity. PMID:24626092

Pre-treatment double- or triple-positive tumor markers are predictive of a poor outcome for patients undergoing radiofrequency ablation for hepatocellular carcinoma.

Science.gov (United States)

Nitta, Hidetoshi; Nakagawa, Shigeki; Kaida, Takayoshi; Arima, Kota; Higashi, Takaaki; Taki, Katsunobu; Okabe, Hirohisa; Hayashi, Hiromitsu; Hashimoto, Daisuke; Chikamoto, Akira; Ishiko, Takatoshi; Beppu, Toru; Baba, Hideo

2017-03-01

We evaluated the therapeutic effect of radiofrequency ablation (RFA) on hepatocellular carcinoma (HCC) according to the number of positive tumor markers. The subjects of this study were 160 patients who underwent percutaneous and surgical RFA for HCC. Patients were divided into negative (n = 51), single- (n = 69), double- (n = 31), and triple-positive (n = 9) tumor marker groups according to the pre-treatment expression of these markers. We looked for any relationships among clinical parameters, outcomes, and tumor markers. The 3-year recurrence-free and overall survival rates of the negative, single-, double-, and triple-positive groups were 30, 19, 16, and 11 % (P = 0.02), and 94, 88, 67, and 37 % (P tumor marker profile was independently associated with local recurrence [hazard ratio (HR) 5.48, 95 % confidence interval (CI) 2.44-12.33, P tumor markers.

Evaluation of Tumor Markers and Their Impact on Prognosis in Gallbladder, Bile Duct and Cholangiocellular Carcinomas - A Pilot Study.

Science.gov (United States)

Liska, Vaclav; Treska, Vladislav; Skalicky, Tomas; Fichtl, Jakub; Bruha, Jan; Vycital, Ondrej; Topolcan, Ondrej; Palek, Richard; Rosendorf, Jachym; Polivka, Jiri; Holubec, Lubos

2017-04-01

The behavior of tumor markers in biliary tract malignancies is not well-known and has been scarcely studied. Such markers could play important roles in diagnostic and prognostic schemes as well as in decision-making about the best treatment strategies. This study analyzed the preoperative serum levels of conventional tumor markers (AFP, CEA, CA 19-9, CA 72-4), proliferative marker thymidine kinase (TK) and cytokeratins (TPA, TPS and CYFRA 21.1) in patients with gallbladder carcinoma, bile duct carcinoma (Klatskin) and cholangiocellular carcinoma, in relation to the patient prognosis. The study aimed in finding the role of tumor markers in not properly investigated diseases, where their importance is often marginalized. The study included 43 patients, who underwent either radical surgical procedure (n=21) or explorative laparotomy without any surgical treatment (n=22) for gallbladder carcinoma, bile duct carcinoma (Klatskin tumor) and cholangiocellular carcinoma (24, 8 and 11 patients, respectively) between 2003 and 2010 at our Department. The association of serum tumor markers and patients' prognosis were assessed for the entire cohort and for each cancer type and also with regard to treatment (radical surgery versus explorative laparotomy). Overall survival (OS) and disease-free interval (DFI) were estimated by the Kaplan-Meier method and statistically evaluated using the LogRank test. DFI was computed only in the subgroup of patients treated by radical surgery. The statistical analysis of tumor markers revealed TK as a poor prognostic factor for shorter DFI (HR=3.5, 95%CI=0.6-21.3, ptumor markers for assessment of prognosis (OS or DFI) in patients with gallbladder carcinoma, bile duct carcinoma, and cholangiocellular carcinoma. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Aerobic Glycolysis as a Marker of Tumor Aggressiveness: Preliminary Data in High Grade Human Brain Tumors

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Andrei G. Vlassenko

2015-01-01

Full Text Available Objectives. Glucose metabolism outside of oxidative phosphorylation, or aerobic glycolysis (AG, is a hallmark of active cancer cells that is not directly measured with standard 18F-fluorodeoxyglucose (FDG positron emission tomography (PET. In this study, we characterized tumor regions with elevated AG defined based on PET measurements of glucose and oxygen metabolism. Methods. Fourteen individuals with high-grade brain tumors underwent structural MR scans and PET measurements of cerebral blood flow (CBF, oxygen (CMRO2 and glucose (CMRGlu metabolism, and AG, using 15O-labeled CO, O2 and H2O, and FDG, and were compared to a normative cohort of 20 age-matched individuals. Results. Elevated AG was observed in most high-grade brain tumors and it was associated with decreased CMRO2 and CBF, but not with significant changes in CMRGlu. Elevated AG was a dramatic and early sign of tumor growth associated with decreased survival. AG changes associated with tumor growth were differentiated from the effects of nonneoplastic processes such as epileptic seizures. Conclusions. Our findings demonstrate that high-grade brain tumors exhibit elevated AG as a marker of tumor growth and aggressiveness. AG may detect areas of active tumor growth that are not evident on conventional FDG PET.

Model-Independent Evaluation of Tumor Markers and a Logistic-Tree Approach to Diagnostic Decision Support

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Weizeng Ni

2014-01-01

Full Text Available Sensitivity and specificity of using individual tumor markers hardly meet the clinical requirement. This challenge gave rise to many efforts, e.g., combing multiple tumor markers and employing machine learning algorithms. However, results from different studies are often inconsistent, which are partially attributed to the use of different evaluation criteria. Also, the wide use of model-dependent validation leads to high possibility of data overfitting when complex models are used for diagnosis. We propose two model-independent criteria, namely, area under the curve (AUC and Relief to evaluate the diagnostic values of individual and multiple tumor markers, respectively. For diagnostic decision support, we propose the use of logistic-tree which combines decision tree and logistic regression. Application on a colorectal cancer dataset shows that the proposed evaluation criteria produce results that are consistent with current knowledge. Furthermore, the simple and highly interpretable logistic-tree has diagnostic performance that is competitive with other complex models.

Cell proliferation markers in the transplanted canine transmissible venereal tumor

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F.G.A. Santos

2011-12-01

Full Text Available Adult male mongrel dogs were subcutaneously transplanted with the canine transmissible venereal tumor (TVT on the hypogastric region. Twelve specimens of tumors were collected, half during the proliferative phase and the other half during the regressive phase. Fragments of the tumor were fixed in 10% buffered formalin and routinely processed for light microscopy. Sections of 4µm were stained by Schorr or AgNOR or either immunostained for MIB1 (Ki67. Schorr stain, AgNOR and MIB1 showed an increased proliferative activity through mitotic index, nuclear argyrophilic protein stain and cycling tumoral cells in the growing tumors, respectively. All of the three cell proliferation markers were able to distinguish the TVT in both evolution phases. MIB1 monoclonal antibody was the best in the morphologic evaluation of growth and regression of TVT. This resulted in higher values than AgNORs counting and mitotic index. MIB1 immunostaining was the most effective parameter of the proliferative activity of TVT. However, a significant correlation has been detected only between mitosis counting and AgNORs.

Molecular markers for tumor cell dissemination in female cancers

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Obermayr, E.

2009-01-01

In the fight against cancer many advances have been made in early detection and treatment of the disease during the last few decades. Nevertheless, many patients still die of cancer due to metastatic spreading of the disease. Tumor cell dissemination may occur very early and usually is not discovered at the time of initial diagnosis. In these cases, the mere excision of the primary tumor is an insufficient treatment. Microscopic tumor residues will remain in the blood, lymph nodes, or the bone marrow and will cause disease recurrence. To improve the patient's prognosis, a sensitive tool for the detection of single tumor cells supplementing conventional diagnostic procedures is required. As the blood is more easily accessible than the bone marrow or tissue biopsies, we intended to identify gene markers for the detection of circulating tumor cells in the blood of cancer patients. We focused on patients with breast, ovarian, endometrial or cervical cancer. Starting from a genome-wide gene expression analysis of tumor cells and blood cells, we found six genes higher expression levels in cancer patients compared to healthy women. These findings suggest that an increased expression of these genes in the blood indicates the presence of circulating tumor cells inducing future metastases and thus the need for adjuvant therapy assisting the primary treatment. Measuring the expression levels of these six genes in the blood may supplement conventional diagnostic tests and improve the patient's prognosis. (author) [de

Correlation Between Bone Scintigraphy and Tumor Markers in Patients with Breast Carcinoma

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Amela Begić

2006-02-01

Full Text Available A characteristic feature of many cancer types is their ability to metastasise to the skeleton. Bone is the most common site of metastatic invasion, after hematogenous spreading of breast cancer. Early detection of bone metastases is mandatory in the evaluation and management of these patients. Bone scintigraphy is commonly performed in detection and evaluation bone metastases. Tumor markers are present in healthy individuals as well as in patients with malignant diseases but in different concentration. Aim of study was to correlate serum levels of tumor marker Ca (15-3, CEA and presence of bone metastases detected by bone scintigraphy. Study included 25 patients with breast cancer, previously surgically treated. All patients underwent whole body scintigraphy. Ca (15-3 and CEA was measured by radioimmunoassay. Presence, number of bone metastases were correlated with Ca (15-3 and CEA levels. Median age of patients included in study was 50 varying from 30 to 67. Bone scintigraphy revealed bone metastases in 16 (64% patients. A weak correlation was found between number of metastases and level of Ca (15-3 (r=0.139, p=0.254. Significant differences in Ca (15-3 level was found in patient with metastases compared to patients without metastases (chi square 0, p=1.0. Good correlation was found between number of metastases and serum level of CEA. Correlation between level of two tumor markers Ca (15-3 and CEA was a weak (r = 0.096 , p=0.323. Bone scintigraphy is a sensitive diagnostic toll for detecting breast cancer metastases to bone. Serum levels of tumor markes in isolation can not give complete accuracy about bone metastases.

Clinical evaluation of thyroxine-binding globulin (TBG) as a marker of liver tumors

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Terui, S

1984-03-01

This investigation was undertaken to evaluate thyroxine-binding globulin (TGB) as a marker of liver tumors, in conjection with the liver scintigram. Of 30 patients with primary hepatocellular carcinoma (PHC), 22 (73.3%) showed significantly higher TBG concentrations. Eight patients (26.7%) showed normal TBG concentrations. In the case of 27 our of 30 patients with definite liver tumors, defects were apparent on the scintigrams. But seven of them had normal TBG concentrations in spite of the defects on the scintigrams. Out of 33 postoperative patients with liver metastasis, 28 (84%) had a raised TBG concentration. Only five (15.2%) had a normal TBG level. In 31 patients (93.9%) out of 33 with liver metastasis, a definite diagnosis was made on the basis of the liver scintigram. In 28 (90.3%) of these 31 people, the TBG concentration was higher than normal. Among 63 patients with liver tumors, both primary and metastatic, the test sensitivity for liver tumors was 92.1% (58/63) based on the accuracy of the liver scintigram. It was 79.4% (50/63) based on the TBG measurement. Why TBG increases to such an extent in spite of the euthyroid state remains unexplained. But it may be concluded that elevated TBG with positive liver scintigram furnishes a sensitive, fairly reliable, nonspecific tumor marker to determine liver tumors, especially in the case of liver metastasis.

Clinical evaluation of thyroxine-binding globulin (TBG) as a marker of liver tumors

International Nuclear Information System (INIS)

Terui, S.

1984-01-01

This investigation was undertaken to evaluate thyroxine-binding globulin (TGB) as a marker of liver tumors, in conjection with the liver scintigram. Of 30 patients with primary hepatocellular carcinoma (PHC), 22 (73.3%) showed significantly higher TBG concentrations. Eight patients (26.7%) showed normal TBG concentrations. In the case of 27 our of 30 patients with definite liver tumors, defects were apparent on the scintigrams. But seven of them had normal TBG concentrations in spite of the defects on the scintigrams. Out of 33 postoperative patients with liver metastasis, 28 (84%) had a raised TBG concentration. Only five (15.2%) had a normal TBG level. In 31 patients (93.9%) out of 33 with liver metastasis, a definite diagnosis was made on the basis of the liver scintigram. In 28 (90.3%) of these 31 people, the TBG concentration was higher than normal. Among 63 patients with liver tumors, both primary and metastatic, the test sensitivity for liver tumors was 92.1% (58/63) based on the accuracy of the liver scintigram. It was 79.4% (50/63) based on the TBG measurement. Why TBG increases to such an extent in spite of the euthyroid state remains unexplained. But it may be concluded that elevated TBG with positive liver scintigram furnishes a sensitive, fairly reliable, nonspecific tumor marker to determine liver tumors, especially in the case of liver metastasis. (orig.)

Clinical Significance of Tumor Marker Detection in Patients 
with Advanced Squamous Cell Carcimoma of the Lung

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Ping LIANG

2016-10-01

Full Text Available Background and objective Due to it's concealment and no obvious symptoms, lung squamous carcimoma often has advanced disease when diagnosed. The aims of this study were to describe the characteristics of the disease, to evaluate the clinical importance of detection of multiple tumor markers in patients with squamous cell carcinoma of the lung. Methods The characteristics of all patients with advanced squamous cell lung cancer treated in Beijing Cancer Hospital of Chinese Academy of Medical Sciences during Jan. 2011 to Dec. 2015 were identified by cases reviewing and data extracting. The characteristics, detection levels and sensitivity of multiple tumor makers among patients were described. Results The 260 patients were treated with mean age of (59.4±9.2 years, 85.8% (n=223 of them were male, 14.2% (n=37 of them were female. 78.1% (n=203 of all were smokers and 3.1% (n=8 of patients had family history of tumor. The positive rate of cytokerantin 19 fragment (CYFRA21-1 was 71.2%, which was the highest among five tumor markers. The five tumor markers median level had no statistical significance between different tumor (T stages and node (N stages (all P>0.05, only the positive rate of SCC had statistical significance between different T stages (P=0.035. The combination measurement of CYFRA21-1+carcinogen-embryonic antigen (CEA, CYFRA21-1+CEA+cancer antigen (CA125, CA125+CYFRA21-1+CEA+neuron specific enolase (NSE, and CA125+CYFRA21-1+NSE+CEA+squamous cell carcinoma antigen (SCC were better and had higher clinical values, the positive rates were 82.7%, 84.6%, 85.0% and 86.2%, respectively. Conclusion The positive rate of CYFRA21-1 was the highest and the sensitivity of single test of five tumor markers was low, the combination of multiple tumor markers increased the sensitivity of diagnosis of SQCLC, the combination of CA125, CYFRA21-1 and CEA was the best choice.

Viral-Cellular DNA Junctions as Molecular Markers for Assessing Intra-Tumor Heterogeneity in Cervical Cancer and for the Detection of Circulating Tumor DNA

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Katrin Carow

2017-09-01

Full Text Available The development of cervical cancer is frequently accompanied by the integration of human papillomaviruses (HPV DNA into the host genome. Viral-cellular junction sequences, which arise in consequence, are highly tumor specific. By using these fragments as markers for tumor cell origin, we examined cervical cancer clonality in the context of intra-tumor heterogeneity. Moreover, we assessed the potential of these fragments as molecular tumor markers and analyzed their suitability for the detection of circulating tumor DNA in sera of cervical cancer patients. For intra-tumor heterogeneity analyses tumors of 8 patients with up to 5 integration sites per tumor were included. Tumor islands were micro-dissected from cryosections of several tissue blocks representing different regions of the tumor. Each micro-dissected tumor area served as template for a single junction-specific PCR. For the detection of circulating tumor-DNA (ctDNA junction-specific PCR-assays were applied to sera of 21 patients. Samples were collected preoperatively and during the course of disease. In 7 of 8 tumors the integration site(s were shown to be homogenously distributed throughout different tumor regions. Only one tumor displayed intra-tumor heterogeneity. In 5 of 21 analyzed preoperative serum samples we specifically detected junction fragments. Junction-based detection of ctDNA was significantly associated with reduced recurrence-free survival. Our study provides evidence that HPV-DNA integration is as an early step in cervical carcinogenesis. Clonality with respect to HPV integration opens new perspectives for the application of viral-cellular junction sites as molecular biomarkers in a clinical setting such as disease monitoring.

Endothelial cell marker PAL-E reactivity in brain tumor, developing brain, and brain disease

NARCIS (Netherlands)

Leenstra, S.; Troost, D.; Das, P. K.; Claessen, N.; Becker, A. E.; Bosch, D. A.

1993-01-01

The endothelial cell marker PAL-E is not reactive to vessels in the normal brain. The present study concerns the PAL-E reactivity in brain tumors in contrast to normal brain and nonneoplastic brain disease. A total of 122 specimens were examined: brain tumors (n = 94), nonneoplastic brain disease (n

Elevated levels of serum tumor markers CA 15-3 and CEA are prognostic factors for diagnosis of metastatic breast cancers.

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Lee, Jun Sang; Park, Seho; Park, Ji Min; Cho, Jung Hoon; Kim, Seung Il; Park, Byeong-Woo

2013-10-01

To investigate the prognostic value of tumor markers, cancer antigen 15-3 (CA 15-3) and carcinoembryonic antigen (CEA) levels at diagnosis of systemic recurrence. After primary treatments of locoregional breast cancers, serum CA 15-3 and/or CEA concentrations were regularly measured, and systemic recurrences were identified in 351 patients between January 1999 and December 2009. The association between tumor marker levels at systemic recurrence and survival were investigated by univariate and multivariate analyses. Elevated CA 15-3 and CEA levels were identified in 194 of 349 (55.6 %) and 111 of 308 (36.0 %) patients, respectively, at diagnosis of systemic recurrence. Elevated levels of CA 15-3 and CEA were correlated with visceral or multiple recurrences and elevated preoperative levels. Elevation of CA 15-3 was more prominent in younger patients and in primary node-positive tumors, while CEA was elevated in older patients at diagnosis and in estrogen receptor (ER)-positive tumors. Elevated tumor markers as well as ER negativity, short disease-free interval, and advanced stage at initial diagnosis showed independent prognostic significance on multivariate analysis. Among 306 patients for whom levels of both tumor markers at recurrence were available, 106 patients without elevation of either marker showed significantly better overall survival than those with elevated levels of either one or both markers, and the significance persisted in multivariate analysis. Elevated serum CA 15-3 and CEA levels at recurrence suggest increased tumor burden and may be prognostic for survival for metastatic breast cancer patients.

Rex3 (reduced in expression 3) as a new tumor marker in mouse hepatocarcinogenesis

International Nuclear Information System (INIS)

Braeuning, Albert; Jaworski, Maike; Schwarz, Michael; Koehle, Christoph

2006-01-01

In a previous microarray expression analysis, Rex3, a gene formerly not linked to tumor formation, was found to be highly overexpressed in both Ctnnb1-(β-Catenin) and Ha-ras-mutated mouse liver tumors. Subsequent analyses by in situ hybridization and real-time PCR confirmed a general liver tumor-specific overexpression of the gene (up to 400-fold). To investigate the role of Rex3 in liver tumors, hepatoma cells were transfected with FLAG- and Myc-tagged Rex3 expression vectors. Rex3 was shown to be exclusively localized to the cytoplasm, as determined by fluorescence microscopy and Western blotting. However, forced overexpression of Rex3 did not significantly affect proliferation or stress-induced apoptosis of transfected mouse hepatoma cells. Rex3 mRNA was determined in primary hepatocytes in culture by real-time PCR. In primary mouse hepatocytes, expression of Rex3 increased while cells dedifferentiated in culture. This effect was abolished when hepatocytes were maintained in a differentiated state. Furthermore, expression of Rex3 decreased in mouse liver with age of mice and the expression profile was highly correlated to that of the tumor markers α-fetoprotein and H19. The findings suggest a role of Rex3 as a marker for hepatocyte differentiation/dedifferentiation processes and tumor formation

Development of RIA kits for tumor-markers monitoring

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Suprarop, P.

1997-01-01

All reagents for tumor markers assays are imported from various manufacturers mainly CIS bio international. The average cost of these reagents is ranged from 80-150 bath/test (2-4 dollars test). The screening test for cancers could not be done especially in other regions of Thailand whose budgets and resources are so limited. If the reagents are made locally, many laboratories can perform the tests and use as primary diagnosis, screening or monitor the course of the disease following treatment. In addition, these reagents could help clinicians and give complementary information on the tumor status to improve quality of life in Thailand. Research objectives include: 1. Development of IRMA reagent kits suitable for diagnosing staging and monitoring prostrate and breast cancer. 2. Transfer of technology and reagent kits to relevant laboratories in Thailand. 3. Routine distribution of the reagents kits to the end users

Variation of stemness markers expression in tumor nodules from synchronous multi-focal hepatocellular carcinoma - an immunohistochemical study.

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Lo, Regina Cheuk-Lam; Leung, Carmen Oi-Ning; Chok, Kenneth Siu-Ho; Ng, Irene Oi-Lin

2017-08-01

Advancing knowledge in molecular pathogenesis of hepatocellular carcinoma (HCC) opens up new horizons in the diagnostic, prognostic and therapeutic perspectives. Assessing the expression of molecular targets prior to definitive treatment is gaining importance in clinical practice. In this study, we investigated the variation in expression pattern of stemness markers in synchronous multi-focal HCC. In the first cohort, 21 liver explants with multi-focal HCC were examined for expression of stemness markers EpCAM, Sox9 and CK19 by immunohistochemistry (IHC). Expression data of 50 tumor nodules were analyzed to determine the concordance of expression among nodules in the same livers. In the second cohort, 14 tumor nodules from 6 multi-focal HCC cases proven as intra-hepatic metastasis were examined for Soc9 immunoexpression. In the first cohort, thirty nodules from 16 cases expressed one or more markers, with Sox9 being most frequently expressed. Complete concordance of expression pattern for all 3 markers was observed in 6 cases. Discrepancy of staining degree was noted in 4 cases for EpCAM, 14 cases for Sox9, and 6 cases for CK19. A two-tier or three-tier difference in staining scores was noted in 5 cases for Sox9 and one case for CK19. With Sox9, identical tumor morphology in terms of Edmondson grading and growth pattern did not infer the same degree of immunoexpression; and the largest tumor nodule was not representative of highest IHC score. In the second cohort of intra-hepatic metastasis, complete concordance of Sox9 expression level was observed in 5 out of 6 cases; while the remaining case showed a 1-tier difference of positive staining. Our findings suggested that clonality of tumor nodules is apparently an important factor to infer immunoexpression pattern. When there is limited information to discern multiple primaries versus intra-hepatic metastasis in multi-focal HCC, discordant degree of stemness markers expression among tumor nodules was commonly

Comparison of bone scintigraphy with serum tumor markers of CA 15-3 and carcinoembryonic antigen in patients with breast carcinoma

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Gedik, G. K.; Kiratli, P.O.; Aras, T.; Tascioglu, B.

2006-01-01

To compare the bone scintigraphy findings with a carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA 15-3) levels in breast carcinoma patients. We also investigated the relationship between anatomical bone type and its effect on tumor marker levels. The study was consisted of retrospective evaluation of 120 bone scans of patients with breast carcinoma admitted to the Nuclear Medicine Department, Medical Faculty, Hacettepe University, Ankara, Turkey between January 2003 and December 2004. The mean age of the patients was 54.7 years. We grouped the results of the bone scans into 3 as normal, equivocal and metastatic. Carcinoembryonic antigen and CA 15-3 levels were recorded from the files of the patients. Upper cut levels of 4.8 U/ml for CEA and 38 U/ml for CA 15-3 was accepted. Metastatic bone areas were distributed according to their anatomical location as long, short, flat, irregular and sesamoid and effect of bone type on tumor marker was investigated. In 16 of the patients, bone scintigraphy revealed metastases. Sixty-one patients had normal scans and in 47 patients metastases could not be ruled out. In patients with metastases, CA 15-3 was elevated in 8 and CEA was higher than the upper limit in 6. For CEA and CA 15-3, the anatomical type of bone has no any effect on serum tumor marker concentration between patients with normal and elevated levels of tumor markers in metastatic patients. Tumor markers are not solely enough in predicting bone metastases. Bone scintigraphy and tumor markers should be both used in management of patients with breast carcinoma. The anatomical type of bone has no any effect on elevation of serum tumor marker concentration. (author)

Clinical significance of serum tumor markers for gastric cancer: a systematic review of literature by the Task Force of the Japanese Gastric Cancer Association.

Science.gov (United States)

Shimada, Hideaki; Noie, Tamaki; Ohashi, Manabu; Oba, Koji; Takahashi, Yutaka

2014-01-01

The aim of this review was to evaluate the clinical significance of serum tumor markers, particularly CEA, CA19-9, and CA72-4, in patients with gastric cancer. A systematic literature search was performed using PubMed/MEDLINE with the keywords "gastric cancer" and "tumor marker," to select 4,925 relevant reports published before the end of November 2012. A total of 187 publications contained data for CEA and CA19-9, and 19 publications contained data related to all three tumor markers. The positive rates were 21.1 % for CEA, 27.8 % for CA19-9, and 30.0 % for CA72-4. These three markers were significantly associated with tumor stage and patient survival. Serum markers are not useful for early cancer, but they are useful for detecting recurrence and distant metastasis, predicting patient survival, and monitoring after surgery. Tumor marker monitoring may be useful for patients after surgery because the positive conversion of tumor markers usually occurs 2-3 months before imaging abnormalities. Among other tumor markers, alpha-fetoprotein (AFP) is useful for detecting and predicting liver metastases. Moreover, CA125 and sialyl Tn antigens (STN) are useful for detecting peritoneal metastases. Although no prospective trial has yet been completed to evaluate the clinical significance of these serum markers, this literature survey suggests that combinations of CEA, CA19-9, and CA72-4 are the most effective ways for staging before surgery or chemotherapy. In particular, monitoring tumor markers that were elevated before surgery or chemotherapy could be useful for detection of recurrence or evaluation of the response.

Diagnostic value of combined tumor markers detection for gastric and colorectal cancers

International Nuclear Information System (INIS)

Chen Wenzhang; Dong Lin

2007-01-01

Objective: To investigate the value of combined tumor markers detection in the clinical diagnosis for gastric cancer and colorectal cancel. Methods: The serum concentration of CEA, CA199, CA125, CA242 were measured by radioimmunoassay and Immunoradioassy in 46 patients with gastric cancer, 62 patients with colorectal cancer and 30 controls. Results: The diagnostic sensitivity, specificity, and accuracy of CEA were 37.0%, 96.7%, 59.2% respectively in gastric cancer,and 51.6%, 96.7%, 66.3% respectively in colorectal cancer, those of CA199 were 47.8%, 100.0%, 65.8% in gastric cancer, and 43.5%, 100.0%, 62, 0% in colorectal cancer, those of CA125 were 41.3%, 96.7%, 63.2% in gastric cancer, and 38.7%, 100.0%, 58.7% in colorectal cancer, those of CA242 were 54.3%, 100.0%, 71.5% in gastric cancer, and 51.6%, 100.0%, 67.4% in colorectal cancer. The diagnostic sensitivity specificity and accuracy of combined four markers were 73.9%, 93.3%, 82.9% in gastric cancer, and 77.4%, 96.7%, 83.7% in colorectal cancer. Compared with the respective value of any single marker, the diagnostic sensitivity and accuracy were significantly improved (P<0.05). Conclusion: Combined tumor markers detection could improve the diagnostic sensitivity and accuracy in gastric and colorectal cancers and was helpful for screening. (authors)

Embedding filtering criteria into a wrapper marker selection method for brain tumor classification: an application on metabolic peak area ratios

International Nuclear Information System (INIS)

Kounelakis, M G; Zervakis, M E; Giakos, G C; Postma, G J; Buydens, L M C; Kotsiakis, X

2011-01-01

The purpose of this study is to identify reliable sets of metabolic markers that provide accurate classification of complex brain tumors and facilitate the process of clinical diagnosis. Several ratios of metabolites are tested alone or in combination with imaging markers. A wrapper feature selection and classification methodology is studied, employing Fisher's criterion for ranking the markers. The set of extracted markers that express statistical significance is further studied in terms of biological behavior with respect to the brain tumor type and grade. The outcome of this study indicates that the proposed method by exploiting the intrinsic properties of data can actually reveal reliable and biologically relevant sets of metabolic markers, which form an important adjunct toward a more accurate type and grade discrimination of complex brain tumors

In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors

International Nuclear Information System (INIS)

Busk, Morten; Toustrup, Kasper; Sørensen, Brita S; Alsner, Jan; Horsman, Michael R; Jakobsen, Steen; Overgaard, Jens

2011-01-01

Tumor hypoxia is linked to poor prognosis, but identification and quantification of tissue hypoxia remains a challenge. The hypoxia-specificity of HIF-1α target genes in vivo has been questioned due to the confounding influence of other microenvironmental abnormalities known to affect gene expression (e.g., low pH). Here we describe a new technique that by exploiting intratumoral oxygenation heterogeneity allows us to identify and objectively rank the most robust mRNA hypoxia biomarkers. Mice carrying human (FaDu dd ) or murine (SCCVII) tumors were injected with the PET hypoxia tracer FAZA. Four hours post-injection tumors were removed, frozen, and crushed into milligram-sized fragments, which were transferred individually to pre-weighed tubes containing RNAlater and then weighed. For each fragment radioactivity per tissue mass and expression patterns of selected mRNA biomarkers were analyzed and compared. In both tumour models, fragmentation into pieces weighing 10 to 60 mg resulted in tissue fragments with highly variable relative content of hypoxic cells as evidenced by an up to 13-fold variation in FAZA radioactivity per mass of tissue. Linear regression analysis comparing FAZA retention with patterns of gene expression in individual tissue fragments revealed that CA9, GLUT1 and LOX mRNA levels were equally and strongly correlated to hypoxic extent in FaDu dd . The same link between hypoxia and gene expression profile was observed for CA9 and GLUT1, but not LOX, in SCCVII tumors. Apparent in vivo hypoxia-specificity for other putative molecular markers of tissue hypoxia was considerably weaker. The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis) strengthen the conclusiveness on true hypoxia-specificity of candidate genes while limiting the required number of tumors. Among

In vivo Identification and Specificity assessment of mRNA markers of hypoxia in human and mouse tumors

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Horsman Michael R

2011-02-01

Full Text Available Abstract Background Tumor hypoxia is linked to poor prognosis, but identification and quantification of tissue hypoxia remains a challenge. The hypoxia-specificity of HIF-1α target genes in vivo has been questioned due to the confounding influence of other microenvironmental abnormalities known to affect gene expression (e.g., low pH. Here we describe a new technique that by exploiting intratumoral oxygenation heterogeneity allows us to identify and objectively rank the most robust mRNA hypoxia biomarkers. Methods Mice carrying human (FaDudd or murine (SCCVII tumors were injected with the PET hypoxia tracer FAZA. Four hours post-injection tumors were removed, frozen, and crushed into milligram-sized fragments, which were transferred individually to pre-weighed tubes containing RNAlater and then weighed. For each fragment radioactivity per tissue mass and expression patterns of selected mRNA biomarkers were analyzed and compared. Results In both tumour models, fragmentation into pieces weighing 10 to 60 mg resulted in tissue fragments with highly variable relative content of hypoxic cells as evidenced by an up to 13-fold variation in FAZA radioactivity per mass of tissue. Linear regression analysis comparing FAZA retention with patterns of gene expression in individual tissue fragments revealed that CA9, GLUT1 and LOX mRNA levels were equally and strongly correlated to hypoxic extent in FaDudd. The same link between hypoxia and gene expression profile was observed for CA9 and GLUT1, but not LOX, in SCCVII tumors. Apparent in vivo hypoxia-specificity for other putative molecular markers of tissue hypoxia was considerably weaker. Conclusions The portrayed technique allows multiple pairwise measurements of mRNA transcript levels and extent of hypoxia in individual tumors at a smallest possible volumetric scale which (by limiting averaging effects inherent to whole-tumor analysis strengthen the conclusiveness on true hypoxia-specificity of candidate

Phosphatidylserine is a marker of tumor vasculature and a potential target for cancer imaging and therapy

International Nuclear Information System (INIS)

Ran, Sophia; Thorpe, Philip E.

2002-01-01

Purpose: (1) To determine whether exposure of phosphatidylserine (PS) occurs on vascular endothelium in solid tumors in mice. (2) To determine whether PS exposure can be induced on viable endothelial cells in tissue culture by conditions present in the tumor microenvironment. Methods and Materials: Externalized PS in vivo was detected by injecting mice with a monoclonal anti-PS antibody and examining frozen sections of tumors and normal tissues for anti-PS antibody bound to vascular endothelium. Apoptotic cells were identified by anti-active caspase-3 antibody or by TUNEL assay. PS exposure on cultured endothelial cells was determined by 125 I-annexin V binding. Results: Anti-PS antibody bound specifically to vascular endothelium in six tumor models. The percentage of PS-positive vessels ranged from 4% to 40% in different tumor types. Vascular endothelium in normal organs was unstained. Very few tumor vessels expressed apoptotic markers. Hypoxia/reoxygenation, acidity, inflammatory cytokines, thrombin, or hydrogen peroxide induced PS exposure on cultured endothelial cells without causing loss of viability. Conclusions: Vascular endothelial cells in tumors, but not in normal tissues, externalize PS. PS exposure might be induced by tumor-associated oxidative stress and activating cytokines. PS is an abundant and accessible marker of tumor vasculature and could be used for tumor imaging and therapy

Tumor markers in the diagnosis of primary bladder cancer. A systematic review

NARCIS (Netherlands)

Glas, Afina S.; Roos, Daphne; Deutekom, Marije; Zwinderman, Aeilko H.; Bossuyt, Patrick M.; Kurth, Karl H.

2003-01-01

Purpose: We systematically reviewed the available evidence, and obtained and compared summary estimates of the sensitivity and specificity of cytology and the urine based markers bladder tumor antigen, BTA stat (Polymedco, Redmond, Washington), BTA TRAK (Polymedco), NMP22 (Matritech, Cambridge,

Dosimetric perturbation due to scattered rays released by a gold marker used for tumor tracking in external radiotherapy

International Nuclear Information System (INIS)

Habara, Kosaku; Furukawa, Takashi; Shimozato, Tomohiro; Obata, Yasunori; Aoyama, Yuichi; Kawanami, Ryota; Hayashi, Naoki; Yasui, Keisuke; Matsuura, Kanji

2011-01-01

Image-guided radiation therapy using a gold marker-based tumor tracking technique provides precise patient setup and monitoring. However, the marker consists of high-Z material, and the resulting scattered rays tend to have adverse effects on the dose distribution of radiotherapy. The purpose of this study was to evaluate the dosimetric perturbation due to the use of a gold marker for radiotherapy in the lungs. The relative dose distributions were compared with film measurement, Monte Carlo simulation, and XiO calculation with the multi grid superposition algorithm using two types of virtual lung phantoms, which were composed of tough water phantoms, tough lung phantoms, cork boards, and a 2.0-mm-diameter gold ball. No dose increase and decrease in the vicinity of the gold ball was seen in the XiO calculations, although it was seen in the film measurements and the Monte Carlo simulation. The dose perturbation due to a gold marker cannot be evaluated using XiO calculation with the superposition algorithm when the tumor is near a gold marker (especially within 0.5 cm). To rule out the presence of such dose perturbations due to a gold marker, the distance between the gold marker and the tumor must therefore be greater than 0.5 cm. (author)

Clinically Meaningful Use of Blood Tumor Markers in Oncology

OpenAIRE

Holdenrieder, Stefan; Pagliaro, Lance; Morgenstern, David; Dayyani, Farshid

2016-01-01

Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. H...

