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Sample records for primary tumor circulate

  1. Mutational analysis of circulating tumor cells from colorectal cancer patients and correlation with primary tumor tissue.

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    Anna Lyberopoulou

    Full Text Available Circulating tumor cells (CTCs provide a non-invasive accessible source of tumor material from patients with cancer. The cellular heterogeneity within CTC populations is of great clinical importance regarding the increasing number of adjuvant treatment options for patients with metastatic carcinomas, in order to eliminate residual disease. Moreover, the molecular profiling of these rare cells might lead to insight on disease progression and therapeutic strategies than simple CTCs counting. In the present study we investigated the feasibility to detect KRAS, BRAF, CD133 and Plastin3 (PLS3 mutations in an enriched CTCs cell suspension from patients with colorectal cancer, with the hypothesis that these genes` mutations are of great importance regarding the generation of CTCs subpopulations. Subsequently, we compared CTCs mutational status with that of the corresponding primary tumor, in order to access the possibility of tumor cells characterization without biopsy. CTCs were detected and isolated from blood drawn from 52 colorectal cancer (CRC patients using a quantum-dot-labelled magnetic immunoassay method. Mutations were detected by PCR-RFLP or allele-specific PCR and confirmed by direct sequencing. In 52 patients, discordance between primary tumor and CTCs was 5.77% for KRAS, 3.85% for BRAF, 11.54% for CD133 rs3130, 7.69% for CD133 rs2286455 and 11.54% for PLS3 rs6643869 mutations. Our results support that DNA mutational analysis of CTCs may enable non-invasive, specific biomarker diagnostics and expand the scope of personalized medicine for cancer patients.

  2. The efficacy of lapatinib in metastatic breast cancer with HER2 non-amplified primary tumors and EGFR positive circulating tumor cells: a proof-of-concept study.

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    Justin Stebbing

    Full Text Available Analysis of circulating tumor cells (CTCs provides real-time measures of cancer sub-populations with potential for CTC-directed therapeutics. We examined whether lapatinib which binds both HER2 and EGFR could induce depletion of the EGFR-positive pool of CTCs, which may in turn lead to clinical benefits.Patients with metastatic breast cancer and HER2 non-amplified primary tumors with EGFR-positive CTCs were recruited and lapatinib 1500 mg daily was administered, in a standard two step phase 2 trial.There were no responses leading to termination at the first analysis with 16 patients recruited out of 43 screened. In 6 out of 14 (43% individuals eligible for the efficacy analysis, a decrease in CTCs was observed with most of these having a greater decrease in their EGFR-positive CTC pool.This is one of the first studies of CTC-directed therapeutics and suggests that lapatinib monotherapy is not having any demonstrable clinical effects by reducing the EGFR-positive pool of CTCs in HER2 non-amplified primary tumors. Our attempt to expand the pool of patients eligible for a targeted therapy was unsuccessful; the role of clonal populations in cancer biology and therapeutic strategies to control them will require extensive evaluation in years to come.Clinical trials.gov NCT00820924.

  3. Evaluation of Two Different Analytical Methods for Circulating Tumor Cell Detection in Peripheral Blood of Patients with Primary Breast Cancer

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    B. A. S. Jaeger

    2014-01-01

    Full Text Available Background. Evidence is accumulating that circulating tumor cells (CTC out of peripheral blood can serve as prognostic marker not only in metastatic but also in early breast cancer (BC. Various methods are available to detect CTC. Comparisons between the different techniques, however, are rare. Material and Methods. We evaluate two different methods for CTC enrichment and detection in primary BC patients: the FDA-approved CellSearch System (CSS; Veridex, Warren, USA and a manual immunocytochemistry (MICC. The cut-off value for positivity was ≥1 CTC. Results. The two different nonoverlapping patient cohorts evaluated with one or the other method were well balanced regarding common clinical parameters. Before adjuvant CHT 21.1% (416 out of 1972 and 20.6% (247 out of 1198 of the patients were CTC-positive, while after CHT 22.5% (359 out of 1598 and 16.6% (177 out of 1066 of the patients were CTC-positive using CSS or MICC, respectively. CTC positivity rate before CHT was thus similar and not significantly different (P=0.749, while CTC positivity rate immediately after CHT was significantly lower using MICC compared to CSS (P<0.001. Conclusion. Using CSS or MICC for CTC detection, we found comparable prevalence of CTC before but not after adjuvant CHT.

  4. Brain tumor - primary - adults

    Science.gov (United States)

    ... Vestibular schwannoma (acoustic neuroma) - adults; Meningioma - adults; Cancer - brain tumor (adults) ... Primary brain tumors include any tumor that starts in the brain. Primary brain tumors can start from brain cells, ...

  5. [Circulating tumor cells: cornerstone of personalized medicine].

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    Rafii, A; Vidal, F; Rathat, G; Alix-Panabières, C

    2014-11-01

    Cancer treatment has evolved toward personalized medicine. It is mandatory for clinicians to ascertain tumor biological features in order to optimize patients' treatment. Identification and characterization of circulating tumor cells demonstrated a prognostic value in many solid tumors. Here, we describe the main technologies for identification and characterization of circulating tumor cells and their clinical application in gynecologic and breast cancers. Copyright © 2014. Published by Elsevier Masson SAS.

  6. Microfluidic Platform for Circulating Tumor Cells Isolation

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    Figueras-Mari, I.; Rodriguez-Trujillo, L.; Samitier-Marti, J.

    2016-07-01

    Circulating tumor cells (CTCs) are released from primary tumors into the bloodstream and transported to distant organs, promoting metastasis, which is known to be responsible for most cancer‐related deaths. Currently tumors are not found until symptoms appear or by chance when the patient undergoes a medical test, which in both situations can be too late. Once a tumor is found it is studied from tissue samples obtained directly from the patient in an invasive way. This invasive procedure is known as biopsy and apart from being invasive, it is costly, time consuming and can sometimes be painful and even risky for the patients’ health condition. Therefore, CTCs detection in blood also addressed as “liquid biopsy” would be very useful because by running routine blood analysis CTCs could be detected and collected suggesting tumor presence. However, due to the scarce presence in blood of these cells and to the huge amount of contamination from other cellular components a perfect method providing good capture and purity of CTCs has not been developed yet. In this project, a spiral size sorter microfluidic device has been manufactured and tested in order to determine its performance and limitations. Device performance was tested with different dilutions of healthy donor blood samples mixed with 30 micron particles simulating CTCs. The results obtained from these experiments show very good CTC recovery of up to 100% and the depletion of blood cellular components is around 99.9%. (Author)

  7. Multiple Primary Tumors

    African Journals Online (AJOL)

    2017-12-05

    Dec 5, 2017 ... Multiple primary tumors occur in clinical practice causing diagnostic dilemma. It is not very .... was estrogen receptor negative, progesterone receptor negative, and ... cervical, ovarian, and urinary bladder cancers. Multiple.

  8. Multiple Primary Tumors

    African Journals Online (AJOL)

    2018-02-07

    Feb 7, 2018 ... breast and ascending colon. KEYWORDS: Carcinoid, colorectal cancer, metachronous, synchronous. Multiple Primary Tumors. MA Adeyanju, AA Ilori. Address for correspondence: Dr. MA Adeyanju,. Department of Surgery, Federal Medical Centre, Ebute Metta,. Lagos, Nigeria. E-mail: mbadeyanju@yahoo.