The role of tumor marker CA 15-3 in detection of breast cancer relapse after curative mastectomy

International Nuclear Information System (INIS)

Hyun, In Young; Kim, In Ho; Lee, Moon Hee; Kim, Chul Soo

2004-01-01

The purpose of this study was to determine the utility of tumor marker CA 15-3 in the following: the diagnosis of breast cancer relapse after curative mastectomy, and the differentiation of the value of tumor marker by site of metastases. Two hundred two patients (median age 48 years) with breast cancer included in the follow-up after curative mastectomy. The tumor marker CA 15-3 was determined by IRMA (CIS BIO INTERNATIONAl, France). Test values > 30 U/ml were considered elevated (positive). Among 202 patients, recurrent diseases were found in 16 patients. CA 15-3 was elevated in 5 of 16 patients with recurrences. There was no false-positive patients who had elevated CA 15-3. Sensitivity and specificity of CA 15-3 for detection of breast cancer recurrence were 31%, and 100%. CA 15-3 was elevated in all of the 4 patients with liver metastases. CA 15-3 was elevated in none of the patients who relapsed with metastasis to bone-only or contralateral breast-only. The tumor marker CA 15-3 in the detection of breast cancer relapse after curative mastectomy is specific, but not sensitive. However, it is useful to rule out liver metastases of breast cancer, which indicates bad prognosis

Irradiation-Dependent Effects on Tumor Perfusion and Endogenous and Exogenous Hypoxia Markers in an A549 Xenograft Model

International Nuclear Information System (INIS)

Fokas, Emmanouil; Haenze, Joerg; Kamlah, Florentine; Eul, Bastian G.; Lang, Nico; Keil, Boris; Heverhagen, Johannes T.; Engenhart-Cabillic, Rita; An Hanxiang; Rose, Frank

2010-01-01

Purpose: Hypoxia is a major determinant of tumor radiosensitivity, and microenvironmental changes in response to ionizing radiation (IR) are often heterogenous. We analyzed IR-dependent changes in hypoxia and perfusion in A549 human lung adenocarcinoma xenografts. Materials and Methods: Immunohistological analysis of two exogenously added chemical hypoxic markers, pimonidazole and CCI-103F, and of the endogenous marker Glut-1 was performed time dependently after IR. Tumor vessels and apoptosis were analyzed using CD31 and caspase-3 antibodies. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and fluorescent beads (Hoechst 33342) were used to monitor vascular perfusion. Results: CCI-103F signals measuring the fraction of hypoxic areas after IR were significantly decreased by approximately 50% when compared with pimonidazole signals, representing the fraction of hypoxic areas from the same tumors before IR. Interestingly, Glut-1 signals were significantly decreased at early time point (6.5 h) after IR returning to the initial levels at 30.5 h. Vascular density showed no difference between irradiated and control groups, whereas apoptosis was significantly induced at 10.5 h post-IR. DCE-MRI indicated increased perfusion 1 h post-IR. Conclusions: The discrepancy between the hypoxic fractions of CCI-103F and Glut-1 forces us to consider the possibility that both markers reflect different metabolic alterations of tumor microenvironment. The reliability of endogenous markers such as Glut-1 to measure reoxygenation in irradiated tumors needs further consideration. Monitoring tumor microvascular response to IR by DCE-MRI and measuring tumor volume alterations should be encouraged.

Study of Aided Diagnosis of Hepatic Carcinoma Based on Artificial Neural Network Combined with Tumor Marker Group

Science.gov (United States)

Tan, Shanjuan; Feng, Feifei; Wu, Yongjun; Wu, Yiming

To develop a computer-aided diagnostic scheme by using an artificial neural network (ANN) combined with tumor markers for diagnosis of hepatic carcinoma (HCC) as a clinical assistant method. 140 serum samples (50 malignant, 40 benign and 50 normal) were analyzed for α-fetoprotein (AFP), carbohydrate antigen 125 (CA125), carcinoembryonic antigen (CEA), sialic acid (SA) and calcium (Ca). The five tumor marker values were then used as ANN inputs data. The result of ANN was compared with that of discriminant analysis by receiver operating characteristic (ROC) curve (AUC) analysis. The diagnostic accuracy of ANN and discriminant analysis among all samples of the test group was 95.5% and 79.3%, respectively. Analysis of multiple tumor markers based on ANN may be a better choice than the traditional statistical methods for differentiating HCC from benign or normal.

The importance of tumor marker titers for the indication of immunoscintigraphy with monoclonal antibodies anti-CEA and anti-CA 19.9

International Nuclear Information System (INIS)

Bouvier, J.F.; Charrie, A.; Fleury-Goyon, M.C.; Chauvot, P. et; Lahneche, B.E.

1986-01-01

In 18 patients operated for malignant tumors 20 immunoscintigraphies were done with a monoclonal antibody cocktail (anti-CEA F(ab') 2 and anti-CA 19.9 F(ab') 2 ). Immediately before scintigraphy tumor marker titers in plasma were determined in all cases. Tumor marker levels corresponding to positive or doubtful scintigraphies are analysed. (Author)

Application of support vector machine model for enhancing the diagnostic value of tumor markers in gastric cancer

International Nuclear Information System (INIS)

Wang Hui; Huang Gang

2010-01-01

Objective: To evaluate the early diagnostic value of tumor markers for gastric cancer using support vector machine (SVM) model. Methods: Subjects involved in the study consisted of 262 cases with gastric cancer, 156 cases with benign gastric diseases and 149 healthy controls. From those subjects, five tumor markers, carcinoembryonic antigen (CEA), carbohydrate (CA) 125, CA19-9, alphafetoprotein (AFP) and CA50, were assayed and collected to make the datasets. To modify SVM model to fit the diagnostic classifiers, radial basis function was adopted and kernel function was optimized and validated by grid search and cross validation. For comparative study, methods of combination tests of five markers, Logistic regression, and decision tree were also used. Results: For gastric cancer, the diagnostic accuracy of the combination tests, Logistic regression, decision tree and SVM model were 46.2%, 64.5%, 63.9% and 95.1% respectively. SVM model significantly elevated the diagnostic value comparing with other three methods. Conclusion: The application of SVM model is of high value in enhancing the tumor marker for the diagnosis of gastric cancer. (authors)

Tumor markers as prognostic factors in non-small-cell lung cancer

International Nuclear Information System (INIS)

Nieder, C.; Nestle, U.; Ukena, D.; Niewald, M.; Sybrecht, G.W.; Schnabel, K.

1995-01-01

The data of 300 patients who had been irradiated for their primary tumor were analysed retrospectively. The serum concentrations of CEA, SCCA, NSE, and LDH were available before treatment and 3 months thereafter in a sufficient number of cases. The prognostic factors for survival and progression-free survival resulting from univariate tests were further evaluated by a Cox-proportional-hazards model. The serum levels of the particular tumor markers were pathologically elevated in 25 to 36.5% of the cases. Their values correlated with the stage of the disease and separately the N-stage too. A normalization of increased marker levels after irradiation occurred in 37.5 to 67% of the cases. Survival of patients with increased pretherapeutic values of CEA, SCCA, and LDH was significantly worse compared to those with normal values. In the case of a posttherapeutic return to normal levels, prognosis was significantly better than for those where the elevation persistet. However, after inclusion of all other parameters in multivariate analysis the tumor markers were meaningless. Karnofsky-performance status, total dose of radiotherapy, stage of the disease, and weight-loss evolved as independent prognostic factors for survival. For progression-free survival only stage of the disease was important. All subgroup analyses (restriction on patients with favorable prognosis) showed the same results. A prognostic importance of NSE could not be demonstrated. CEA, SCCA, and LDH were univariate predictors for survival and progression-free survival. But they proved to be dependent on the stage of the disease and were not confirmed as independent variables in the Cox-model. Their importance during the follow-up is diminished by the frequent lack of therapeutic approaches in the case of disease progression. Certainly a more favorable prognosis in case of a posttherapeutic normalization of previously elevated values was found. (orig./MG) [de

Apelin as a marker for monitoring the tumor vessel normalization window during antiangiogenic therapy.

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Zhang, Li; Takara, Kazuhiro; Yamakawa, Daishi; Kidoya, Hiroyasu; Takakura, Nobuyuki

2016-01-01

Antiangiogenic agents transiently normalize tumor vessel structure and improve vessel function, thereby providing a window of opportunity for enhancing the efficacy of chemotherapy or radiotherapy. Currently, there are no reliable predictors or markers reflecting this vessel normalization window during antiangiogenic therapy. Apelin, the expression of which is regulated by hypoxia, and which has well-described roles in tumor progression, is an easily measured secreted protein. Here, we show that apelin can be used as a marker for the vessel normalization window during antiangiogenic therapy. Mice bearing s.c. tumors resulting from inoculation of the colon adenocarcinoma cell line HT29 were treated with a single injection of bevacizumab, a mAb neutralizing vascular endothelial growth factor. Tumor growth, vessel density, pericyte coverage, tumor hypoxia, and small molecule delivery were determined at four different times after treatment with bevacizumab (days 1, 3, 5, and 8). Tumor growth and vessel density were significantly reduced after bevacizumab treatment, which also significantly increased tumor vessel maturity, and improved tumor hypoxia and small molecule delivery between days 3 and 5. These effects abated by day 8, suggesting that a time window for vessel normalization was opened between days 3 and 5 during bevacizumab treatment in this model. Apelin mRNA expression and plasma apelin levels decreased transiently at day 5 post-treatment, coinciding with vessel normalization. Thus, apelin is a potential indicator of the vessel normalization window during antiangiogenic therapy. © 2015 The Authors. Cancer Science published by Wiley Publishing Asia Pty Ltd on behalf of Japanese Cancer Association.

Localization of higher grade tumor foci in potential candidates for active surveillance who opt for radical prostatectomy

Science.gov (United States)

Hong, Sung Kyu; Eastham, James A.; Fine, Samson W.

2013-01-01

Purpose: To investigate actual intraprostatic location of higher graded tumor foci undetected via standard transrectal ultrasound-guided prostate biopsy amongst patients who would be clinically considered appropriate candidates for active surveillance (AS) but underwent radical prostatectomy (RP). Methods: We reviewed entirely-submitted and whole-mounted RP specimens from 169 men who were deemed appropriate for AS clinically, but opted for RP and were found to have higher grade tumors. For each case, tumor nodules were circled and color-coded in a grade-specific manner and digitally scanned to created tumor maps. The locations of tumor foci with Gleason grade ≥4 were stratified by specific sites: anterior, anterolateral, lateral only (not clearly anterior or posterior), posterior, and posterolateral area. Results: Of 169 patients, 86% had clinical stage T1c and 14% T2a. RP Gleason score 7 in all but two men. Higher-grade tumor foci were localized to: anterior (n=66, 39%), anterolateral (n=4, 2%), lateral only (not clearly anterior or posterior) (n=5, 3%), posterior (n=52, 31%), and posterolateral (n=42, 25%) prostate, respectively. Conclusions: Among patients deemed clinically appropriate for AS, higher-grade tumor foci missed by standard prostate biopsies were localized to both the anterior and posterior prostate, without predominance of a particular area. These findings lend additional support to performing repeat standard prostate biopsy in potential candidates for AS and should be considered in efforts to optimize current biopsy strategies for the selection of AS patients. PMID:24392439

Diagnostic value of CEA and CYFRA 21-1 tumor markers in primary lung cancer.

Science.gov (United States)

Okamura, Kyoko; Takayama, Koichi; Izumi, Miiru; Harada, Taishi; Furuyama, Kazuto; Nakanishi, Yoichi

2013-04-01

Lung cancer is sometimes difficult to differentiate from benign lung diseases expressing nodular shadow in imaging study. We assessed the diagnostic value of two commonly used tumor markers in distinguishing primary lung cancer from benign lung disease. The serum levels of carcinoembryonic antigen (CEA) and cytokeratin 19 fragments (CYFRA 21-1) were retrospectively analyzed in 655 lung cancer patients and 237 patients with benign lung disease. The standard cut-off levels of 3.2 ng/mL CEA and 3.5 ng/mL CYFRA 21-1 and twice these respective levels (6.4 ng/mL and 7.0 ng/mL) were used. CEA and CYFRA 21-1 levels were elevated in 32% and 11% of benign lung disease patients, respectively. CEA sensitivity and specificity for lung cancer diagnosis was 69% and 68% respectively, while that for CYFRA 21-1 was 43% and 89%, respectively. Thus, the combined value for the specificity of the two tumor markers was greater than either alone. Patients were grouped depending on their hospital status, and prevalence rates were determined. The prevalence rate of lung cancer in admitted patients was 51%, the prevalence rate of lung cancer in outpatients was 12%, and the prevalence rate of lung cancer identified during health check-ups was 0.1%. Positive predictive values (PPVs) were calculated using Bayes' theorem, and varied with the serum tumor marker and prevalence rate: PPVs of CEA [prevalence rate] were 69.2% [51%], 22.7% [12%], and 0.22% [0.1%], while PPVs of CYFRA 21-1 were 80.3% [51%], 34.8% [12%], and 0.39% [0.1%]. However, PPVs for lung cancer diagnosis at a prevalence rate of 51% were 87.3% or higher when the patient exhibited positive CEA and CYFRA 21-1, or CEA or CYFRA 21-1 levels twice the standard cut-off. Our results indicate that CEA and CYFRA 21-1 are reliable serum tumor markers for the diagnosis of lung cancer in addition to CT scans when combined or used individually at twice the standard cut-off level in high prevalence rate groups. The prevalence rate should

Thrombomodulin as a marker for vascular tumors. Comparative study with factor VIII and Ulex europaeus I lectin.

Science.gov (United States)

Yonezawa, S; Maruyama, I; Sakae, K; Igata, A; Majerus, P W; Sato, E

1987-10-01

Thrombomodulin (TM) is a newly described endothelial cell-associated protein that functions as a potent natural anticoagulant by converting thrombin from a procoagulant protease to an anticoagulant. Various vascular tumors were characterized with immunoperoxidase staining with the use of a polyclonal anti-TM serum. The staining patterns of TM were compared with those of Factor VIII-related antigen (FVIII-RAG) and Ulex europaeus agglutinin-I (UEA-I), which have been used as markers for endothelial cells. The results showed that TM is a specific and a highly sensitive marker for angiosarcomas in comparison with FVIII-RAG or UEA-I. In contrast, UEA-I is more sensitive for benign vascular tumors than TM or FVIII-RAG. The other mesenchymal tumors of nonvascular origin showed negative staining for three endothelial markers. These results indicate that TM is a new specific and sensitive tool for the diagnosis of angiosarcomas.

Optimum location of external markers using feature selection algorithms for real-time tumor tracking in external-beam radiotherapy: a virtual phantom study.

Science.gov (United States)

Nankali, Saber; Torshabi, Ahmad Esmaili; Miandoab, Payam Samadi; Baghizadeh, Amin

2016-01-08

In external-beam radiotherapy, using external markers is one of the most reliable tools to predict tumor position, in clinical applications. The main challenge in this approach is tumor motion tracking with highest accuracy that depends heavily on external markers location, and this issue is the objective of this study. Four commercially available feature selection algorithms entitled 1) Correlation-based Feature Selection, 2) Classifier, 3) Principal Components, and 4) Relief were proposed to find optimum location of external markers in combination with two "Genetic" and "Ranker" searching procedures. The performance of these algorithms has been evaluated using four-dimensional extended cardiac-torso anthropomorphic phantom. Six tumors in lung, three tumors in liver, and 49 points on the thorax surface were taken into account to simulate internal and external motions, respectively. The root mean square error of an adaptive neuro-fuzzy inference system (ANFIS) as prediction model was considered as metric for quantitatively evaluating the performance of proposed feature selection algorithms. To do this, the thorax surface region was divided into nine smaller segments and predefined tumors motion was predicted by ANFIS using external motion data of given markers at each small segment, separately. Our comparative results showed that all feature selection algorithms can reasonably select specific external markers from those segments where the root mean square error of the ANFIS model is minimum. Moreover, the performance accuracy of proposed feature selection algorithms was compared, separately. For this, each tumor motion was predicted using motion data of those external markers selected by each feature selection algorithm. Duncan statistical test, followed by F-test, on final results reflected that all proposed feature selection algorithms have the same performance accuracy for lung tumors. But for liver tumors, a correlation-based feature selection algorithm, in

Relationship of preoperative gastric cancer CT enhancement ratio and perfusion parameters with serum tumor marker levels and proliferation molecule expression in tumor lesions

Directory of Open Access Journals (Sweden)

Yong-Hong Wang

2017-06-01

Full Text Available Objective: To study the relationship of preoperative gastric cancer CT enhancement ratio and perfusion parameters with serum tumor marker levels and proliferation molecule expression in tumor lesions. Methods: A total of 68 patients with gastric cancer treated in the Second Hospital of Yulin City between May 2012 and May 2016 were chosen as observation group and sub-divided into early and middle gastric cancer group (n=41 and advanced gastric cancer group (n=27 according to the tumor stage; 50 patients diagnosed with benign gastric diseases in our hospital during the same period were selected as benign gastric lesion group. CT enhancement rate and perfusion parameters of three groups of patients were detected by CT scan, serum tumor marker levels were evacuated by enzyme-linked immunosorbent assay (ELISA, and the proliferation gene mRNA expression levels were detected by RTPCR method. Results: CER, AF, BV and CL levels of advanced gastric cancer group were higher than those of early and middle gastric cancer group and benign gastric lesion group; serum CA72-4, CA19-9, CA125 and CEA contents of advanced gastric cancer group were higher than those of early and middle gastric cancer group and benign gastric lesion group; CADM1, miRNA-34a and Cystatin M mRNA expression in tissue of advanced gastric cancer group were lower than those of early and middle gastric cancer group and benign gastric lesion group while Survivin and I2PP2A mRNA expression were higher than those of early and middle gastric cancer group and benign gastric lesion group. The Pearson test showed that the CT enhancement rate and perfusion parameters in patients with gastric cancer are directly correlated with the serum tumor marker levels and the proliferation gene expression in tumor lesions. Conclusion: Preoperative gastric cancer CT enhancement rate and perfusion parameters are directly related to the tumor malignancy, and can be used as a reliable method for the long-term tumor

Clinical usefulness of CEA, CA19-9, and CYFRA 21-1 as tumor markers for urothelial bladder carcinoma.

Science.gov (United States)

Washino, Satoshi; Hirai, Masaru; Matsuzaki, Atsushi; Kobayashi, Yutaka

2011-01-01

To evaluate the usefulness of measuring serum CEA, CA19-9, and CYFRA 21-1 levels for the diagnosis and monitoring of bladder cancer. Serum levels of CEA, CA19-9, and CYFRA 21-1 were measured in 85 patients with bladder cancer. The absolute level of each marker and the positive rate were compared with the clinical stage and histological grade of the tumor. Changes of the markers were assessed in patients with or without disease progression, and the correlations between survival and positivity/negativity of these markers were also evaluated. A higher serum level of CYFRA 21-1 was significantly correlated with higher tumor stage (p CEA and CA19-9 levels did not differ significantly among each stage and grade. The CYFRA 21-1 level increased significantly along with disease progression (from 7.33 ± 13.3 to 55.9 ± 127 ng/ml, p marker of advanced- and high-grade urothelial carcinoma of the bladder. It is useful for monitoring this disease and for predicting the prognosis. In contrast, the clinical usefulness of CEA and CA19-9 as tumor markers was not demonstrated. Copyright © 2011 S. Karger AG, Basel.

Tumor markers CEA and CA 19-9 correlate with radiological imaging in metastatic colorectal cancer patients receiving first-line chemotherapy.

Science.gov (United States)

Michl, M; Koch, J; Laubender, R P; Modest, D P; Giessen, C; Schulz, Ch; Heinemann, V

2014-10-01

In patients with metastatic colorectal cancer (mCRC), radiological imaging represents the current standard to evaluate the efficacy of chemotherapy. However, with growing knowledge about tumor biology, other diagnostic tools become of interest which can supplement radiology. The aim of the present study was to examine the correlation of tumor and serum markers with radiological imaging in patients with mCRC receiving first-line therapy. Patients were included if tumor (carcinoembryonic antigen (CEA), carbohydrate antigen 19-9 (CA 19-9)) and serum marker (lactatdehydrogenase (LDH), γ-glutamyltransferase (γGT), alkaline phosphatase (AP), C-reactive protein (CRP), leucocyte count (WBC), hemoglobin (Hb)) levels were available at baseline and at least two times during treatment. The decline and increase of tumor and serum markers over time were approximated for each patient by estimating slopes depending on the radiological assessment. A linear mixed effects multiple regression model for each subject was used to evaluate the intra-class correlation of these slopes modeling tumor and serum marker changes with radiological imaging. Data of 124 patients (41 female, 83 male; median age 62.9 years, range 27-85) who received first-line chemotherapy for mCRC from 11/2007 to 04/2010 were analyzed retrospectively. CEA level slopes (n = 49; slopes = 102) differed between radiologically determined progressive disease (PD) and partial response (PR) (p = 0.005) and between PD and stable disease (SD) (p = 0.042). CA 19-9 level slopes (n = 57; slopes = 127) also showed a significant difference between PD and PR (p = 0.002) and PD and SD (p = 0.058). Furthermore, CRP slopes (n = 62; slopes = 134) differed significantly between PD and PR (p = 0.009). For LDH, ALP, γGT, Hb, and WBC, no correlations were observed. The results indicate the correlation of the tumor markers CEA, CA 19-9, and the serum marker CRP with radiological imaging in

Short interspersed CAN SINE elements as prognostic markers in canine mammary neoplasia.

Science.gov (United States)

Gelaleti, Gabriela B; Granzotto, Adriana; Leonel, Camila; Jardim, Bruna V; Moschetta, Marina G; Carareto, Claudia M A; Zuccari, Debora Ap P C

2014-01-01

The genome of mammals is characterized by a large number of non-LTR retrotransposons, and among them, the CAN SINEs are characteristics of the canine species. Small amounts of DNA freely circulate in normal blood serum and high amounts are found in human patients with cancer, characterizing it as a candidate tumor-biomarker. The aim of this study was to estimate, through its absolute expression, the number of copies of CAN SINE sequences present in free circulating DNA of female dogs with mammary cancer, in order to correlate with the clinical and pathological characteristics and the follow-up period. The copy number of CAN SINE sequences was estimated by qPCR in 28 female dogs with mammary neoplasia. The univariate analysis showed an increased number of copies in female dogs with mammary tumor in female dogs >10 years old (p=0.02) and tumor time >18 months (pSINE fragments can be good markers for the detection of tumor DNA in blood and may characterize it as a marker of poor prognosis, being related to female dogs with shorter survival times. This estimate can be used as a prognostic marker in non-invasive breast cancer research and is useful in predicting tumor progression and patient monitoring.

Analysis of the results of serum tumor markers in patients with multiple abnormal concentrations in bone imagines

International Nuclear Information System (INIS)

Wu Xingyong; Jiang Min; Geng Jun; Hu Desheng; He Jian; Fan Xiandong

2008-01-01

To study the serum tumor markers in patients with multiple abnormal concentration of radiopharmaceuticals in whole body bone imagine, 73 patients with malignancy were under a whole body bone scan. The serum tumor markers levels of AFP, CEA, CA125, CA15-3 and CA19-9 were measured in 73 patients and 37 normal people. The results showed that there was significant difference only on serum CEA level (P<0.005), and no significant difference on CA125, CA15-3 and CA19-9 levels (P<0.05) between 36 patients with multiple abnormal concentration and the others with normal bone imagine. The serum levels of CEA, CA125 and CA19-9 in patients were significant higher than that of normal controls (P<0.005). Combined the whole body bone scan and detection of serum tumor markers might be regarded as clinical significance for the diagnosis of bone metastases. (authors)

Circulating levels of cell adhesion molecule L1 as a prognostic marker in gastrointestinal stromal tumor patients

International Nuclear Information System (INIS)

Zander, Hilke; Kaifi, Jussuf; Rawnaq, Tamina; Wedemeyer, Max von; Tachezy, Michael; Kunkel, Miriam; Wolters, Gerrit; Bockhorn, Maximilian; Schachner, Melitta; Izbicki, Jakob R

2011-01-01

L1 cell adhesion molecule (CD171) is expressed in many malignant tumors and its expression correlates with unfavourable outcome. It thus represents a target for tumor diagnosis and therapy. An earlier study conducted by our group identified L1 expression levels in primary gastrointestinal stromal tumors (GIST) as a prognostic marker. The aim of the current study was to compare L1 serum levels of GIST patients with those of healthy controls and to determine whether levels of soluble L1 in sera could serve as a prognostic marker. Using a sensitive enzyme-linked immunosorbent assay (ELISA), soluble L1 was measured in sera of 93 GIST patients und 151 healthy controls. Soluble L1 levels were then correlated with clinicopathological data. Median levels of soluble L1 were significantly higher (p < 0.001; Mann-Whitney U test) in sera of GIST patients compared to healthy individuals. Median soluble L1 levels were particularly elevated in patients with recurrence and relapse (p < 0.05; Mann Whitney U test). These results suggest that high soluble L1 levels predict poor prognosis and may thus be a promising tumor marker that can contribute to individualise therapy

A method of surface marker location optimization for tumor motion estimation in lung stereotactic body radiation therapy

International Nuclear Information System (INIS)

Lu, Bo; Park, Justin C.; Fan, Qiyong; Kahler, Darren; Liu, Chihray; Chen, Yunmei

2015-01-01

Purpose: Accurately localizing lung tumor localization is essential for high-precision radiation therapy techniques such as stereotactic body radiation therapy (SBRT). Since direct monitoring of tumor motion is not always achievable due to the limitation of imaging modalities for treatment guidance, placement of fiducial markers on the patient’s body surface to act as a surrogate for tumor position prediction is a practical alternative for tracking lung tumor motion during SBRT treatments. In this work, the authors propose an innovative and robust model to solve the multimarker position optimization problem. The model is able to overcome the major drawbacks of the sparse optimization approach (SOA) model. Methods: The principle-component-analysis (PCA) method was employed as the framework to build the authors’ statistical prediction model. The method can be divided into two stages. The first stage is to build the surrogate tumor matrix and calculate its eigenvalues and associated eigenvectors. The second stage is to determine the “best represented” columns of the eigenvector matrix obtained from stage one and subsequently acquire the optimal marker positions as well as numbers. Using 4-dimensional CT (4DCT) and breath hold CT imaging data, the PCA method was compared to the SOA method with respect to calculation time, average prediction accuracy, prediction stability, noise resistance, marker position consistency, and marker distribution. Results: The PCA and SOA methods which were both tested were on all 11 patients for a total of 130 cases including 4DCT and breath-hold CT scenarios. The maximum calculation time for the PCA method was less than 1 s with 64 752 surface points, whereas the average calculation time for the SOA method was over 12 min with 400 surface points. Overall, the tumor center position prediction errors were comparable between the two methods, and all were less than 1.5 mm. However, for the extreme scenarios (breath hold), the

National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines for use of tumor markers in clinical practice

DEFF Research Database (Denmark)

Sturgeon, Catharine M; Hoffman, Barry R; Chan, Daniel W

2008-01-01

BACKGROUND: This report presents updated National Academy of Clinical Biochemistry Laboratory Medicine Practice Guidelines summarizing quality requirements for the use of tumor markers. METHODS: One subcommittee developed guidelines for analytical quality relevant to serum and tissue-based tumor...... questions to ensure selection of the appropriate test, adherence to good clinical and laboratory practices (e.g., minimization of the risk of incorrect patient and/or specimen identification, tube type, or timing), use of internationally standardized and well-characterized methods, careful adherence...... records. Also mandatory is extensive validation encompassing all stages of analysis before introduction of new technologies such as microarrays and mass spectrometry. Provision of high-quality tumor marker services is facilitated by dialogue involving researchers, diagnostic companies, clinical...

Multiplex detection of tumor markers with photonic suspension array

Energy Technology Data Exchange (ETDEWEB)

Zhao Yuanjin; Zhao Xiangwei [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Pei Xiaoping [Department of Hematology, Affiliated Zhongda Hospital, Southeast University, Nanjing 210009 (China); Hu Jing; Zhao Wenju [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Chen Baoan [Department of Hematology, Affiliated Zhongda Hospital, Southeast University, Nanjing 210009 (China); Gu Zhongze [State Key Laboratory of Bioelectronics, School of Biological Science and Medical Engineering, Southeast University, Nanjing 210096 (China); Laboratory of Environment and Biosafety, Research Institute of Southeast University in Suzhou, Dushu Lake Higher Education Town, Suzhou 215123 (China)], E-mail: gu@seu.edu.cn

2009-02-02

A novel photonic suspension array was developed for multiplex immunoassay. The carries of this array were silica colloidal crystal beads (SCCBs). The codes of these carriers are the characteristic reflection peak originated from their structural periodicity, and therefore they do not suffer from fading, bleaching, quenching, and chemical instability. In addition, because no dyes or materials related with fluorescence are included, the fluorescence background of SCCBs is very low. With a sandwich format, the proposed suspension array was used for simultaneous multiplex detection of tumor markers in one test tube. The results showed that the four tumor markers, {alpha}-fetoprotein (AFP), carcinoembryonic antigen (CEA), carcinoma antigen 125 (CA 125) and carcinoma antigen 19-9 (CA 19-9) could be assayed in the ranges of 1.0-500 ng mL{sup -1}, 1.0-500 ng mL{sup -1}, 1.0-500 U mL{sup -1} and 3.0-500 U mL{sup -1} with limits of detection of 0.68 ng mL{sup -1}, 0.95 ng mL{sup -1}, 0.99 U mL{sup -1} and 2.30 U mL{sup -1} at 3{sigma}, respectively. The proposed array showed acceptable accuracy, detection reproducibility, storage stability and the results obtained were in acceptable agreement with those from parallel single-analyte test of practical clinical sera. This technique provides a new strategy for low cost, automated, and simultaneous multiplex immunoassay.

Diagnostic significance of tumor markers CEA, CA50 and CA19-9 for colorectal cancer

International Nuclear Information System (INIS)

Chen Yumei; Huang Gang

2005-01-01

Objective: To investigate the expression and diagnostic significance of three serum tumor markers (CEA, CA50, CA19-9) in patients with colorectal cancer, with special emphasis on their combined assay. Methods: Serum CEA, CA19-9 levels (with chemiluminescence immunoassay) and CA50 levels (with immunoradiometric assay) were determined in 94 patients with colorectal cancer, 20 patients with benign colorectal disorders and 37 controls. Results: The expressions of the serum tumor markers were significantly higher in patients with colorectal cancer than those in patients with benign colorectal disorders and controls (P<0.05). There was no significant difference between the levels in the latter two groups. CEA assay had the highest sensitivity (57.4%) and specificity (85.9%). Combined assay of the three could enhance both the sensitivity (62.7%) and specificity (96.5%). The serum levels of the markers were significantly higher in patients with colonic cancer than those in patients with rectal cancer (P<0.05). The levels were positively correlated with the size of the growth and stage of the disease. Serum tumor marker levels were also significantly higher in patients with metastasis (regional/distant) than those in patients without metastasis (P<0.05). Conclusion: Determination of serum CEA, CA50 and CA19-9 levels had definite value for the diagnosis and assessment of the pathology as well as biologic behavior colorectal cancer. Combined assay of the three could enhance the diagnostic sensitivity and specificity. (authors)

Relationship between bone scintigraphy and tumor markers in patients with breast cancer

International Nuclear Information System (INIS)

Yildiz, M.; Oral, B.

2004-01-01

The aim of this study is to specify the precise role of bone scintigraphy and serum carcinoembryonic antigen (CEA) and breast cancer-associated antigen (CA) 15-3 assays in the monitoring of breast cancers in order to optimize their use and to determine whether it is possible to guide the prescription of bone scan by the use of CEA and CA 15-3 assays in the monitoring of breast cancer. For this purpose, from November 1997 to May 2002, 98 consecutive female breast cancer patients (median age, 52 years; range 35-77 years) underwent bone scintigraphy during follow-up. In these patients values of tumor markers were compared with the results of bone scintigraphy. Some of the patients with bone metastasis were checked repeatedly at intervals of 6 to 12 months, resulting in 49 patients with bone metastasis and 74 patients without bone metastasis being included in the study. In patients with bone metastasis, serum CEA levels were abnormal in 23/49 cases and CA 15-3 serum concentrations were elevated above the cut-off in 33/49 cases. Among patients without bone metastasis, CEA and CA 15-3 serum concentrations were normal in 50/74 and 55/74 cases respectively. The combination of the two markers improved the diagnostic sensitivity. Although serial tumor marker measurements are an efficient and cost effective method of monitoring disease progression, it does not allow prediction of the bone scan results; so it is not justifiable to reject a bone scintigraphy on the basis of these markers. (author)

Gastrointestinal stromal tumors, somatic mutations and candidate genetic risk variants.

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Katie M O'Brien

Full Text Available Gastrointestinal stromal tumors (GISTs are rare but treatable soft tissue sarcomas. Nearly all GISTs have somatic mutations in either the KIT or PDGFRA gene, but there are no known inherited genetic risk factors. We assessed the relationship between KIT/PDGFRA mutations and select deletions or single nucleotide polymorphisms (SNPs in 279 participants from a clinical trial of adjuvant imatinib mesylate. Given previous evidence that certain susceptibility loci and carcinogens are associated with characteristic mutations, or "signatures" in other cancers, we hypothesized that the characteristic somatic mutations in the KIT and PDGFRA genes in GIST tumors may similarly be mutational signatures that are causally linked to specific mutagens or susceptibility loci. As previous epidemiologic studies suggest environmental risk factors such as dioxin and radiation exposure may be linked to sarcomas, we chose 208 variants in 39 candidate genes related to DNA repair and dioxin metabolism or response. We calculated adjusted odds ratios (ORs and 95% confidence intervals (CIs for the association between each variant and 7 categories of tumor mutation using logistic regression. We also evaluated gene-level effects using the sequence kernel association test (SKAT. Although none of the association p-values were statistically significant after adjustment for multiple comparisons, SNPs in CYP1B1 were strongly associated with KIT exon 11 codon 557-8 deletions (OR = 1.9, 95% CI: 1.3-2.9 for rs2855658 and OR = 1.8, 95% CI: 1.2-2.7 for rs1056836 and wild type GISTs (OR = 2.7, 95% CI: 1.5-4.8 for rs1800440 and OR = 0.5, 95% CI: 0.3-0.9 for rs1056836. CYP1B1 was also associated with these mutations categories in the SKAT analysis (p = 0.002 and p = 0.003, respectively. Other potential risk variants included GSTM1, RAD23B and ERCC2. This preliminary analysis of inherited genetic risk factors for GIST offers some clues about the disease's genetic

CRX is a diagnostic marker of retinal and pineal lineage tumors.

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Sandro Santagata

2009-11-01

Full Text Available CRX is a homeobox transcription factor whose expression and function is critical to maintain retinal and pineal lineage cells and their progenitors. To determine the biologic and diagnostic potential of CRX in human tumors of the retina and pineal, we examined its expression in multiple settings.Using situ hybridization and immunohistochemistry we show that Crx RNA and protein expression are exquisitely lineage restricted to retinal and pineal cells during normal mouse and human development. Gene expression profiling analysis of a wide range of human cancers and cancer cell lines also supports that CRX RNA is highly lineage restricted in cancer. Immunohistochemical analysis of 22 retinoblastomas and 13 pineal parenchymal tumors demonstrated strong expression of CRX in over 95% of these tumors. Importantly, CRX was not detected in the majority of tumors considered in the differential diagnosis of pineal region tumors (n = 78. The notable exception was medulloblastoma, 40% of which exhibited CRX expression in a heterogeneous pattern readily distinguished from that seen in retino-pineal tumors.These findings describe new potential roles for CRX in human cancers and highlight the general utility of lineage restricted transcription factors in cancer biology. They also identify CRX as a sensitive and specific clinical marker and a potential lineage dependent therapeutic target in retinoblastoma and pineoblastoma.

Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

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Lopci, Egesta; Olivari, Laura [Humanitas Clinical and Research Hospital, Nuclear Medicine Department, Rozzano, MI (Italy); Toschi, Luca; Marchetti, Silvia; Pistillo, Daniela [Humanitas Clinical and Research Hospital, Oncology, Rozzano, Milan (Italy); Grizzi, Fabio; Castino, Giovanni Francesco; Cortese, Nina; Qehajaj, Dorina [Humanitas Clinical and Research Hospital, Department of Immunology and Inflammation, Rozzano, Milan (Italy); Rahal, Daoud [Humanitas Clinical and Research Hospital, Department of Pathology, Rozzano, Milan (Italy); Alloisio, Marco [Humanitas Clinical and Research Hospital, Thoracic Surgery, Rozzano, Milan (Italy); Roncalli, Massimo [Humanitas Clinical and Research Hospital, Department of Pathology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Allavena, Paola [Humanitas University, Rozzano, Milan (Italy); Santoro, Armando [Humanitas Clinical and Research Hospital, Oncology, Rozzano, Milan (Italy); Humanitas University, Rozzano, Milan (Italy); Marchesi, Federica [Humanitas Clinical and Research Hospital, Department of Immunology and Inflammation, Rozzano, Milan (Italy); University of Milan, Department of Medical Biotechnologies and Translational Medicine, Milan (Italy); Chiti, Arturo [Humanitas Clinical and Research Hospital, Nuclear Medicine Department, Rozzano, MI (Italy); Humanitas University, Rozzano, Milan (Italy)

2016-10-15

(rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho = 0.45; p = 0.001), CD8 TILs and PD-L1 (rho = 0.41; p = 0.003), CD68-TAMs and PD-L1 (rho = 0.30; p = 0.027), PD-1 and PD-L1 (rho = 0.26; p = 0.059). With respect to patients' outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p = 0.002, 0.004, and <0.001, respectively). The present study shows a direct association between metabolic parameters on FDG-PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors. (orig.)

Correlation of metabolic information on FDG-PET with tissue expression of immune markers in patients with non-small cell lung cancer (NSCLC) who are candidates for upfront surgery

International Nuclear Information System (INIS)

Lopci, Egesta; Olivari, Laura; Toschi, Luca; Marchetti, Silvia; Pistillo, Daniela; Grizzi, Fabio; Castino, Giovanni Francesco; Cortese, Nina; Qehajaj, Dorina; Rahal, Daoud; Alloisio, Marco; Roncalli, Massimo; Allavena, Paola; Santoro, Armando; Marchesi, Federica; Chiti, Arturo

2016-01-01

(rho = 0.33; p = 0.017 and rho = 0.36; p = 0.009, respectively). The other tissue markers correlated as follows: CD8 TILs and PD-1 (rho = 0.45; p = 0.001), CD8 TILs and PD-L1 (rho = 0.41; p = 0.003), CD68-TAMs and PD-L1 (rho = 0.30; p = 0.027), PD-1 and PD-L1 (rho = 0.26; p = 0.059). With respect to patients' outcome, SUVmax, SUVmean, and disease stage showed a statistically significant correlation with DFS (p = 0.002, 0.004, and <0.001, respectively). The present study shows a direct association between metabolic parameters on FDG-PET and the expression of tumor-related immunity markers, suggesting a potential role for FDG-PET to characterize the tumor microenvironment and select NSCLC patients candidate to checkpoint inhibitors. (orig.)

Cancer in silico drug discovery: a systems biology tool for identifying candidate drugs to target specific molecular tumor subtypes.

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San Lucas, F Anthony; Fowler, Jerry; Chang, Kyle; Kopetz, Scott; Vilar, Eduardo; Scheet, Paul

2014-12-01

Large-scale cancer datasets such as The Cancer Genome Atlas (TCGA) allow researchers to profile tumors based on a wide range of clinical and molecular characteristics. Subsequently, TCGA-derived gene expression profiles can be analyzed with the Connectivity Map (CMap) to find candidate drugs to target tumors with specific clinical phenotypes or molecular characteristics. This represents a powerful computational approach for candidate drug identification, but due to the complexity of TCGA and technology differences between CMap and TCGA experiments, such analyses are challenging to conduct and reproduce. We present Cancer in silico Drug Discovery (CiDD; scheet.org/software), a computational drug discovery platform that addresses these challenges. CiDD integrates data from TCGA, CMap, and Cancer Cell Line Encyclopedia (CCLE) to perform computational drug discovery experiments, generating hypotheses for the following three general problems: (i) determining whether specific clinical phenotypes or molecular characteristics are associated with unique gene expression signatures; (ii) finding candidate drugs to repress these expression signatures; and (iii) identifying cell lines that resemble the tumors being studied for subsequent in vitro experiments. The primary input to CiDD is a clinical or molecular characteristic. The output is a biologically annotated list of candidate drugs and a list of cell lines for in vitro experimentation. We applied CiDD to identify candidate drugs to treat colorectal cancers harboring mutations in BRAF. CiDD identified EGFR and proteasome inhibitors, while proposing five cell lines for in vitro testing. CiDD facilitates phenotype-driven, systematic drug discovery based on clinical and molecular data from TCGA. ©2014 American Association for Cancer Research.

Circulating tumor cells and miRNAs as prognostic markers in neuroendocrine neoplasms.

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Zatelli, Maria Chiara; Grossrubatscher, Erika Maria; Guadagno, Elia; Sciammarella, Concetta; Faggiano, Antongiulio; Colao, Annamaria

2017-06-01

The prognosis of neuroendocrine neoplasms (NENs) is widely variable and has been shown to associate with several tissue- and blood-based biomarkers in different settings. The identification of prognostic factors predicting NEN outcome is of paramount importance to select the best clinical management for these patients. Prognostic markers have been intensively investigated, also taking advantage of the most modern techniques, in the perspective of personalized medicine and appropriate resource utilization. This review summarizes the available data on the possible role of circulating tumor cells and microRNAs as prognostic markers in NENs. © 2017 Society for Endocrinology.

Tumor-associated auto-antibodies as early detection markers for ovarian cancer?

DEFF Research Database (Denmark)

Kaaks, Rudolf; Fortner, Renée Turzanski; Hüsing, Anika

2018-01-01

.08-0.40] for CTAG1A, CTAG2 and NUDT1 to 0.23 [0.10-0.44] for P53 (0.33 [0.11-0.68] for high-grade serous tumors). However, at longer lead-times the ability of these AAb markers to distinguish future ovarian cancer cases from controls declined rapidly; at lead times >1 year, SE98 estimates were close to zero (all...... invasive cases, range: 0.01-0.11). Compared to CA125 alone, combined logistic regression scores of AAbs and CA125 did not improve detection sensitivity at equal level of specificity. The added value of these selected AAbs as markers for ovarian cancer beyond CA125 for early detection is therefore limited...

The Diagnostic and Prognostic Value of Tumor Markers (CEA, SCC, CYFRA 21-1, TPS) in Head and Neck Cancer Patients.

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Barak, Vivian; Meirovitz, Amichay; Leibovici, Vera; Rachmut, Jacob; Peretz, Tamar; Eliashar, Ron; Gross, Menachem

2015-10-01

Establishing prognostic factors is very important in the management of cancer patients. Our aim was to evaluate the clinical significance of a panel of tumor markers, including CEA (Carcino Embryonic Antigen), SCC (Squamous Cell Carcinoma Antigen), TPS (Tissue Polypeptide Specific Antigen) and CYFRA 21-1 in head and neck cancer patients, for assessing treatment response and prognosis of patients. We evaluated 312 blood samples from 143 head and neck cancer patients, from several sub-groups: 82 Larynx Carcinoma pre- and 38 post-therapy, 46 Oral Cavity pre and 29 post-therapy, 12 nasopharynx, 16 parotid and other salivary gland patients. Blood tumor markers levels were evaluated by conventional ELISA assays. Correlations of marker levels to stage of disease, lymph node involvement and therapy, were performed. Serum levels of all four tumor markers were higher before therapy and decreased thereafter in all patients. The decrease in TPS level following therapy was significant (p=0.03). Significantly higher levels of TPS and similarly higher levels of the other tumor markers were demonstrated in advanced disease (stages III and IV) patients, as opposed to early disease (stages I and II) patients (p=0.012). Node positive patients had significantly higher TPS levels as compared to node negative (p=0.02). The same trend was shown by the other markers as well, but did not reach statistical significance. TPS was best correlated to survival of patients; those having low levels had the best clinical outcome and longer survival. CEA, SCC, TPS and CYFRA 21-1 can all serve as useful tumor markers in HNC patients. They assessed response to therapy and were prognostic for recurrence. TPS proved to be the most sensitive predictor of advanced disease and poor prognosis. Copyright© 2015 International Institute of Anticancer Research (Dr. John G. Delinassios), All rights reserved.

GLUT1 expression in malignant tumors and its use as an immunodiagnostic marker

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Kátia C. Carvalho

2011-01-01

Full Text Available OBJECTIVE: To analyze glucose transporter 1 expression patterns in malignant tumors of various cell types and evaluate their diagnostic value by immunohistochemistry. INTRODUCTION: Glucose is the major source of energy for cells, and glucose transporter 1 is the most common glucose transporter in humans. Glucose transporter 1 is aberrantly expressed in several tumor types. Studies have implicated glucose transporter 1 expression as a prognostic and diagnostic marker in tumors, primarily in conjunction with positron emission tomography scan data. METHODS: Immunohistochemistry for glucose transporter 1 was performed in tissue microarray slides, comprising 1955 samples of malignant neoplasm from different cell types. RESULTS: Sarcomas, lymphomas, melanomas and hepatoblastomas did not express glucose transporter 1. Fortyseven per cent of prostate adenocarcinomas were positive, as were 29% of thyroid, 10% of gastric and 5% of breast adenocarcinomas. Thirty-six per cent of squamous cell carcinomas of the head and neck were positive, as were 42% of uterine cervix squamous cell carcinomas. Glioblastomas and retinoblastomas showed membranous glucose transporter 1 staining in 18.6% and 9.4% of all cases, respectively. Squamous cell carcinomas displayed membranous expression, whereas adenocarcinomas showed cytoplasmic glucose transporter 1 expression. CONCLUSION: Glucose transporter 1 showed variable expression in various tumor types. Its absence in sarcomas, melanomas, hepatoblastomas and lymphomas suggests that other glucose transporters mediate the glycolytic pathway in these tumors. The data suggest that glucose transporter 1 is a valuable immunohistochemical marker that can be used to identify patients for evaluation by positron emission tomography scan. The function of cytoplasmic glucose transporter 1 in adenocarcinomas must be further examined.

Apprasial of the diagnostic value of combined detection of serum tumor markers (AFP, CEA, SF, TSA) for common malignancies

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Han Jingyin

2005-01-01

Objective: To assess the detection rate of common malignancies with combined determination of four serum tumor markers (AFP, CEA, SF, TSA). Methods: Serum AFP, CEA, SF (with RIA) and TSA (with biochemical method) contents were determined in 612 patients with various kinds of proved malignancies. Results: Positive rates of combined determination of these four tumor markers for detection of common malignancies were: 95.2%(79/83) for liver carcinoma, 92.6% (125/135) for lung carcinoma, 88.5% (115/130) for gastric cancer, 83.3% (60/72) for colorectal cancer, 84.2% (85/101) for breast cancer, 90.0% (9/10) for chorionepithelioma and 88.9% (72/81) for ovarian cancer. Conclusion: Combined determination of these four tumor markers for screening malignancies is simple, cheap, practical and worth popularization. (authors)

Optimum location of external markers using feature selection algorithms for real‐time tumor tracking in external‐beam radiotherapy: a virtual phantom study

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Nankali, Saber; Miandoab, Payam Samadi; Baghizadeh, Amin

2016-01-01

In external‐beam radiotherapy, using external markers is one of the most reliable tools to predict tumor position, in clinical applications. The main challenge in this approach is tumor motion tracking with highest accuracy that depends heavily on external markers location, and this issue is the objective of this study. Four commercially available feature selection algorithms entitled 1) Correlation‐based Feature Selection, 2) Classifier, 3) Principal Components, and 4) Relief were proposed to find optimum location of external markers in combination with two “Genetic” and “Ranker” searching procedures. The performance of these algorithms has been evaluated using four‐dimensional extended cardiac‐torso anthropomorphic phantom. Six tumors in lung, three tumors in liver, and 49 points on the thorax surface were taken into account to simulate internal and external motions, respectively. The root mean square error of an adaptive neuro‐fuzzy inference system (ANFIS) as prediction model was considered as metric for quantitatively evaluating the performance of proposed feature selection algorithms. To do this, the thorax surface region was divided into nine smaller segments and predefined tumors motion was predicted by ANFIS using external motion data of given markers at each small segment, separately. Our comparative results showed that all feature selection algorithms can reasonably select specific external markers from those segments where the root mean square error of the ANFIS model is minimum. Moreover, the performance accuracy of proposed feature selection algorithms was compared, separately. For this, each tumor motion was predicted using motion data of those external markers selected by each feature selection algorithm. Duncan statistical test, followed by F‐test, on final results reflected that all proposed feature selection algorithms have the same performance accuracy for lung tumors. But for liver tumors, a correlation‐based feature

Tumor Hypoxia: Causative Mechanisms, Microregional Heterogeneities, and the Role of Tissue-Based Hypoxia Markers.

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Vaupel, Peter; Mayer, Arnulf

Tumor hypoxia is a hallmark of solid malignant tumor growth, profoundly influences malignant progression and contributes to the development of therapeutic resistance. Pathogenesis of tumor hypoxia is multifactorial, with contributions from both acute and chronic factors. Spatial distribution of hypoxia within tumors is markedly heterogeneous and often changes over time, e.g., during a course of radiotherapy. Substantial changes in the oxygenation status can occur within the distance of a few cell layers, explaining the inability of currently used molecular imaging techniques to adequately assess this crucial trait. Due to the possible importance of tumor hypoxia for clinical decision-making, there is a great demand for molecular tools which may provide the necessary resolution down to the single cell level. Exogenous and endogenous markers of tumor hypoxia have been investigated for this purpose. Their potential use may be greatly enhanced by multiparametric in situ methods in experimental and human tumor tissue.

The role of tumor markers (CEA, TPA, CA 19-9) in colon and rectum carcinomas

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Cangemi, V.; Volpino, P.; Fiori, E.; Giammarco, A.; Piat, G.

1987-01-01

We have evaluated the diagnostic efficacy (sensitivity, specificity, accuracy, predictive malignancy index) of CEA, TPA, CA 19-9 in colon and rectum tumors (56 cases), the difference in behaviour of these markers in relation to the stage and grading of the cancer, their reliability regarding postsurgical relapses and/or metastases. The sensitivity of CEA (>10 ng/ml), TPA (>130 U/L), CA 19-9 (>37 u/ml) for diagnostic purpose was rather limited (28.6% - 30% - 18.5%) with a malignancy prediction value of 100% - 81.8% - 62.5%. With regard to relapses and/or metastases, the diagnostic efficacy of the marker proved to be evident only for CEA, TPA, CA 19-9 value greater than 25 ng/ml, 250 U/L and 100 u/ml. The use of thethree markers together was certainly an advantage both for primitive tumors (sensitivity: 52.8%) and relapses and/or metastases after surgery (sensitivity: 66.7%)

The Diagnostic Value of Transvaginal Sonograph (TVS), Color Doppler, and Serum Tumor Marker CA125, CEA, and AFP in Ovarian Cancer.

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Zhang, Fang; Zhang, Zhou-Long

2015-06-01

The purpose of this study is to investigate the diagnostic value of transvaginal sonograph (TVS), color Doppler, and serum tumor marker CA125, CEA, and AFP in ovarian cancer. From June, 2011 to May, 2013, 102 cases with adnexal mass were recruited in this study (32 cases of malignant ovarian cancer and 70 cases of benign ovarian tumor according to pathological diagnosis). TVS, color Doppler, and serum tumor markers were used for tumor diagnosis. The sensitivity, specifity, positive prediction, negative prediction, and Youden's index were analyzed. Of the 102 patients, 32 were diagnosed with malignant ovarian cancer and 70 were diagnosed with benign ovarian tumor according to pathological diagnosis. Based on TVS results, 37 cases were malignant while 65 cases were benign. Based on color Doppler results, 34 cases were malignant while 68 cases were benign. Based on TVS and color Doppler results, 35 cases were malignant while 65 were benign. Based on CA125 test results, 34 cases were malignant while 68 cases were benign. Based on CEA test results, 8 cases were malignant and 94 cases were benign. Bases on AFP test results, 9 cases were malignant while 93 cases were benign. Based on the results of combination tumor marker test, 38 cases were malignant while 64 cases were benign. The combination of TVS, color Doppler, and tumor marker test showed optimal diagnostic value with a sensitivity of 90.63 %, specificity of 97.14 %, positive prediction of 93.94 %, negative prediction of 98.55 %, and Youden's index of 94.02 %. The combination of TVS, color Doppler, and tumor marker test is of great diagnostic value, which should be widely used in clinical practice.

Clinical value of multi-tumor markers detection with (CEA, CA19-9, CA72-4) for diagnosis of gastric malignancy

International Nuclear Information System (INIS)

Liu Yun; Li Jiangang

2007-01-01

Objective: To assess the clinical value of multi-tumor markers detection with (CEA, CA19-9, CA72-4) for diagnosis of gastric malignancy. Methods: Serum CEA, CA19-9, CA72-4 contents were measured with IRMA in 228 patients with gastric malignancies, 152 patients with benign gastric disorders and 200 controls. Results: The positive rates of single marker detection were all above 70% and that of CA72-4 was the highest (84.21%), next was CA19-9 (75.43%). Three tumor markers were all negative in only 4 cases (false negative rate was 1.75% ). So combined detection of 3 tumor markers could improve the positive rate to 98.25%. With combined determination of two markers, double positive rate for different sets of combinations was: 61.84% for CA72-4 + CA19-9, 51.31% for CA72-4 + CEA and 48.24% for CEA + CA19-9. Conclusion: It was suggested that for screening, CA72-4 was the first choice in single marker detections, and CA72-4 + CA19-9 was the first choice for combined detections of two markers. For follow-up, a combination of 2 markers with highest positive rate for the specific histopathologic type (i. e. carcinoma, leiomyosarcoma or lymphosarcoma) should be used throughout the study. (authors)

Clinical use of serum TRA-1-60 as tumor marker in patients with germ cell cancer

DEFF Research Database (Denmark)

Lajer, Henrik; Daugaard, Gedske; Andersson, Anna-Maria

2002-01-01

TRA-1-60 antigen has been related to the presence of embryonal germ cell carcinoma (EC) and carcinoma in situ. Our study further investigated the clinical efficacy of TRA-1-60 as a serum tumor marker for germ cell cancer in the testis. Three groups of patients with germ cell tumors were included:...

Fluorodeoxyglucose positron emission tomography and chemotherapy-related tumor marker expression in non-small cell lung cancer

International Nuclear Information System (INIS)

Duan, Xiao-Yi; Wang, Wen; Wang, Jian-Sheng; Shang, Jin; Gao, Jun-Gang; Guo, You-Min

2013-01-01

The chemotherapy resistance of non-small cell lung cancer (NSCLC) remains a clinic challenge and is closely associated with several biomarkers including epidermal growth factor receptor (EGFR) (Drugs 72(Suppl 1):28–36, 012.), p53 (Med Sci Monit 11(6):HY11–HY20, 2005.) and excision repair cross complementing gene 1 (ERCC1) (J Thorac Oncol 8(5):582–586, 2013.). Fluorodeoxyglucose positron emission tomography (FDG–PET) is the best non-invasive surrogate for tumor biology with the maximal standardized uptake values (SUV max ) being the most important paradigm. However, there are limited data correlating FDG-PET with the chemotherapy resistant tumor markers. The purpose of this study was to determine the correlation of chemotherapy related tumor marker expression with FDG–PET SUV max in NSCLC. FDG–PET SUV max was calculated in chemotherapy naïve patients with NSCLC (n = 62) and immunohistochemical analysis was performed for EGFR, p53 or ERCC1 on the intraoperative NSCLC tissues. Each tumor marker was assessed independently by two pathologists using common grading criteria. The SUV max difference based on the histologic characteristics, gender, differentiation, grading and age as well as correlation analysis among these parameters were performed. Multiple stepwise regression analysis was further performed to determine the primary predictor for SUV max and the receiver operating characteristics (ROC) curve analysis was performed to detect the optimized sensitivity and specificity for SUV max in suggesting chemotherapy resistant tumor markers. The significant tumor type (P = 0.045), differentiation (P = 0.021), p53 (P = 0.000) or ERCC1 (P = 0.033) positivity dependent differences of SUV max values were observed. The tumor differentiation is significantly correlated with SUV max (R = -0.327), tumor size (R = -0.286), grading (R = -0.499), gender (R = 0.286) as well as the expression levels for p53 (R = -0.605) and ERCC1 (R = -0.644). The expression level of p53

Magnetic Resonance Spectroscopic Imaging of Tumor Metabolic Markers for Cancer Diagnosis, Metabolic Phenotyping, and Characterization of Tumor Microenvironment

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Qiuhong He

2004-01-01

Full Text Available Cancer cells display heterogeneous genetic characteristics, depending on the tumor dynamic microenvironment. Abnormal tumor vasculature and poor tissue oxygenation generate a fraction of hypoxic tumor cells that have selective advantages in metastasis and invasion and often resist chemo- and radiation therapies. The genetic alterations acquired by tumors modify their biochemical pathways, which results in abnormal tumor metabolism. An elevation in glycolysis known as the “Warburg effect” and changes in lipid synthesis and oxidation occur. Magnetic resonance spectroscopy (MRS has been used to study tumor metabolism in preclinical animal models and in clinical research on human breast, brain, and prostate cancers. This technique can identify specific genetic and metabolic changes that occur in malignant tumors. Therefore, the metabolic markers, detectable by MRS, not only provide information on biochemical changes but also define different metabolic tumor phenotypes. When combined with the contrast-enhanced Magnetic Resonance Imaging (MRI, which has a high sensitivity for cancer diagnosis, in vivo magnetic resonance spectroscopic imaging (MRSI improves the diagnostic specificity of malignant human cancers and is becoming an important clinical tool for cancer management and care. This article reviews the MRSI techniques as molecular imaging methods to detect and quantify metabolic changes in various tumor tissue types, especially in extracranial tumor tissues that contain high concentrations of fat. MRI/MRSI methods have been used to characterize tumor microenvironments in terms of blood volume and vessel permeability. Measurements of tissue oxygenation and glycolytic rates by MRS also are described to illustrate the capability of the MR technology in probing molecular information non-invasively in tumor tissues and its important potential for studying molecular mechanisms of human cancers in physiological conditions.

MAP17 and SGLT1 protein expression levels as prognostic markers for cervical tumor patient survival.

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Marco Perez

Full Text Available MAP17 is a membrane-associated protein that is overexpressed in human tumors. Because the expression of MAP17 increases reactive oxygen species (ROS generation through SGLT1 in cancer cells, in the present work, we investigated whether MAP17 and/or SGLT1 might be markers for the activity of treatments involving oxidative stress, such as cisplatin or radiotherapy. First, we confirmed transcriptional alterations in genes involved in the oxidative stress induced by MAP17 expression in HeLa cervical tumor cells and found that Hela cells expressing MAP17 were more sensitive to therapies that induce ROS than were parental cells. Furthermore, MAP17 increased glucose uptake through SGLT receptors. We then analyzed MAP17 and SGLT1 expression levels in cervical tumors treated with cisplatin plus radiotherapy and correlated the expression levels with patient survival. MAP17 and SGLT1 were expressed in approximately 70% and 50% of cervical tumors of different types, respectively, but they were not expressed in adenoma tumors. Furthermore, there was a significant correlation between MAP17 and SGLT1 expression levels. High levels of either MAP17 or SGLT1 correlated with improved patient survival after treatment. However, the patients with high levels of both MAP17 and SGLT1 survived through the end of this study. Therefore, the combination of high MAP17 and SGLT1 levels is a marker for good prognosis in patients with cervical tumors after cisplatin plus radiotherapy treatment. These results also suggest that the use of MAP17 and SGLT1 markers may identify patients who are likely to exhibit a better response to treatments that boost oxidative stress in other cancer types.

Gene methylation profiles of normal mucosa, and benign and malignant colorectal tumors identify early onset markers

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Vatn Morten

2008-12-01

Full Text Available Abstract Background Multiple epigenetic and genetic changes have been reported in colorectal tumors, but few of these have clinical impact. This study aims to pinpoint epigenetic markers that can discriminate between non-malignant and malignant tissue from the large bowel, i.e. markers with diagnostic potential. The methylation status of eleven genes (ADAMTS1, CDKN2A, CRABP1, HOXA9, MAL, MGMT, MLH1, NR3C1, PTEN, RUNX3, and SCGB3A1 was determined in 154 tissue samples including normal mucosa, adenomas, and carcinomas of the colorectum. The gene-specific and widespread methylation status among the carcinomas was related to patient gender and age, and microsatellite instability status. Possible CIMP tumors were identified by comparing the methylation profile with microsatellite instability (MSI, BRAF-, KRAS-, and TP53 mutation status. Results The mean number of methylated genes per sample was 0.4 in normal colon mucosa from tumor-free individuals, 1.2 in mucosa from cancerous bowels, 2.2 in adenomas, and 3.9 in carcinomas. Widespread methylation was found in both adenomas and carcinomas. The promoters of ADAMTS1, MAL, and MGMT were frequently methylated in benign samples as well as in malignant tumors, independent of microsatellite instability. In contrast, normal mucosa samples taken from bowels without tumor were rarely methylated for the same genes. Hypermethylated CRABP1, MLH1, NR3C1, RUNX3, and SCGB3A1 were shown to be identifiers of carcinomas with microsatellite instability. In agreement with the CIMP concept, MSI and mutated BRAF were associated with samples harboring hypermethylation of several target genes. Conclusion Methylated ADAMTS1, MGMT, and MAL are suitable as markers for early tumor detection.

Possible application of tumor marker radioimmunoassay in diagnosis of testicular and prostatic carcinomas

Energy Technology Data Exchange (ETDEWEB)

Kausitz, J

1988-10-01

Determinations of alpha fetoprotein and chorionic gonadotropin levels by radioimmunoassay in 340 patients with germ cell tumors of the testes have confirmed that tumor markers are suitable prognostic parameters, facilitate assessment of the clinical stage, are sensitive parameters of the efficacy of chemotherapy and enable early detection of relapses. In a group of 71 patients with prostate cancer, systematic determination of prostate specific antigen levels proved to be a reliable method of monitoring and a sensitive method of detecting remote metastases. (author). 5 figs., 13 tabs., 23 refs.

Proteomic profiling identifies markers for inflammation-related tumor-fibroblast interaction.

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Drev, Daniel; Bileck, Andrea; Erdem, Zeynep N; Mohr, Thomas; Timelthaler, Gerald; Beer, Andrea; Gerner, Christopher; Marian, Brigitte

2017-01-01

Cancer associated fibroblasts are activated in the tumor microenvironment and contribute to tumor progression, angiogenesis, extracellular matrix remodeling, and inflammation. To identify proteins characteristic for fibroblasts in colorectal cancer we used liquid chromatography-tandem mass spectrometry to derive protein abundance from whole-tissue homogenates of human colorectal cancer/normal mucosa pairs. Alterations of protein levels were determined by two-sided t test with greater than threefold difference and an FDR of matrix organization, TGFβ receptor signaling and angiogenesis mainly originating from the stroma. Most prominent were increased abundance of SerpinB5 in the parenchyme and latent transforming growth factor β-binding protein, thrombospondin-B2, and secreted protein acidic-and-cysteine-rich in the stroma. Extracellular matrix remodeling involved collagens type VIII, XII, XIV, and VI as well as lysyl-oxidase-2. In silico analysis of mRNA levels demonstrated altered expression in the tumor and the adjacent normal tissue as compared to mucosa of healthy individuals indicating that inflammatory activation affected the surrounding tissue. Immunohistochemistry of 26 tumor specimen confirmed upregulation of SerpinB5, thrombospondin B2 and secreted protein acidic-and-cysteine-rich. This study demonstrates the feasibility of detecting tumor- and compartment-specific protein-signatures that are functionally meaningful by proteomic profiling of whole-tissue extracts together with mining of RNA expression datasets. The results provide the basis for further exploration of inflammation-related stromal markers in larger patient cohorts and experimental models.

The comparison of nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) with Ki67 proliferation marker expression in common skin tumors.

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Zduniak, Krzysztof; Agrawal, Siddarth; Symonowicz, Krzysztof; Jurczyszyn, Kamil; Ziółkowski, Piotr

2014-03-01

Nuclear ubiquitous casein and cyclin-dependent kinases substrate (NUCKS) is a chromosomal protein of unknown function. Its amino acid composition and structure of its DNA binding domain resemble those of high mobility group A (HMGA) proteins which are associated with various malignancies. Since changes in expression of HMGA are considered as a marker of tumor progression, it is possible that similar changes in expression of NUCKS could be a useful tool in diagnosis of malignant skin tumors. To investigate this assumption we used specific antibodies against NUCKS for immunohistochemistry of squamous (SCC) and basal cell carcinoma (BCC) as well as keratoacanthoma (KA). We found high expression of NUCKS in nuclei of SCC and BCC cells which exceeded expression of the well-known proliferation marker Ki67. Expression of NUCKS in benign KA was much below that of malignant tumors. With the present study and based on our previous experience we would like to suggest the NUCKS protein as a novel proliferation marker for immunohistochemical evaluation of formalin-fixed and paraffin-embedded skin tumor specimens. We would like to emphasize that NUCKS abundance in malignant skin tumors is higher than that of the well-known proliferation marker Ki67, thus allowing more precise assessment of tumor proliferation potential.

Serum tumor marker CA 125 for monitoring ovarian cancer during follow-up

DEFF Research Database (Denmark)

Tuxen, Malgorzata K.; Sölétormos, G; Dombernowsky, P

2002-01-01

CA 125 is currently widely applied in the management of patients with ovarian cancer. However, a change in results of CA 125, which should be considered significant, has not been defined. The aim of this study was to investigate the ability of CA 125 to signal progressive ovarian cancer during fo...... utility of serological tumor markers in patients with ovarian cancer....

Alternative fiducial markers for Vero real-time tumor tracking radiotherapy: A phantom study

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Park, Shin-Hyung; Kim, Jae-Chul; Kim, Sung Joon

2016-12-01

The objective of this study was to investigate the feasibility of potential fiducial markers consisting of various materials in a Vero real-time tumor-tracking (RTTT) system. In order to determine the applicability of fiducial markers for the Vero RTTT system, we tested various markers consisting of 8 kinds of material (titanium, stainless steel, high-carbon steel, pure steel, copper, silver, tantalum, and gold) with various diameters ranging from 0.3 mm to 1.6 mm and a length of 5 mm. Additionally, a commercial gold coil marker (Visicoil™, IBA dosimetry, Schwarzenbruck, Germany) of diameter 0.5 mm and length 1 cm was included for evaluation. The radiologic visibility on kV fluoroscopy/kV CT scan images of the fiducial markers was evaluated. The detectability on the RTTT system was tested using a two-dimensional moving phantom (Brainlab AG, Feldkirchen, Germany), producing sinusoidal motion. The target center's accuracy was evaluated by calculating the deviation of the position of a metal sphere from the center on the dose profile. Dose profiles were measured using Gafchromic EBT2 films (International Specialty Products, NJ, USA). All markers were visible on kV fluoroscopy/kV CT while markers with atomic number ≥ 25.7 were detectable on the Vero RTTT system. All the detected markers showed excellent geometric accuracy.

Tumor markers as baseline for indication to chemo- and radiotherapy

International Nuclear Information System (INIS)

Senn, H.J.; Kantonsspital Sankt Gallen

1986-01-01

Most Tumor markers (TM) are neither organ- nor tumor-specific. Their growing number is presently more disturbing than helpful for the clinician and their present potential as an indication-basis for radio- and/or chemotherapy can be roughly summarized in 3 categories: 1) High specificity and high clinical value: Examples are beta-HCG in female chorio-CA, AFP and beta-HCG in testicular tumors, calcitonin in medullary thyroid CA and subclasses of immunglobulins in lymphoproliferative disorders. 2) High specificity and low clinical value: Examples are AFP in primary liver CA, CEA in colon cancer, CA 19-9 in pancreatic CA and CA 125 in ovarian CA. Despite of their high specificity, detection of 'earlier relapse' does not serve the purpose of important treatment decisions due to the current lack of salvage therapy. 3) Low specificity and low clinical value: Most of the rest of TM, for which there is no clinically proven basis, which renders their use neither interesting nor economical. The clinical value of TM belonging to the 'second category' at present time, will reach clinical usefulness as soon as secondary curative treatment will be available for those clinical situations. (orig.) [de

Profiling tumor-associated markers for early detection of malignant mesothelioma: an epidemiologic study

Czech Academy of Sciences Publication Activity Database

Amati, M.; Tomasetti, M.; Scartozzi, M.; Mariotti, L.; Alleva, R.; Pignotti, E.; Borghi, B.; Valentino, M.; Governa, M.; Neužil, Jiří; Santarelli, L.

2008-01-01

Roč. 17, č. 1 (2008), s. 163-170 ISSN 1055-9965 R&D Projects: GA AV ČR IAA500520602 Institutional research plan: CEZ:AV0Z50520514; CEZ:AV0Z50520701 Keywords : malignant mesothelioma * tumor markers * asbestos Subject RIV: EB - Genetics ; Molecular Biology Impact factor: 4.770, year: 2008

The diagnostic value of tumor markers and endoscopy in patients with gastric disorders

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Ozgur Turk

2015-04-01

Conclusions: Tumor markers cannot detect any kind of digestive system malignancy. Physicians must pay attention to premalignant lesions due to gastric cancer development. We must pay more attention to diagnose gastric malignancy in patients who have increased CEA and CA 19-9 levels. [Arch Clin Exp Surg 2015; 4(2.000: 74-78

Comparison of Lumipulse® G1200 with Kryptor and Modular E170 for the measurement of 7 tumor markers

OpenAIRE

Marlet , Julien; Bernard , Maguy

2014-01-01

"This is the pre-peer reviewed version of the following article: "Comparison of LUMIPULSE® G1200 With Kryptor and Modular E170 for the Measurement of Seven Tumor Markers", which has been published in final form at http://onlinelibrary.wiley.com/doi/10.1002/jcla.21802/abstract. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."; Background: Tumor marker measurements are becoming essential for prognosis and follow-up of patien...

Clinical value of assays of multiple serum tumor markers in conjunction with 18F-FDG SPECT for discriminating malignant from benign lung disorders

International Nuclear Information System (INIS)

Zhang Chunyan; Wang Linglong; Tu Liping; Yu Yuefang; Zhu Weijie; Cai Ao; Gao Shuxing

2006-01-01

Objective: To evaluate the clinical value of assays of multiple tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung disorders. Methods: A total of 62 patients with malignant and benign lung diseases un- derwent 18 F-FDG SPECT examination and tests for serum tumor markers CEA, CA50, CA199 and CA242, alone or combined. The sensitivity, specificity, accuracy of these tests were examined. Results: The sensitivity, specificity accuracy of 18 F-FDG SPECT for the diagnosis of malignant lung tumors were 85.7 (30/35), 59.3 (16/27) and 74.2(46/62) respectively, those of each of serum CEA, CA199, CA50, CA242 levels in diagnosing malignant lung tumors were 22.9(8/35), 92.6(25/27), 59.7(33/62), 14.3(5/35), 100(27/27), 51.6 (32/62), 34.3 (12/35), 85.2 (23/27), 56.5 (35/62), 28.6 (10/35), 85.2 (23/27) and 53.2 (33/62) respectively, those of assays of multiple serum tumor markers for diagnosis of malignant lung tumors were 85.7 (30/35), 85.2 (23/27) and 85.5 (53/62) respectively, those of assays of multiple tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung nodules were 88.6(31/35), 85.2(23/27) and 87.1 (54/62) respectively. Conclusion: Assays of multiple serum tumor markers in conjunction with 18 F-FDG SPECT for discriminating malignant from benign lung disorders can yield higher sensitivity, specialty and accuracy, making a significant contribution to clinical application. (authors)

Predicting Response to Chemotherapy based on Tumor Marker Trend in Patients with Testicular Cancer

Czech Academy of Sciences Publication Activity Database

Nekulová, M.; Pecen, Ladislav; Kocák, I.; Šimíčková, M.; Frgala, T.; Pilný, R.; Valík, D.

2004-01-01

Roč. 8, - (2004), s. 70 ISSN 1211-8869. [CECHTUMA 2004. 01.10.2004-03.10.2004, Prague] Institutional research plan: CEZ:AV0Z1030915 Keywords : evaluation of therapy response * model of tumor markers decrease * testicular cancer Subject RIV: BB - Applied Statistics, Operational Research

Uterine Tumor Resembling Ovarian Sex Cord Tumor (UTROSCT) Commonly Exhibits Positivity With Sex Cord Markers FOXL2 and SF-1 but Lacks FOXL2 and DICER1 Mutations.

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Croce, Sabrina; de Kock, Leanne; Boshari, Talia; Hostein, Isabelle; Velasco, Valerie; Foulkes, William D; McCluggage, W Glenn

2016-07-01

Uterine tumor resembling ovarian sex cord tumor (UTROSCT) is a rare neoplasm which morphologically and immunohistochemically exhibits overlap with an ovarian sex cord tumor. Although many of these neoplasms are positive with markers of ovarian sex cord-stromal tumors, staining is often limited and the pathogenesis of UTROSCT is unknown. To further explore the sex cord lineage of UTROSCT, we studied 19 of these neoplasms and examined the expression of 2 recently described markers of ovarian sex cord-stromal tumors, FOXL2, and steroidogenic factor-1. We also undertook FOXL2 and DICER1 mutation analysis in these cases; a somatic missense mutation in codon C134W (402C→G) of FOXL2 gene has been demonstrated in the vast majority (>95%) of ovarian adult granulosa cell tumors and somatic DICER1 mutations are found in approximately 60% of ovarian Sertoli-Leydig cell tumors. Ten of 19 cases (53%) exhibited nuclear immunoreactivity with FOXL2 and 11 of 19 (58%) exhibited nuclear staining with steroidogenic factor-1. Neither FOXL2 nor DICER1 mutations were identified in any case where there was sufficient tumor tissue for analysis (18 and 9 cases, respectively). Despite exhibiting an immunophenotype characteristic of a sex cord-stromal tumor, mutations in FOXL2 and DICER1, the 2 most common mutations hitherto reported in ovarian sex cord-stromal tumors, are not a feature of UTROSCT.