  9. Circulating tumor cells: utopia or reality?

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    Conteduca, Vincenza; Zamarchi, Rita; Rossi, Elisabetta; Condelli, Valentina; Troiani, Laura; Aieta, Michele

    2013-09-01

    Circulating tumor cells (CTCs) could be considered a sign of tumor aggressiveness, but highly sensitive and specific methods of CTC detection are necessary owing to the rarity and heterogeneity of CTCs in peripheral blood. This review summarizes recent studies on tumor biology, with particular attention to the metastatic cascade, and the molecular characterization and clinical significance of CTCs. Recent technological approaches to enrich and detect these cells and challenges of CTCs for individualized cancer treatment are also discussed. This review also provides an insight into the positive and negative features of the future potential applications of CTC detection, which sometimes remains still a 'utopia', but its actual utility remains among the fastest growing research fields in oncology.

  10. Circulating Tumor Cells in Prostate Cancer

    International Nuclear Information System (INIS)

    Hu, Brian; Rochefort, Holly; Goldkorn, Amir

    2013-01-01

    Circulating tumor cells (CTCs) can provide a non-invasive, repeatable snapshot of an individual patient’s tumor. In prostate cancer, CTC enumeration has been extensively studied and validated as a prognostic tool and has received FDA clearance for use in monitoring advanced disease. More recently, CTC analysis has been shifting from enumeration to more sophisticated molecular characterization of captured cells, which serve as a “liquid biopsy” of the tumor, reflecting molecular changes in an individual’s malignancy over time. Here we will review the main CTC studies in advanced and localized prostate cancer, highlighting the important gains as well as the challenges posed by various approaches, and their implications for advancing prostate cancer management

  11. Circulating Tumor Cells Measurements in Hepatocellular Carcinoma

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    Franck Chiappini

    2012-01-01

    Full Text Available Liver cancer is the fifth most common cancer in men and the seventh in women. During the past 20 years, the incidence of HCC has tripled while the 5-year survival rate has remained below 12%. The presence of circulating tumor cells (CTC reflects the aggressiveness nature of a tumor. Many attempts have been made to develop assays that reliably detect and enumerate the CTC during the development of the HCC. In this case, the challenges are (1 there are few markers specific to the HCC (tumor cells versus nontumor cells and (2 they can be used to quantify the number of CTC in the bloodstream. Another technical challenge consists of finding few CTC mixed with million leukocytes and billion erythrocytes. CTC detection and identification can be used to estimate prognosis and may serve as an early marker to assess antitumor activity of treatment. CTC can also be used to predict progression-free survival and overall survival. CTC are an interesting source of biological information in order to understand dissemination, drug resistance, and treatment-induced cell death. Our aim is to review and analyze the different new methods existing to detect, enumerate, and characterize the CTC in the peripheral circulation of patients with HCC.

  12. Clinical applications of circulating tumor DNA and circulating tumor cells in pancreatic cancer.

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    Riva, Francesca; Dronov, Oleksii I; Khomenko, Dmytro I; Huguet, Florence; Louvet, Christophe; Mariani, Pascale; Stern, Marc-Henri; Lantz, Olivier; Proudhon, Charlotte; Pierga, Jean-Yves; Bidard, Francois-Clement

    2016-03-01

    Pancreatic ductal adenocarcinoma (PDAC) is the most frequent pancreatic cancer type and is characterized by a dismal prognosis due to late diagnosis, local tumor invasion, frequent distant metastases and poor sensitivity to current therapy. In this context, circulating tumor cells and circulating tumor DNA constitute easily accessible blood-borne tumor biomarkers that may prove their clinical interest for screening, early diagnosis and metastatic risk assessment of PDAC. Moreover these markers represent a tool to assess PDAC mutational landscape. In this review, together with key biological findings, we summarize the clinical results obtained using "liquid biopsies" at the different stages of the disease, for early and metastatic diagnosis as well as monitoring during therapy. Copyright © 2016 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  13. Circulating Tumor Cells, Enumeration and Beyond

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    Hou, Jian-Mei [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Krebs, Matthew [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Ward, Tim; Morris, Karen; Sloane, Robert [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); Blackhall, Fiona [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom); Christie Hospital Foundation NHS Trust, Manchester M20 4BX (United Kingdom); Dive, Caroline, E-mail: cdive@picr.man.ac.uk [Clinical and Experimental Pharmacology Group, Paterson Institute for Cancer Research, Manchester M20 4BX (United Kingdom); School of Cancer and Enabling Sciences, University of Manchester, Manchester Cancer Research Centre, Manchester Academic Health Sciences Centre, Manchester M20 4BX (United Kingdom)

    2010-06-09

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  14. Circulating tumor cells in breast cancer.

    Science.gov (United States)

    Bidard, Francois-Clement; Proudhon, Charlotte; Pierga, Jean-Yves

    2016-03-01

    Over the past decade, technically reliable circulating tumor cell (CTC) detection methods allowed the collection of large datasets of CTC counts in cancer patients. These data can be used either as a dynamic prognostic biomarker or as tumor material for "liquid biopsy". Breast cancer appears to be the cancer type in which CTC have been the most extensively studied so far, with level-of-evidence-1 studies supporting the clinical validity of CTC count in both early and metastatic stage. This review summarizes and discusses the clinical results obtained in breast cancer patients, the issues faced by the molecular characterization of CTC and the biological findings about cancer biology and metastasis that were obtained from CTC. Copyright © 2016 The Authors. Published by Elsevier B.V. All rights reserved.

  15. Circulating tumor cells: clinical validity and utility.

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    Cabel, Luc; Proudhon, Charlotte; Gortais, Hugo; Loirat, Delphine; Coussy, Florence; Pierga, Jean-Yves; Bidard, François-Clément

    2017-06-01

    Circulating tumor cells (CTCs) are rare tumor cells and have been investigated as diagnostic, prognostic and predictive biomarkers in many types of cancer. Although CTCs are not currently used in clinical practice, CTC studies have accumulated a high level of clinical validity, especially in breast, lung, prostate and colorectal cancers. In this review, we present an overview of the current clinical validity of CTCs in metastatic and non-metastatic disease, and the main concepts and studies investigating the clinical utility of CTCs. In particular, this review will focus on breast, lung, colorectal and prostate cancer. Three major topics concerning the clinical utility of CTC are discussed-(1) treatment based on CTCs used as liquid biopsy, (2) treatment based on CTC count or CTC variations, and (3) treatment based on CTC biomarker expression. A summary of published or ongoing phase II and III trials is also presented.