Development of a Prognostic Marker for Lung Cancer Using Analysis of Tumor Evolution

Science.gov (United States)

2016-08-01

Bambanker cell freezing medium (Lymphotec Inc., Tokyo, Japan ). Prior to FACS, isolated tumor cells were stained with mouse anti-human CD45RA PE/Cy7... clone L48, BD Biosciences, San Jose, CA) and Aqua Vital Dye (Invitrogen, Carlsbad, CA). CD45 is a blood cell marker used to separate blood cells from

Integration of gene-based markers in a pearl millet genetic map for identification of candidate genes underlying drought tolerance quantitative trait loci

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Sehgal Deepmala

2012-01-01

Full Text Available Abstract Background Identification of genes underlying drought tolerance (DT quantitative trait loci (QTLs will facilitate understanding of molecular mechanisms of drought tolerance, and also will accelerate genetic improvement of pearl millet through marker-assisted selection. We report a map based on genes with assigned functional roles in plant adaptation to drought and other abiotic stresses and demonstrate its use in identifying candidate genes underlying a major DT-QTL. Results Seventy five single nucleotide polymorphism (SNP and conserved intron spanning primer (CISP markers were developed from available expressed sequence tags (ESTs using four genotypes, H 77/833-2, PRLT 2/89-33, ICMR 01029 and ICMR 01004, representing parents of two mapping populations. A total of 228 SNPs were obtained from 30.5 kb sequenced region resulting in a SNP frequency of 1/134 bp. The positions of major pearl millet linkage group (LG 2 DT-QTLs (reported from crosses H 77/833-2 × PRLT 2/89-33 and 841B × 863B were added to the present consensus function map which identified 18 genes, coding for PSI reaction center subunit III, PHYC, actin, alanine glyoxylate aminotransferase, uridylate kinase, acyl-CoA oxidase, dipeptidyl peptidase IV, MADS-box, serine/threonine protein kinase, ubiquitin conjugating enzyme, zinc finger C- × 8-C × 5-C × 3-H type, Hd3, acetyl CoA carboxylase, chlorophyll a/b binding protein, photolyase, protein phosphatase1 regulatory subunit SDS22 and two hypothetical proteins, co-mapping in this DT-QTL interval. Many of these candidate genes were found to have significant association with QTLs of grain yield, flowering time and leaf rolling under drought stress conditions. Conclusions We have exploited available pearl millet EST sequences to generate a mapped resource of seventy five new gene-based markers for pearl millet and demonstrated its use in identifying candidate genes underlying a major DT-QTL in this species. The reported gene

Effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer

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Jian-Ping Zhong

2017-05-01

Full Text Available Objective: To study the effect of Xiao Chaihu Tang combined with intravenous chemotherapy on tumor markers and immune function in patients with advanced breast cancer. Methods: 76 patients with advanced breast cancer treated in our hospital between May 2012 and November 2015 were collected and divided into the combined treatment group (n=34 who accepted Xiao Chaihu Tang combined with intravenous chemotherapy and the control group (n=42 who accepted intravenous chemotherapy alone according to different treatment, and the treatment cycle was 3 months for both groups. Before treatment and 3 months after treatment, ELISA method was used to detect serum levels of broad-spectrum tumor markers and breast cancerspecific tumor markers; flow cytometer was used to detect cellular immune function index levels, and turbidimetric immunoassay was used to detect humoral immune function index levels in peripheral blood. Results: Before treatment, differences in serum tumor marker levels as well as cellular immunity and humoral immunity index levels in peripheral blood were not statistically significant between two groups of patients (P>0.05; after 3 months of treatment, broad-spectrum tumor markers carcinoembryonic antigen (CEA, carbohydrate antigen 153 (CA153 and carbohydrate antigen 125 (CA125 levels in serum of combined treatment group were lower than those of control group, and breast cancer-specific tumor markers insulin-like growth factor-1 (IGF-1, midkine (MK, soluble E-cadherin (sEC and thymidine kinase 1 (TK1 levels were lower than those of control group (P<0.05; CD3+ and CD4+ T lymphocyte levels as well as CD4+/CD8+ ratio in peripheral blood of combined treatment group were higher than those of control group while CD8+ T lymphocyte level was lower than that of control group, and immunoglobulin G (IgG, immunoglobulin A (IgA and immunoglobulin M (IgM levels in peripheral blood were higher than those of control group (P<0.05. Conclusions: Xiao Chaihu Tang

Serum tumor markers CEA, CYFRA21-1, and CA-125 are associated with worse prognosis in advanced non-small-cell lung cancer (NSCLC).

Science.gov (United States)

Cedrés, Susana; Nuñez, Isaac; Longo, Marina; Martinez, Pablo; Checa, Eva; Torrejón, Davis; Felip, Enriqueta

2011-05-01

Serum tumor markers are considered a negative prognostic factor in early-stages NSCLC but its role in advanced disease is controversial. The aim of this study is to analyze the prognostic value of tumor markers in advanced NSCLC. Two hundred and seventy seven patients diagnosed in our institution were retrospectively reviewed. Baseline prognostic factors analyzed were gender, histology and brain metastases. Baseline patients characteristics: median age 63 years (30-81 years); males 84.4%, stage IV: 61.7%; adenocarcinoma 38.6%, squamous carcinoma 22.4%. High levels of CEA, CYFRA21-1, and CA125 levels were detected in 179 (55.9%), 119 (65%), and 129 (46.6%) patients respectively. Significant higher levels of CEA and CA125 at baseline were present in adenocarcinoma (P CEA, CYFRA21-1, and CA125 was 5.3 months (m), 3.5 m and 4.6 m versus 7.4 m, 6.2 m and 7.5 m in patients with normal levels (P tumor markers was 10.0 m vs 14.0 m (P = 0.085) for CEA; 5.6 vs 12.1 m for CYFRA21-1 (P = .002), and 8.7 vs 14.0 (P = .03) for CA125. In the multivariate analysis high levels of tumor markers, histology and clinical stage were significant correlated with worse prognostic. Patients with all the tumor markers elevated presented the worst prognosis (3.6 m for PFS and 7.1 m for OS, P tumor markers at baseline are correlated with worse survival in stage III-IV NSCLC patients. Copyright © 2011 Elsevier Inc. All rights reserved.

Screening of specific nucleic acid aptamers binding tumor markers in the serum of the lung cancer patients and identification of their activities.

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Li, Kun; Xiu, Chen-Lin; Gao, Li-Ming; Liang, Hua-Gang; Xu, Shu-Feng; Shi, Ming; Li, Jian; Liu, Zhi-Wei

2017-07-01

Lung cancer is by far the leading cause of cancer death in the world. Despite the improvements in diagnostic methods, the status of early detection was not achieved. So, a new diagnostic method is needed. The aim of this study is to obtain the highly specific nucleic acid aptamers with strong affinity to tumor markers in the serum of the lung cancer patients for targeting the serum. Aptamers specifically binding to tumor markers in the serum of the lung cancer patients were screened from the random single-stranded DNA library with agarose beads as supports and the serum as a target by target-substituting subtractive SELEX technique and real-time quantitative polymerase chain reaction technique. Subsequently, the secondary single-stranded DNA library obtained by 10 rounds of screening was amplified to double-stranded DNA, followed by high-throughput genome sequence analysis to screen aptamers with specific affinity to tumor markers in the serum of the lung cancer patients. Finally, six aptamers obtained by 10 rounds of screening were identified with high specific affinity to tumor markers in the serum of the lung cancer patients. Compared with other five aptamers, the aptamer 43 was identified both with the highest specificity to bind target molecule and without any obvious affinity to non-specific proteins. The screened aptamers have relatively high specificity to combine tumor markers in the serum of the lung cancer patients, which provides breakthrough points for early diagnosis and treatment of lung cancer.

Frequent silencing of the candidate tumor suppressor TRIM58 by promoter methylation in early-stage lung adenocarcinoma.

Science.gov (United States)

Kajiura, Koichiro; Masuda, Kiyoshi; Naruto, Takuya; Kohmoto, Tomohiro; Watabnabe, Miki; Tsuboi, Mitsuhiro; Takizawa, Hiromitsu; Kondo, Kazuya; Tangoku, Akira; Imoto, Issei

2017-01-10

In this study, we aimed to identify novel drivers that would be epigenetically altered through aberrant methylation in early-stage lung adenocarcinoma (LADC), regardless of the presence or absence of tobacco smoking-induced epigenetic field defects. Through genome-wide screening for aberrantly methylated CpG islands (CGIs) in 12 clinically uniform, stage-I LADC cases affecting six non-smokers and six smokers, we identified candidate tumor-suppressor genes (TSGs) inactivated by hypermethylation. Through systematic expression analyses of those candidates in panels of additional tumor samples and cell lines treated or not treated with 5-aza-deoxycitidine followed by validation analyses of cancer-specific silencing by CGI hypermethylation using a public database, we identified TRIM58 as the most prominent candidate for TSG. TRIM58 was robustly silenced by hypermethylation even in early-stage primary LADC, and the restoration of TRIM58 expression in LADC cell lines inhibited cell growth in vitro and in vivo in anchorage-dependent and -independent manners. Our findings suggest that aberrant inactivation of TRIM58 consequent to CGI hypermethylation might stimulate the early carcinogenesis of LADC regardless of smoking status; furthermore, TRIM58 methylation might be a possible early diagnostic and epigenetic therapeutic target in LADC.

Effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer

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Qi Pan

2017-09-01

Full Text Available Objective: To investigate the effect of Kanglaite combined with chemotherapy on myelosuppression, immune function and tumor markers levels in patients with breast cancer. Methods: A total of 90 breast cancer patients in our hospital were randomly divided into control group (45 cases and observation group (45 cases. The two groups received CAF chemotherapy, and the observation group was additionally given Kanglaite injection (200 mL/d for 2 weeks continuously. Both groups had chemotherapy for 6 courses. The effect on myelosuppression, immune function and tumor markers levels was detected and compared before and after treatment in two groups. Results: After treatment, myelosuppression was found in both groups, and the levels of leukocyte, hemoglobin and platelet decreased significantly compared with before treatment (P0.05, and the levels of immune function indexes (CD3+, CD4+, CD4+/ CD8+ of the observation group were significantly higher than those in the control group （P<0.05） . After treatment, the levels of two tumor markers (CEA, CA15-3 decreased significantly than before treatment in both groups (P<0.05, and the decrease amplitude in the observation group was higher than that in the control group (P<0.05. Conclusions: Kanglaite combined with chemotherapy has evident therapeutic effect on breast cancer. It can alleviate the myelosuppression caused by chemotherapy, improve immune function, and reduce the concentration of tumor markers in patients with breast cancer.

Is a comparative clinical trial for breast cancer tumor markers to monitor disease recurrence warranted? A value of information analysis.

Science.gov (United States)

Thariani, Rahber; Henry, Norah Lynn; Ramsey, Scott D; Blough, David K; Barlow, Bill; Gralow, Julie R; Veenstra, David L

2013-05-01

Breast cancer tumor markers are used by some clinicians to screen for disease recurrence risk. Since there is limited evidence of benefit, additional research may be warranted. To assess the potential value of a randomized clinical trial of breast tumor marker testing in routine follow-up of high-risk, stage II-III breast cancer survivors. We developed a decision-analytic model of tumor marker testing plus standard surveillance every 3-6 months for 5 years. The expected value of sample information was calculated using probabilistic simulations and was a function of: the probability of selecting the optimal monitoring strategy with current versus future information; the impact of choosing the nonoptimal strategy; and the size of the population affected. The value of information for a randomized clinical trial involving 9000 women was US$214 million compared with a cost of US$30-60 million to conduct such a trial. The probability of making an alternate, nonoptimal decision and choosing testing versus no testing was 32% with current versus future information from the trial. The impact of a nonoptimal decision was US$2150 and size of population impacted over 10 years was 308,000. The value of improved information on overall survival was US$105 million, quality of life US$37 million and test performance US$71 million. Conducting a randomized clinical trial of breast cancer tumor markers appears to offer a good societal return on investment. Retrospective analyses to assess test performance and evaluation of patient quality of life using tumor markers may also offer valuable areas of research. However, alternative investments may offer even better returns in investments and, as such, the trial concept deserves further study as part of an overall research-portfolio evaluation.

An Efficient Strategy Combining SSR Markers- and Advanced QTL-seq-driven QTL Mapping Unravels Candidate Genes Regulating Grain Weight in Rice.

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Daware, Anurag; Das, Sweta; Srivastava, Rishi; Badoni, Saurabh; Singh, Ashok K; Agarwal, Pinky; Parida, Swarup K; Tyagi, Akhilesh K

2016-01-01

Development and use of genome-wide informative simple sequence repeat (SSR) markers and novel integrated genomic strategies are vital to drive genomics-assisted breeding applications and for efficient dissection of quantitative trait loci (QTLs) underlying complex traits in rice. The present study developed 6244 genome-wide informative SSR markers exhibiting in silico fragment length polymorphism based on repeat-unit variations among genomic sequences of 11 indica, japonica, aus , and wild rice accessions. These markers were mapped on diverse coding and non-coding sequence components of known cloned/candidate genes annotated from 12 chromosomes and revealed a much higher amplification (97%) and polymorphic potential (88%) along with wider genetic/functional diversity level (16-74% with a mean 53%) especially among accessions belonging to indica cultivar group, suggesting their utility in large-scale genomics-assisted breeding applications in rice. A high-density 3791 SSR markers-anchored genetic linkage map (IR 64 × Sonasal) spanning 2060 cM total map-length with an average inter-marker distance of 0.54 cM was generated. This reference genetic map identified six major genomic regions harboring robust QTLs (31% combined phenotypic variation explained with a 5.7-8.7 LOD) governing grain weight on six rice chromosomes. One strong grain weight major QTL region ( OsqGW5.1 ) was narrowed-down by integrating traditional QTL mapping with high-resolution QTL region-specific integrated SSR and single nucleotide polymorphism markers-based QTL-seq analysis and differential expression profiling. This led us to delineate two natural allelic variants in two known cis -regulatory elements (RAV1AAT and CARGCW8GAT) of glycosyl hydrolase and serine carboxypeptidase genes exhibiting pronounced seed-specific differential regulation in low (Sonasal) and high (IR 64) grain weight mapping parental accessions. Our genome-wide SSR marker resource (polymorphic within/between diverse

CD56 Expression in Odontogenic Cysts and Tumors.

Science.gov (United States)

Jaafari-Ashkavandi, Zohreh; Dehghani-Nazhvani, Ali; Razmjouyi, Faranak

2014-01-01

Background and aims. Odontogenic cysts and tumors have a wide spectrum of clinical characteristics that lead to the different management strategies. Since definite diagnosis is difficult in some cases, it has been suggested that CD56 may be a candidate marker for definitive diagnosis of some odontogenic tumors. The present study was designed to examine CD56 expression in lesions with histopathological similarities. Materials and methods. In this cross-sectional, analytical study the subjects were 22 ameloblastomas, 13 dentigerous cysts, 10 keratocystic odontogenic tumors (KCOT), 4 adenomatoid odontogenic tumors (AOT), 3 orthokeratinized odonto-genic cysts, 3 calcifying odontogenic cysts (COC) and one glandular odontogenic cyst (GOC). All the samples were examined for CD56 immunoreactivity. Data were analyzed using chi-square test. Results. Twenty cases (91%) of ameloblastomas, 3 (75%) AOT, 4 (40%) KCOT and one case of GOC were positive for CD56. None of the dentigerous cysts, COC and orthokeratinized odontogenic cysts was CD56-positive. There was a significant difference in the CD56 expression between ameloblastoma and dentigerous cyst, as well as COC. Also, KCOT showed significantly higher expression than orthokeratinized odontogenic cyst. Conclusion. In this study CD56 expression was limited to the odontogenic tumors and more aggressive cystic lesions. This marker can be a useful aid for distinguishing cysts and tumors from similar lesions.

Migrating glioma cells express stem cell markers and give rise to new tumors upon xenografting

DEFF Research Database (Denmark)

Munthe, Sune; Sørensen, Mia D; Thomassen, Mads

2016-01-01

Glioblastoma (GBM) is the most frequent and malignant brain tumor with an overall survival of only 14.6 months. Although these tumors are treated with surgery, radiation and chemotherapy, recurrence is inevitable. A critical population of tumor cells in terms of therapy, the so-called cancer stem......-like phenotype is currently lacking. In the present study, the aim was to characterize the phenotype of migrating tumor cells using a novel migration assay based on serum-free stem cell medium and patient-derived spheroid cultures. The results showed pronounced migration of five different GBM spheroid cultures......-related genes and the HOX-gene list in migrating cells compared to spheroids. Determination of GBM molecular subtypes revealed that subtypes of spheroids and migrating cells were identical. In conclusion, migrating tumor cells preserve expression of stem cell markers and functional CSC characteristics. Since...

Immunohistochemical study of tumor markers (CEA, TPA, CA19-9, POA and Ferritin) and pancreatic exocrine enzymes(Amylase and Elastase 1) in pancreatic tumors

OpenAIRE

脇谷, 勇夫

1987-01-01

The distribution of carcinoembryonic antigen (CEA), tissue polypeptide antigen (TPA), carbohydrate antigen 19-9 (CA19-9), pancreatic oncofetal antigen (POA), Ferritin, Amylase and Elastase 1 was studied immunohistochemically using an immunoperoxidase method in 26 conventional histopathologic sections of pancreatic tumor. CEA and CA19-9 were regarded as markers secreted into the glandular lumina from cancer cells, but TPA and POA were not. The expression of these markers was different from one...

Detection of tumor markers in prostate cancer and comparison of sensitivity between real time and nested PCR.

Science.gov (United States)

Matsuoka, Takayuki; Shigemura, Katsumi; Yamamichi, Fukashi; Fujisawa, Masato; Kawabata, Masato; Shirakawa, Toshiro

2012-06-27

The objective of this study is to investigate and compare the sensitivity in conventional PCR, quantitative real time PCR, nested PCR and western blots for detection of prostate cancer tumor markers using prostate cancer (PCa) cells. We performed conventional PCR, quantitative real time PCR, nested PCR, and western blots using 5 kinds of PCa cells. Prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and androgen receptor (AR) were compared for their detection sensitivity by real time PCR and nested PCR. In real time PCR, there was a significant correlation between cell number and the RNA concentration obtained (R(2)=0.9944) for PSA, PSMA, and AR. We found it possible to detect these markers from a single LNCaP cell in both real time and nested PCR. By comparison, nested PCR reached a linear curve in fewer PCR cycles than real time PCR, suggesting that nested PCR may offer PCR results more quickly than real time PCR. In conclusion, nested PCR may offer tumor maker detection in PCa cells more quickly (with fewer PCR cycles) with the same high sensitivity as real time PCR. Further study is necessary to establish and evaluate the best tool for PCa tumor marker detection.

Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

Directory of Open Access Journals (Sweden)

Søren Kristiansen

2015-01-01

Full Text Available The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.

Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer.

Science.gov (United States)

Kristiansen, Søren; Jørgensen, Lars Mønster; Hansen, Morten Høgh; Nielsen, Dorte; Sölétormos, György

2015-01-01

The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the interrelationship between protein tumor markers, the global DNA hypomethylation, and hypermethylated genes in serum from patients with advanced disease. Twenty-nine patients with histologically proven advanced breast cancer received first-line chemotherapy with epirubicin. Samples were collected prior to each treatment and prospectively analyzed for CA 15-3, CEA, and TPA. The same samples were retrospectively analyzed for the concentration of hypermethylated RASSF1A and for global DNA hypomethylation using LINE-1. Among patients with elevated concentrations of the protein markers, concordance could be observed between serial changes of the hypermethylated RASSF1A gene and the protein markers. Among patients with lower concentrations, RASSF1A could only be detected periodically. There was discordance between changes of the hypomethylated LINE-1 as compared to the protein markers. Circulating hypermethylated RASSF1A and protein markers may have similar kinetics during monitoring of tumor burden. Further investigations are needed to determine whether any of the hypermethylated DNA genes may provide predictive information during monitoring.

News and views on tumor markers: The use of radioactive antibodies against cell-bound antigens

International Nuclear Information System (INIS)

Kleist, S. von

1984-01-01

It was doubtless due to the phenomenal progress in the field of tumor immunology that took place during the last 20 years, that today we dispose not only of highly sensitive immunological tests like the RIA or EIA, but also of most specific reagents like monospecific polyclonal and monoclonal antibodies. In this context the discovery in human carcinomas of tumor-associated antigens was of prime importance, especially since some of them were found to have clinical relevance as so-called tumor markers. It has been shown that there is a direct correlation between the absolute tumor burden and the blood concentration of these substances. Based on animal models a new technology for tumor and metastases detection was developed in recent years, that used polyvalent or monoclonal antibodies prepared against tumor-associated antigens. This technique called radioimmuno-detection (RAID), especially in the hands of experts, may be superior in many instances to conventional radiology, radionuclide scanning or ultra-sonographic techniques. (orig.) [de

Radioimmunoassay for determination of tumor markers in the diagnosis of rectal cancer recurrences

International Nuclear Information System (INIS)

Ozhiganov, E.L.; Kuznetsova, L.F.

1991-01-01

The levels of tumor markers were determined in patients with rectal cancer recurrences by radioimmunoassay. An increase in a CEA level was observed most frequently. An increase in the levels of α-fetoprotein, ferritin and β 2 -microglobulin was observed. It was shown that the most specific and effective diagnostic test of rectal cancer recurrences was the determination of a CEA level

Tumor Mesenchymal Stem-Like Cell as a Prognostic Marker in Primary Glioblastoma

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Seon-Jin Yoon

2016-01-01

Full Text Available The isolation from brain tumors of tumor mesenchymal stem-like cells (tMSLCs suggests that these cells play a role in creating a microenvironment for tumor initiation and progression. The clinical characteristics of patients with primary glioblastoma (pGBM positive for tMSLCs have not been determined. This study analyzed samples from 82 patients with pGBM who had undergone tumor removal, pathological diagnosis, and isolation of tMSLC from April 2009 to October 2014. Survival, extent of resection, molecular markers, and tMSLC culture results were statistically evaluated. Median overall survival was 18.6 months, 15.0 months in tMSLC-positive patients and 29.5 months in tMSLC-negative patients (P=0.014. Multivariate cox regression model showed isolation of tMSLC (OR = 2.5, 95% CI = 1.1~5.6, P=0.021 showed poor outcome while larger extent of resection (OR = 0.5, 95% CI = 0.2~0.8, P=0.011 has association with better outcome. The presence of tMSLCs isolated from the specimen of pGBM is associated with the survival of patient.

Study on the clinical value of combined determination of six tumor marker for diagnosis of pulmonary carcinoma

International Nuclear Information System (INIS)

Chen Zhong; Liu Yun; Liu Li; Lu Xiaopeng; Zhang Jun; Li Jiangang; Zhu Zili

2006-01-01

Objective: To study the clinical applicability of single/combined determination of six tumor markers (CEA, CA125, CA50, CA19-9, CA153, CYFRA21-1) for diagnosis of pulmonary carcinoma. Methods: Serum contents of these six tumor markers were determined with RIA in 130 patients with pulmonary carcinoma, 40 patients with various benign pulmonary disorders, and 45 controls. Results: (1) Only two false positive cases were found in the 40 patients with benign pulmonary disorders (CA125, n=1, CA153 n=1). (2) Positive rate of single marker in patients with pulmonary cancer: CYFRA21-1 (79.23%)>CA153 (61.53%) > CA125(58.46%)> CA19-9(57.69%) > CEA(46.92%) > CA50(43.84%). (3) Combined determination of CYFRA21-1 with any one of the other 5 markers would increase the positive rate to 86.15%-89.23%. (4) Mean value of any marker in the malignant cases were over 4 folds of that in the benign cases-high diagnostic credibility. (5) Histology of the malignancy (squamous cell carcinoma or adenocarcinoma) made no difference on the positive rate of the markers with the exception of a slight higher positive rate of CA19-9 in adenocarcinomas. Conclusion: The authors believe that combined determination of CYFRA21-1 with CA153 would be the first choice for diagnosis of pulmonary carcinoma, followed by CYFRA21-1 + CA125 or CA19-9. (authors)

Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

Science.gov (United States)

Diaz-Cano, Salvador J.

2012-01-01

Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma), mechanisms of intercellular transference of genetic information (exosomes), and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning. PMID:22408433

Comparison of the value of PCNA and Ki-67 as markers of cell proliferation in ameloblastic tumor

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Mosqueda-Taylor, Adalberto; Molina-Frechero, Nelly; Mori-Estevez, Ana D.; Sánchez-Acuña, Guillermo

2013-01-01

Objectives: The aim of this study was to compare among PCNAand Ki-67 as the most reliable immunohistochemical marker for evaluating cell proliferation in ameloblastic tumors. Study Design: Observational, retrospective, and descriptive study of a large series of ameloblastic tumors, composed of 161 ameloblastomas and four ameloblastic carcinomas, to determine and compare PCNA and Ki-67 expression using immunohistochemistry techniques. Results: When analyzing Ki-67 positivity, the desmoplastic ameloblastoma demonstrated a significantly lower proliferation rate (1.9%) compared with the solid/multicystic and unicystic ameloblastomas and ameloblastic carcinomas (p<0.05), whereas the ameloblastic carcinomas displayed a significantly higher rate compared with all of the other ameloblastomas (48.7%) (p<0.05). When analyzing cell proliferation with PCNA, we found significant differences only between the ameloblastic carcinomas (93.3%) and the desmoplastic ameloblastomas (p<0.05). When differences between the immunopositivity for PCNA and Ki-67 were compared, the percentages were higher for PCNA in all types of ameloblastomas and ameloblastic carcinomas. In all cases, the percentages were greater than 80%, whereas the immunopositivity for Ki-67 was significantly lower; for example, the ameloblastic carcinoma expressed the highest positivity and only reached 48.7%, compared to 93.3% when we used PCNA. Conclusions: In the present study, when we used the proliferation cell marker Ki-67, the percentages of positivity were more specific and varied among the different types of ameloblastomas, suggesting that Ki-67 is a more specific marker for the proliferation of ameloblastic tumor cells. Key words:Ameloblastomas, ameloblastic carcinoma, PCNA, Ki-67, cell proliferation markers. PMID:23229269

Preoperative CEA and CA 19-9 are prognostic markers for survival after curative resection for ductal adenocarcinoma of the pancreas - a retrospective tumor marker prognostic study.

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Distler, Marius; Pilarsky, Eva; Kersting, Stephan; Grützmann, Robert

2013-01-01

The prognosis for patients with ductal adenocarcinoma of the pancreas (PDAC) remains poor even after curative resection. Carbohydrate antigen 19-9 (CA 19-9) and the carcinoembryonic antigen (CEA) are the most widely used serum-based tumor markers for the diagnosis and follow up of pancreatic cancer. In our analysis we aim to assess the prognostic value of a combination of both tumor markers in patients with pancreatic ductal adenocarcinoma (PDAC). Between 01/1995 and 08/2012 we performed a total of 264 pancreatic resections due to PDAC. Patients were stratified into 3 groups in regard to their preoperative tumor marker levels. Survival was compared between the groups using Kaplan Meier analysis and log rank test. Univariate subgroup analysis and multivariate analysis were performed. For 259 cases complete follow up could be obtained. In patients with low preoperative CEA and CA 19-9 levels (group 1 n = 91) the mean survival was 33.3 month (CI 95% 25.1-41.5). If one of the analyzed tumor markers (CEA/CA19-9) was preoperatively elevated above the cut-off level (group 2 n = 106) mean survival was 28.5 month (CI 95% 22.1-35.1). 62 patients showed preoperative elevation of both, CEA and CA 19-9 (group 3); mean survival in this group was 23.9 month (CI 95% 13.9-33.9), p > 0.01. Multivariate analysis confirmed preoperative CEA/CA 19-9 level as independent prognostic factor (HR 1.299). Preoperative CEA and CA 19-9 levels correlate with patient prognosis after curative pancreatic resection due to PDAC. This is especially true for the most frequently pT 3/4 stages of PDAC. Even if CEA and CA 19-9 might not be appropriate for screening, its serum levels should therefore be determined prior to operation and taken into account when resectability or operability is doubtful. Copyright © 2013 Surgical Associates Ltd. Published by Elsevier Ltd. All rights reserved.

High Retention and Safety of Percutaneously Implanted Endovascular Embolization Coils as Fiducial Markers for Image-Guided Stereotactic Ablative Radiotherapy of Pulmonary Tumors

International Nuclear Information System (INIS)

Hong, Julian C.; Yu Yao; Rao, Aarti K.; Dieterich, Sonja; Maxim, Peter G.; Le, Quynh-Thu; Diehn, Maximilian; Sze, Daniel Y.; Kothary, Nishita; Loo, Billy W.

2011-01-01

Purpose: To compare the retention rates of two types of implanted fiducial markers for stereotactic ablative radiotherapy (SABR) of pulmonary tumors, smooth cylindrical gold 'seed' markers ('seeds') and platinum endovascular embolization coils ('coils'), and to compare the complication rates associated with the respective implantation procedures. Methods and Materials: We retrospectively analyzed the retention of percutaneously implanted markers in 54 consecutive patients between January 2004 and June 2009. A total of 270 markers (129 seeds, 141 coils) were implanted in or around 60 pulmonary tumors over 59 procedures. Markers were implanted using a percutaneous approach under computed tomography (CT) guidance. Postimplantation and follow-up imaging studies were analyzed to score marker retention relative to the number of markers implanted. Markers remaining near the tumor were scored as retained. Markers in a distant location (e.g., pleural space) were scored as lost. CT imaging artifacts near markers were quantified on radiation therapy planning scans. Results: Immediately after implantation, 140 of 141 coils (99.3%) were retained, compared to 110 of 129 seeds (85.3%); the difference was highly significant (p < 0.0001). Of the total number of lost markers, 45% were reported lost during implantation, but 55% were lost immediately afterwards. No additional markers were lost on longer-term follow-up. Implanted lesions were peripherally located for both seeds (mean distance, 0.33 cm from pleural surface) and coils (0.34 cm) (p = 0.96). Incidences of all pneumothorax (including asymptomatic) and pneumothorax requiring chest tube placement were lower in implantation of coils (23% and 3%, respectively) vs. seeds (54% and 29%, respectively; p = 0.02 and 0.01). The degree of CT artifact was similar between marker types. Conclusions: Retention of CT-guided percutaneously implanted coils is significantly better than that of seed markers. Furthermore, implanting coils is at

Evaluation of tumor markers (HER-2/neu oncoprotein, CEA, and CA 15.3) in patients with locoregional breast cancer: prognostic value.

Science.gov (United States)

Molina, Rafael; Augé, Jose M; Escudero, Jose M; Filella, Xavier; Zanon, Gabriel; Pahisa, Jaume; Farrus, Blanca; Muñoz, Montserrat; Velasco, Martin

2010-06-01

Tumor markers were studied in the sera of 883 untreated patients with primary breast cancer diagnosed between 1989 and 2007. Abnormal human epidermal growth factor receptor 2 (HER-2)/neu levels (>15 ng/mL) were found in 9.5%, carcinoembryonic antigen (CEA) in 15.9%, and cancer antigen (CA) 15.3 in 19.7% of the patients. One or more tumor markers were abnormal in 305 (34.5%) of the 883 studied patients. Significantly higher serum HER-2/neu levels were found in patients with tissue overexpression of this oncoprotein (p CEA, CA 15.3, and HER-2/neu (only in those patients with tissue overexpression) serum levels were related with tumor stage (tumor size and nodal involvement) and steroid receptors (higher values in estrogen receptor-negative (ER-) tumors). Univariate analysis showed that HER-2/neu serum levels were prognostic factors in disease-free survival (DFS) and overall survival (OS) only in patients with tissue overexpression. Multivariate analysis in 834 patients show that nodal involvement, tumor size, ER, CEA, and adjuvant treatment were independent prognostic factors in DFS and OS. When only patients with HER-2/neu overexpression in tissue were studied, tumor size, nodal involvement, and tumor markers (one or another positive) were independent prognostic factors for both DFS and OS. HER-2/neu serum levels were also an independent prognostic factor, with CEA, ER, and nodes in 106 patients treated with neoadjuvant treatment. In summary, serum HER-2/neu, CEA, and CA 15.3 are useful tools in the prognostic evaluation of patients with primary breast cancer.

Levels of some molecular and biochemical tumor markers in Egyptian patients with different grades and stages of bladder cancer

International Nuclear Information System (INIS)

Abd-elgoad, E.I.; Elkashef, H.S.; Hanfy, A.; El-maghraby, T.

2003-01-01

This study enrolled 64 patients with bladder cancer disease, 54 of them treated by surgery and 10 by radiotherapy. The patients were classified according to their clinical data that include infection with bilharziasis, grade, stage and type of tumor. The present study included determination of telomerase activity in tissue and urine using molecular methods and the levels of nuclear matrix protein 22 (NMP22) and fibronectin in urine. The applied tumor markers showed significant differences in malignant patients compared to control. The same picture was noticed in case of patients received radiotherapy but less pronounced. The results revealed that there is significant correlation between the three tumor markers and the grade of tumor, while NMP22 and fibronectin correlated with stage. Moreover, fibronectin only have significant correlation with the infection with the bilharziasis. The results indicated that determination of telomerase, fibronectin and NMP22 can give clear idea about the development of malignancy and may help in the prediction of cancer recurrence

Correlation Between PSMA and VEGF Expression as Markers for LNCaP Tumor Angiogenesis

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Paulus Tsui

2005-01-01

Full Text Available Our aim is the identification and correlation of changes in tumor-associated protein expression which results from therapy. LNCaP tumors, excised from nude mice treated either by orchiectomy or with the chemotherapeutic agent paclitaxel, were evaluated for the expression of proteins and receptors associated with growth, differentiation, and angiogenesis using immunohistologic procedures. Compared to untreated control tumors, both treatments reduced the expression of vascular endothelial growth factor (VEGF, prostate-specific membrane antigen (PSMA, prostate-specific antigen (PSA, androgen receptor (AR, and epidermal growth factor receptor (EGFR. The effect of paclitaxel treatment on AR expression was the most significant (P=.005. Of particular interest was identifying a significant correlation (P<.000801 between PSMA and VEGF expression regardless of treatment modality. These altered expressions suggest that PSMA may also be a marker for angiogenesis and could represent a target for deliverable agents recognizing either prostatic tumors or endothelial development. Cell surface PSMA would then present a unique target for treatment of patients early in their development of prostatic metastases.

CEA in activated macrophages. New diagnostic possibilities for tumor markers in early colorectal cancer.

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Japink, Dennis; Leers, Mathie P G; Sosef, Meindert N; Nap, Marius

2009-08-01

Serum tumor markers show low sensitivity, making them unsuitable for early detection of cancer. Activated macrophages (AM) from peripheral blood can accumulate tumor marker substances and facilitate early detection in prostate cancer. Here it was investigated whether carcinoembryonic antigen (CEA)-containing macrophages (CEACM) can be used to detect colorectal cancer (CRC) at earlier stages than can serum CEA. Peripheral blood was collected from patients with CRC (n=48), inflammatory colorectal disease (n=5) and from healthy controls (n=18). After separating and labeling AM with CD14-APC/CD16-FITC, AM were intracellularly labeled with anti-CEA antibody and flow cytometrically analyzed. Serum CEA and C-reactive protein (CRP) were measured. The fraction-size of CEACM discriminated between controls and CRC patients, irrespective of AJCC stage (AJCC stage I-IV, pCEA values were significantly elevated in AJCC stage II, III and IV (p=0.02, 0.006 and <0.0001, respectively). Combining CEACM with CRP levels separated CRC from inflammatory colorectal disease. CEACM combined with CRP appears to have diagnostic potential in early CRC.

Intratumoral macrophages contribute to epithelial-mesenchymal transition in solid tumors

International Nuclear Information System (INIS)

Bonde, Anne-Katrine; Tischler, Verena; Kumar, Sushil; Soltermann, Alex; Schwendener, Reto A

2012-01-01

Several stromal cell subtypes including macrophages contribute to tumor progression by inducing epithelial-mesenchymal transition (EMT) at the invasive front, a mechanism also linked to metastasis. Tumor associated macrophages (TAM) reside mainly at the invasive front but they also infiltrate tumors and in this process they mainly assume a tumor promoting phenotype. In this study, we asked if TAMs also regulate EMT intratumorally. We found that TAMs through TGF-β signaling and activation of the β-catenin pathway can induce EMT in intratumoral cancer cells. We depleted macrophages in F9-teratocarcinoma bearing mice using clodronate-liposomes and analyzed the tumors for correlations between gene and protein expression of EMT-associated and macrophage markers. The functional relationship between TAMs and EMT was characterized in vitro in the murine F9 and mammary gland NMuMG cells, using a conditioned medium culture approach. The clinical relevance of our findings was evaluated on a tissue microarray cohort representing 491 patients with non-small cell lung cancer (NSCLC). Gene expression analysis of F9-teratocarcinomas revealed a positive correlation between TAM-densities and mesenchymal marker expression. Moreover, immunohistochemistry showed that TAMs cluster with EMT phenotype cells in the tumors. In vitro, long term exposure of F9-and NMuMG-cells to macrophage-conditioned medium led to decreased expression of the epithelial adhesion protein E-cadherin, activation of the EMT-mediating β-catenin pathway, increased expression of mesenchymal markers and an invasive phenotype. In a candidate based screen, macrophage-derived TGF-β was identified as the main inducer of this EMT-associated phenotype. Lastly, immunohistochemical analysis of NSCLC patient samples identified a positive correlation between intratumoral macrophage densities, EMT markers, intraepithelial TGF-β levels and tumor grade. Data presented here identify a novel role for macrophages in EMT

Registration accuracy and possible migration of internal fiducial gold marker implanted in prostate and liver treated with real-time tumor-tracking radiation therapy (RTRT)

International Nuclear Information System (INIS)

Kitamura, Kei; Shirato, Hiroki; Shimizu, Shinichi; Shinohara, Nobuo; Harabayashi, Toru; Shimizu, Tadashi; Kodama, Yoshihisa; Endo, Hideho; Onimaru, Rikiya; Nishioka, Seiko; Aoyama, Hidefumi; Tsuchiya, Kazuhiko; Miyasaka, Kazuo

2002-01-01

Background and purpose: We have developed a linear accelerator synchronized with a fluoroscopic real-time tumor-tracking system to reduce errors due to setup and organ motion. In the real-time tumor-tracking radiation therapy (RTRT) system, the accuracy of tumor tracking depends on the registration of the marker's coordinates. The registration accuracy and possible migration of the internal fiducial gold marker implanted into prostate and liver was investigated. Materials and methods: Internal fiducial gold markers were implanted in 14 patients with prostate cancer and four patients with liver tumors. Computed tomography (CT) was carried out as a part of treatment planning in the 18 patients. A total of 72 follow-up CT scans were taken. We calculated the relative relationship between the coordinates of the center of mass (CM) of the organs and those of the marker. The discrepancy in the CM coordinates during a follow-up CT compared to those recorded during the planning CT was used to study possible marker migration. Results: The standard deviation (SD) of interobserver variations in the CM coordinates was within 2.0 and 0.4 mm for the organ and the marker, respectively, in seven observers. Assuming that organs do not shrink, grow, or rotate, the maximum SD of migration error in each direction was estimated to be less than 2.5 and 2.0 mm for liver and prostate, respectively. There was no correlation between the marker position and the time after implantation. Conclusion: The degree of possible migration of the internal fiducial marker was within the limits of accuracy of the CT measurement. Most of the marker movement can be attributed to the measurement uncertainty, which also influences registration in actual treatment planning. Thus, even with the gold marker and RTRT system, a planning target volume margin should be used to account for registration uncertainty

Integrating molecular markers into the World Health Organization classification of CNS tumors: a survey of the neuro-oncology community.

Science.gov (United States)

Aldape, Kenneth; Nejad, Romina; Louis, David N; Zadeh, Gelareh

2017-03-01

Molecular markers provide important biological and clinical information related to the classification of brain tumors, and the integration of relevant molecular parameters into brain tumor classification systems has been a widely discussed topic in neuro-oncology over the past decade. With recent advances in the development of clinically relevant molecular signatures and the 2016 World Health Organization (WHO) update, the views of the neuro-oncology community on such changes would be informative for implementing this process. A survey with 8 questions regarding molecular markers in tumor classification was sent to an email list of Society for Neuro-Oncology members and attendees of prior meetings (n=5065). There were 403 respondents. Analysis was performed using whole group response, based on self-reported subspecialty. The survey results show overall strong support for incorporating molecular knowledge into the classification and clinical management of brain tumors. Across all 7 subspecialty groups, ≥70% of respondents agreed to this integration. Interestingly, some variability is seen among subspecialties, notably with lowest support from neuropathologists, which may reflect their roles in implementing such diagnostic technologies. Based on a survey provided to the neuro-oncology community, we report strong support for the integration of molecular markers into the WHO classification of brain tumors, as well as for using an integrated "layered" diagnostic format. While membership from each specialty showed support, there was variation by specialty in enthusiasm regarding proposed changes. The initial results of this survey influenced the deliberations underlying the 2016 WHO classification of tumors of the central nervous system. © The Author(s) 2017. Published by Oxford University Press on behalf of the Society for Neuro-Oncology.

Tumor markers in breast cancer- European Group on Tumor Markers recommendations

DEFF Research Database (Denmark)

Molina, Rafael; Barak, Vivian; van Dalen, Arie

2005-01-01

in the selection of patients for treatment with hormone therapy, while HER-2 is essential in selecting patients with advanced breast cancer for treatment with Herceptin (trastuzumab). Urokinase plasminogen activator and plasminogen activator inhibitor 1 are recently validated prognostic markers for lymph node...

Production and Purification of Monoclonal Antibody Against Tumor Marker of TPA

Directory of Open Access Journals (Sweden)

Seyyed Amir Abbas Ghodrat

2016-05-01

Full Text Available Considering the invasive nature of cancer cells, one of the most important and best indicator of them is the markers inside them. One of the most important markers that observed in some types of cancer cells in various parts of the body is the Cytokeratin. Tissue plasminogen activator antigen (TPA is a Cytokeratin composed of molecules with various molecular weights. The level of TPA serum as associated with cellular growth level and tumorization of cells. In this research, the hybrid of spleen cells in BALB/c female mouse with myeloma cells was conducted with a ratio of 10:1. The resulting monoclonal antibodies were confirmed by SDS-PAGE and western blot. Protein G chromatography was utilized to purify monoclonal antibodies. The results for determining isotypes showed IgM and IgG classes. The titer of the antibody obtained from various clones was capable of identifying Cytokeratin antigen with a dilution of 1/10000. The resulting antibodies were finally confirmed by western blot and all the 5 resulting monoclonal antibodies were capable of identifying a 48 kDa protein. The results indicate that with the help of TPA marker and the monoclonal antibodies produced against them, this marker can be recognized quickly with great accuracy in suspicious cases of cancer. Thus, appropriate measures will be taken to prevent and fight off its probable side effects. This factor can be further used to build a diagonal kit with high sensitivity.

Human endothelial precursor cells express tumor endothelial marker 1/endosialin/CD248.

Science.gov (United States)

Bagley, Rebecca G; Rouleau, Cecile; St Martin, Thia; Boutin, Paula; Weber, William; Ruzek, Melanie; Honma, Nakayuki; Nacht, Mariana; Shankara, Srinivas; Kataoka, Shiro; Ishida, Isao; Roberts, Bruce L; Teicher, Beverly A

2008-08-01

Angiogenesis occurs during normal physiologic processes as well as under pathologic conditions such as tumor growth. Serial analysis of gene expression profiling revealed genes [tumor endothelial markers (TEM)] that are overexpressed in tumor endothelial cells compared with normal adult endothelial cells. Because blood vessel development of malignant tumors under certain conditions may include endothelial precursor cells (EPC) recruited from bone marrow, we investigated TEM expression in EPC. The expression of TEM1 or endosialin (CD248) and other TEM has been discovered in a population of vascular endothelial growth factor receptor 2+/CD31+/CD45-/VE-cadherin+ EPC derived from human CD133+/CD34+ cells. EPC share some properties with fully differentiated endothelial cells from normal tissue, yet reverse transcription-PCR and flow cytometry reveal that EPC express higher levels of endosialin at the molecular and protein levels. The elevated expression of endosialin in EPC versus mature endothelial cells suggests that endosialin is involved in the earlier stages of tumor angiogenesis. Anti-endosialin antibodies inhibited EPC migration and tube formation in vitro. In vivo, immunohistochemistry indicated that human EPC continued to express endosialin protein in a Matrigel plug angiogenesis assay established in nude mice. Anti-endosialin antibodies delivered systemically at 25 mg/kg were also able to inhibit circulating murine EPC in nude mice bearing s.c. SKNAS tumors. EPC and bone marrow-derived cells have been shown previously to incorporate into malignant blood vessels in some instances, yet they remain controversial in the field. The data presented here on endothelial genes that are up-regulated in tumor vasculature and in EPC support the hypothesis that the angiogenesis process in cancer can involve EPC.

Tumor Heterogeneity: Mechanisms and Bases for a Reliable Application of Molecular Marker Design

Directory of Open Access Journals (Sweden)

Salvador J. Diaz-Cano

2012-02-01

Full Text Available Tumor heterogeneity is a confusing finding in the assessment of neoplasms, potentially resulting in inaccurate diagnostic, prognostic and predictive tests. This tumor heterogeneity is not always a random and unpredictable phenomenon, whose knowledge helps designing better tests. The biologic reasons for this intratumoral heterogeneity would then be important to understand both the natural history of neoplasms and the selection of test samples for reliable analysis. The main factors contributing to intratumoral heterogeneity inducing gene abnormalities or modifying its expression include: the gradient ischemic level within neoplasms, the action of tumor microenvironment (bidirectional interaction between tumor cells and stroma, mechanisms of intercellular transference of genetic information (exosomes, and differential mechanisms of sequence-independent modifications of genetic material and proteins. The intratumoral heterogeneity is at the origin of tumor progression and it is also the byproduct of the selection process during progression. Any analysis of heterogeneity mechanisms must be integrated within the process of segregation of genetic changes in tumor cells during the clonal expansion and progression of neoplasms. The evaluation of these mechanisms must also consider the redundancy and pleiotropism of molecular pathways, for which appropriate surrogate markers would support the presence or not of heterogeneous genetics and the main mechanisms responsible. This knowledge would constitute a solid scientific background for future therapeutic planning.

Analysis in patients of the Hospital A.C. Camargo of two tumors markers: CA-72.4 and CYFRA-21.1

International Nuclear Information System (INIS)

Barbuto, Jose Alexandre Marzagao; Oda, Emilia Emiko; Oliveira, Ricardo Manoel de

1995-01-01

The behavior of two tumor markers, CA-72.4 and CYFRA-19.9 was analysed in patients of the Hospital A.C. Camargo. The measurement of CA-272.4 serum levels was performed by an automated chemo luminescence assay in 49 patients and proved useful in the two groups analyzed, patients with esophageal tumors and with gastric tumors. In both cases, there was an increase in sensitivity when measurements of this marker was added to that of carcinoembryonic antigen (CEA) and of CA-19.9. The most sensitive associations were of CA-72.4 and CA-19.9 for esophageal tumors and of CA-72.4 and CEA for the gastric tumors. The maker CYFRA-21.1 was analyzed by a radioimmunoassay in 102 normal blood donors and in 20 patients with lung cancer. Among these, CYFRA-21.1 was altered in 55% of the cases. Therefore, CYFRA-21.1 could be considered, as the neuron-specific enolase (NSE), very useful tool for the follow-up lung cancer patients. (author)

Evaluation of the CRACTES and BIANTA Programs for the Result Interpretation of Tumor Marker Assessment

Czech Academy of Sciences Publication Activity Database

Pecen, Ladislav; Topolčan, O.; Nekulová, M.; Šimíčková, M.; Kaušitz, J.; Eben, Kryštof; Vondráček, Jiří; Pikner, R.; Holubec, L.

2000-01-01

Roč. 15, č. 1 (2000), s. 57-58 ISSN 0886-3849. [International Conference on Human Tumor Markers /17./. 23.03.2000-24.03.2000, Hong Kong] Grant - others:IGA MZ ČR(CZ) NC4780; IGA MZ ČR(CZ) NC4746 Institutional research plan: AV0Z1030915

Quantification of respiration-induced esophageal tumor motion using fiducial markers and four-dimensional computed tomography.

Science.gov (United States)

Jin, Peng; Hulshof, Maarten C C M; de Jong, Rianne; van Hooft, Jeanin E; Bel, Arjan; Alderliesten, Tanja

2016-03-01

Respiration-induced tumor motion is an important geometrical uncertainty in esophageal cancer radiation therapy. The aim of this study was to quantify this motion using fiducial markers and four-dimensional computed tomography (4DCT). Twenty esophageal cancer patients underwent endoscopy-guided marker implantation in the tumor volume and 4DCT acquisition. The 4DCT data were sorted into 10 breathing phases and the end-of-inhalation phase was selected as reference. We quantified for each visible marker (n=60) the motion in each phase and derived the peak-to-peak motion magnitude throughout the breathing cycle. The motion was quantified and analyzed for four different regions and in three orthogonal directions. The median(interquartile range) of the peak-to-peak magnitudes of the respiration-induced marker motion (left-right/anterior-posterior/cranial-caudal) was 1.5(0.5)/1.6(0.5)/2.9(1.4) mm for the proximal esophagus (n=6), 1.5(1.4)/1.4(1.3)/3.7(2.6) mm for the middle esophagus (n=12), 2.6(1.3)/3.3(1.8)/5.4(2.9) mm for the distal esophagus (n=25), and 3.7(2.1)/5.3(1.8)/8.2(3.1) mm for the proximal stomach (n=17). The variations in the results between the three directions, four regions, and patients suggest the need of individualized region-dependent anisotropic internal margins. Therefore, we recommend using markers with 4DCT to patient-specifically adapt the internal target volume (ITV). Without 4DCT, 3DCTs at the end-of-inhalation and end-of-exhalation phases could be alternatively applied for ITV individualization. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

Assessment of serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer after DC-CIK combined with intravenous chemotherapy

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Lei-Fan Li

2016-12-01

Full Text Available Objective: To study the effect of DC-CIK combined with intravenous chemotherapy on serum tumor markers, tumor cell apoptosis and immune response in patients with advanced colon cancer. Methods: A total of 79 patients with advanced colon cancer conservatively treated in our hospital between May 2012 and October 2015 were retrospectively studied and divided into DC-CIK group and intravenous chemotherapy group according to different therapeutic regimens, DC-CIK group received DC-CIK combined with intravenous chemotherapy and intravenous chemotherapy group received conventional intravenous chemotherapy. After three cycles of chemotherapy, the content of tumor markers in serum, expression levels of apoptotic molecules in tumor lesions as well as immune function indexes were determined. Results: After 3 cycles of chemotherapy, CEA, CA199, CA242, HIF-1α, IL-4, IL-5 and IL-10 content in serum of DC-CIK group were significantly lower than those of intravenous chemotherapy group; p53, FAM96B, PTEN, PHLPP, ASPP2 and RASSF10 mRNA content in tumor lesions of DC-CIK group were significantly higher than those of intravenous chemotherapy group; the fluorescence intensity of CD3, CD4 and CD56 on peripheral blood mononuclear cell surface of DC-CIK group were significantly higher than those of intravenous chemotherapy group while the fluorescence intensity of CD8 and CD25 were significantly lower than those of intravenous chemotherapy group; IL-2 and IFN-γ content in serum of DC-CIK group were significantly higher than those of intravenous chemotherapy group while IL-4, IL-5 and IL-10 content were significantly lower than those of intravenous chemotherapy group. Conclusions: DC-CIK combined with intravenous chemotherapy has better effect on killing colon cancer cells and inducing colon cancer cell apoptosis than conventional intravenous chemotherapy, and can also improve the body's anti-tumor immune response.

Small renal masses: The molecular markers associated with outcome of patients with kidney tumors 7 cm or less

Science.gov (United States)

Spirina, L. V.; Usynin, Y. A.; Kondakova, I. V.; Yurmazov, Z. A.; Slonimskaya, E. M.; Pikalova, L. V.

2016-08-01

The investigation of molecular mechanisms of tumor cell behavior in small renal masses is required to achieve the better cancer survival. The aim of the study is to find molecular markers associated with outcome of patients with kidney tumors 7 cm or less. A homogenous group of 20 patients T1N0M0-1 (mean age 57.6 ± 2.2 years) with kidney cancer was selected for the present analysis. The content of transcription and growth factors was determined by ELISA. The levels of AKT-mTOR signaling pathway components were measured by Western blotting analysis. The molecular markers associated with unfavorable outcome of patients with kidney tumors 7 cm or less were high levels of NF-kB p50, NF-kB p65, HIF-1, HIF-2, VEGF and CAIX. AKT activation with PTEN loss also correlated with the unfavorable outcome of kidney cancer patients with tumor size 7 cm or less. It is observed that the biological features of kidney cancer could predict the outcome of patients.

Evaluation of Lumipulse® G1200 for the measurement of six tumor markers: Comparison with AIA® 2000.

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de Rancher, Marie-Aude Robert; Oudart, Jean-Baptiste; Maquart, François-Xavier; Monboisse, Jean Claude; Ramont, Laurent

2016-11-01

Tumor marker assays are daily practiced, for screening and follow up of cancers. Interassay precision is an important parameter for the interpretation of the kinetics of the markers, in order to conclude to the efficiency or failure of treatment. The aim of this study was to compare two automated Immunoassay analyzers, Lumipulse® G1200 and AIA® 2000. Both analyzers used an immunoassay system but with different antibodies. Six tumor markers commonly used were studied: AFP, PSA, CA 19-9, CA 15-3, CA 125 and CEA. 253 samples have been collected over a period of one month and analyzed by both analyzers. Regression of Passing-Badblock and Bland-Altman diagram were used to analyze the results for AFP (n=36), PSA (n=39), CA-125 (n=40), CA 15-3 (n=40), CA 19-9 (n=46) and CEA (n=52) were performed. Analytical performances of Lumipulse® G1200 highlighted the good inter-run and intra-run precision of the analyzer. We obtained a good correlation coefficient between Lumipulse G1200® and AIA 2000®, >0.96 for most markers except CA 19-9 which provided a correlation coefficient significantly lower than that obtained with other markers. The concordance for all markers was >94% except for CA 19-9 (83.7%). This study showed a good correlation between the two analyzers and, therefore, a transfer from one analyzer to the other is possible for the different markers studied. However, we found here the classical difficulty to transfer this type of analysis, due to the absence of method standardization. This difficulty was particularly illustrated by CA19-9. Copyright © 2016 The Canadian Society of Clinical Chemists. Published by Elsevier Inc. All rights reserved.

Imaging tumor endothelial marker 8 using an 18F-labeled peptide

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Quan, Qimeng; Yang, Min; Gao, Haokao; Zhu, Lei; Lin, Xin; Guo, Ning; Chen, Xiaoyuan; Zhang, Guixiang; Eden, Henry S.; Niu, Gang

2011-01-01

Tumor endothelial marker 8 (TEM8) has been reported to be upregulated in both tumor cells and tumor-associated endothelial cells in several cancer types. TEM8 antagonists and TEM8-targeted delivery of toxins have been developed as effective cancer therapeutics. The ability to image TEM8 expression would be of use in evaluating TEM8-targeted cancer therapy. A 13-meric peptide, KYNDRLPLYISNP (QQM), identified from the small loop in domain IV of protective antigen of anthrax toxin was evaluated for TEM8 binding and labeled with 18 F for small-animal PET imaging in both UM-SCC1 head-and-neck cancer and MDA-MB-435 melanoma models. A modified ELISA showed that QQM peptide bound specifically to the extracellular vWA domain of TEM8 with an IC 50 value of 304 nM. Coupling 4-nitrophenyl 2- 18 F-fluoropropionate with QQM gave almost quantitative yield and a high specific activity (79.2 ± 7.4 TBq/mmol, n = 5) of 18 F-FP-QQM at the end of synthesis. 18 F-FP-QQM showed predominantly renal clearance and had significantly higher accumulation in TEM8 high-expressing UM-SCC1 tumors (2.96 ± 0.84 %ID/g at 1 h after injection) than TEM8 low-expressing MDA-MB-435 tumors (1.38 ± 0.56 %ID/g at 1 h after injection). QQM peptide bound specifically to the extracellular domain of TEM8. 18 F-FP-QQM peptide tracer would be a promising lead compound for measuring TEM8 expression. Further efforts to improve the affinity and specificity of the tracer and to increase its metabolic stability are warranted. (orig.)

Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

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Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon [Korea Institute of Radiological and Medical Sciences, Seoul (Korea, Republic of)

2008-05-15

Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells.

Promising markers for the detection of premature senescence tumor cells induced by ionizing radiation: Cathepsin D and eukaryotic translation elongation factor 1

International Nuclear Information System (INIS)

Byun, Hae-Ok; Han, Na-Kyung; Lee, Jae-Seon

2008-01-01

Recently, it has been proved that induction of senescence could be a promising way of tumor treatment. Senescence was originally described in normal human cells undergoing a finite number of divisions before permanent growth arrest. It has now become regarded more broadly as a general biological program of terminal growth arrest. A variety of stresses such as ionizing radiation (IR), oxidative stress, oncogenic transformation, DNA damaging agents triggers stress-induced premature senescence, i.e. rapid and permanent cell growth arrest. Therefore, premature senescence is bona fide barrier to tumorigenesis and hallmark of premalignant tumors. However, there is lack of obvious markers for senescent tumor cells. To identify useful premature senescence markers for tumor cells, we monitored the changes of protein expression profile in IR-induced premature senescence MCF7 human breast cancer cells. We identified biomarkers which evidently changed their expression levels in ionizing radiation-induced senescenct tumor cells

INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

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Mashima, Hirosato, E-mail: hmashima1-tky@umin.ac.jp [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan); Ohno, Hideki [Division of Advanced Medical Science, The Institute of Medical Science, The University of Tokyo, 4-6-1 Shirokanedai, Minato-ku, Tokyo 108-8639 (Japan); Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide [Department of Gastroenterology, Akita University Graduate School of Medicine, 1-1-1 Hondo, Akita 010-8543 (Japan)

2013-03-22

Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors.

INSL5 may be a unique marker of colorectal endocrine cells and neuroendocrine tumors

International Nuclear Information System (INIS)

Mashima, Hirosato; Ohno, Hideki; Yamada, Yumi; Sakai, Toshitaka; Ohnishi, Hirohide

2013-01-01

Highlights: ► INSL5 is expressed in enteroendocrine cells along the colorectum. ► INSL5 is expressed increasingly from proximal colon to rectum. ► INSL5 co-localizes rarely with chromogranin A. ► All rectal neuroendocrine tumors examined expressed INSL5. -- Abstract: Insulin-like peptide 5 (INSL5) is a member of the insulin superfamily, and is a potent agonist for RXFP4. We have shown that INSL5 is expressed in enteroendocrine cells (EECs) along the colorectum with a gradient increase toward the rectum. RXFP4 is ubiquitously expressed along the digestive tract. INSL5-positive EECs have little immunoreactivity to chromogranin A (CgA) and might be a unique marker of colorectal EECs. CgA-positive EECs were distributed normally along the colorectum in INSL5 null mice, suggesting that INSL5 is not required for the development of CgA-positive EECs. Exogenous INSL5 did not affect the proliferation of human colon cancer cell lines, and chemically-induced colitis in INSL5 null mice did not show any significant changes in inflammation or mucosal healing compared to wild-type mice. In contrast, all of the rectal neuroendocrine tumors examined co-expressed INSL5 and RXFP4. INSL5 may be a unique marker of colorectal EECs, and INSL5–RXFP4 signaling might play a role in an autocrine/paracrine fashion in the colorectal epithelium and rectal neuroendocrine tumors

P63 marker Expression in Usual Skin Cancers Compared With Non Tumoral Skin Lesions

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Abdolhamid Esmaili

2017-07-01

Full Text Available Background: Non-melanoma skin cancers including basal cell carcinoma and squamous cell carcinoma are the most common cancers in human. The aim of this study was to determine the expression of P63 marker in usual skin cancers compared with non-tomoral skin lesions. Materials and Methods: In this cross-sectional study, sampling was performed from archival blocks of Shahid Mohammadi hospital patients during 2010-2011. 60 samples (including 30 samples of non tumoral skin lesions and 30 samples of basal cell carcinoma and squamous cell carcinoma were studied and evaluation of p63 gene expression was done with Immunohistochemistry method. T-test and Chi-square were used for analysis of data. Results: P63 gene were expressed in 4 cases (13.33 % of non tumoral lesions and all tumoral lesions (100 %. In tumoral lesions, 5 cases (16.66 % showed 1+ severity experssion, 11 cases (36.66% 2 + severity experssion and 14 cases (46.66 % 3+severity experssion. All 4 non tumoral lesions shoed 1+ severity experssion of P63gene. Conclusion: The results of this study indicated that the incidence and severity of gene expression of P63 can be use for differentiation between basal cell carcinoma and squamous cell carcinoma as well as non-tumoral skin lesions. 

Changes of serum tumor markers, immunoglobulins, TNF-α and hs-CRP levels in patients with breast cancer and its clinical significance

Institute of Scientific and Technical Information of China (English)

Jian-Gang Dai; Yong-Feng Wu; Mei Li

2017-01-01

Objective: To study the serum tumor markers, immunoglobulin, TNF-α and hs-CRP in breast cancer in different pathological stages of the concentration, and to analyze the clinical significance of early diagnosis of breast cancer. Methods: A total of 130 patients with breast cancer were divided into stage I, II, III and IV according to clinical pathology. In addition, 40 patients with benign breast disease and 35 healthy subjects were selected as benign breast disease group and control group. Serum tumor markers, immunoglobulins, TNF-αand hs-CRP concentrations were measured and compared of all subjects. Results: There were no significant difference in serum tumor markers, immunoglobulin and inflammatory factors between the control group and the benign breast cancer group. The level of serum tumor markers in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum CA125, CA153 and CEA were gradually increased with the severity enhancing from stage I and IV of breast cancer, and he difference was statistically significant. The level of serum immunoglobulin in breast cancer group was significantly higher than that in control group and benign breast cancer group. The levels of serum IgG and IgM increased gradually severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. The level of serum TNF-α and hs-CRP in serum of breast cancer group was significantly higher than that of control group and benign breast cancer group. The serum levels of TNF-α and hs-CRP increased gradually with severity enhancing from stage I and IV of breast cancer, and the difference was statistically significant. Conclusion: The level of serum tumor markers in breast cancer patients is increasing. Humoral and inflammatory responses are activated to varying degrees and increase with the aggregation of disease. They may involve regulating the occurrence and metastasis of breast

Simultaneous quantitative detection of multiple tumor markers with a rapid and sensitive multicolor quantum dots based immunochromatographic test strip.

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Wang, Chunying; Hou, Fei; Ma, Yicai

2015-06-15

A novel multicolor quantum dots (QDs) based immunochromatographic test strip (ICTS) was developed for simultaneous quantitative detection of multiple tumor markers, by utilizing alpha fetoprotein (AFP) and carcinoembryonic antigen (CEA) as models. The immunosensor could realize simultaneous quantitative detection of tumor markers with only one test line and one control line on the nitrocellulose membrane (NC membrane) due to the introduction of multicolor QDs. In this method, a mixture of mouse anti-AFP McAb and mouse anti-CEA McAb was coated on NC membrane as test line and goat anti-mouse IgG antibody was coated as control line. Anti-AFP McAb-QDs546 conjugates and anti-CEA McAb-QDs620 conjugates were mixed and applied to the conjugate pad. Simultaneous quantitative detection of multiple tumor markers was achieved by detecting the fluorescence intensity of captured QDs labels on test line and control line using a test strip reader. Under the optimum conditions, AFP and CEA could be detected as low as 3 ng/mL and 2 ng/mL in 15 min with a sample volume of 80 μL, and no obvious cross-reactivity was observed. The immunosensor was validated with 130 clinical samples and in which it exhibited high sensitivity (93% for AFP and 87% for CEA) and specificity (94% for AFP and 97% for CEA). The immunosensor also demonstrated high recoveries (87.5-113% for AFP and 90-97.3% for CEA) and low relative standard deviations (RSDs) (2.8-6.2% for AFP and 4.9-9.6% for CEA) when testing spiked human serum. This novel multicolor QDs based ICTS provides an easy and rapid, simultaneous quantitative detecting strategy for point-of-care testing of tumor markers. Copyright © 2014 Elsevier B.V. All rights reserved.

Mucins CA 125, CA 19.9, CA 15.3 and TAG-72.3 as tumor markers in patients with lung cancer: comparison with CYFRA 21-1, CEA, SCC and NSE.

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Molina, Rafael; Auge, Jose Maria; Escudero, Jose Miguel; Marrades, Ramon; Viñolas, Nuria; Carcereny, Emilio; Ramirez, Jose; Filella, Xavier

2008-01-01

Tumor marker serum levels were prospectively studied in 289 patients with suspected, but unconfirmed, lung cancer and in 513 patients with lung cancer [417 non-small cell lung cancer (NSCLC) patients and 96 small cell lung cancer (SCLC) patients]. In patients with benign disease, abnormal serum levels were found for the following tumor markers: CEA (in 6.6% of patients); CA 19.9 (6.2%); CA 125 (28.7%); NSE (0.7%); CYFRA (8.7%); TAG-72.3 (4.2%); SCC (3.5%), and CA 15.3 (3.5%). Excluding patients with renal failure or liver diseases, tumor marker specificity improved with abnormal levels in 0.5% for NSE, 0.9% for SCC, 2.8% for CEA, CA 15.3 and TAG-72.3, 3.8% for CA 19.9, 4.2% for CYFRA and 21.4% for CA 125. Excluding CA 125, one of the markers was abnormal in 15% of patients without malignancy. Tumor marker sensitivity was related to cancer histology and tumor extension. NSE had the highest sensitivity in SCLC and CYFRA and CEA in NSCLC. Significantly higher concentrations of CEA, SCC, CA 125, CA 15.3 and TAG-72.3 were found in NSCLC than in SCLC. Likewise, significantly higher CEA (p tumors. Using a combination of 3 tumor markers (CEA, CYFRA 21-1 in all histologies, SCC in squamous tumors and CA 15.3 in adenocarcinomas), a high sensitivity may be achieved in all histological types. Tumor markers may be useful in the histological differentiation of NSCLC and SCLC. Using specific criteria for the differentiation of SCLC and NSCLC, the sensitivity was 84.2 and 68.8%, the specificity was 93.8 and 99.7%, the positive predictive value was 98.3 and 98.5% and the negative predictive value was 57.7 and 93.3%, respectively. Copyright 2008 S. Karger AG, Basel.

Combined Evaluation of AFP, CA15-3, CA125, CA19-9, and CEA Tumor Markers in Patients with Hepatitis B and C.

Science.gov (United States)

Assmar, Mehdi; Yeganeh, Sara; Mansourghanaei, Fariborz; Amirmozafari, Nour

2016-12-01

This study aimed to determine the role of tumor markers AFP, CA15-3, CA125, CA19-9 and CEA in patients with hepatitis B and C. This descriptive cross-sectional study was performed from Oct 2012 to Oct 2014. Serum samples of 129 patients with hepatitis B and C referred to Guilan Liver and Digestive Disease Research Center in Rasht, Iran were collected and checked for the existence of the listed tumor markers by ELISA. No increase in serum levels of tumor marker CA19-9, CEA and CA15-3 were seen in patients with hepatitis ( P >0.05). In patients with hepatitis B, increase in CA125 were observed ( P =0.03). In hepatitis C patients, there was an increase in AFP levels ( P =0.03). The levels of AFP and CA125 markers were high in hepatitis C and hepatitis B, respectively. However, the increased levels were not seen is malignancy. Due to the small sample size, further study is necessary to find the reasons of the increase.

The inflammation markers in serum of tumor-bearing rats after plasmonic photothermal therapy

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Bucharskaya, Alla B.; Maslyakova, Galina N.; Terentyuk, Georgy S.; Afanasyeva, Galina A.; Navolokin, Nikita A.; Zakharova, Natalia B.; Khlebtsov, Boris N.; Khlebtsov, Nikolai G.; Bashkatov, Alexey N.; Genina, Elina A.; Tuchin, Valery V.

2018-02-01

We report on plasmonic photothermal therapy of rats with inoculated cholangiocarcinoma through the intratumoral injection of PEG-coated gold nanorods followed by CW laser light irradiation. The length and diameter of gold nanorods were 41+/-8 nm and 10+/-2 nm, respectively; the particle mass-volume concentration was 400 μg/mL, which corresponds to the optical density of 20 at the wavelength 808 nm. The tumor-bearing rats were randomly divided into three groups: (1) without any treatment (control); (2) with only laser irradiation of tumor; (3) with intratumoral administration of gold nanorods and laser irradiation of tumors. An hour before laser irradiation, the animals were injected intratumorally with gold nanorod solutions in the amount of 30% of the tumor volume. The infrared 808-nm laser with power density of 2.3 W/cm2 was used for plasmonic photothermal therapy (PTT). The withdraw of animals from the experiment was performed 24 h after laser exposure. The content of lipid peroxidation products and molecular markers of inflammation (TNF-α, IGF-1, VEGF-C) was determined by ELISA test in serum of rats. The standard histological techniques with hematoxylin and eosin staining were used for morphological examination of tumor tissues. It was revealed that the significant necrotic changes were noted in tumor tissue after plasmonic photothermal therapy, which were accompanied by formation of inflammatory reaction with release of proinflammatory cytokines and lipid peroxidation products into the bloodstream

Menstrual Cycle Dependent Variability for Serum Tumor Markers CEA, AFP, CA 19-9, CA 125 and CA 15-3 in Healthy Women

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Ayşe Binnur Erbağci

1999-01-01

Full Text Available Information on menstrual cycle dependent variation of tumor markers in healthy women is a subject of diagnostic efficiency and has an impact in elucidating the normal function of these markers. In this study midfollicular and midluteal concentrations of serum CEA, AFP, CA 19-9, CA 125, CA 15-3 and their relations with LH, FSH, prolactin, estradiol and progesterone were evaluated during ovulatory cycles in a group of 23 healthy female individuals. Samples were collected on the 7th and 21st day of the same menstrual cycle. Tumor marker and hormone concentrations were determined with chemiluminescence or electrochemiluminescence EIA methods. A significant phase-dependent difference was observed for CA 15-3, midluteal concentrations (mean ± SEM; 26.33 ± 1.56 U/ml higher than the midfollicular (mean ± SEM; 19.27 ± 1.49 U/ml concentrations (p < 0.001. But an obvious difference for other tumor markers investigated did not exist. Significant correlations of follicular and luteal CA 125 levels with body mass index of the subjects were observed (r:0.52, p < 0.05 and r:0.57, p < 0.005, respectively.

Detection of lung tumor movement in real-time tumor-tracking radiotherapy

International Nuclear Information System (INIS)

Shimizu, Shinichi; Shirato, Hiroki; Ogura, Shigeaki; Akita-Dosaka, Hirotoshi; Kitamura, Kei; Nishioka, Takeshi; Kagei, Kenji; Nishimura, Masaji; Miyasaka, Kazuo

2001-01-01

Purpose: External radiotherapy for lung tumors requires reducing the uncertainty due to setup error and organ motion. We investigated the three-dimensional movement of lung tumors through an inserted internal marker using a real-time tumor-tracking system and evaluated the efficacy of this system at reducing the internal margin. Methods and Materials: Four patients with lung cancer were analyzed. A 2.0-mm gold marker was inserted into the tumor. The real-time tumor-tracking system calculates and stores three-dimensional coordinates of the marker 30 times/s. The system can trigger the linear accelerator to irradiate the tumor only when the marker is located within the predetermined 'permitted dislocation'. The value was set at ±1 to ±3 mm according to the patient's characteristics. We analyzed 10,413-14,893 data sets for each of the 4 patients. The range of marker movement during normal breathing (beam-off period) was compared with that during gated irradiation (beam-on period) by Student's t test. Results: The range of marker movement during the beam-off period was 5.5-10.0 mm in the lateral direction (x), 6.8-15.9 mm in the craniocaudal direction (y) and 8.1-14.6 mm in the ventrodorsal direction (z). The range during the beam-on period was reduced to within 5.3 mm in all directions in all 4 patients. A significant difference was found between the mean of the range during the beam-off period and the mean of the range during the beam-on period in the x (p=0.007), y (p=0.025), and z (p=0.002) coordinates, respectively. Conclusion: The real-time tumor-tracking radiotherapy system was useful to analyze the movement of an internal marker. Treatment with megavoltage X-rays was properly given when the tumor marker moved into the 'permitted dislocation' zone from the planned position

Tumor-related markers in histologically normal margins correlate with locally recurrent oral squamous cell carcinoma: a retrospective study.

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Wang, Xinhong; Chen, Si; Chen, Xinming; Zhang, Cuicui; Liang, Xueyi

2016-02-01

Oral squamous cell carcinoma (OSCC) is characterized by a high rate of local recurrence (LR) even when the surgical margins are considered histopathologically 'normal'. The aim of our study was to determine the relationship between early tumor-related markers detected in histologically normal margins (HNM) and LR as well as disease-free survival in OSCC. The loss of heterozygosity (LOH) of markers on 9p21 (D9s1747, RPS6, D9s162) and 17p13 (TP53) and the immunostaining results of the corresponding mutant P53, P14, P15, and P16 proteins were assessed and correlated with LR and disease-free survival in 71 OSCC patients who had HNM. Fifteen of 71 patients with HNM developed LR. The presence of the following molecular markers in surgical margins was significantly correlated with the development of LR: LOH on chromosome 9p21 (D9s1747 + RPS6 + D9s162), any LOH, P16, and P53 (chi-square test, P tumor-related markers in histologically 'normal' resection margins may be a useful method for assessing LR in OSCC patients. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Checking the Course of Colorectal Carcinoma Follow up Using Mathematical Classification of Tumor Marker Profiles

Czech Academy of Sciences Publication Activity Database

Holubec jr., L.; Botterlich, N.; Topolčan, O.; Finek, J.; Pikner, R.; Pecen, Ladislav; Holubec, L.