  16. Circulating Tumor Cells, Enumeration and Beyond

    International Nuclear Information System (INIS)

    Hou, Jian-Mei; Krebs, Matthew; Ward, Tim; Morris, Karen; Sloane, Robert; Blackhall, Fiona; Dive, Caroline

    2010-01-01

    The detection and enumeration of circulating tumor cells (CTCs) has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology

  17. Circulating Tumor Cells, Enumeration and Beyond

    Directory of Open Access Journals (Sweden)

    Jian-Mei Hou

    2010-06-01

    Full Text Available The detection and enumeration of circulating tumor cells (CTCs has shown significant clinical utility with respect to prognosis in breast, colorectal and prostate cancers. Emerging studies show that CTCs can provide pharmacodynamic information to aid therapy decision making. CTCs as a ‘virtual and real-time biopsy’ have clear potential to facilitate exploration of tumor biology, and in particular, the process of metastasis. The challenge of profiling CTC molecular characteristics and generating CTC signatures using current technologies is that they enrich rather than purify CTCs from whole blood; we face the problem of looking for the proverbial ‘needle in the haystack’. This review summarizes the current methods for CTC detection and enumeration, focuses on molecular characterization of CTCs, unveils some aspects of CTC heterogeneity, describes attempts to purify CTCs and scans the horizon for approaches leading to comprehensive dissection of CTC biology.

  18. Fragment Length of Circulating Tumor DNA.

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    Underhill, Hunter R; Kitzman, Jacob O; Hellwig, Sabine; Welker, Noah C; Daza, Riza; Baker, Daniel N; Gligorich, Keith M; Rostomily, Robert C; Bronner, Mary P; Shendure, Jay

    2016-07-01

    Malignant tumors shed DNA into the circulation. The transient half-life of circulating tumor DNA (ctDNA) may afford the opportunity to diagnose, monitor recurrence, and evaluate response to therapy solely through a non-invasive blood draw. However, detecting ctDNA against the normally occurring background of cell-free DNA derived from healthy cells has proven challenging, particularly in non-metastatic solid tumors. In this study, distinct differences in fragment length size between ctDNAs and normal cell-free DNA are defined. Human ctDNA in rat plasma derived from human glioblastoma multiforme stem-like cells in the rat brain and human hepatocellular carcinoma in the rat flank were found to have a shorter principal fragment length than the background rat cell-free DNA (134-144 bp vs. 167 bp, respectively). Subsequently, a similar shift in the fragment length of ctDNA in humans with melanoma and lung cancer was identified compared to healthy controls. Comparison of fragment lengths from cell-free DNA between a melanoma patient and healthy controls found that the BRAF V600E mutant allele occurred more commonly at a shorter fragment length than the fragment length of the wild-type allele (132-145 bp vs. 165 bp, respectively). Moreover, size-selecting for shorter cell-free DNA fragment lengths substantially increased the EGFR T790M mutant allele frequency in human lung cancer. These findings provide compelling evidence that experimental or bioinformatic isolation of a specific subset of fragment lengths from cell-free DNA may improve detection of ctDNA.

  19. Circulating Tumor Cells Versus Circulating Tumor DNA in Colorectal Cancer: Pros and Cons.

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    Tan, Carlyn Rose C; Zhou, Lanlan; El-Deiry, Wafik S

    2016-06-01

    Circulating tumor cells (CTCs) and circulating tumor DNA (ctDNA) are emerging noninvasive multifunctional biomarkers in liquid biopsy allowing for early diagnosis, accurate prognosis, therapeutic target selection, spatiotemporal monitoring of metastasis, as well as monitoring response and resistance to treatment. CTCs and ctDNA are released from different tumor types at different stages and contribute complementary information for clinical decision. Although big strides have been taken in technology development for detection, isolation and characterization of CTCs and sensitive and specific detection of ctDNA, CTC-, and ctDNA-based liquid biopsies may not be widely adopted for routine cancer patient care until the suitability, accuracy, and reliability of these tests are validated and more standardized protocols are corroborated in large, independent, prospectively designed trials. This review covers CTC- and ctDNA-related technologies and their application in colorectal cancer. The promise of CTC-and ctDNA-based liquid biopsies is envisioned.

  20. Circulating tumor cells in melanoma patients.

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    Gary A Clawson

    Full Text Available Circulating tumor cells (CTCs are of recognized importance for diagnosis and prognosis of cancer patients. With melanoma, most studies do not show any clear relationship between CTC levels and stage of disease. Here, CTCs were enriched (∼400X from blood of melanoma patients using a simple centrifugation device (OncoQuick, and 4 melanocyte target RNAs (TYR, MLANA, MITF, and MIF were quantified using QPCR. Approximately one-third of melanoma patients had elevated MIF and MLANA transcripts (p<0.0001 and p<0.001, respectively compared with healthy controls. In contrast, healthy controls had uniformly higher levels of TYR and MITF than melanoma patients (p<0.0001. There was a marked shift of leukocytes into the CTC-enriched fractions (a 430% increase in RNA recovery, p<0.001, and no relationship between CTC levels and stage of disease was found. CTCs were captured on microfabricated filters and cultured. Captured melanoma CTCs were large cells, and consisted of 2 subpopulations, based on immunoreactivity. One subpopulation (∼50% stained for both pan-cytokeratin (KRT markers and the common leukocyte marker CD-45, whereas the second subpopulation stained for only KRT. Since similar cells are described in many cancers, we also examined blood from colorectal and pancreatic cancer patients. We observed analogous results, with most captured CTCs staining for both CD-45/KRT markers (and for the monocyte differentiation marker CD-14. Our results suggest that immature melanocyte-related cells (expressing TYR and MITF RNA may circulate in healthy controls, although they are not readily detectable without considerable enrichment. Further, as early-stage melanomas develop, immature melanocyte migration into the blood is somehow curtailed, whereas a significant proportion of patients develop elevated CTC levels (based on MIF and MLANA RNAs. The nature of the captured CTCs is consistent with literature describing leukocyte/macrophage-tumor cell fusion hybrids

  1. Isolation of Circulating Tumor Cells by Dielectrophoresis

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    Peter R. C. Gascoyne

    2014-03-01

    Full Text Available Dielectrophoresis (DEP is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a the principles of DEP; (b the biological basis for the dielectric differences between CTCs and blood cells; (c why such differences are expected to be present for all types of tumors; and (d instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  2. Isolation of Circulating Tumor Cells by Dielectrophoresis

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    Gascoyne, Peter R. C., E-mail: pgascoyn@mdanderson.org [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Shim, Sangjo [Department of Imaging Physics Research, The University of Texas M.D. Anderson Cancer Center Unit 951, 1515 Holcombe Boulevard, Houston, TX 77030 (United States); Department of Biomedical Engineering, The University of Texas at Austin, 1 University Station, C0800, Austin, TX 78712 (United States); Present address: Micro & Nanotechnology Laboratory, University of Illinois at Urbana-Champaign, Urbana, 208 North Wright Street, Urbana, IL 61801 (United States)

    2014-03-12

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies.