2002-01-01

Roč. 23, Suppl.1 (2002), s. 57 ISSN 1010-4283. [Meeting of the International Society for Oncodevelopmental Biology and Medicine /30./. 08.09.2002-12.09.2002, Boston] R&D Projects: GA MŠk ME 438 Institutional research plan: AV0Z1030915 Keywords : tumor markers * colorectal CA * mathematical classification Subject RIV: BA - General Mathematics

Localization of higher grade tumor foci in potential candidates for active surveillance who opt for radical prostatectomy

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Sung Kyu Hong

2013-12-01

Conclusions: Among patients deemed clinically appropriate for AS, higher-grade tumor foci missed by standard prostate biopsies were localized to both the anterior and posterior prostate, without predominance of a particular area. These findings lend additional support to performing repeat standard prostate biopsy in potential candidates for AS and should be considered in efforts to optimize current biopsy strategies for the selection of AS patients.

Evaluation of a CLEIA automated assay system for the detection of a panel of tumor markers.

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Falzarano, Renato; Viggiani, Valentina; Michienzi, Simona; Longo, Flavia; Tudini, Silvestra; Frati, Luigi; Anastasi, Emanuela

2013-10-01

Tumor markers are commonly used to detect a relapse of disease in oncologic patients during follow-up. It is important to evaluate new assay systems for a better and more precise assessment, as a standardized method is currently lacking. The aim of this study was to assess the concordance between an automated chemiluminescent enzyme immunoassay system (LUMIPULSE® G1200) and our reference methods using seven tumor markers. Serum samples from 787 subjects representing a variety of diagnoses, including oncologic, were analyzed using LUMIPULSE® G1200 and our reference methods. Serum values were measured for the following analytes: prostate-specific antigen (PSA), alpha-fetoprotein (AFP), carcinoembryonic antigen (CEA), cancer antigen 125 (CA125), carbohydrate antigen 15-3 (CA15-3), carbohydrate antigen 19-9 (CA19-9), and cytokeratin 19 fragment (CYFRA 21-1). For the determination of CEA, AFP, and PSA, an automatic analyzer based on chemiluminescence was applied as reference method. To assess CYFRA 21-1, CA125, CA19-9, and CA15-3, an immunoradiometric manual system was employed. Method comparison by Passing-Bablok analysis resulted in slopes ranging from 0.9728 to 1.9089 and correlation coefficients from 0.9977 to 0.9335. The precision of each assay was assessed by testing six serum samples. Each sample was analyzed for all tumor biomarkers in duplicate and in three different runs. The coefficients of variation were less than 6.3 and 6.2 % for within-run and between-run variation, respectively. Our data suggest an overall good interassay agreement for all markers. The comparison with our reference methods showed good precision and reliability, highlighting its usefulness in clinical laboratory's routine.

Real-time tumor-tracking radiotherapy for adrenal tumors

International Nuclear Information System (INIS)

Katoh, Norio; Onimaru, Rikiya; Sakuhara, Yusuke; Abo, Daisuke; Shimizu, Shinichi; Taguchi, Hiroshi; Watanabe, Yoshiaki; Shinohara, Nobuo; Ishikawa, Masayori; Shirato, Hiroki

2008-01-01

Purpose: To investigate the three-dimensional movement of internal fiducial markers near the adrenal tumors using a real-time tumor-tracking radiotherapy (RTRT) system and to examine the feasibility of high-dose hypofractionated radiotherapy for the adrenal tumors. Materials and methods: The subjects considered in this study were 10 markers of the 9 patients treated with RTRT. A total of 72 days in the prone position and 61 treatment days in the supine position for nine of the 10 markers were analyzed. All but one patient were prescribed 48 Gy in eight fractions at the isocenter. Results: The average absolute amplitude of the marker movement in the prone position was 6.1 ± 4.4 mm (range 2.3-14.4), 11.1 ± 7.1 mm (3.5-25.2), and 7.0 ± 3.5 mm (3.9-12.5) in the left-right (LR), craniocaudal (CC), and anterior-posterior (AP) directions, respectively. The average absolute amplitude in the supine position was 3.4 ± 2.9 mm (0.6-9.1), 9.9 ± 9.8 mm (1.1-27.1), and 5.4 ± 5.2 mm (1.7-26.6) in the LR, CC, and AP directions, respectively. Of the eight markers, which were examined in both the prone and supine positions, there was no significant difference in the average absolute amplitude between the two positions. No symptomatic adverse effects were observed within the median follow-up period of 16 months (range 5-21 months). The actuarial freedom-from-local-progression rate was 100% at 12 months. Conclusions: Three-dimensional motion of a fiducial marker near the adrenal tumors was detected. Hypofractionated RTRT for adrenal tumors was feasible for patients with metastatic tumors

A novel classifier based on three preoperative tumor markers predicting the cancer-specific survival of gastric cancer (CEA, CA19-9 and CA72-4).

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Guo, Jing; Chen, Shangxiang; Li, Shun; Sun, Xiaowei; Li, Wei; Zhou, Zhiwei; Chen, Yingbo; Xu, Dazhi

2018-01-12

Several studies have highlighted the prognostic value of the individual and the various combinations of the tumor markers for gastric cancer (GC). Our study was designed to assess establish a new novel model incorporating carcino-embryonic antigen (CEA), carbohydrate antigen 19-9 (CA19-9), carbohydrate antigen 72-4 (CA72-4). A total of 1,566 GC patients (Primary cohort) between Jan 2000 and July 2013 were analyzed. The Primary cohort was randomly divided into Training set (n=783) and Validation set (n=783). A three-tumor marker classifier was developed in the Training set and validated in the Validation set by multivariate regression and risk-score analysis. We have identified a three-tumor marker classifier (including CEA, CA19-9 and CA72-4) for the cancer specific survival (CSS) of GC (ptumor marker classifier is closely associated with the CSS of GC and may serve as a novel model for future decisions concerning treatments.

Treatment Outcome and Prognostic Molecular Markers of Supratentorial Primitive Neuroectodermal Tumors.

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Seo Hee Choi

Full Text Available To identify prognostic factors and define the optimal management of patients with supratentorial primitive neuroectodermal tumors (sPNETs, we investigated treatment outcomes and explored the prognostic value of specific molecular markers.A total of 47 consecutive patients with pathologically confirmed sPNETs between May 1985 and June 2012 were included. Immunohistochemical analysis of LIN28, OLIG2, and Rad51 expression was performed and correlated with clinical outcome.With a median follow-up of 70 months, 5-year overall survival (OS and progression-free survival (PFS was 55.5% and 40%, respectively, for all patients. Age, surgical extent, and radiotherapy were significant prognostic factors for OS and PFS. Patients who received initially planned multimodal treatment without interruption (i.e., radiotherapy and surgery (≥subtotal resection, with or without chemotherapy showed significantly higher 5-year OS (71.2% and PFS (63.1%. In 29 patients with available tumor specimens, tumors with high expression of either LIN28 or OLIG2 or elevated level of Rad51 were significantly associated with poorer prognosis.We found that multimodal treatment improved outcomes for sPNET patients, especially when radiotherapy and ≥subtotal resection were part of the treatment regimen. Furthermore, we confirmed the prognostic significance of LIN28 and OLIG2 and revealed the potential role of Rad51 in sPNETs.

Clinical impact of [18F]FDG-PET in patients with suspected recurrent breast cancer based on asymptomatically elevated tumor marker serum levels. A preliminary report

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Liu, Chiu-Shong; Lin, Cheng-Chieh; Kao, Chia-Hung; Yen, Ruoh-Fang

2002-01-01

The purpose of this study was to evaluate retrospectively the impact of [ 18 F]fluorodeoxyglucose positron emission tomography (FDG-PET) on the detection of recurrent breast cancer based on asymptomatically elevated tumor markers levels. Whole-body FDG-PET was performed in 30 patients with suspected recurrent breast cancer and asymptomatic tumor marker increase but negative or equivocal other imaging modality results. A blood sample was drawn in each case for marker assay (CA 15-3 and CEA) on the same day as the FDG-PET. All of these 30 asymptomatic patients had either CA 15-3>32 U/ml or CEA>5 ng/ml. The final diagnosis of recurrent breast cancer was established by operation/biopsy histopathological findings or clinical follow-up for >1 year by additional morphological imaging techniques. Among the 30 patients, the final diagnosis of recurrent breast cancer was established in 38 sites in 28 patients. FDG-PET accurately detected 35/38 sites in 25/28 patients with recurrence. The diagnostic sensitivity and accuracy of FDG-PET in patients with suspected recurrent breast cancer and asymptomatically elevated tumor markers were 96 and 90%, respectively. FDG-PET is a useful technique for detecting recurrent breast cancer suspected from asymptomatically elevated tumor markers levels and has an important clinical impact on the management of these patients. (author)

Clinical Evaluation of Tumor Markers for Diagnosis in Patients with Non-small Cell Lung Cancer in China.

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Ma, Li; Xie, Xiao-Wei; Wang, Hai-Yan; Ma, Ling-Yun; Wen, Zhong-Guang

2015-01-01

To evaluate the value of combined detection of serum carcinoembryonic antigen (CEA), cytokeratin 19 fragment (CYFRA21-1), and carbohydrateantigen 125 (CA125) for the clinical diagnosis of non- small cell lung cancer (NSCLC). Serum CEA, CYFRA21-1 and CA125 were assessed in 140 patients with NSCLC, 90 patients with benign lung disease and 90 normal control subjects, and differences of expression were compared in each group, and joint effects of these tumor markers in the diagnosis of NSCLC were analyzed. Serum CEA, CYFRA21-1 and CA125 in patients with NSCLC were significantly higher than those with benign lung disease and normal controls (PCEA, CYFRA21-1 and CA125 were 49.45%, 59.67%, and 44.87% respectively. As expected, combinations of these tumor markers improved their sensitivity for NSCLC. The combined detection of CEA+CYFRA21-1 was the most cost-effective combination which had higher sensitivity and specificity in NSCLC. Elevation of serum CEA and CYFRA21-1 was significantly associated with pathological types (PCEA, CYFRA21-1 and CA125 was significantly associated with TNM staging (PCEA, CYFRA21-1 and CA125 is of diagnostic value in the diagnosis of lung cancer, and a joint detection of these three tumor markers, could greatly improve the sensitivity of diagnosis on NSCLC. Combined detection of CEA+CYFRA21-1 proved to be the most economic and practical strategy in diagnosis of NSCLC, which can be used to screen the high-risk group.

The evaluation of diagnostic value of the tumor markers: CCSA-2 and CEA in colorectal cancer.

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Knychalski, Bartłomiej; Lukieńczuk, Tadeusz

2012-02-01

Finding the biomarker or biomarkers with high sensitivity and specificity in colorectal cancer, and thus a high diagnostic value will determine their clinical usefulness in clinical practice. An effective noninvasive blood test would be an ideal method to detect colorectal cancer. Discovered in 2007 a novel tumor marker CCSA-2 showes a promising results in patients with colorectal cancer. THE AIM OF THE STUDY was the evaluation of diagnostic and clinical value of a novel marker - colon cancer specific antigen-2 (CCSA-2) in colorectal adenocarcinoma in comparison to carcinoembryonic antigen (CEA) in patients operated during the years 2008 to 2010 at Wrocław Medical University 1st Department and Clinic of General, Gastroenterological and Endocrinologic Surgery. The study was performed on 40 patients with colorectal cancer and 40 patients in control group consisted of healthy subjects who had colonoscopy examinations with negative results (no pathology in the colon was found). The obtained results were statistically analyzed using nonparametric tests - Mann Whitney U and Kruskal-Wallis and Spearman's rank correlation coefficients. To determine the clinical value of CCSA-2 and CEA in those groups, their sensitivity and specifity was evaluated using ROC analysis. This analysis determines the accuracy and diagnostic value of both tests. There was a positive correlation between markers in patients with colorectal cancer and a statistically significant relationship according to which respondents with higher concentrations of CCSA-2 also have higher concentrations of CEA (R=0.754, ptumor markers increase and correlate with the clinical progression of the disease. Accuracy of CCSA-2 test using ROC analysis showed a slightly lower measurement of antigen CCSA-2 as diagnostic value in colorectal cancer in comparison to measurement of antigen CEA (accuracy of tests: CCSA-2 - 52%, CEA - 60%). CCSA-2 as a single tumor marker has a low diagnostic value in colorectal cancer because

National Academy of Clinical Biochemistry laboratory medicine practice guidelines for use of tumor markers in testicular, prostate, colorectal, breast, and ovarian cancers

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Sturgeon, Catharine M.; Duffy, Michael J.; Stenman, Ulf-Håkan

2008-01-01

BACKGROUND: Updated National Academy of Clinical Biochemistry (NACB) Laboratory Medicine Practice Guidelines for the use of tumor markers in the clinic have been developed. METHODS: Published reports relevant to use of tumor markers for 5 cancer sites--testicular, prostate, colorectal, breast...... for differential diagnosis of nonseminomatous and seminomatous germ cell tumors. Prostate-specific antigen (PSA) is not recommended for prostate cancer screening, but may be used for detecting disease recurrence and monitoring therapy. Free PSA measurement data are useful for distinguishing malignant from benign...... prostatic disease when total PSA is cancer, carcinoembryonic antigen is recommended (with some caveats) for prognosis determination, postoperative surveillance, and therapy monitoring in advanced disease. Fecal occult blood testing may be used for screening asymptomatic adults 50...

Application of tumor markers SCC-Ag, CEA, and TPA in patients with cervical precancerous lesions.

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Farzaneh, Farah; Shahghassempour, Shapour; Noshine, Bahram; Arab, Maliheh; Yaseri, Mehdi; Rafizadeh, Mitra; Alizadeh, Kamyab

2014-01-01

To determine the potential clinical utility of tumor markers CEA, TPA, and SCC-Ag for early detection of cervical precancerous lesions. A case-control study was carried out on 120 women (46 patients with histologically confirmed cervical precancerous lesions and 74 healthy controls). The significance of serum selected tumor markers in early detection of cervical intraepithelial neoplasia (CIN) were assessed. Of the case group, the rates of CIN I, II, III, was 69.6%, 23.9%, and 6.5%, respectively. According to the manufacturer's cut-off values of 2 ng/ml, 5 ng/ml, and 70 U/ml for SCC-Ag, CEA and TPA tests, in that order, SCC-Ag test had a sensitivity of 13%, but CEA and TPA tests could not distinguish between case and control groups. The diagnostic sensitivities were highest at cut-off values of 0.55 ng/ml for SCC-Ag, 2.6 ng/ ml for CEA, and 25.5 U/ml for TPA which were 93%, 61%, and 50%, respectively. However, the area under the receiver operating characteristic curve was the largest for SCC-Ag (0.95 vs. 0.61 and 0.60 for CEA and TPA, respectively). Moreover, there was a highly significant direct correlation between SCC-Ag concentration and the degree of cervical precancerous lesions (r=0.847, ptumor marker in Iranian patients with CIN and it needs to be more evaluated by studies with larger populationa.

Clinical value of combined detection of serum tumor markers and whole body bone scan for diagnosis of bone metastases from breast cancer

International Nuclear Information System (INIS)

Gao Chao; Zhao Jing; Liu Desheng; Zhang Jingchuan; Ji Xuejing; Hou Xiancun

2007-01-01

Objective: To study the clinical value of serum tumor marker determination and whole body bone scan for diagnosis of bone metastases from breast cancer. Methods: Serum tumor markers (CA15-3, CEA, TSGF)were detected with GLIA and whole body bone scan were investigated by SPECT in 124 breast cancer patients. Results: In 124 patients, 38 patients were diagnosed as positive for bone metastases with whole body bone scan. The positive predicting values of CA15-3, CEA, TSGF were 76.78%, 80% and 82.14%, and the negative predicting values of CA15-3, GEA, TSGF were 82.41%, 86.74% and 84.29% respectively. The levels of CA15-3, CEA, TSGF in patients with bone metastases were significantly higher than those in patients without metastasis and the controls (P<0.01). Conclusion: Determination of levels of serum tumor markers CA15-3, CEA, TSGF is helpful for diagnosis of bone metastases from breast cancer. Combined detection of GA15-3, CEA, TSGF could increase the sensitivity and accuracy of diagnosing bone metastases. (authors)

The diagnostic value of serum tumor markers CEA, CA19-9, CA125, CA15-3, and TPS in metastatic breast cancer.

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Wang, Weigang; Xu, Xiaoqin; Tian, Baoguo; Wang, Yan; Du, Lili; Sun, Ting; Shi, Yanchun; Zhao, Xianwen; Jing, Jiexian

2017-07-01

This study aims to understand the diagnostic value of serum tumor markers carcinoembryonic antigen (CEA), cancer antigen 19-9 (CA19-9), cancer antigen 125 (CA125), cancer antigen 15-3 (CA15-3), and tissue polypeptide-specific antigen (TPS) in metastatic breast cancer (MBC). A total of 164 metastatic breast cancer patients in Shanxi Cancer Hospital were recruited between February 2016 and July 2016. 200 breast cancer patients without metastasis in the same period were randomly selected as the control group. The general characteristics, immunohistochemical, and pathological results were investigated between the two groups, and tumor markers were determined. There were statistical differences in the concentration and the positive rates of CEA, CA19-9, CA125, CA15-3, and TPS between the MBC and control group (Ptumor marker at 56.7% and 97.0%, respectively. In addition, two tumor markers were used for the diagnosis of MBC and the CEA and TPS combination had the highest diagnostic sensitivity with 78.7%, while the CA15-3 and CA125 combination had the highest specificity of 91.5%. Analysis of tumor markers of 164 MBC found that there were statistical differences in the positive rates of CEA and CA15-3 between bone metastases and other metastases (χ 2 =6.00, P=0.014; χ 2 =7.32, P=0.007, respectively). The sensitivity and specificity values of the CEA and CA15-3 combination in the diagnosis of bone metastases were 77.1% and 45.8%, respectively. The positive rate of TPS in the lung metastases group was lower than in other metastases (χ 2 =8.06, P=0.005).There were significant differences in the positive rates of CA15-3 and TPS between liver metastases and other metastases (χ 2 =15.42, Ptumor markers have varying diagnostic value. Copyright © 2017 Elsevier B.V. All rights reserved.

Comparative study between 131I-MIBG scintigraphy and other tumor markers in diagnosis of neuroblastoma

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Ohsawa, Yoshihiro; Iwafuchi, Makoto; Odano, Ikuo; Yamagiwa, Iwao.

1989-01-01

In order to prove the clinical usefulness in diagnosis of neuroblastoma, comparative studies between iodine-131 metaiodobenzylguanidine ( 131 I-MIBG) scintigraphy and other related tumor markers were attempted. Sixteen children diagnosed as having a neuroblastoma in recent 2 years were examined. In 5 postoperative patients in complete remission, who were negative to other tumor markers, showed no pathological accumulation of 131 I-MIBG (specificity 100%). In other 11 patients with remains of neuroblastoma, 131 I-MIBG was negative only in 2 patients (sensitivity 82%) and these 2 patients showed negative urinary excretion of catecholamine metabolites (VMA). (Negative urinary VMA was proved in 3 of 11 patients). Serum neuron-specific enolase (NSE) was elevated in all 8 preoperative patients, but only in 2 of 11 postoperative patients. On the other hand 131 I-MIBG was positive in 9 among these 11 postoperative patients in whom neuroblastoma remained. Similar relationship was obtained between 131 I-MIBG scintigraphy and serum LDH. On the basis of our present experience, we like to regard 131 I-MIBG scintigraphy as one of the most sensitive parameters for neuroblastoma during a follow-up period after treatment. (author)

The relationship between Glasgow Prognostic Score and serum tumor markers in patients with advanced non-small cell lung cancer.

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Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-05-10

Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non-small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21-1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21-1 were 1.5 ng/ml (0.1-3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7-35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4-89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9-134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (PGPS, CEA and GPS, TPS and GPS. The Spearman's rank correlation coefficient were 0.67 (P GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated with CYFRA21-1, CEA and TPS in patients with advanced NSCLC. However, GPS was more efficient in predicting prognosis of advanced NSCLC than these three single prognosis related tumor markers.

Hypoxia marker labeling in tumor biopsies: quantification of labeling variation and criteria for biopsy sectioning

International Nuclear Information System (INIS)

Thrall, Donald E.; Rosner, Gary L.; Azuma, Chieko; McEntee, Margaret C.; Raleigh, James A.

1997-01-01

Background and purpose: The error associated with using biopsy-based methods for assessing parameters reflective of the tumor microenvironment depends on the variability in distribution of the parameter throughout the tumor and the biopsy sample. Some attention has been given to intratumoral distribution of parameters, but little attention has been given to their intrabiopsy distribution. We evaluated the intrabiopsy distribution of CCI-103F, a 2-nitroimidazole hypoxia marker. Materials and methods: The hypoxia marker CCI-103F was studied in dogs bearing spontaneous solid tumors. Two biopsies were taken from each of seven tumors, for a total of 14 biopsies. Biopsies were serially sectioned and four to six contiguous slides from each 100-150 μm of the biopsy were used to formulate the best estimate of CCI-103F labeled area throughout the biopsy sample. One, two or four slides were then randomly selected from each biopsy and the labeled area, based on this limited sample, was compared to the estimate obtained from counting all available slides. Random sampling of slides was repeated 1000 times for each biopsy sample. Results: CCI-103F labeling variance throughout the biopsy decreased as the estimated overall labeled area in the biopsy decreased. The error associated with estimating the overall labeled area in a biopsy from a randomly selected subset of slides decreased as the number of slides increased, and as the overall labeled area in the biopsy decreased. No minimally labeled biopsy was classified as unlabeled based on limited sampling. Conclusion: With regard to CCI-103F labeling, quantification of the labeled area in four randomly selected slides from a biopsy can provide, in most biopsies, an estimate of the labeled area in the biopsy within an absolute range of ±0.05

Stability of percutaneously implanted markers for lung stereotactic radiotherapy

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Persson, Gitte Bjørnsen Fredberg; Josipovic, Mirjana; Von Der Recke, Peter

2013-01-01

The purpose of this study was to evaluate the stability of complex markers implanted into lung tumors throughout a course of stereotactic body radiotherapy (SBRT). Fifteen patients referred for lung SBRT were prospectively included. Radio-opaque markers were implanted percutaneously, guided...... mm in one or more registrations throughout the SBRT course. This is the first study to evaluate stability of complex markers implanted percutaneously into lung tumors for image guidance in SBRT. We conclude that the observed stability of marker position within the tumor indicates that complex markers...... can be used as surrogates for tumor position during a short course of SBRT as long as the uncertainties related to their position within the tumor are incorporated into the planning target volume....

Clinical impact of [{sup 18}F]FDG-PET in patients with suspected recurrent breast cancer based on asymptomatically elevated tumor marker serum levels. A preliminary report

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Liu, Chiu-Shong; Lin, Cheng-Chieh; Kao, Chia-Hung [China Medical Coll., Taichung, Taiwan (China). Hospital; Shen, Yeh-You [Shin Kong Wu Ho-Su Memorial Hospital, Taipei, Taiwan (China); Yen, Ruoh-Fang [National Taiwan Univ., Taipei, Taiwan (China). Hospital

2002-07-01

The purpose of this study was to evaluate retrospectively the impact of [{sup 18}F]fluorodeoxyglucose positron emission tomography (FDG-PET) on the detection of recurrent breast cancer based on asymptomatically elevated tumor markers levels. Whole-body FDG-PET was performed in 30 patients with suspected recurrent breast cancer and asymptomatic tumor marker increase but negative or equivocal other imaging modality results. A blood sample was drawn in each case for marker assay (CA 15-3 and CEA) on the same day as the FDG-PET. All of these 30 asymptomatic patients had either CA 15-3>32 U/ml or CEA>5 ng/ml. The final diagnosis of recurrent breast cancer was established by operation/biopsy histopathological findings or clinical follow-up for >1 year by additional morphological imaging techniques. Among the 30 patients, the final diagnosis of recurrent breast cancer was established in 38 sites in 28 patients. FDG-PET accurately detected 35/38 sites in 25/28 patients with recurrence. The diagnostic sensitivity and accuracy of FDG-PET in patients with suspected recurrent breast cancer and asymptomatically elevated tumor markers were 96 and 90%, respectively. FDG-PET is a useful technique for detecting recurrent breast cancer suspected from asymptomatically elevated tumor markers levels and has an important clinical impact on the management of these patients. (author)

Effect of DC-CIK treatment on tumor markers and T cell subsets in patients with advanced ovarian cancer

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Jie-Qun Guo

2016-10-01

Full Text Available Objective: To investigate the effects of dendritic cells (DC and cytokine induced killer cells (CIK on tumor markers and T cell subsets in peripheral blood of patients with advanced ovarian cancer. Methods: A total of 100 cases of patients with advanced ovarian cancer who were proved by operation and pathology in the department of gynecologic oncology in our hospital were selected from April 2013 to April 20l6, and randomly divided into experimental group and control group, the control group was treated with TC (Taxinol+Cisplat chemotherapy alone, the experimental group was treated with DC-CIK combined with chemotherapy. Before and after treatment, the changes of CD3+, CD4+, CD8+, CD4+/CD8+, CD4+/CD25+, NK cells in peripheral blood and serum tumor markers (CA125, CA19-9, HE4 were detected. Results: Before treatment, the phenotypes of T cell subsets in the two groups were not significantly different; in the experimental group after treatment, the levels of CD3+, CD4+, CD4+/CD8+, and NK cells were increased,while the levels of CD4+/CD25+ and CD8+ were decreased, compared with before treatment, the differences were statistically significant; the phenotype changes of T cells were not statistically significant before and after treatment in the control group; after treatment, there were significant differences in the levels of CD4+, CD8+, CD4+/CD8+, CD4+/CD25+ and NK cells between the two groups. Before treatment, there were no significant differences in HE4 value, CA125 value and CA19-9 value between the two groups; after treatment, the tumor markers in the two groups were all decreased, and the difference was significant as compared with those before treatment; after treatment, the CA125 value, CA19-9 value and HE4 value were (73.68±79.46 U/mL, (54.32±32.85 U/mL and (69.57±39.85 pmol/L respectively, the values of three tumor markers were compared with the control group, with a statistical difference. Conclusion: DC-CIK treatment can improve the

Investigations of relevance of the tumor marker neopterine for therapeutic decision and control of progress in mammary carcinoma

International Nuclear Information System (INIS)

Hacker, I; Lauterbach, H.; Kob, D.

1989-01-01

The value of serum neopterin as tumor marker was verified in 104 breast cancer patients. Based on the results the evaluation of neopterin cannot be recommended, neither for the decision of treatment after primary therapy nor for monitoring of the breast cancer. (author)

Serum levels of CA15-3, AFP, CA19-9 and CEA tumor markers in cancer care and treatment of patients with impaired renal function on hemodialysis.

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Estakhri, Rasoul; Ghahramanzade, Ali; Vahedi, Amir; Nourazarian, Alireza

2013-01-01

Since renal failure causes decrease in tumor marker excretion, use of these markers in cancer care and treatment in patients with renal insufficiency or hemodialysis is controversial. The aim of this study was to investigate differences of serum levels of tumor markers CA15-3, AFP, CA19-9 and CEA in patients with impaired renal function. A total of 100 patients referred to the Tabriz Immam Reza and Amiralmomenin hospital from June 2010 to November 2011 were selected for study. Subjects were divided to 3 groups of healthy, dialysis and renal failure but non hemodialysis cases, the last category being re-grouped based on creatinine clearance. No significant relationship between different groups in serum levels of CEA (P=0.99) and CA19-9 (P=0.29) tumor markers was found. A significant correlation was observed between serum levels of AFP (PCEA (r=0.05, P=0.625). Creatinine clearance significantly correlated with AFP (Ptumor markers in patients with impaired renal function should be performed with special precautions.

Computerized method for estimation of the location of a lung tumor on EPID cine images without implanted markers in stereotactic body radiotherapy

International Nuclear Information System (INIS)

Arimura, H; Toyofuku, F; Higashida, Y; Onizuka, Y; Terashima, H; Egashira, Y; Shioyama, Y; Nomoto, S; Honda, H; Nakamura, K; Yoshidome, S; Anai, S

2009-01-01

The purpose of this study was to develop a computerized method for estimation of the location of a lung tumor in cine images on an electronic portal imaging device (EPID) without implanted markers during stereotactic body radiotherapy (SBRT). Each tumor region was segmented in the first EPID cine image, i.e., reference portal image, based on a multiple-gray level thresholding technique and a region growing technique, and then the image including the tumor region was cropped as a 'tumor template' image. The tumor location was determined as the position in which the tumor template image took the maximum cross-correlation value within each consecutive portal image, which was acquired in cine mode on the EPID in treatment. EPID images with 512 x 384 pixels (pixel size: 0.56 mm) were acquired at a sampling rate of 0.5 frame s -1 by using energies of 4, 6 or 10 MV on linear accelerators. We applied our proposed method to EPID cine images (226 frames) of 12 clinical cases (ages: 51-83, mean: 72) with a non-small cell lung cancer. As a result, the average location error between tumor points obtained by our method and the manual method was 1.47 ± 0.60 mm. This preliminary study suggests that our method based on the tumor template matching technique might be feasible for tracking the location of a lung tumor without implanted markers in SBRT.

Preclinical assessment of hypoxic marker specificity and sensitivity

International Nuclear Information System (INIS)

Iyer, Renuka V.; Engelhardt, Edward L.; Stobbe, Corinne C.; Schneider, Richard F.; Chapman, J. Donald

1998-01-01

Purpose: In the search for a sensitive, accurate, and noninvasive technique for quantifying human tumor hypoxia, our laboratory has synthesized several potential radiodiagnostic agents. The purpose of this study was to assess and compare the hypoxic marking properties of both radioiodinated and Tc-99m labeled markers in appropriate test systems which can predict for in vivo activity. Materials and Methods: Preclinical assessment of hypoxic marker specificity and sensitivity employed three laboratory assays with tumor cells in vitro and in vivo. Radiolabeled marker uptake and/or binding to whole EMT-6 tumor cells under extremely hypoxic and aerobic conditions was measured and their ratio defined hypoxia-specific factor (HSF). Marker specificity to hypoxic tumor tissue was estimated from its selective avidity to two rodent tumors in vivo, whose radiobiologic hypoxic fractions (HF) had been measured. The ratios of % injected dose/gram (%ID/g) of marker at various times in EMT-6 tumor tissue relative to that in the blood and muscle of scid mice were used to quantify hypoxia-specific activity. This tumor in this host exhibited an average radiobiologic HF of ∼35%. As well, nuclear medicine images were acquired from R3327-AT (HF ≅15%) and R3327-H (no measurable HF) prostate carcinomas growing in rats to distinguish between marker avidity due to hypoxia versus perfusion. Results: The HSF for FC-103 and other iodinated markers were higher (5-40) than those for FC-306 and other Tc-99m labeled markers. The latter did not show hypoxia-specific uptake into cells in vitro. Qualitative differences were observed in the biodistribution and clearance kinetics of the iodinated azomycin nucleosides relative to the technetium chelates. The largest tumor/blood (T/B) and tumor/muscle (T/M) ratios were observed for compounds of the azomycin nucleoside class in EMT-6 tumor-bearing scid mice. These markers also showed a 3-4 x higher uptake into R3327-AT tumors relative to the well

FDG uptake in cold and heat treated MCF-7 cells, comparison with cell viability, apoptosis, and tumor marker changes

International Nuclear Information System (INIS)

Zhang, C.; Sun, X.; Huang, G.; Liu, J.

2007-01-01

Full text: Objectives-To investigate the FDG uptake changes in cold and hyperthermia therapy and its correlation with cell viability, apoptosis and tumor marker changes. Methods: An in vitro cultured breast adenocarcinoma cell line, MCF- 7, was divided into 5 groups. Hyperthermia group: cell was treated in 43 degree centigrade 30 min. Hypothermia group: cell was treated in 0 degree centigrade 30 min. Hypo- and hyperthermia group: cell was treated in 0 degree centigrade 30 min and 43 degree centigrade 30 min. chemotherapy group: cell was treated with 21 microgram Cisplatin for 6 hours. And Control group: cell was untreated. The levels 18F-labelled FDG uptake, a 3-(4, 5-dimethylthiazol-2-yl)- 2, 5-diphenyltetrazoliumbromide viability assay, flow cytometry assay and tumor markers (CA153, CA125) were detected at 24 hour and 48 hour. Results: The change of 18F- FDG uptake (which came out at the 24h) is early than tumor marker (which came out at the 48h) under our study conditions. In treated MCF-7 cells, the levels of 18F-labelled FDG uptake were significantly lower than control group. The levels of 18F-FDG uptake depression were well correlated with cell viability and apoptosis data. Conclusion: FDG uptake is sensitive and well correlated with cell viability and apoptosis assay, and can be used for early response monitoring in hypo- and hyperthermia therapy. (author)

NSE, CEA and SCC - a useful combination of tumor markers in lung cancer

International Nuclear Information System (INIS)

Fischbach, W.; Jany, B.

1988-01-01

The usefulness of neuronspecific enolase (NSE), CEA, and of the tumor associated antigen SSC was investigated in 61 patients with histologically proven lung cancer (small cell lung cancer n=25, adenocarcinoma n=14, squamous cell carcinoma n=18 and large cell carcinoma n=4). The sensitivity of NSE was 93.3% in small cell lung cancer (SCLC), whereas in adeno- and squamous cell carcinoma only 8 or 13%, resp., elevated serum NSE were found. CEA was the most sensitive marker for adenocarcinoma (58.3%). Contrary to NSE, however, CEA does not allow any conclusions concerning differential diagnosis as pathological serum concentrations were also observed in 46.6% both in small cell lung cancer and in squamous cell carcinoma. SCC demonstrated a sensitivity of 53% in squamous cell carcinoma. Elevated serum levels were also found in adenocarcinoma (41.6%), but never in small lung cancer. For all three markers tested, high serum concentrations were predominantly present in patients with advanced disease state. (orig.) [de

Clinical applicability of determination of serum tumor markers (CEA, CA15-3 and CA125) levels changes for assessment of efficacy of chemotherapy in patients with breast cancer

International Nuclear Information System (INIS)

Xu Junying; Liu Chaoying; Li Jiang; Hu Hong; Wang Runjie

2009-01-01

Objective: To study the usefulness of monitoring changes of serum levels of tumor markers (CEA, CA15-3 and CA125) for assessment of efficacy of chemotherapy in patients with breast cancer. Methods: Serum CEA, CA15-3 and CA125 levels were measured with CLIA three days before beginning 1st course of appropriate chemotherapy and 3 weeks after completing 2nd course of treatment in 45 patients with advanced breast cancer (TNM stage III, n=20, stage IV n=25). Results: Expressed as CR, PR, SD and PD as defined by the changes of serum tumor markers levels (according to Bac D.J. et al) were compared with clinically observed ones (WHO standard). The serum levels of Cea, CA15-3 decreased markedly in the CR and PR groups of patients but increased markedly in PD patients (P 0.05). The coincidence rate between the results observed clinically and results derived from tumor marker changes was 50.0% for CEA, 55.6% for CA15-3, 31.1% for CA125 and 73% for three markers combined. Conclusion: Combined determination of the changes of serum levels of three tumor marker would help to make a reasonably satisfactory assessment of efficacy of chemotherapy in patients with breast cancer. (authors)

The effect of high level natural ionizing radiation on expression of PSA, CA19-9 and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran

International Nuclear Information System (INIS)

Heidari, Mohammad Hassan; Porghasem, Mohsen; Mirzaei, Nazanin; Mohseni, Jafar Hesam; Heidari, Matine; Azargashb, Eznollah; Movafagh, Abolfazl; Heidari, Reihane; Molouki, Aidin; Larijani, Leila

2014-01-01

Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of Ramsar being considerably higher. CEA level did not show any difference. Although some of the volunteers tested positive to the markers, they were in good health as confirmed by the physician. Moreover, the high number of positive markers in Noshahr was considerable. Therefore, future study is needed to further validate this result and to determine the level of positivity to tumor markers in both cities. -- Highlights: • Expression of three tumor markers was examined in 80 volunteers from Ramsar. • There was a significant difference in the levels of PSA and CA19-9 markers. • Some of the volunteers from the control city of Noshahr also tested positive. • Radiation might have caused an adaptive response in people of Ramsar. • Further study is necessary to re-confirm the positivity to tumor marker

Candidate Gene Identification with SNP Marker-Based Fine Mapping of Anthracnose Resistance Gene Co-4 in Common Bean.

Science.gov (United States)

Burt, Andrew J; William, H Manilal; Perry, Gregory; Khanal, Raja; Pauls, K Peter; Kelly, James D; Navabi, Alireza

2015-01-01

Anthracnose, caused by Colletotrichum lindemuthianum, is an important fungal disease of common bean (Phaseolus vulgaris). Alleles at the Co-4 locus confer resistance to a number of races of C. lindemuthianum. A population of 94 F4:5 recombinant inbred lines of a cross between resistant black bean genotype B09197 and susceptible navy bean cultivar Nautica was used to identify markers associated with resistance in bean chromosome 8 (Pv08) where Co-4 is localized. Three SCAR markers with known linkage to Co-4 and a panel of single nucleotide markers were used for genotyping. A refined physical region on Pv08 with significant association with anthracnose resistance identified by markers was used in BLAST searches with the genomic sequence of common bean accession G19833. Thirty two unique annotated candidate genes were identified that spanned a physical region of 936.46 kb. A majority of the annotated genes identified had functional similarity to leucine rich repeats/receptor like kinase domains. Three annotated genes had similarity to 1, 3-β-glucanase domains. There were sequence similarities between some of the annotated genes found in the study and the genes associated with phosphoinositide-specific phosphilipases C associated with Co-x and the COK-4 loci found in previous studies. It is possible that the Co-4 locus is structured as a group of genes with functional domains dominated by protein tyrosine kinase along with leucine rich repeats/nucleotide binding site, phosphilipases C as well as β-glucanases.

Effects of Thoracic Paravertebral Block on Postoperative Analgesia and Serum Level of Tumor Marker in Lung Cancer Patients Undergoing Video-assisted Thoracoscopic Surgery

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Jiheng CHEN

2015-02-01

Full Text Available Background and objective Perioperative management of pain associated with the prognosis of cancer patients. Optimization of perio-perative analgesia method, then reduce perioperative stress response, reduce opioiddosage, to reduce or even avoid systemic adverse reactions and elevated levels of tumor markers. Serum levels of tumor markers in patients with lung cancer are closely related to tumor growth. Clinical research reports on regional anesthesia effect on tumor markers for lung cancer are still very little in domesticliterature. The aim of this study is to evaluate the effects of thoracic paraverte-bral block on postoperative analgesia and serum level of tumor marker in lung cancer patients undergoing video-assisted thoracoscopic surgery. Methods Lung cancer patients undergoing video-assisted thoracoscopic surgery were randomly divided into 2 groups (n=20 in each group. The patients in group G were given only general anesthesia. The thoracic paravertebral blockade (PVB was performed before general anesthesia in patients of group GP. The effect of PVB was judged by testing area of block. Patient controlled intravenous analgesia (PCIA pump started before the end of surgery in 2 groups. Visual analogue scale (VAS score was recorded after extubation 2 h (T1, 24 h (T2 and 48 h (T3 after surgery and the times of PCIA and the volume of analgesic drugs used were recorded during 48 h after surgery. The serum levels of carcino-embryonic antigen (CEA, carbohydrate antigen 199 (CA199, carbohydrate antigen 125 (CA125, neuron-specific enolase (NSE, cytokeratin 19 fragment (CYFRA21-1 and squamous cell carcinoma (SCC in 40 lung cancer cases undergoing video-assisted thoracoscopic lobectomy were measured before operation and 24 h after operation. Results Forty American Society of Anesthesiologists (ASA physical status I or II patients, aged 20 yr-70 yr, body mass index (BMI 18 kg/m2-25 kg/m2, scheduled for elective video-assisted thoraeoscopic lobectomy

How could Decision Support System Based on Non-Linear Model Help to Interpret Tumor Marker Measurments in Oncology

Czech Academy of Sciences Publication Activity Database

Pecen, Ladislav; Eben, Kryštof; Vondráček, Jiří; Holubec, L.; Topolčan, O.; Pikner, R.; Kausitz, J.; Nekulová, M.; Šimíčková, M.

2002-01-01

Roč. 23, Suppl.1 (2002), s. 38 ISSN 1010-4283. [Meeting of the International Society for Oncodevelopmental Biology and Medicine /30./. 08.09.2002-12.09.2002, Boston] Institutional research plan: AV0Z1030915 Keywords : tumor markers * decision support systems Subject RIV: BA - General Mathematics

Dynamic observation on changes of serum tumor markers levels after implantation of 125I radioactive seeds as treatment for several malignancies

International Nuclear Information System (INIS)

Sun Qihe; Yang Jiali; Gao Mingzhong

2005-01-01

Objective: To study the dynamic changes of serum levels of several tumor markers after implantation of 125 I seeds as treatment for breast, prostate and lung malignancies. Methods: Serum CA15-3 (in 48 cases of breast cancer), PSA (in 59 cases of prostate cancer) and CYFRA21-1 (in 59 cases of lung cancer) levels were measured with RIA both before and after implantation of 125 I seeds as treatment. Furthermore, dynamic observation on the serum markers levels was carried out every 3 months in ten patients in each category. Results: After treatment, levels of these markers dropped significantly. Dynamic observation revealed that in the 10 cases of breast cancer, the levels of CA15-3 dropped continually. However, in the 10 cases of prostatic cancer, the disease got worse and the PSA levels kept increasing. In the lung cancer group, the CYFRA21-1 levels rose markedly and all patients expired before 9 months. Conclusion: Dynamic observation on changes of serum tumor markers (CA15-3, PSA, CYFRA21-1) levels after 125 I seed implantation treatment was of definite prognostic value. (authors)

Evaluation of the Novel Monoclonal Antibody Against DOG1 as a Diagnostic Marker for Gastrointestinal Stromal Tumors

International Nuclear Information System (INIS)

Abdel-Hadi, M.; Hamam, S.M.; Bessa, S.S.

2009-01-01

Gastrointestinal stromal tumors (GISTs) are the most common mesenchymal tumors of the gastrointestinal tract. With the growing effectiveness and availability of first and second-generation tyrosine kinase inhibitor (TKI) drugs, the accurate diagnosis of GIST has become imperative. The problem is that some GISTs with KIT or Alpha-type platelet-derived growth factor receptor (PDGFRA) mutations may have low KIT expression by immunohistochemistry yet will still benefit from TKI drugs. Molecular analysis is a costly and laborious process. Therefore the emergence of a new sensitive immunohistochemical marker for GISTs would be ideal. Recently antibodies against D iscovered on GIST-1 ( DOG1) have been generated. The aim of this study was to evaluate the monoclonal DOG1.1 antibody as a diagnostic marker for GISTs and to compare immunohistochemical staining and diagnostic efficacy of DOG1.1 with that of KIT in GISTs. Materials and Methods: Forty seven paraffin embedded GISTs were immuno stained with both Kit and DOG1.1 antibodies. Immunoreactivity was graded semiquantitatively from 0 to 4. Some other mesenchymal tumors were included in the study and stained for both markers to test for their specificity. Results: Out of the 47 GISTs, 44 were immunoreactive for both KIT and DOG1.1 antibodies (93.62%). Two cases (4.25%) were KIT-positive DOG-negative and the remaining case was DOG-positive KIT-negative (2.13%). A statistically significant concordance was found between KIT and DOG1.1 immunoreactivity (p=0.004), with moderate agreement between immunostaining scores (kappa =0.379). As regards tumor site, a statistically significant association was found between high DOG1.1 scores and gastric GIST (p=0.008). High KIT and DOG1.1 immunostaining scores were significantly associated with high risk tumors (p=0.002 and p=0.002 respectively). DOG1.1 immunoreactivity was focal in more than half of the cases. The overall diagnostic accuracy of DOG1.1 was 96.5%, with a specificity and

Glycolysis-related gene induction and ATP reduction during fractionated irradiation. Markers for radiation responsiveness of human tumor xenografts

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Goetze, K.; Meyer, S.S.; Mueller-Klieser, W. [University Medical Center Mainz Univ. (Germany). Inst. of Physiology and Pathophysiology; Yaromina, A. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; Zips, D. [University Hospital Tuebingen (Germany). Dept. of Radiation Oncology; Baumann, M. [Technical Univ. Dresden (Germany). OncoRay - National Center for Radiation Research in Oncology; University Hospital Dresden Technical Univ. Dresden (Germany). Dept. of Radiation Oncology

2013-09-15

Background and purpose: Lactate was previously shown to be a prognostic but not a predictive pre-therapeutic marker for radiation response of tumor xenografts. We hypothesize that metabolic changes during fractionated irradiation may restrict the predictiveness of lactate regarding tumor radiosensitivity. Materials and methods: Tumor xenografts were generated in nude mice by implanting 4 head and neck squamous cell carcinoma lines with different sensitivities to fractionated irradiation. Tumors were irradiated with up to 15 fractions of 2 Gy over a period of 3 weeks, and ATP and lactate levels were measured in vital tumor areas with induced metabolic bioluminescence imaging. Corresponding changes in mRNA expression of glycolysis-related genes were determined by quantitative RT-PCR. Results: Lactate content decreased significantly in 3 out of 4 cell lines in the course of irradiation showing no correlation with cell line-specific radiosensitivity. Radiation-induced changes in ATP levels and glycolysis-related mRNA expression, however, only occurred in radiosensitive or intermediately radioresistant xenografts, whereas these parameters remained unchanged in radioresistant tumors. Conclusion: Sensitivity-related differences in the transcriptional response of tumors to radiotherapy may be exploited in the clinic for better individualization of tumor treatment. (orig.)

Four-dimensional treatment planning and fluoroscopic real-time tumor tracking radiotherapy for moving tumor

International Nuclear Information System (INIS)

Shirato, Hiroki; Shimizu, Shinichi; Kitamura, Kei; Nishioka, Takeshi; Kagei, Kenji; Hashimoto, Seiko; Aoyama, Hidefumi; Kunieda, Tatsuya; Shinohara, Nobuo; Dosaka-Akita, Hirotoshi; Miyasaka, Kazuo

2000-01-01

Purpose: To achieve precise three-dimensional (3D) conformal radiotherapy for mobile tumors, a new radiotherapy system and its treatment planning system were developed and used for clinical practice. Methods and Materials: We developed a linear accelerator synchronized with a fluoroscopic real-time tumor tracking system by which 3D coordinates of a 2.0-mm gold marker in the tumor can be determined every 0.03 second. The 3D relationships between the marker and the tumor at different respiratory phases are evaluated using CT image at each respiratory phase, whereby the optimum phase can be selected to synchronize with irradiation (4D treatment planning). The linac is triggered to irradiate the tumor only when the marker is located within the region of the planned coordinates relative to the isocenter. Results: The coordinates of the marker were detected with an accuracy of ± 1 mm during radiotherapy in the phantom experiment. The time delay between recognition of the marker position and the start or stop of megavoltage X-ray irradiation was 0.03 second. Fourteen patients with various tumors were treated by conformal radiotherapy with a 'tight' planning target volume (PTV) margin. They were surviving without relapse or complications with a median follow-up of 6 months. Conclusion: Fluoroscopic real-time tumor tracking radiotherapy following 4D treatment planning was developed and shown to be feasible to improve the accuracy of the radiotherapy for mobile tumors

Low penetrance breast cancer susceptibility loci are associated with specific breast tumor subtypes

DEFF Research Database (Denmark)

Broeks, Annegien; Schmidt, Marjanka K; Sherman, Mark E

2011-01-01

Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtype...... stratification might help in the identification and characterization of novel risk factors for breast cancer subtypes. This may eventually result in further improvements in prevention, early detection and treatment.......Breast cancers demonstrate substantial biological, clinical and etiological heterogeneity. We investigated breast cancer risk associations of eight susceptibility loci identified in GWAS and two putative susceptibility loci in candidate genes in relation to specific breast tumor subtypes. Subtypes...... were defined by five markers (ER, PR, HER2, CK5/6, EGFR) and other pathological and clinical features. Analyses included up to 30 040 invasive breast cancer cases and 53 692 controls from 31 studies within the Breast Cancer Association Consortium. We confirmed previous reports of stronger associations...

[Impact of the implementation of a protocol for the adequate and safe use of tumor markers].

Science.gov (United States)

Mérida de la Torre, Francisco Javier; Moreno Campoy, Elvira Eva; Martos Crespo, Francisco

2015-12-21

Improper clinical use of tumor markers (TM) may cause unnecessary additional studies to confirm or refute a positive result. After observing 2 adverse events due to a wrong use of TM, a protocol for improving their use was implemented. The objective of this study was to determine the impact of the implementation of the protocol. This was a pre-postintervention study, where analytical requests of carcinoembryonic antigen, CA15.3, CA19.9 and CA125 were analyzed during one year in patients not undergoing checking of neoplasia. A protocol was implemented and physicians were trained as recommended by the European Group on Tumor Markers, limiting its use to monitor the disease and its treatment. The study period was 2010-2014. The total number of requests dropped 50.81% and the percentage of adequacy of TM increased, each year, from 31.03 to 77.91%. The implementation of a protocol for the proper use of TM contributes to a safer use, avoiding incorrect studies and unnecessary and harmful tests for the patient. Copyright © 2015 Elsevier España, S.L.U. All rights reserved.

AgNOR Count in Resting Cells (Resting NOR Is a New Prognostic Marker in Invasive Bladder Tumor

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Mitsuro Tomobe

2001-01-01

Full Text Available Purpose: We have previously demonstrated that the AgNOR count in proliferating cells is a predictor of tumor recurrence in superficial bladder tumor (J. Urol. 162 (1999, 63–68. In the present study, we evaluate the type of AgNOR associated with cell cycles as a prognostic factor in invasive bladder tumor using a double staining technique employing both AgNOR and MIB-1 labelling. Materials and methods: Forty-four paraffin sections of invasive bladder tumors were stained simultaneously with AgNOR and MIB-1. The number of AgNORs in proliferating (MIB-1 positive or resting (MIB-1 negative cells were counted from a total of 100 nuclei. Correlations between MIB-1 associated AgNOR count and clinicopathological parameters were statistically analyzed. Results: The AgNOR count in proliferating cells (proliferating NOR was significantly higher than that in resting cells (resting NOR (p < 0.01. The resting NOR in tumors with distant metastases was significantly higher than that in tumors without metastases (p < 0.05. Patients with a low resting NOR tumor had a better prognosis than those with a high resting NOR tumor, whereas the proliferating NOR was not associated with survival. Survival analysis revealed that the resting NOR was the most powerful prognostic marker in patients with invasive bladder tumor (p < 0.05. Conclusions: Resting NOR had a predictive value in the prognosis of patients with invasive bladder tumor. Keywords: Transitional cell carcinoma, invasive, resting cell, AgNORs, MIB-1

Concordance of Hypermethylated DNA and the Tumor Markers CA 15-3, CEA, and TPA in Serum during Monitoring of Patients with Advanced Breast Cancer

DEFF Research Database (Denmark)

Kristiansen, Søren; Jørgensen, Lars Mønster; Høgh Hansen, Morten

2015-01-01

The serological protein tumor markers CA 15-3, CEA, and TPA are frequently used to monitor tumor burden among metastatic breast cancer patients. Breast cancer is associated with global DNA hypomethylation and hypermethylation of some promoter regions. No monitoring study has yet investigated the ...

Stemness-related markers in cancer

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Wenxiu Zhao

2017-01-01

Full Text Available Cancer stem cells (CSCs, with their self-renewal ability and multilineage differentiation potential, are a critical subpopulation of tumor cells that can drive tumor initiation, growth, and resistance to therapy. Like embryonic and adult stem cells, CSCs express markers that are not expressed in normal somatic cells and are thus thought to contribute toward a “stemness” phenotype. This review summarizes the current knowledge of stemness-related markers in human cancers, with a particular focus on important transcription factors, protein surface markers, and signaling pathways.

Characterization of novel tumor stroma markers identified by gene expression profiling of human cancer tissues and 3D co-culture models

International Nuclear Information System (INIS)

Rupp, C.

2010-01-01

The tumor stroma plays an important role in tumorigenesis. During cancer progression it undergoes changes in architecture, gene expression and secretion of proteolytic enzymes that are essential for the invasive and metastatic phenotype of malignant tumors. Cancer associated fibroblasts (Cafes) represent the major cellular component of the stroma and recent studies demonstrated the prognostic and therapeutic significance of CaF-related molecular signatures. The identification and characterization of genes and signaling pathways involved in the molecular interactions between tumor and stromal cells has been the focus of this study. For that purpose we have used two complementary approaches: the identification of novel tumor stroma targets in human colon cancer samples using whole genome Affymetrix GeneChip analysis and the validation of theses targets in a newly established of 3D co-culture model that mimics the cellular and molecular heterogeneity of human cancers. We have demonstrated increased expression of gene sets related to hypoxia, epithelial-to-mesenchymal transition (EMT) and TGFβ pathway activation in CAFs vs their normal counterparts in both systems. The putative TGFβ target IGFBP7 (insulin-like growth factor binding protein 7) was identified as a tumor stroma marker of epithelial cancers and as a tumor antigen in mesenchyme-derived sarcomas. IGFPB7 was shown to promote anchorage-independent growth in malignant mesenchymal cells and malignant epithelial cells with an EMT-phenotype, whereas a tumor suppressor function was observed in tumor epithelial cells. In summary, we have demonstrated that a number of important signaling pathways involved in cancer progression and metastasis are specifically dysregulated in the tumor stroma both in our in vivo screen and in the in vitro 3D model, illustrating the value of these approaches for the identification and characterization of novel stromal markers. (author) [de

Comparison between clinical significance of serum proinflammatory proteins (IL-6 and CRP) and classic tumor markers (CEA and CA 19-9) in gastric cancer.

Science.gov (United States)

Lukaszewicz-Zając, Marta; Mroczko, Barbara; Gryko, Mariusz; Kędra, Bogusław; Szmitkowski, Maciej

2011-06-01

Gastric cancer (GC) is a second most common cause of cancer-related death and represents an inflammation-driven malignancy. It has been suggested that interleukin 6 (IL-6) and C-reactive protein (CRP) play a potential role in the growth and progression of GC. The aim of the present study was to compare clinical significance of IL-6 and CRP with classic tumor markers-carcinoembryonic antigen (CEA) and carbohydrate antigen (CA 19-9) in GC patients. The study included 92 patients with GC and 70 healthy subjects. The serum concentrations of IL-6, CEA and CA 19-9 were determined using immunoenzyme assays, whereas CRP using immunoturbidimetric method. We defined the diagnostic criteria and prognostic value for proteins tested. In GC patients, the serum concentrations of all the proteins tested were significantly higher than in healthy subjects. The IL-6, CEA and CA 19-9 levels correlated with nodal metastases, while CRP with tumor stage, gastric wall invasion, presence of nodal and distant metastases. Diagnostic sensitivity of IL-6 was higher (85%) than those of other markers (CRP 66%, CA 19-9 34%, CEA 22%) and increased in combined use with CRP or CEA (88%). The area under ROC curve for IL-6 was larger than those of CRP and classic tumor markers (CEA and CA 19-9). None of the proteins tested was independent prognostic factor for the survival of GC patients. Our findings indicate better usefulness of serum proinflammatory proteins-IL-6 and CRP than classic tumor markers-CEA and CA 19-9 in the diagnosis of GC.

Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer.

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Yingbo Shao

Full Text Available The utility of measuring carcinoembryonic antigen(CEA and cancer antigen 15-3 (CA15-3 levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients.Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and outcomes were analyzed.Elevated serum levels of CEA and CA15-3 were identified in 47 (10.9% and 60(13.9% patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM stage exhibited higher proportion of elevated CEA and CA15-3 levels. The elevation of CEA levels was significantly greater in patients with HER2 positive tumors, and the elevation of CA15-3 levels was significantly greater in ER negative breast patients. Univariate and multivariate Cox's regression analysis revealed that elevated preoperative CEA and CA 15-3 levels were independent prognostic factors for DFS and OS. When considering the combination of both markers levels, patients with both elevated markers presented the worst survival. Independent prognostic significance of elevated preoperative serum CEA and CA15-3 levels were reconfirmed in Luminal B breast cancer.Preoperative serum levels of CEA and CA15-3 are independent prognostic parameters for breast cancer.

Elevated Levels of Serum Tumor Markers CEA and CA15-3 Are Prognostic Parameters for Different Molecular Subtypes of Breast Cancer.

Science.gov (United States)

Shao, Yingbo; Sun, Xianfu; He, Yaning; Liu, Chaojun; Liu, Hui

2015-01-01

The utility of measuring carcinoembryonic antigen(CEA) and cancer antigen 15-3 (CA15-3) levels in patients with breast cancer remains controversial. The present study aims to investigate the prognostic value of preoperative serum CEA and CA15-3 levels in breast cancer patients. Serum preoperative CEA and CA 15-3 concentration levels were measured in a total of 432 breast cancer patients. The association of tumor markers levels with clinicopathological parameters and outcomes were analyzed. Elevated serum levels of CEA and CA15-3 were identified in 47 (10.9%) and 60(13.9%) patients, respectively. Larger tumor size, advanced axillary lymph nodal and TNM stage exhibited higher proportion of elevated CEA and CA15-3 levels. The elevation of CEA levels was significantly greater in patients with HER2 positive tumors, and the elevation of CA15-3 levels was significantly greater in ER negative breast patients. Univariate and multivariate Cox's regression analysis revealed that elevated preoperative CEA and CA 15-3 levels were independent prognostic factors for DFS and OS. When considering the combination of both markers levels, patients with both elevated markers presented the worst survival. Independent prognostic significance of elevated preoperative serum CEA and CA15-3 levels were reconfirmed in Luminal B breast cancer. Preoperative serum levels of CEA and CA15-3 are independent prognostic parameters for breast cancer.

Candidate Gene Identification with SNP Marker-Based Fine Mapping of Anthracnose Resistance Gene Co-4 in Common Bean.

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Andrew J Burt

Full Text Available Anthracnose, caused by Colletotrichum lindemuthianum, is an important fungal disease of common bean (Phaseolus vulgaris. Alleles at the Co-4 locus confer resistance to a number of races of C. lindemuthianum. A population of 94 F4:5 recombinant inbred lines of a cross between resistant black bean genotype B09197 and susceptible navy bean cultivar Nautica was used to identify markers associated with resistance in bean chromosome 8 (Pv08 where Co-4 is localized. Three SCAR markers with known linkage to Co-4 and a panel of single nucleotide markers were used for genotyping. A refined physical region on Pv08 with significant association with anthracnose resistance identified by markers was used in BLAST searches with the genomic sequence of common bean accession G19833. Thirty two unique annotated candidate genes were identified that spanned a physical region of 936.46 kb. A majority of the annotated genes identified had functional similarity to leucine rich repeats/receptor like kinase domains. Three annotated genes had similarity to 1, 3-β-glucanase domains. There were sequence similarities between some of the annotated genes found in the study and the genes associated with phosphoinositide-specific phosphilipases C associated with Co-x and the COK-4 loci found in previous studies. It is possible that the Co-4 locus is structured as a group of genes with functional domains dominated by protein tyrosine kinase along with leucine rich repeats/nucleotide binding site, phosphilipases C as well as β-glucanases.

Development of a real-time internal and external marker tracking system for particle therapy: a phantom study using patient tumor trajectory data.

Science.gov (United States)

Cho, Junsang; Cheon, Wonjoong; Ahn, Sanghee; Jung, Hyunuk; Sheen, Heesoon; Park, Hee Chul; Han, Youngyih

2017-09-01

Target motion-induced uncertainty in particle therapy is more complicated than that in X-ray therapy, requiring more accurate motion management. Therefore, a hybrid motion-tracking system that can track internal tumor motion and as well as an external surrogate of tumor motion was developed. Recently, many correlation tests between internal and external markers in X-ray therapy have been developed; however, the accuracy of such internal/external marker tracking systems, especially in particle therapy, has not yet been sufficiently tested. In this article, the process of installing an in-house hybrid internal/external motion-tracking system is described and the accuracy level of tracking system was acquired. Our results demonstrated that the developed in-house external/internal combined tracking system has submillimeter accuracy, and can be clinically used as a particle therapy system as well as a simulation system for moving tumor treatment. © The Author 2017. Published by Oxford University Press on behalf of The Japan Radiation Research Society and Japanese Society for Radiation Oncology.

Surrogate MRI markers for hyperthermia-induced release of doxorubicin from thermosensitive liposomes in tumors.

Science.gov (United States)

Peller, Michael; Willerding, Linus; Limmer, Simone; Hossann, Martin; Dietrich, Olaf; Ingrisch, Michael; Sroka, Ronald; Lindner, Lars H

2016-09-10

The efficacy of systemically applied, classical anti-cancer drugs is limited by insufficient selectivity to the tumor and the applicable dose is limited by side effects. Efficacy could be further improved by targeting of the drug to the tumor. Using thermosensitive liposomes (TSL) as a drug carrier, targeting is achieved by control of temperature in the target volume. In such an approach, effective local hyperthermia (40-43°C) (HT) of the tumor is considered essential but technically challenging. Thus, visualization of local heating and drug release using TSL is considered an important tool for further improvement. Visualization and feasibility of chemodosimetry by magnetic resonance imaging (MRI) has previously been demonstrated using TSL encapsulating both, contrast agent (CA) and doxorubicin (DOX) simultaneously in the same TSL. Dosimetry has been facilitated using T1-relaxation time change as a surrogate marker for DOX deposition in the tumor. To allow higher loading of the TSL and to simplify clinical development of new TSL formulations a new approach using a mixture of TSL either loaded with DOX or MRI-CA is suggested. This was successfully tested using phosphatidyldiglycerol-based TSL (DPPG2-TSL) in Brown Norway rats with syngeneic soft tissue sarcomas (BN175) implanted at both hind legs. After intravenous application of DOX-TSL and CA-TSL, heating of one tumor above 40°C for 1h using laser light resulted in highly selective DOX uptake. The DOX-concentration in the heated tumor tissue compared to the non-heated tumor showed an almost 10-fold increase. T1 and additional MRI surrogate parameters such as signal phase change were correlated to intratumoral DOX concentration. Visualization of DOX delivery in the sense of a chemodosimetry was demonstrated. Although phase-based MR-thermometry was affected by CA-TSL, phase information was found suitable for DOX concentration assessment. Local differences of DOX concentration in the tumors indicated the need for

Prognostic features and markers for testicular cancer management

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Eddy S Leman

2010-01-01

Full Text Available Testicular neoplasm accounts for about 1% of all cancers in men. Over the last 40 years, the incidence of testicular cancer has increased in northern European male populations for unknown reasons. When diagnosed at early stage, testicular cancer is usually curable with a high survival rate. In the past three decades, successful multidisciplinary approaches for the management of testicular cancer have significantly increased patient survival rates. Utilization of tumor markers and accurate prognostic classification has also contributed to successful therapy. In this article, we highlight the most commonly used tumor markers and several potential "novel" markers for testicular cancer as part of the ongoing effort in biomarker research and discovery. In addition, this article also identifies several key prognostic features that have been demonstrated to play a role in predicting relapse. These features include tumor size, rete testis invasion, lymphovascular invasion, and tumor histology. Together with tumor markers, these prognostic factors should be taken into account for risk-adapted management of testicular cancer.

Predictive and prognostic value of preoperative serum tumor markers is EGFR mutation-specific in resectable non-small-cell lung cancer

Science.gov (United States)

Jiang, Richeng; Wang, Xinyue; Li, Kai

2016-01-01

Background The predictive and prognostic value of carcinoembryonic antigen (CEA), cytokeratin-19 fragments (Cyfra21-1), squamous cell carcinoma antigen (SCCA) and neuron-specific enolase (NSE) has been investigated in non-small-cell lung cancer (NSCLC) patients. However, few studies have directly focused on the association between these markers and epidermal growth factor receptor (EGFR) mutation status or mutation subtypes. Patients and methods We retrospectively analyzed 1016 patients with stage I-IIIA NSCLC who underwent complete resection between 2008 and 2012. Correlations between serum tumor marker levels and EGFR mutations and survival parameters were analyzed and prognostic factors were identified. Results Cyfra21-1 levels (P = 0.032 for disease-free survival [DFS]; P CEA levels (P CEA (P = 0.005) and clinical stage were predictive factors of DFS, while elevated CEA (P = 0.005) and Cyfra21-1 (P = 0.027) were independent prognostic factors. Conclusion Cyfra21-1 and CEA exhibit different predictive and prognostic values between EGFR-mutated and wild-type adenocarcinomas, as well as between EGFR mutation subtypes. The prognostic impact of preoperative serum tumor markers should be evaluated together with EGFR mutation status. PMID:27072585

Intrinsic structural variation of the complex microsatellite marker MYCL1 in Finnish and Somali populations and its relevance to gastrointestinal tumors

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Hanna Vauhkonen

2006-01-01

Full Text Available The structurally complex MYCL1 microsatellite marker is often used to determine microsatellite instability in colorectal cancers but the allelic variation of this marker has remained largely uncharacterized in both populations and in cancers. Our study describes the allelic distributions of MYCL1 in Finnish (n = 117 and Somali population samples (n = 61 of non-related individuals and compares this distribution with the instability pattern obtained from 61 gastrointestinal tumors.

Behavior of Lipiodol Markers During Image Guided Radiotherapy of Bladder Cancer

International Nuclear Information System (INIS)

Chai Xiangfei; Herk, Marcel van; Kamer, Jeroen B. van de; Remeijer, Peter; Bex, Axel; Betgen, Anja; De Reijke, Theo M.; Hulshof, Maarten C.C.M.; Pos, Floris J.; Bel, Arjan

2010-01-01

Purpose: To investigate the stability of a novel type of markers used in partial bladder tumor irradiation and tumor deformation as indicated by the markers. Materials and Methods: In 15 patients with solitary bladder cancer, lipiodol was injected in the bladder wall during flexible cystoscopy to identify the tumor. A planning CT scan was made, followed by daily cone-beam CT (CBCT) scans during treatment. To study the accuracy of using these markers for image guidance, uncertainties U1 and U2 were calculated, which were defined as the difference between submask registration (covering single marker) and the average of all submask registrations and the difference between the submask registration and the general mask registration (including all markers), respectively. Finally, to study tumor deformation, the relative movement of each marker pair was correlated with the relative bladder volume (RBV). Results: The analyzed patients had 2.3 marker injections on average. The lipiodol spot size was 0.72 ± 1.1 cm 3 . The intensity of spots in both CT and CBCT was significantly higher than the surrounding bladder tissue. The uncertainties U1 and U2 were comparable, and the uncertainties in left-right direction (0.14-0.19 cm) were smaller than those in cranial-caudal and anterior-posterior directions (0.19-0.32 cm). The relative marker movement of within-zone marker pairs was much smaller (and has less dependence on the RBV) than across-zones marker pairs. Conclusions: Lipiodol markers are a feasible method to track bladder tumor by using online CBCT. Tumor deformation is observed, especially for tumors that cross the defined bladder zones.

Behavior of Lipiodol Markers During Image Guided Radiotherapy of Bladder Cancer

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Chai Xiangfei, E-mail: x.chai@amc.uva.n [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Herk, Marcel van [Department of Radiation Oncology, The Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Kamer, Jeroen B. van de [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Remeijer, Peter [Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Bex, Axel [Department of Urology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Betgen, Anja [Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); De Reijke, Theo M [Department of Urology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hulshof, Maarten C.C.M. [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Pos, Floris J [Department of Radiation Oncology, Netherlands Cancer Institute, Antoni van Leeuwenhoek Hospital, Amsterdam (Netherlands); Bel, Arjan [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

2010-05-01

Purpose: To investigate the stability of a novel type of markers used in partial bladder tumor irradiation and tumor deformation as indicated by the markers. Materials and Methods: In 15 patients with solitary bladder cancer, lipiodol was injected in the bladder wall during flexible cystoscopy to identify the tumor. A planning CT scan was made, followed by daily cone-beam CT (CBCT) scans during treatment. To study the accuracy of using these markers for image guidance, uncertainties U1 and U2 were calculated, which were defined as the difference between submask registration (covering single marker) and the average of all submask registrations and the difference between the submask registration and the general mask registration (including all markers), respectively. Finally, to study tumor deformation, the relative movement of each marker pair was correlated with the relative bladder volume (RBV). Results: The analyzed patients had 2.3 marker injections on average. The lipiodol spot size was 0.72 +- 1.1 cm{sup 3}. The intensity of spots in both CT and CBCT was significantly higher than the surrounding bladder tissue. The uncertainties U1 and U2 were comparable, and the uncertainties in left-right direction (0.14-0.19 cm) were smaller than those in cranial-caudal and anterior-posterior directions (0.19-0.32 cm). The relative marker movement of within-zone marker pairs was much smaller (and has less dependence on the RBV) than across-zones marker pairs. Conclusions: Lipiodol markers are a feasible method to track bladder tumor by using online CBCT. Tumor deformation is observed, especially for tumors that cross the defined bladder zones.

A preclinical model for noninvasive imaging of hypoxia-induced gene expression; comparison with an exogenous marker of tumor hypoxia

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Wen Bixiu; Burgman, Paul; Zanzonico, Pat; O' Donoghue, Joseph; Li, Gloria C.; Ling, C. Clifton [Memorial Sloan-Kettering Cancer Center, Department of Medical Physics, New York (United States); Cai Shangde; Finn, Ron [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York (United States); Serganova, Inna [Memorial Sloan-Kettering Cancer Center, Department of Neurology, New York (United States); Blasberg, Ronald; Gelovani, Juri [Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York (United States); Memorial Sloan-Kettering Cancer Center, Department of Neurology, New York (United States)

2004-11-01

Hypoxia is associated with tumor aggressiveness and is an important cause of resistance to radiation therapy and chemotherapy. Assays of tumor hypoxia could provide selection tools for hypoxia-modifying treatments. The purpose of this study was to develop and characterize a rodent tumor model with a reporter gene construct that would be transactivated by the hypoxia-inducible molecular switch, i.e., the upregulation of HIF-1. The reporter gene construct is the herpes simplex virus 1-thymidine kinase (HSV1-tk) fused with the enhanced green fluorescent protein (eGFP) under the regulation of an artificial hypoxia-responsive enhancer/promoter. In this model, tumor hypoxia would up-regulate HIF-1, and through the hypoxia-responsive promoter transactivate the HSV1-tkeGFPfusion gene. The expression of this reporter gene can be assessed with the {sup 124}I-labeled reporter substrate 2'-fluoro-2'-deoxy-1-{beta}-d-arabinofuranosyl-5-iodouracil ({sup 124}I-FIAU), which is phosphorylated by the HSV1-tk enzyme and trapped in the hypoxic cells. Animal positron emission tomography (microPET) and phosphor plate imaging (PPI) were used in this study to visualize the trapped {sup 124}I-FIAU, providing a distribution of the hypoxia-induced molecular events. The distribution of {sup 124}I-FIAU was also compared with that of an exogenous hypoxic cell marker, {sup 18}F-fluoromisonidazole (FMISO). Our results showed that {sup 124}I-FIAU microPET imaging of the hypoxia-induced reporter gene expression is feasible, and that the intratumoral distributions of {sup 124}I-FIAU and {sup 18}F-FMISO are similar. In tumor sections, detailed radioactivity distributions were obtained with PPI which also showed similarity between {sup 124}I-FIAU and {sup 18}F-FMISO. This reporter system is sufficiently sensitive to detect hypoxia-induced transcriptional activation by noninvasive imaging and might provide a valuable tool in studying tumor hypoxia and in validating existing and future

The relationship between glasgow prognostic score and serum tumor markers in patients with advanced non-small cell lung cancer

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Jiang, Ai-Gui; Chen, Hong-Lin; Lu, Hui-Yu

2015-01-01

Glasgow Prognostic Score (GPS) has been reported as a powerful prognostic tool for patients with advanced non–small cell lung cancer (NSCLC). The aim of this study was to assess the relationship between GPS and prognosis related tumor markers in patients with advanced NSCLC. We included 138 advanced NSCLC patients and twenty healthy controls in the study. GPS was calculated by combined serum C-reactive protein (CRP) and albumin. Three serum tumor markers, which included cytokeratin 19 fragment antigen 21-1 (CYFRA21–1), carcinoembryonic antigen (CEA) and tissue polypeptide specific antigen (TPS), were detected by enzyme-linked immunosorbent assay (ELISA). GPS and tumor markers were all assessed before chemotherapy. All patients received at least 2 courses of cisplatin-based chemotherapy. After that, 2 to 5 years follow-up was conducted. Median levels of CYFRA21–1 were 1.5 ng/ml (0.1–3.1 ng/ml) in healthy controls, and 4.6 ng/ml (0.7–35.2 ng/ml) in GPS 0 advanced NSCLC, 11.2 ng/ml (0.4–89.2) ng/ml in GPS 1 advanced NSCLC, and 15.7 ng/ml (2.9–134.6 ng/ml) in GPS 2 advanced NSCLC, respectively. Median levels of CYFRA21-1 were higher in NSCLC patients than in healthy controls, and CYFRA21-1 increased gradually according to GPS category in NSCLC patients (P < 0.05). Similar results were found for median levels of CEA and TPS in healthy controls and NSCLC patients (P < 0.05). In NSCLC patients, positive correlations were found between CYFRA21-1 and GPS, CEA and GPS, TPS and GPS. The Spearman’s rank correlation coefficient were 0.67 (P < 0.05), 0.61 (P < 0.05) and 0.55 (P < 0.05), respectively. Survival analyses showed GPS was an independent prognostic factor for advanced NSCLC. CYFRA21-1(>3.3 ng/ml) and TPS (>80 U/l) were related with the prognosis of advanced NSCLC by univariate analyses, but multivariate analyses showed CYFRA21-1, TPS and CEA were not the independent prognostic factors for advanced NSCLC. Our results showed GPS were positive correlated

Comparison of the Serum Tumor Markers S100 and Melanoma-inhibitory Activity (MIA) in the Monitoring of Patients with Metastatic Melanoma Receiving Vaccination Immunotherapy with Dendritic Cells.