  3. Isolation of Circulating Tumor Cells by Dielectrophoresis

    International Nuclear Information System (INIS)

    Gascoyne, Peter R. C.; Shim, Sangjo

    2014-01-01

    Dielectrophoresis (DEP) is an electrokinetic method that allows intrinsic dielectric properties of suspended cells to be exploited for discrimination and separation. It has emerged as a promising method for isolating circulation tumor cells (CTCs) from blood. DEP-isolation of CTCs is independent of cell surface markers. Furthermore, isolated CTCs are viable and can be maintained in culture, suggesting that DEP methods should be more generally applicable than antibody-based approaches. The aim of this article is to review and synthesize for both oncologists and biomedical engineers interested in CTC isolation the pertinent characteristics of DEP and CTCs. The aim is to promote an understanding of the factors involved in realizing DEP-based instruments having both sufficient discrimination and throughput to allow routine analysis of CTCs in clinical practice. The article brings together: (a) the principles of DEP; (b) the biological basis for the dielectric differences between CTCs and blood cells; (c) why such differences are expected to be present for all types of tumors; and (d) instrumentation requirements to process 10 mL blood specimens in less than 1 h to enable routine clinical analysis. The force equilibrium method of dielectrophoretic field-flow fractionation (DEP-FFF) is shown to offer higher discrimination and throughput than earlier DEP trapping methods and to be applicable to clinical studies

  4. Primary malignant small bowel tumor

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    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk [Kosin College, Pusan (Korea, Republic of)

    1990-07-15

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings.

  5. Primary malignant small bowel tumor

    International Nuclear Information System (INIS)

    Oh, Kyung Seung; Suh, Ho Jong; Kim, So Sun; Kim, Ho Joon; Chun, Byung Hee; Joh, Young Duk

    1990-01-01

    Small bowel tumors are rarely detected unless there is intestinal obstruction or bleeding. In the seven years 1982-1988, at Kosin Medical Center, 25 primary malignant small bowel tumors were studied radiographically with barium and / or computed tomography (CT). CT revealed gastrointestinal abnormalities in 20 patients. In ten, lesion were identified by upper G-I series, in 15 by small bowel series, and in addition, in 3 by colon enema. The most common malignant small bowel tumor was adenocarcinoma (N=15) and was next common lymphoma (N=7). On barium study, primary adenocarcinoma appeared as an irregular stricture (66.7%) and polypoid mass with intussusception was most prominent finding in lymphoma. Leiomyosarcoma appeared as an exophytic mass with excavation or ulceration. CT was found to be accurate in detecting wall thickening, complications and other associated findings. In conclusion, barium study was useful in the diagnosis of primary malignant small bowel tumor and CT was more accurate in detecting secondary findings

  6. Circulating tumor cells in lung cancer.

    Science.gov (United States)

    Young, Rachel; Pailler, Emma; Billiot, Fanny; Drusch, Françoise; Barthelemy, Amélie; Oulhen, Marianne; Besse, Benjamin; Soria, Jean-Charles; Farace, Françoise; Vielh, Philippe

    2012-01-01

    Circulating tumor cells (CTCs) have emerged as potential biomarkers in several cancers such as colon, prostate, and breast carcinomas, with a correlation between CTC number and patient prognosis being established by independent research groups. The detection and enumeration of CTCs, however, is still a developing field, with no universal method of detection suitable for all types of cancer. CTC detection in lung cancer in particular has proven difficult to perform, as CTCs in this type of cancer often present with nonepithelial characteristics. Moreover, as many detection methods rely on the use of epithelial markers to identify CTCs, the loss of these markers during epithelial-to-mesenchymal transition in certain metastatic cancers can render these methods ineffective. The development of personalized medicine has led to an increase in the advancement of molecular characterization of CTCs. The application of techniques such as FISH and RT-PCR to detect EGFR, HER2, and KRAS abnormalities in lung, breast, and colon cancer, for example, could be used to characterize CTCs in real time. The use of CTCs as a 'liquid biopsy' is therefore an exciting possibility providing information on patient prognosis and treatment efficacy. This review summarizes the state of CTC detection today, with particular emphasis on lung cancer, and discusses the future applications of CTCs in helping the clinician to develop new strategies in patient treatment. Copyright © 2012 S. Karger AG, Basel.

  7. Circulating tumor cells and circulating tumor DNA: What surgical oncologists need to know?

    Science.gov (United States)

    Cabel, L; Proudhon, C; Mariani, P; Tzanis, D; Beinse, G; Bieche, I; Pierga, J-Y; Bidard, F-C

    2017-05-01

    As a result of recent progress in detection techniques, circulating tumor DNA (ctDNA) and circulating tumor cells (CTC) can now be accurately detected in the blood of most cancer patients. While these new biomarkers can provide a better understanding of key biological mechanisms underlying cancer growth and dissemination, they also open up a wide range of possible clinical applications in medical oncology, radiation oncology and surgical oncology. In this review, we summarize the results obtained with ctDNA and CTC together with their potential future clinical applications in the field of surgical oncology, with particular focus on the perioperative setting of various types of cancer. These applications include, but are not limited to, cancer screening, early diagnosis, prognostic assessment, evaluation and management of preoperative systemic or local therapies, post-surgical detection of minimal residual disease and early detection of cancer relapse. Copyright © 2017 Elsevier Ltd, BASO ~ The Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

  8. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor; Kong, Say Li; Sengupta, Debarka; Tan, Iain B; Phyo, Wai Min; Lee, Daniel; Hu, Min; Iliescu, Ciprian; Alexander, Irina; Goh, Wei Lin; Rahmani, Mehran; Suhaimi, Nur-Afidah Mohamed; Vo, Jess H; Tai, Joyce A; Tan, Joanna H; Chua, Clarinda; Ten, Rachel; Lim, Wan Jun; Chew, Min Hoe; Hauser, Charlotte; van Dam, Rob M; Lim, Wei-Yen; Prabhakar, Shyam; Lim, Bing; Koh, Poh Koon; Robson, Paul; Ying, Jackie Y; Hillmer, Axel M; Tan, Min-Han

    2016-01-01

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

  9. Tumor-derived circulating endothelial cell clusters in colorectal cancer.

    KAUST Repository

    Cima, Igor

    2016-06-29

    Clusters of tumor cells are often observed in the blood of cancer patients. These structures have been described as malignant entities for more than 50 years, although their comprehensive characterization is lacking. Contrary to current consensus, we demonstrate that a discrete population of circulating cell clusters isolated from the blood of colorectal cancer patients are not cancerous but consist of tumor-derived endothelial cells. These clusters express both epithelial and mesenchymal markers, consistent with previous reports on circulating tumor cell (CTC) phenotyping. However, unlike CTCs, they do not mirror the genetic variations of matched tumors. Transcriptomic analysis of single clusters revealed that these structures exhibit an endothelial phenotype and can be traced back to the tumor endothelium. Further results show that tumor-derived endothelial clusters do not form by coagulation or by outgrowth of single circulating endothelial cells, supporting a direct release of clusters from the tumor vasculature. The isolation and enumeration of these benign clusters distinguished healthy volunteers from treatment-naïve as well as pathological early-stage (≤IIA) colorectal cancer patients with high accuracy, suggesting that tumor-derived circulating endothelial cell clusters could be used as a means of noninvasive screening for colorectal cancer. In contrast to CTCs, tumor-derived endothelial cell clusters may also provide important information about the underlying tumor vasculature at the time of diagnosis, during treatment, and throughout the course of the disease.

  10. Clinical relevance and biology of circulating tumor cells

    Science.gov (United States)

    2011-01-01

    Most breast cancer patients die due to metastases, and the early onset of this multistep process is usually missed by current tumor staging modalities. Therefore, ultrasensitive techniques have been developed to enable the enrichment, detection, isolation and characterization of disseminated tumor cells in bone marrow and circulating tumor cells in the peripheral blood of cancer patients. There is increasing evidence that the presence of these cells is associated with an unfavorable prognosis related to metastatic progression in the bone and other organs. This review focuses on investigations regarding the biology and clinical relevance of circulating tumor cells in breast cancer. PMID:22114869

  11. Circulating tumor cell isolation and diagnostics: toward routine clinical use

    NARCIS (Netherlands)

    Stolpe, van de A.; Pantel, K.; Sleijfer, S.; Terstappen, L.W.; Toonder, den J.M.J.

    2011-01-01

    From February 7–11, 2011, the multidisciplinary Lorentz Workshop Circulating Tumor Cell (CTC) Isolation and Diagnostics: Toward Routine Clinical Use was held in Leiden (The Netherlands) to discuss progress and define challenges and potential solutions for development of clinically useful circulating

  12. Glycan Markers as Potential Immunological Targets in Circulating Tumor Cells.

    Science.gov (United States)

    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.

  13. Liquid Biopsy for Cancer: Circulating Tumor Cells, Circulating Free DNA or Exosomes?

    Directory of Open Access Journals (Sweden)

    Wei Zhang

    2017-02-01

    Full Text Available Precision medicine and personalized medicine are based on the development of biomarkers, and liquid biopsy has been reported to be able to detect biomarkers that carry information on tumor development and progression. Compared with traditional ‘solid biopsy’, which cannot always be performed to determine tumor dynamics, liquid biopsy has notable advantages in that it is a noninvasive modality that can provide diagnostic and prognostic information prior to treatment, during treatment and during progression. In this review, we describe the source, characteristics, technology for detection and current situation of circulating tumor cells, circulating free DNA and exosomes used for diagnosis, recurrence monitoring, prognosis assessment and medication planning.

  14. Recent Advances in the Molecular Characterization of Circulating Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Lowes, Lori E. [London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 4L6 (Canada); Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1 (Canada); Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 4L6 (Canada); Allan, Alison L., E-mail: alison.allan@lhsc.on.ca [London Regional Cancer Program, London Health Sciences Centre, London, ON N6A 4L6 (Canada); Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1 (Canada); Department of Oncology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 4L6 (Canada); Lawson Health Research Institute, London, ON N6C 2R5 (Canada)

    2014-03-13

    Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch{sup ®} system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a “real-time liquid biopsy” that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing.

  15. Recent Advances in the Molecular Characterization of Circulating Tumor Cells

    International Nuclear Information System (INIS)

    Lowes, Lori E.; Allan, Alison L.

    2014-01-01

    Although circulating tumor cells (CTCs) were first observed over a century ago, lack of sensitive methodology precluded detailed study of these cells until recently. However, technological advances have now facilitated the identification, enumeration, and characterization of CTCs using a variety of methods. The majority of evidence supporting the use of CTCs in clinical decision-making has been related to enumeration using the CellSearch ® system and correlation with prognosis. Growing evidence also suggests that CTC monitoring can provide an early indication of patient treatment response based on comparison of CTC levels before and after therapy. However, perhaps the greatest potential that CTCs hold for oncology lies at the level of molecular characterization. Clinical treatment decisions may be more effective if they are based on molecular characteristics of metastatic cells rather than on those of the primary tumor alone. Molecular characterization of CTCs (which can be repeatedly isolated in a minimally invasive fashion) provides the opportunity for a “real-time liquid biopsy” that allows assessment of genetic drift, investigation of molecular disease evolution, and identification of actionable genomic characteristics. This review focuses on recent advances in this area, including approaches involving immunophenotyping, fluorescence in situ hybridization (FISH), multiplex RT-PCR, microarray, and genomic sequencing

  16. Expression profiling of circulating tumor cells in metastatic breast cancer

    Czech Academy of Sciences Publication Activity Database

    Lang, J.; Scott, J.H.; Wolf, D.M.; Novák, Petr; Punj, V.; Magbanua, M.J.M.; Zhu, W.Z.; Mineyev, N.; Haqq, CH.; Crothers, J.

    2015-01-01

    Roč. 149, č. 1 (2015), s. 121-131 ISSN 0167-6806 Institutional support: RVO:60077344 Keywords : Circulating tumor cells * Micrometastases * Breast cancer * EpCAM Subject RIV: FD - Oncology ; Hematology Impact factor: 4.085, year: 2015

  17. Quantifying HER-2 expression on Circulating Tumor Cells by ACCEPT

    NARCIS (Netherlands)

    Zeune, Leonie Laura; van Dalum, Guus; Decraene, C.; Proudhon, C.; Fehm, T.; Neubauer, Hans; Rack, B.; Alunni-fabbroni, Marianna; Terstappen, L.W.M.M.; van Gils, Stephanus A.; Brune, Christoph

    2017-01-01

    Circulating tumor cells (CTCs) isolated from blood can be probed for the expression of treatment targets. Immunofluorescence is often used for both the enumeration of CTC and the determination of protein expression levels related to treatment targets. Accurate and reproducible assessment of such

  18. Importance of circulating tumor cells in newly diagnosed colorectal cancer

    NARCIS (Netherlands)

    van Dalum, Guus; Stam, Gerrit-Jan; Scholten, Loes F.A.; Mastboom, Walter J.B.; Vermes, I.; Tibbe, Arjan G.J.; De Groot, Marco R.; Terstappen, Leonardus Wendelinus Mathias Marie

    2015-01-01

    Presence of circulating tumor cells (CTC) is associated with poor prognosis in patients with metastatic colorectal cancer (CRC). The present study was conducted to determine if the presence of CTC prior to surgery and during follow‑up in patients with newly diagnosed non-metastatic CRC can identify

  19. Prognostic Importance of Circulating Tumor Cells in Nonsmall Cell ...

    African Journals Online (AJOL)

    Purpose: To investigate the prognostic value of circulating tumor cells (CTCs) and to predict the treatment response in a non-small cell lung cancer (NSCLC). Methodology: A single-center prospective study involving 93 patients with NSCLC was conducted. Blood samples were analyzed for CTC count before and after ...

  20. A Review of Circulating Tumor DNA in Hepatobiliary Malignancies

    Directory of Open Access Journals (Sweden)

    Kabir Mody

    2018-06-01

    Full Text Available Circulating tumor DNA (ctDNA is released into circulation (blood specifically from tumor cells undergoing metabolic secretion, apoptosis, or necrosis, carries tumor-specific genetic or epigenetic alterations. Technologies enabling clinical evaluation of ctDNA continue to advance rapidly and allow for the assessment of patient-specific tumoral genetic and epigenetic alterations. This holds great potential for earlier detection of disease, serial monitoring of tumor heterogeneity, identification of therapeutic targets, and evaluation of treatment response and mechanisms of resistance. Hepatobiliary malignancies are often diagnosed late, recur commonly, yield limited available tumor on biopsy, and harbor several genomic alterations with potential therapeutic impacts. Patients suffering from or at risk for these diseases thus stand to benefit immensely from this technology. Herein, we review the limited literature pertaining to the potential for ctDNA technologies in such patients. Patients with these cancers stand to benefit greatly from the application of ctDNA technologies, and concerted efforts at further investigation of such are ongoing and greatly needed.

  1. Circulating tumor DNA functions as an alternative for tissue to overcome tumor heterogeneity in advanced gastric cancer.