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Uslu, Ugur; Schliep, Stefan; Schliep, Klaus; Erdmann, Michael; Koch, Hans-Uwe; Parsch, Hans; Rosenheinrich, Stina; Anzengruber, Doris; Bosserhoff, Anja Katrin; Schuler, Gerold; Schuler-Thurner, Beatrice

2017-09-01

In patients with melanoma, early dissemination via lymphatic and hematogenous routes is frequently seen. Thus, besides clinical follow-up examination and imaging, reliable melanoma-specific serological tumor markers are needed. We retrospectively compared two serum markers for melanoma, S100 and melanoma-inhibitory activity (MIA), for monitoring of patients with metastatic melanoma under either adjuvant or therapeutic vaccination immunotherapy with dendritic cells (DC). Serum was obtained from a total of 100 patients (28 patients in stage III and 72 patients in stage IV, according to the American Joint Committee on Cancer 2002) at regular intervals during therapy, accompanied by follow-up imaging. When relapse was detected, both markers often remained within normal range. In contrast, in patients with metastatic measurable disease receiving therapeutic and not adjuvant DC vaccination, an increase of both markers was a strong indicator for disease progression. When comparing both markers in the whole study population, MIA showed a superior sensitivity to detect disease progression. S100 and MIA are highly sensitive tumor markers for monitoring of patients with melanoma with current metastases, but less sensitive for monitoring of tumor-free patients. In the current study, MIA had a slightly superior sensitivity to detect progressive disease compared to S100 and seems to be more useful in monitoring of patients with metastatic melanoma receiving immunotherapy. Copyright© 2017, International Institute of Anticancer Research (Dr. George J. Delinasios), All rights reserved.

Eukaryotic elongation factor 2 is a prognostic marker and its kinase a potential therapeutic target in HCC.

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Pott, Leona L; Hagemann, Sascha; Reis, Henning; Lorenz, Kristina; Bracht, Thilo; Herold, Thomas; Skryabin, Boris V; Megger, Dominik A; Kälsch, Julia; Weber, Frank; Sitek, Barbara; Baba, Hideo A

2017-02-14

Hepatocellular carcinoma is a cancer with increasing incidence and largely refractory to current anticancer drugs. Since Sorafenib, a multikinase inhibitor has shown modest efficacy in advanced hepatocellular carcinoma additional treatments are highly needed. Protein phosphorylation via kinases is an important post-translational modification to regulate cell homeostasis including proliferation and apoptosis. Therefore kinases are valuable targets in cancer therapy. To this end we performed 2D differential gel electrophoresis and mass spectrometry analysis of phosphoprotein-enriched lysates of tumor and corresponding non-tumorous liver samples to detect differentially abundant phosphoproteins to screen for novel kinases as potential drug targets. We identified 34 differentially abundant proteins in phosphoprotein enriched lysates. Expression and distribution of the candidate protein eEF2 and its phosphorylated isoform was validated immunohistochemically on 78 hepatocellular carcinoma and non-tumorous tissue samples. Validation showed that total eEF2 and phosphorylated eEF2 at threonine 56 are prognostic markers for overall survival of HCC-patients. The activity of the regulating eEF2 kinase, compared between tumor and non-tumorous tissue lysates by in vitro kinase assays, is more than four times higher in tumor tissues. Functional analyzes regarding eEF2 kinase were performed in JHH5 cells with CRISPR/Cas9 mediated eEF2 kinase knock out. Proliferation and growth is decreased in eEF2 kinase knock out cells. eEF2 and phosphorylated eEF2 are prognostic markers for survival of hepatocellular carcinoma patients and the regulating eEF2 kinase is a potential drug target for tumor therapy.

Are there tumor suppressor genes on chromosome 4p in sporadic colorectal carcinoma?

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Zheng, Hai-Tao; Jiang, Li-Xin; Lv, Zhong-Chuan; Li, Da-Peng; Zhou, Chong-Zhi; Gao, Jian-Jun; He, Lin; Peng, Zhi-Hai

2008-01-07

To study the candidate tumor suppressor genes (TSG) on chromosome 4p by detecting the high frequency of loss of heterozygosity (LOH) in sporadic colorectal carcinoma in Chinese patients. Seven fluorescent labeled polymorphic microsatellite markers were analyzed in 83 cases of colorectal carcinoma and matched normal tissue DNA by PCR. PCR products were electrophoresed on an ABI 377 DNA sequencer. Genescan 3.7 and Genotype 3.7 software were used for LOH scanning and analysis. The same procedure was performed by the other six microsatellite markers spanning D4S3013 locus to make further detailed deletion mapping. Comparison between LOH frequency and clinicopathological factors was performed by c2 test. Data were collected from all informative loci. The average LOH frequency on 4p was 24.25%, and 42.3% and 35.62% on D4S405 and D4S3013 locus, respectively. Adjacent markers of D4S3013 displayed a low LOH frequency (4p15.2) and D4S405 (4p14) locus are detected. Candidate TSG, which is involved in carcinogenesis and progression of sporadic colorectal carcinoma on chromosome 4p, may be located between D4S3017 and D4S2933 (about 1.7 cm).

Interfractional Position Variation of Pancreatic Tumors Quantified Using Intratumoral Fiducial Markers and Daily Cone Beam Computed Tomography

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Horst, Astrid van der, E-mail: a.vanderhorst@amc.uva.nl [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Wognum, Silvia; Dávila Fajardo, Raquel; Jong, Rianne de [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Hooft, Jeanin E. van; Fockens, Paul [Department of Gastroenterology and Hepatology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands); Tienhoven, Geertjan van; Bel, Arjan [Department of Radiation Oncology, Academic Medical Center, University of Amsterdam, Amsterdam (Netherlands)

2013-09-01

Purpose: The aim of this study was to quantify interfractional pancreatic position variation using fiducial markers visible on daily cone beam computed tomography (CBCT) scans. In addition, we analyzed possible migration of the markers to investigate their suitability for tumor localization. Methods and Materials: For 13 pancreatic cancer patients with implanted Visicoil markers, CBCT scans were obtained before 17 to 25 fractions (300 CBCTs in total). Image registration with the reference CT was used to determine the displacement of the 2 to 3 markers relative to bony anatomy and to each other. We analyzed the distance between marker pairs as a function of time to identify marker registration error (SD of linear fit residuals) and possible marker migration. For each patient, we determined the mean displacement of markers relative to the reference CT (systematic position error) and the spread in displacements (random position error). From this, we calculated the group systematic error, Σ, and group random error, σ. Results: Marker pair distances showed slight trends with time (range, −0.14 to 0.14 mm/day), possibly due to tissue deformation, but no shifts that would indicate marker migration. The mean SD of the fit residuals was 0.8 mm. We found large interfractional position variations, with for 116 of 300 (39%) fractions a 3-dimensional vector displacement of >10 mm. The spread in displacement varied significantly (P<.01) between patients, from a vector range of 9.1 mm to one of 24.6 mm. For the patient group, Σ was 3.8, 6.6, and 3.5 mm; and σ was 3.6, 4.7 and 2.5 mm, in left–right, superior–inferior, and anterior–posterior directions, respectively. Conclusions: We found large systematic displacements of the fiducial markers relative to bony anatomy, in addition to wide distributions of displacement. These results for interfractional position variation confirm the potential benefit of using fiducial markers rather than bony anatomy for daily online

Clinically Meaningful Use of Blood Tumor Markers in Oncology.

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Holdenrieder, Stefan; Pagliaro, Lance; Morgenstern, David; Dayyani, Farshid

2016-01-01

Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs) were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.

Clinically Meaningful Use of Blood Tumor Markers in Oncology

Directory of Open Access Journals (Sweden)

Stefan Holdenrieder

2016-01-01

Full Text Available Before the introduction of modern imaging techniques and the recent developments in molecular diagnosis, tumor markers (TMs were among the few available diagnostic tools for the management of cancer patients. Easily obtained from serum or plasma samples, TMs are minimally invasive and convenient, and the associated costs are low. Single TMs were traditionally used but these have come under scrutiny due to their low sensitivity and specificity when used, for example, in a screening setting. However, recent research has shown superior performance using a combination of multiple TMs as a panel for assessment, or as part of validated algorithms that also incorporate other clinical factors. In addition, newer TMs have been discovered that have an increased sensitivity and specificity profile for defined malignancies. The aim of this review is to provide a concise overview of the appropriate uses of both traditional and newer TMs and their roles in diagnosis, prognosis, and the monitoring of patients in current clinical practice. We also look at the future direction of TMs and their integration with other diagnostic modalities and other emerging serum based biomarkers, such as circulating nucleic acids, to ultimately advance diagnostic performance and improve patient management.

Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

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Yang, Qian; Roehrl, Michael H.; Wang, Julia Y.

2018-01-01

We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins. PMID:29423100

[Prognostic and predictive molecular markers for urologic cancers].

Science.gov (United States)

Hartmann, A; Schlomm, T; Bertz, S; Heinzelmann, J; Hölters, S; Simon, R; Stoehr, R; Junker, K

2014-04-01

Molecular prognostic factors and genetic alterations as predictive markers for cancer-specific targeted therapies are used today in the clinic for many malignancies. In recent years, many molecular markers for urogenital cancers have also been identified. However, these markers are not clinically used yet. In prostate cancer, novel next-generation sequencing methods revealed a detailed picture of the molecular changes. There is growing evidence that a combination of classical histopathological and validated molecular markers could lead to a more precise estimation of prognosis, thus, resulting in an increasing number of patients with active surveillance as a possible treatment option. In patients with urothelial carcinoma, histopathological factors but also the proliferation of the tumor, mutations in oncogenes leading to an increasing proliferation rate and changes in genes responsible for invasion and metastasis are important. In addition, gene expression profiles which could distinguish aggressive tumors with high risk of metastasis from nonmetastasizing tumors have been recently identified. In the future, this could potentially allow better selection of patients needing systemic perioperative treatment. In renal cell carcinoma, many molecular markers that are associated with metastasis and survival have been identified. Some of these markers were also validated as independent prognostic markers. Selection of patients with primarily organ-confined tumors and increased risk of metastasis for adjuvant systemic therapy could be clinically relevant in the future.

Tumor budding is a strong and reproducible prognostic marker in T3N0 colorectal cancer.

LENUS (Irish Health Repository)

Wang, Lai Mun

2012-02-01

BACKGROUND: Tumor budding along the advancing front of colorectal adenocarcinoma is an early event in the metastatic process. A reproducible, prognostic budding scoring system based on outcomes in early stage colorectal cancer has not been established. DESIGN: One hundred twenty-eight T3N0M0 colorectal carcinoma patients with known outcome were identified. Tumor budding was defined as isolated tumor cells or clusters of <5 cells at the invasive tumor front. Tumor bud counts were generated in 5 regions at 200x by 2 pathologists (conventional bud count method). The median bud count per case was used to divide cases into low (median=0) and high budding (median > or =1) groups. Forty cases were reevaluated to assess reproducibility using the conventional and a novel rapid bud count method. RESULTS: Fifty-seven (45%) carcinomas had high and 71 (55%) had low budding scores. High budding was associated with an infiltrative growth pattern (P<0.0001) and lymphovascular invasion (P=0.005). Five-year cancer-specific survival was significantly poorer in high compared with low budding groups: 63% versus 91%, respectively, P<0.0001. Multivariate analysis demonstrated tumor budding to be independently prognostic (hazard ratio=4.76, P<0.001). Interobserver agreement was at least equivalent comparing the conventional to the rapid bud count methods: 87.5% agreement (kappa=0.75) versus 92.5% agreement (kappa=0.85), respectively. CONCLUSIONS: Tumor budding is a strong, reproducible, and independent prognostic marker of outcome that is easily assessed on hematoxylin and eosin slides. This may be useful for identifying the subset of T3N0M0 patients at high risk of recurrence who may benefit from adjuvant therapy.

Rrp1b, a new candidate susceptibility gene for breast cancer progression and metastasis.

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Nigel P S Crawford

2007-11-01

Full Text Available A novel candidate metastasis modifier, ribosomal RNA processing 1 homolog B (Rrp1b, was identified through two independent approaches. First, yeast two-hybrid, immunoprecipitation, and functional assays demonstrated a physical and functional interaction between Rrp1b and the previous identified metastasis modifier Sipa1. In parallel, using mouse and human metastasis gene expression data it was observed that extracellular matrix (ECM genes are common components of metastasis predictive signatures, suggesting that ECM genes are either important markers or causal factors in metastasis. To investigate the relationship between ECM genes and poor prognosis in breast cancer, expression quantitative trait locus analysis of polyoma middle-T transgene-induced mammary tumor was performed. ECM gene expression was found to be consistently associated with Rrp1b expression. In vitro expression of Rrp1b significantly altered ECM gene expression, tumor growth, and dissemination in metastasis assays. Furthermore, a gene signature induced by ectopic expression of Rrp1b in tumor cells predicted survival in a human breast cancer gene expression dataset. Finally, constitutional polymorphism within RRP1B was found to be significantly associated with tumor progression in two independent breast cancer cohorts. These data suggest that RRP1B may be a novel susceptibility gene for breast cancer progression and metastasis.

Predictive markers of efficacy for an angiopoietin-2 targeting therapeutic in xenograft models.

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Gallen Triana-Baltzer

Full Text Available The clinical efficacy of anti-angiogenic therapies has been difficult to predict, and biomarkers that can predict responsiveness are sorely needed in this era of personalized medicine. CVX-060 is an angiopoietin-2 (Ang2 targeting therapeutic, consisting of two peptides that bind Ang2 with high affinity and specificity, covalently fused to a scaffold antibody. In order to optimize the use of this compound in the clinic the construction of a predictive model is described, based on the efficacy of CVX-060 in 13 cell line and 2 patient-derived xenograft models. Pretreatment size tumors from each of the models were profiled for the levels of 27 protein markers of angiogenesis, SNP haplotype in 5 angiogenesis genes, and somatic mutation status for 11 genes implicated in tumor growth and/or vascularization. CVX-060 efficacy was determined as tumor growth inhibition (TGI% at termination of each study. A predictive statistical model was constructed based on the correlation of these efficacy data with the marker profiles, and the model was subsequently tested by prospective analysis in 11 additional models. The results reveal a range of CVX-060 efficacy in xenograft models of diverse tissue types (0-64% TGI, median = 27% and define a subset of 3 proteins (Ang1, EGF, Emmprin, the levels of which may be predictive of TGI by Ang2 blockade. The direction of the associations is such that better efficacy correlates with high levels of target and low levels of compensatory/antagonizing molecules. This effort has revealed a set of candidate predictive markers for CVX-060 efficacy that will be further evaluated in ongoing clinical trials.

Genome‐wide DNA methylation analysis identifies MEGF10 as a novel epigenetically repressed candidate tumor suppressor gene in neuroblastoma

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Charlet, Jessica; Tomari, Ayumi; Dallosso, Anthony R.; Szemes, Marianna; Kaselova, Martina; Curry, Thomas J.; Almutairi, Bader; Etchevers, Heather C.; McConville, Carmel; Malik, Karim T. A.

2016-01-01

Neuroblastoma is a childhood cancer in which many children still have poor outcomes, emphasising the need to better understand its pathogenesis. Despite recent genome‐wide mutation analyses, many primary neuroblastomas do not contain recognizable driver mutations, implicating alternate molecular pathologies such as epigenetic alterations. To discover genes that become epigenetically deregulated during neuroblastoma tumorigenesis, we took the novel approach of comparing neuroblastomas to neural crest precursor cells, using genome‐wide DNA methylation analysis. We identified 93 genes that were significantly differentially methylated of which 26 (28%) were hypermethylated and 67 (72%) were hypomethylated. Concentrating on hypermethylated genes to identify candidate tumor suppressor loci, we found the cell engulfment and adhesion factor gene MEGF10 to be epigenetically repressed by DNA hypermethylation or by H3K27/K9 methylation in neuroblastoma cell lines. MEGF10 showed significantly down‐regulated expression in neuroblastoma tumor samples; furthermore patients with the lowest‐expressing tumors had reduced relapse‐free survival. Our functional studies showed that knock‐down of MEGF10 expression in neuroblastoma cell lines promoted cell growth, consistent with MEGF10 acting as a clinically relevant, epigenetically deregulated neuroblastoma tumor suppressor gene. © 2016 The Authors. Molecular Carcinogenesis Published by Wiley Periodicals, Inc. PMID:27862318

Effects of oxaliplatin, leucovorin and fluorouracil on serum tumor markers, VEGF, CRP and matrix metalloproteinases in patients with advanced esophageal cancer

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Lei Lei

2017-08-01

Full Text Available Objective: To investigate the effects of oxaliplatin, leucovorin and fluorouracil on serum tumor markers, VEGF, CRP and matrix metalloproteinases in patients with advanced esophageal cancer. Methods: From March 2012 to March 2017 a total of 248 patients with advanced esophageal cancer were selected as the study subjects. According to random data table, they were divided into control group (n=123 and observation group (n=125 according to random data table. The control group was treated with cisplatin combined with fluorouracil, leucovorin chemotherapy, and patients in the observation group received oxaliplatin, leucovorin and fluorouracil chemotherapy, all patients were treated for 2 cycles. The changes of serum tumor markers, VEGF, CRP and matrix metalloproteinase levels in the two groups before and after treatment was compared. Results: Before treatment, there was no significant difference of the levels of serum CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 between the control group and the observation group. Compared with the group before treatment, the levels of CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 in the two groups were significantly lower. After treatment, the level of CA125, CA19-9, CEA, VEGF, CRP, MMP-2 and MMP-9 in the observation group was significantly lower than those of the control group. Conclusion: Oxaliplatin, leucovorin and fluorouracil chemotherapy can effectively reduce the levels of serum tumor markers, VEGF, CRP and matrix metalloproteinase in patients with advanced esophageal cancer, it has important clinical value.

CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

International Nuclear Information System (INIS)

Olsson, Eleonor; Lövgren, Kristina; Fernö, Mårten; Grabau, Dorthe; Borg, Åke; Hegardt, Cecilia; Honeth, Gabriella; Bendahl, Pär-Ola; Saal, Lao H; Gruvberger-Saal, Sofia; Ringnér, Markus; Vallon-Christersson, Johan; Jönsson, Göran; Holm, Karolina

2011-01-01

The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC) compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44 + /CD24 - phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S) isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in specific oncogenic signaling pathways. Efforts to link CD44 to

CD44 isoforms are heterogeneously expressed in breast cancer and correlate with tumor subtypes and cancer stem cell markers

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Vallon-Christersson Johan

2011-09-01

Full Text Available Abstract Background The CD44 cell adhesion molecule is aberrantly expressed in many breast tumors and has been implicated in the metastatic process as well as in the putative cancer stem cell (CSC compartment. We aimed to investigate potential associations between alternatively spliced isoforms of CD44 and CSCs as well as to various breast cancer biomarkers and molecular subtypes. Methods We used q-RT-PCR and exon-exon spanning assays to analyze the expression of four alternatively spliced CD44 isoforms as well as the total expression of CD44 in 187 breast tumors and 13 cell lines. ALDH1 protein expression was determined by IHC on TMA. Results Breast cancer cell lines showed a heterogeneous expression pattern of the CD44 isoforms, which shifted considerably when cells were grown as mammospheres. Tumors characterized as positive for the CD44+/CD24- phenotype by immunohistochemistry were associated to all isoforms except the CD44 standard (CD44S isoform, which lacks all variant exons. Conversely, tumors with strong expression of the CSC marker ALDH1 had elevated expression of CD44S. A high expression of the CD44v2-v10 isoform, which retain all variant exons, was correlated to positive steroid receptor status, low proliferation and luminal A subtype. The CD44v3-v10 isoform showed similar correlations, while high expression of CD44v8-v10 was correlated to positive EGFR, negative/low HER2 status and basal-like subtype. High expression of CD44S was associated with strong HER2 staining and also a subgroup of basal-like tumors. Unsupervised hierarchical cluster analysis of CD44 isoform expression data divided tumors into four main clusters, which showed significant correlations to molecular subtypes and differences in 10-year overall survival. Conclusions We demonstrate that individual CD44 isoforms can be associated to different breast cancer subtypes and clinical markers such as HER2, ER and PgR, which suggests involvement of CD44 splice variants in

Detection of Tumor Markers in Prostate Cancer and Comparison of Sensitivity between Real Time and Nested PCR

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Matsuoka, Takayuki; Shigemura, Katsumi; Yamamichi, Fukashi; Fujisawa, Masato; Kawabata, Masato; Shirakawa, Toshiro

2012-01-01

The objective of this study is to investigate and compare the sensitivity in conventional PCR, quantitative real time PCR, nested PCR and western blots for detection of prostate cancer tumor markers using prostate cancer (PCa) cells. We performed conventional PCR, quantitative real time PCR, nested PCR, and western blots using 5 kinds of PCa cells. Prostate specific antigen (PSA), prostate specific membrane antigen (PSMA), and androgen receptor (AR) were compared for their detection sensitivi...

Proteomic profiling reveals candidate markers for arsenic-induced skin keratosis.

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Guo, Zhiling; Hu, Qin; Tian, Jijing; Yan, Li; Jing, Chuanyong; Xie, Heidi Qunhui; Bao, Wenjun; Rice, Robert H; Zhao, Bin; Jiang, Guibin

2016-11-01

Proteomics technology is an attractive biomarker candidate discovery tool that can be applied to study large sets of biological molecules. To identify novel biomarkers and molecular targets in arsenic-induced skin lesions, we have determined the protein profile of arsenic-affected human epidermal stratum corneum by shotgun proteomics. Samples of palm and foot sole from healthy subjects were analyzed, demonstrating similar protein patterns in palm and sole. Samples were collected from the palms of subjects with arsenic keratosis (lesional and adjacent non-lesional samples) and arsenic-exposed subjects without lesions (normal). Samples from non-exposed healthy individuals served as controls. We found that three proteins in arsenic-exposed lesional epidermis were consistently distinguishably expressed from the unaffected epidermis. One of these proteins, the cadherin-like transmembrane glycoprotein, desmoglein 1 (DSG1) was suppressed. Down-regulation of DSG1 may lead to reduced cell-cell adhesion, resulting in abnormal epidermal differentiation. The expression of keratin 6c (KRT6C) and fatty acid binding protein 5 (FABP5) were significantly increased. FABP5 is an intracellular lipid chaperone that plays an essential role in fatty acid metabolism in human skin. This raises a possibility that overexpression of FABP5 may affect the proliferation or differentiation of keratinocytes by altering lipid metabolism. KRT6C is a constituent of the cytoskeleton that maintains epidermal integrity and cohesion. Abnormal expression of KRT6C may affect its structural role in the epidermis. Our findings suggest an important approach for future studies of arsenic-mediated toxicity and skin cancer, where certain proteins may represent useful biomarkers of early diagnoses in high-risk populations and hopefully new treatment targets. Further studies are required to understand the biological role of these markers in skin pathogenesis from arsenic exposure. Copyright © 2016 Elsevier Ltd

Diagnostic values of serum tumor markers Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP in oral/oropharyngeal squamous cell carcinoma

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Yuan CS

2016-06-01

Full Text Available Chuanshu Yuan, Kai Yang, Hong Tang, Dan Chen Department of Oral and Maxillofacial Surgery, the First Affiliated Hospital of Chongqing Medical University, Chongqing, People’s Republic of China Background: At present, the research on serum tumor markers in the early diagnosis of malignant tumors has aroused widespread concern. The aim of this study was to investigate the diagnostic values of serum tumor markers cytokeratin 19 fragment (Cyfra21-1, squamous cell carcinoma antigen (SCCAg, ferritin, carcinoembryonic antigen (CEA, carbohydrate antigen 19-9 (CA19-9, and α-fetoprotein (AFP for patients with oral/oropharyngeal squamous carcinoma (OSCC/OPSCC. Methods: One hundred and sixty-nine cases of patients with OSCC/OPSCC as the experimental group, 86 cases of oral benign tumor patients as the control group, and 30 cases of healthy people as the normal control group were studied. The levels of serum Cyfra21-1, SCCAg, ferritin, CEA, CA19-9, and AFP were measured using electrochemiluminescence immunoassay. Results: The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in patients with OSCC/OPSCC were significantly higher than those of benign tumor and healthy control group (P<0.05. The levels of CA19-9 and AFP showed no significant difference between patients with OSCC/OPSCC, benign tumor, and healthy group (P>0.05. The level of serum Cyfra21-1 in patients with early OSCC/OPSCC (stage I + II was significantly higher than that of benign tumor and healthy control group (P<0.05. However, the levels of serum SCCAg, ferritin, CEA, CA19-9, and AFP showed no significant difference between patients with early OSCC/OPSCC, benign tumor, and healthy control group (P>0.05. The levels of serum Cyfra21-1, SCCAg, ferritin, and CEA in the middle-late stage of patients with OSCC/OPSCC (stage III + IV were significantly higher than those of patients with the early OSCC/OPSCC, benign tumor, and healthy control group (P<0.05. The diagnostic cutoff levels of Cyfra21

Duct- and Acinar-Derived Pancreatic Ductal Adenocarcinomas Show Distinct Tumor Progression and Marker Expression

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Rute M.M. Ferreira

2017-10-01

Full Text Available The cell of origin of pancreatic ductal adenocarcinoma (PDAC has been controversial. Here, we show that identical oncogenic drivers trigger PDAC originating from both ductal and acinar cells with similar histology but with distinct pathophysiology and marker expression dependent on cell of origin. Whereas acinar-derived tumors exhibited low AGR2 expression and were preceded by pancreatic intraepithelial neoplasias (PanINs, duct-derived tumors displayed high AGR2 and developed independently of a PanIN stage via non-mucinous lesions. Using orthotopic transplantation and chimera experiments, we demonstrate that PanIN-like lesions can be induced by PDAC as bystanders in adjacent healthy tissues, explaining the co-existence of mucinous and non-mucinous lesions and highlighting the need to distinguish between true precursor PanINs and PanIN-like bystander lesions. Our results suggest AGR2 as a tool to stratify PDAC according to cell of origin, highlight that not all PanIN-like lesions are precursors of PDAC, and add an alternative progression route to the current model of PDAC development.

Molecular Markers for Prostate Cancer in Formalin-Fixed Paraffin-Embedded Tissues

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Tamara Sequeiros

2013-01-01

Full Text Available Prostate cancer (PCa is the most frequently diagnosed type of cancer in developed countries. The decisive method of diagnosis is based on the results of biopsies, morphologically evaluated to determine the presence or absence of cancer. Although this approach leads to a confident diagnosis in most cases, it can be improved by using the molecular markers present in the tissue. Both miRNAs and proteins are considered excellent candidates for biomarkers in formalin-fixed paraffin-embedded (FFPE tissues, due to their stability over long periods of time. In the last few years, a concerted effort has been made to develop the necessary tools for their reliable measurement in these types of samples. Furthermore, the use of these kinds of markers may also help in establishing tumor grade and aggressiveness, as well as predicting the possible outcomes in each particular case for the different treatments available. This would aid clinicians in the decision-making process. In this review, we attempt to summarize and discuss the potential use of microRNA and protein profiles in FFPE tissue samples as markers to better predict PCa diagnosis, progression, and response to therapy.

Analyses of susceptibility to radiation-induced tumors: Prkdc, a candidate modifier of lymphomas

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Mori, Nobuko; Okumoto, Masaaki; Nakao, Ren

2003-01-01

BALB/cHeA (BALB/c) mice are susceptible to radiation-induced lymphomas, while STS/A (STS) mice are resistant. To analyze the difference in susceptibility between these two strains of mice, we have performed 3 independent studies: 1) mapping of apoptosis susceptibility gene Rapopl (chromosome 16) and identification of Prkdc as a candidate modifier of apoptosis as well as lymphomas, 2) analysis of congenic lines for Lyr, a gene responsible for the lymphoma resistance of STS mice on chromosome 4, 3) genetic analyses of lymphoma susceptibility using a backcross [(BALB/c x STS)F 1 x STS]. Analysis of Rapopl congenic lines indicated a minor contribution of the STS allele at the Rapopl (Prkdc) locus to the lymphoma resistance of STS mice. On the other hand, homozygous STS alleles at Lyr had a substantial, but less potent, effect on radiation lymphomagenesis. Furthermore, there was no single marker where the potent resistance of the STS mice was achieved with the homozygous STS alleles. These results suggest potential involvement of another loci in the resistance of STS mice. (author)

Clinical significance of combined determination of several tumor markers (including CYFRA21-1, NSE, CA-50 and CEA) in patients with pulmonary cancer

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Zhu Mingfeng; Wen Chijun; Zhu Cuiying

2005-01-01

Objective: To enhance the diagnosis of pulmonary cancer by determination of optimal combinations of various tumor markers. Methods: Serum CYFRA 21-1 , NSE, CA-50 (with RIA) and CEA (with CLIA) contents were determined in 107 patients with various types of pulmonary cancers, 66 patients with various benign pulmonary diseases and 59 controls. Results: It was revealed that CYFRA 21-1 determination was most sensitive for detection of squamous cell carcinoma. The same was true for CEA in the detection of adenocarcinoma. NSE determination was very specific for small cell carcinoma. Combined determinations of either CYFRA 21- l + NSE or CYFRA 21-1 + NSE + CEA were excellent for general screening. Conclusion: Combined determination of these tumor markers could be applied expediently as supplementary diagnostic measure for pulmonary malignancies. (authors)

CEA A BIOCHEMICAL MARKER FOR DIAGNOSIS AND PROGNOSIS OF GASTROINTESTINAL CANCER

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Prathibha; Vishnu Datt

2016-01-01

Serum tumor markers (TM) are widely used for diagnosis and monitoring of treatment of cancer. Carcinoembryonic Antigen (CEA) is one of the most widely investigated tumor markers in gastrointestinal (GI) cancers. Estimation of circulating tumor markers is a non- invasive quantitative method. Serum levels of CEA were studied for diagnosis and prognosis of gastrointestinal malignancies. 140 subjects were undertaken out of which 35 normal and remaining 105 were GI cancer patients. Ser...

Identification of a panel of sensitive and specific DNA methylation markers for lung adenocarcinoma

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Hagen Jeffrey A

2007-10-01

Full Text Available Abstract Background Lung cancer is the number one cancer killer of both men and women in the United States. Three quarters of lung cancer patients are diagnosed with regionally or distantly disseminated disease; their 5-year survival is only 15%. DNA hypermethylation at promoter CpG islands shows great promise as a cancer-specific marker that would complement visual lung cancer screening tools such as spiral CT, improving early detection. In lung cancer patients, such hypermethylation is detectable in a variety of samples ranging from tumor material to blood and sputum. To date the penetrance of DNA methylation at any single locus has been too low to provide great clinical sensitivity. We used the real-time PCR-based method MethyLight to examine DNA methylation quantitatively at twenty-eight loci in 51 primary human lung adenocarcinomas, 38 adjacent non-tumor lung samples, and 11 lung samples from non-lung cancer patients. Results We identified thirteen loci showing significant differential DNA methylation levels between tumor and non-tumor lung; eight of these show highly significant hypermethylation in adenocarcinoma: CDH13, CDKN2A EX2, CDX2, HOXA1, OPCML, RASSF1, SFPR1, and TWIST1 (p-value Conclusion The identification of eight CpG island loci showing highly significant hypermethylation in lung adenocarcinoma provides strong candidates for evaluation in patient remote media such as plasma and sputum. The four most highly ranked loci, CDKN2A EX2, CDX2, HOXA1 and OPCML, which show significant DNA methylation even in stage IA tumor samples, merit further investigation as some of the most promising lung adenocarcinoma markers identified to date.

High CD49f expression is associated with osteosarcoma tumor progression: a study using patient-derived primary cell cultures.

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Penfornis, Patrice; Cai, David Z; Harris, Michael R; Walker, Ryan; Licini, David; Fernandes, Joseph D A; Orr, Griffin; Koganti, Tejaswi; Hicks, Chindo; Induru, Spandana; Meyer, Mark S; Khokha, Rama; Barr, Jennifer; Pochampally, Radhika R

2014-08-01

Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49f(hi) /CD90(lo) cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49f(hi) /CD90(lo) cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs. © 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Peculiarities in the CT findings of germ cell tumors in various tumor localizations

International Nuclear Information System (INIS)

Tazoe, Makoto; Miyagami, Mitsusuke; Tsubokawa, Takashi

1991-01-01

The CT findings of 17 germ cell tumors were studied in relation to the locations of the tumor, the pathological diagnoses, and the tumor markers (AFP and HCG). Generally, the CT findings of germ cell tumors depended on the pathological diagnoses more strongly than on the location of the tumors. On plain CT of 7 germ cell tumors in the pineal region, all of them demonstrated heterogeneous findings. Hydrocephalus was seen in 6 cases (86%) and calcification in 6 cases (86%) of the germ cell tumors in the pineal region. Calcification and hydrocephalus that appeared more often than in other regions were characteristic of germ cell tumors of the pineal region. The germ cell tumors in the basal ganglia had a slightly homogenous high density, with small cysts and calcification in most of them on plain CT. On enhanced CT, the tumors were moderately enhanced in all cases located in the basal ganglia. Four cases of germ cell tumors located in the basal ganglia revealed the dilatation of lateral ventricle due to hemispheric atrophy in the tumor side. The germ cell tumors showing an increase in the tumor markers such as AFP and HCG, which were usually malignant germ cell tumors, were strongly enhanced on enhanced CT. (author)

Tumor-specific loss of 11p15.5 alleles in del11p13 Wilms tumor and in familial adrenocortical carcinoma

International Nuclear Information System (INIS)

Henry, I.; Grandjouan, S.; Couillin, P.

1989-01-01

The authors have compared constitutional and tumor genotypes in nine cases of hereditary Wilms tumor (WT) and in three unrelated cases of familial adrenocortical carcinoma (ADCC). Since susceptibility to these tumors can be observed in malformation syndromes associated with a constitutional deletion of band 11p13 (WT) and with a constitutional duplication of band 11p15.5 (WT, ADCC), they investigated these two candidate regions by using 11p polymorphic markers. As expected, somatic chromosomal events, resulting in a loss of heterozygosity limited to region 11p15.5, were observed in the tumor of two familial cases of adrenocortical carcinoma. Surprisingly, however, analysis of the WT of two patients with a constitutional deletion of band 11p13, associated with aniridia, genitourinary abnormalities, and mental retardation (WAGR syndrome), revealed a loss of heterozygosity limited to region 11p15.5. These data therefore suggest that observation of a specific loss of heterozygosity may not necessarily point to the site of the initial germinal mutation. Together with previous similar observations of a loss of heterozygosity limited to 11p15.5 in breast cancer and in rhabdomyosarcoma, the data suggest that region 11p15.5 may carry a non-tissue-specific gene that could be involved in genetic predisposition, in tumor progression, or in both

Molecular markers in glioma.

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Ludwig, Kirsten; Kornblum, Harley I

2017-09-01

Gliomas are the most malignant and aggressive form of brain tumors, and account for the majority of brain cancer related deaths. Malignant gliomas, including glioblastoma are treated with radiation and temozolomide, with only a minor benefit in survival time. A number of advances have been made in understanding glioma biology, including the discovery of cancer stem cells, termed glioma stem cells (GSC). Some of these advances include the delineation of molecular heterogeneity both between tumors from different patients as well as within tumors from the same patient. Such research highlights the importance of identifying and validating molecular markers in glioma. This review, intended as a practical resource for both clinical and basic investigators, summarizes some of the more well-known molecular markers (MGMT, 1p/19q, IDH, EGFR, p53, PI3K, Rb, and RAF), discusses how they are identified, and what, if any, clinical relevance they may have, in addition to discussing some of the specific biology for these markers. Additionally, we discuss identification methods for studying putative GSC's (CD133, CD15, A2B5, nestin, ALDH1, proteasome activity, ABC transporters, and label-retention). While much research has been done on these markers, there is still a significant amount that we do not yet understand, which may account for some conflicting reports in the literature. Furthermore, it is unlikely that the investigator will be able to utilize one single marker to prospectively identify and isolate GSC from all, or possibly, any gliomas.