    Science.gov (United States)

    Gao, Jing; Wang, Haixing; Zang, Wanchun; Li, Beifang; Rao, Guanhua; Li, Lei; Yu, Yang; Li, Zhongwu; Dong, Bin; Lu, Zhihao; Jiang, Zhi; Shen, Lin

    2017-09-01

    Overcoming tumor heterogeneity is a major challenge for personalized treatment of gastric cancer, especially for human epidermal growth factor receptor-2 targeted therapy. Analysis of circulating tumor DNA allows a more comprehensive analysis of tumor heterogeneity than traditional biopsies in lung cancer and breast cancer, but little is known in gastric cancer. We assessed mutation profiles of ctDNA and primary tumors from 30 patients with advanced gastric cancer, then performed a comprehensive analysis of tumor mutations by multiple biopsies from five patients, and finally analyzed the concordance of HER2 amplification in ctDNA and paired tumor tissues in 70 patients. By comparing with a single tumor sample, ctDNA displayed a low concordance of mutation profile, only approximately 50% (138/275) somatic mutations were found in paired tissue samples, however, when compared with multiple biopsies, most DNA mutations in ctDNA were also shown in paired tumor tissues. ctDNA had a high concordance (91.4%, Kappa index = 0.784, P < 0.001) of HER2 amplification with tumor tissues, suggesting it might be an alternative for tissue. It implied that ctDNA-based assessment could partially overcome the tumor heterogeneity, and might serve as a potential surrogate for HER2 analysis in gastric cancer. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  2. Scanning electron microscopy of primary bone tumors

    International Nuclear Information System (INIS)

    Pool, R.R.; Kerner, B.

    1975-01-01

    Critical-point-drying of tumor tissue fixed in a glutaraldehyde-paraformaldehyde solution and viewed by scanning electron microscopy (SEM) provides a 3-dimensional view of tumor cells and their matrices. This report describes the SEM appearance of three primary bone tumors: a canine osteosarcoma of the distal radius, a feline chondrosarcoma of the proximal tibia and a canine fibrosarcoma of the proximal humerus. The ultrastructural morphology is compared with the histologic appearance of each tumor

  3. Circulating Tumor DNA Analysis for Liver Cancers and Its Usefulness as a Liquid BiopsySummary

    Directory of Open Access Journals (Sweden)

    Atsushi Ono

    2015-09-01

    Full Text Available Background & Aims: Circulating tumor DNA (ctDNA carrying tumor-specific sequence alterations has been found in the cell-free fraction of blood. Liver cancer tumor specimens are difficult to obtain, and noninvasive methods are required to assess cancer progression and characterize underlying genomic features. Methods: We analyzed 46 patients with hepatocellular carcinoma who underwent hepatectomy or liver transplantation and for whom whole-genome sequencing data was available. We designed personalized assays targeting somatic rearrangements of each tumor to quantify serum ctDNA. Exome sequencing was performed using cell-free DNA paired primary tumor tissue DNA from a patient with recurrent liver cancer after transcatheter arterial chemoembolization (TACE. Results: We successfully detected ctDNA from 100 μL of serum samples in 7 of the 46 patients before surgery, increasing with disease progression. The cumulative incidence of recurrence and extrahepatic metastasis in the ctDNA-positive group were statistically significantly worse than in the ctDNA-negative group (P = .0102 and .0386, respectively. Multivariate analysis identified ctDNA (OR 6.10; 95% CI, 1.11–33.33, P = .038 as an independent predictor of microscopic vascular invasion of the portal vein (VP. We identified 45 nonsynonymous somatic mutations in cell-free DNA after TACE and 71 nonsynonymous somatic mutations in primary tumor tissue by exome sequencing. We identified 25 common mutations in both samples, and 83% of mutations identified in the primary tumor could be detected in the cell-free DNA. Conclusions: The presence of ctDNA reflects tumor progression, and detection of ctDNA can predict VP and recurrence, especially extrahepatic metastasis within 2 years. Our study demonstrated the usefulness of ctDNA detection and sequencing analysis of cell-free DNA for personalized treatment of liver cancer. Keywords: Circulating Tumor DNA, Exome Sequencing, Hepatocellular

  4. The importance of circulating tumor products as „liquid biopsies” in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Alina Miscoci

    2018-04-01

    Full Text Available Liquid biopsies represent an array of plasma analysis tests that are studied to evaluate and identify circulating tumor products, especially circulating tumor cells (CTCs and circulating tumor DNA (ctDNA. Examining such biomarkers in the plasma of colorectal cancer patients has attracted attention due to its clinical significance in the treatment of malignant diseases. Given that tissue samples are sometimes challenging to procure or unsatisfactory for genomic profiling from patients with colorectal cancer, trustworthy biomarkers are mandatory for guiding treatment, monitoring therapeutic response, and detecting recurrence. This review considers the relevance of flowing tumor products like circulating tumor cells (CTCs, circulating tumor DNA (ctDNA, circulating messenger RNA (mRNA, circulating micro RNA (miRNA, circulating exosomes, and tumor educated platelets (TEPs for patients with colorectal cancer.

  5. The Mutational Landscape of Circulating Tumor Cells in Multiple Myeloma

    Directory of Open Access Journals (Sweden)

    Yuji Mishima

    2017-04-01

    Full Text Available The development of sensitive and non-invasive “liquid biopsies” presents new opportunities for longitudinal monitoring of tumor dissemination and clonal evolution. The number of circulating tumor cells (CTCs is prognostic in multiple myeloma (MM, but there is little information on their genetic features. Here, we have analyzed the genomic landscape of CTCs from 29 MM patients, including eight cases with matched/paired bone marrow (BM tumor cells. Our results show that 100% of clonal mutations in patient BM were detected in CTCs and that 99% of clonal mutations in CTCs were present in BM MM. These include typical driver mutations in MM such as in KRAS, NRAS, or BRAF. These data suggest that BM and CTC samples have similar clonal structures, as discordances between the two were restricted to subclonal mutations. Accordingly, our results pave the way for potentially less invasive mutation screening of MM patients through characterization of CTCs.

  6. Circulating cell-free DNA and circulating tumor cells, the "liquid biopsies" in ovarian cancer.

    Science.gov (United States)

    Cheng, Xianliang; Zhang, Lei; Chen, Yajuan; Qing, Chen

    2017-11-13

    Limited understanding of ovarian cancer (OC) genome portrait has hindered the therapeutic advances. The serial monitoring of tumor genotypes is becoming increasingly attainable with circulating cell-free DNA (cf-DNA) and circulating tumor cells (CTCs) emerging as "liquid biopsies". They represent non-invasive biomarkers and are viable, as they can be isolated from human plasma, serum and other body fluids. Molecular characterization of circulating tumor DNA (ct-DNA) and CTCs offer unique potentials to better understand the biology of metastasis and resistance to therapies. The liquid biopsies may also give innovative insights into the process of rapid and accurate identification, resistant genetic alterations and a real time monitoring of treatment responses. In addition, liquid biopsies are shedding light on elucidating signal pathways involved in invasiveness and metastasis competence; but the detection and molecular characterization of ct-DNA and CTCs are still challenging, since they are rare, and the amount of available samples are very limited. This review will focus on the clinical potential of ct-DNA and CTCs in both the early and advanced diagnosis, prognosis, and in the identification of resistance mutations in OC.

  7. Molecular characterization of circulating colorectal tumor cells defines genetic signatures for individualized cancer care

    Science.gov (United States)

    Kong, Say Li; Liu, Xingliang; Suhaimi, Nur-Afidah Mohamed; Koh, Kenneth Jia Hao; Hu, Min; Lee, Daniel Yoke San; Cima, Igor; Phyo, Wai Min; Lee, Esther Xing Wei; Tai, Joyce A.; Foong, Yu Miin; Vo, Jess Honganh; Koh, Poh Koon; Zhang, Tong; Ying, Jackie Y.; Lim, Bing; Tan, Min-Han; Hillmer, Axel M.

    2017-01-01

    Studies on circulating tumor cells (CTCs) have largely focused on platform development and CTC enumeration rather than on the genomic characterization of CTCs. To address this, we performed targeted sequencing of CTCs of colorectal cancer patients and compared the mutations with the matched primary tumors. We collected preoperative blood and matched primary tumor samples from 48 colorectal cancer patients. CTCs were isolated using a label-free microfiltration device on a silicon microsieve. Upon whole genome amplification, we performed amplicon-based targeted sequencing on a panel of 39 druggable and frequently mutated genes on both CTCs and fresh-frozen tumor samples. We developed an analysis pipeline to minimize false-positive detection of somatic mutations in amplified DNA. In 60% of the CTC-enriched blood samples, we detected primary tumor matching mutations. We found a significant positive correlation between the allele frequencies of somatic mutations detected in CTCs and abnormal CEA serum level. Strikingly, we found driver mutations and amplifications in cancer and druggable genes such as APC, KRAS, TP53, ERBB3, FBXW7 and ERBB2. In addition, we found that CTCs carried mutation signatures that resembled the signatures of their primary tumors. Cumulatively, our study defined genetic signatures and somatic mutation frequency of colorectal CTCs. The identification of druggable mutations in CTCs of preoperative colorectal cancer patients could lead to more timely and focused therapeutic interventions. PMID:28978093

  8. Bone marrow micrometastases and circulating tumor cells: current aspects and future perspectives

    International Nuclear Information System (INIS)

    Müller, Volkmar; Pantel, Klaus

    2004-01-01

    Early tumor cell dissemination at the single-cell level can be revealed in patients with breast cancer by using sensitive immunocytochemical and molecular assays. Recent clinical studies involving more than 4000 breast cancer patients demonstrated that the presence of disseminated tumor cells in bone marrow at primary diagnosis is an independent prognostic factor. In addition, various assays for the detection of circulating tumor cells in the peripheral blood have recently been developed and some studies also suggest a potential clinical relevance of this measure. These findings provide the basis for the potential use of disseminated tumor cells in bone marrow or blood as markers for the early assessment of therapeutic response in prospective clinical trials

  9. Primary primitive neuroectodermal tumor of the cervix

    Science.gov (United States)

    Li, Bo; Ouyang, Ling; Han, Xue; Zhou, Yang; Tong, Xin; Zhang, Shulang; Zhang, Qingfu

    2013-01-01

    Primary primitive neuroectodermal tumors (PNETs) are rare and high-grade malignant tumors that mostly occur in children and young adults. The most common sites are the trunk, limbs, and retroperitoneum. Herein, we present a case of a PNET involving the cervix uteri in a 27-year-old woman. The lesion showed characteristic histologic features of a PNET and was positive for the immunohistochemical markers cluster of differentiation (CD) 99, vimentin, neuron-specific enolase, neural cell adhesion molecule 1 (CD56), and CD117 (c-kit), further defining the tumor while helping to confirm PNET. The clinical Stage IIIB tumor was treated with chemotherapy and radiotherapy. PMID:23836982

  10. Circulating Tumor Cells: From Theory to Nanotechnology-Based Detection

    Science.gov (United States)

    Ming, Yue; Li, Yuanyuan; Xing, Haiyan; Luo, Minghe; Li, Ziwei; Chen, Jianhong; Mo, Jingxin; Shi, Sanjun

    2017-01-01

    Cancer stem cells with stem-cell properties are regarded as tumor initiating cells. Sharing stem-cell properties, circulating tumor cells (CTCs) are responsible for the development of metastasis, which significant affects CTC analysis in clinical practice. Due to their extremely low occurrence in blood, however, it is challenging to enumerate and analyze CTCs. Nanotechnology is able to address the problems of insufficient capture efficiency and low purity of CTCs owing to the unique structural and functional properties of nanomaterials, showing strong promise for CTC isolation and detection. In this review, we discuss the role of stem-like CTCs in metastases, provide insight into recent progress in CTC isolation and detection approaches using various nanoplatforms, and highlight the role of nanotechnology in the advancement of CTC research. PMID:28203204

  11. Brown tumor of mandible with primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Ali, S.K.; Khan, F.A.; Siddiq, A.; Hanif, M.S.

    2011-01-01

    Parathyroid hormone (PTH) is secreted and released by the parathyroid glands, the activity of which is controlled by the ionized serum calcium level. Increased PTH secretion results in hyperparathyroidism. Hyperparathyroidism is classified as primary, secondary and tertiary types. Primary hyperparathyroidism is characterized by increased parathyroid hormone secretion occurring as a result of abnormality in one or more of the parathyroid glands. Brown tumors are non-neoplastic lesions as a result of abnormal bone metabolism in cases of hyperparathyroidism, creating a local destructive phenomenon. A rare case of a young female patient with brown tumors in her mandible associated with primary hyperparathyroidism, is reported. (author)

  12. Heterogeneity of estrogen receptor expression in circulating tumor cells from metastatic breast cancer patients.

    Directory of Open Access Journals (Sweden)

    Anna Babayan

    Full Text Available BACKGROUND: Endocrine treatment is the most preferable systemic treatment in metastatic breast cancer patients that have had an estrogen receptor (ER positive primary tumor or metastatic lesions, however, approximately 20% of these patients do not benefit from the therapy and demonstrate further metastatic progress. One reason for failure of endocrine therapy might be the heterogeneity of ER expression in tumor cells spreading from the primary tumor to distant sites which is reflected in detectable circulating tumor cells (CTCs. METHODS: A sensitive and specific staining protocol for ER, keratin 8/18/19, CD45 was established. Peripheral blood from 35 metastatic breast cancer patients with ER-positive primary tumors was tested for the presence of CTCs. Keratin 8/18/19 and DAPI positive but CD45 negative cells were classified as CTCs and evaluated for ER staining. Subsequently, eight individual CTCs from four index patients (2 CTCs per patient were isolated and underwent whole genome amplification and ESR1 gene mutation analysis. RESULTS: CTCs were detected in blood of 16 from 35 analyzed patients (46%, with a median of 3 CTCs/7.5 ml. In total, ER-negative CTCs were detected in 11/16 (69% of the CTC positive cases, including blood samples with only ER-negative CTCs (19% and samples with both ER-positive and ER-negative CTCs (50%. No correlation was found between the intensity and/or percentage of ER staining in the primary tumor with the number and ER status of CTCs of the same patient. ESR1 gene mutations were not found. CONCLUSION: CTCs frequently lack ER expression in metastatic breast cancer patients with ER-positive primary tumors and show a considerable intra-patient heterogeneity, which may reflect a mechanism to escape endocrine therapy. Provided single cell analysis did not support a role of ESR1 mutations in this process.

  13. Heterogeneity of Estrogen Receptor Expression in Circulating Tumor Cells from Metastatic Breast Cancer Patients

    Science.gov (United States)

    Babayan, Anna; Hannemann, Juliane; Spötter, Julia; Müller, Volkmar

    2013-01-01

    Background Endocrine treatment is the most preferable systemic treatment in metastatic breast cancer patients that have had an estrogen receptor (ER) positive primary tumor or metastatic lesions, however, approximately 20% of these patients do not benefit from the therapy and demonstrate further metastatic progress. One reason for failure of endocrine therapy might be the heterogeneity of ER expression in tumor cells spreading from the primary tumor to distant sites which is reflected in detectable circulating tumor cells (CTCs). Methods A sensitive and specific staining protocol for ER, keratin 8/18/19, CD45 was established. Peripheral blood from 35 metastatic breast cancer patients with ER-positive primary tumors was tested for the presence of CTCs. Keratin 8/18/19 and DAPI positive but CD45 negative cells were classified as CTCs and evaluated for ER staining. Subsequently, eight individual CTCs from four index patients (2 CTCs per patient) were isolated and underwent whole genome amplification and ESR1 gene mutation analysis. Results CTCs were detected in blood of 16 from 35 analyzed patients (46%), with a median of 3 CTCs/7.5 ml. In total, ER-negative CTCs were detected in 11/16 (69%) of the CTC positive cases, including blood samples with only ER-negative CTCs (19%) and samples with both ER-positive and ER-negative CTCs (50%). No correlation was found between the intensity and/or percentage of ER staining in the primary tumor with the number and ER status of CTCs of the same patient. ESR1 gene mutations were not found. Conclusion CTCs frequently lack ER expression in metastatic breast cancer patients with ER-positive primary tumors and show a considerable intra-patient heterogeneity, which may reflect a mechanism to escape endocrine therapy. Provided single cell analysis did not support a role of ESR1 mutations in this process. PMID:24058649

  14. Fetal Primary Cardiac Tumors During Perinatal Period

    Directory of Open Access Journals (Sweden)

    Shi-Min Yuan

    2017-06-01

    Full Text Available Fetal primary cardiac tumors are rare, but they may cause complications, which are sometimes life threatening, including arrhythmias, hydrops fetalis, ventricular outflow/inflow obstruction, cardiac failure, and even sudden death. Among fetal primary cardiac tumors, rhabdomyomas are most common, followed by teratomas, fibromas, hemangiomas, and myxomas. Everolimus, a mammalian target of rapamycin inhibitor, has been reported to be an effective drug to cause tumor remission in three neonates with multiple cardiac rhabdomyomas. Neonatal cardiac surgery for the resection of primary cardiac tumors found by fetal echocardiography has been reported sporadically. However, open fetal surgery for pericardial teratoma resection, which was performed successfully via a fetal median sternotomy in one case report, could be a promising intervention to rescue these patients with large pericardial effusions. These recent achievements undoubtedly encourage further development in early management of fetal cardiac tumors. Owing to the rarity of fetal primary cardiac tumors, relevant information in terms of prenatal diagnosis, treatment, and prognosis remains to be clarified.

  15. Risk interrelationship among multiple primary tumors

    Science.gov (United States)

    Safi, Mohammed; Sun, Xiuhua; Wang, Lifen; Zhang, Xinwei; Song, Jicheng; Ameen, Mohammed

    2018-01-01

    Abstract Rationale: Along with advanced management in oncology, great progress has been recently achieved in the studies of multiple primary tumors. Several reports have studied the coexistence between lymphoma and either renal cell carcinoma (RCC) or Warthin tumor. However, the level of coexistence between these cases remains unclear due to the absence of a distinct link between them. Patient concerns: We present a unique case of multiple primary tumors (lymphoma, RCC, and Warthin tumor) in an 80-year-old man and a review of the literature on the coexistence of RCC with lymphoma and lymphoma with Warthin tumor. Diagnosis: With a history of RCC, the patient had a freely movable lump under his left ear, and the pathological report indicated Hodgkin lymphoma and Warthin tumor. Intervention: RCC and Warthin tumor of the patient were surgically treated, followed by 2 cycles (14 days per cycle) of Epirubicin 40 mg day 1, Bleomycin 8 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1. The chemotherapy protocol was then changed to Epirubicin 40 mg day 1, Vincristine 2 mg day 1, and Dacarbazine 500 mg day 1 for 7 cycles. Outcomes: After the last day of chemotherapy, the patient showed a complete response. Lessons: To the best of our knowledge, this paper is the first to report a case of multiple primary tumors with a complete response. For their early detection, favorable prognosis, and correlation identification, we suggest a transitive relation between these coexisting tumors. Therefore, similar studies should be conducted. PMID:29642151

  16. Perspective on Cancer Therapeutics Utilizing Analysis of Circulating Tumor Cells

    Directory of Open Access Journals (Sweden)

    Keun-Yeong Jeong

    2018-04-01

    Full Text Available Various methods are available for cancer screening, and the methods are performed depending on the origin site of cancer. Among these methods, biopsy followed by medical imaging is the most common. After cancer progression is determined, an optimal treatment—such as surgery, chemotherapy, and/or radiation therapy—is selected. A new assay has been developed that detects circulating tumor cells (CTCs. Tracking changes in CTCs may reveal important tumoral sensitivity information or resistance patterns to specific regimens and prompt changes in therapy on a personalized basis. Characterization of CTCs at the DNA, RNA, and protein levels is important for gaining insight for clinical applications. A small number of CTCs can be analyzed to obtain genome information such as the progression of cancer including metastasis, even in a single cluster. Although many clinical studies, particularly CTC enumeration and detection of specific oncogene expression, have increased the success rate of diagnosis and predicting prognosis, there is no consensus regarding the technical approaches and various aspects of the methodology, making it difficult to standardize optimal methods for CTC analysis. However, ongoing technological advances are currently being achieved and large-scale clinical studies are being conducted. Applying CTC analysis in the clinic would be very useful for advancing diagnosis, prognosis prediction, and therapeutics.

  17. Computerized tomographic evaluation of primary brain tumors

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Jin Ok; Lee, Jong Soon; Jeon, Doo Sung; Kim, Hong Soo; Rhee, Hak Song [Presbyterian Mediacal center, Cheonju (Korea, Republic of); Kim, Jong Deok [Inje Medical College, Paik Hospital, Pusan (Korea, Republic of)

    1985-10-15

    In a study of primary brain tumors 104 cases having satisfactory clinical, operative and histological proofs were analyzed by computerized tomography at Presbyterian Medical Center from May, 1982 to April 1985. The results were as follows: 1. The male to female ratio of primary brain tumor was 54 : 46. 2. The 2nd decade group (26%) was the most prevalent age group, followed by the 5th decade (16.3%), 1st decade (14.4%) , 3rd decade (12.5%), 4th decade (11.5%), 6th decade (10.6%), 7th decade (8.7%) in that order. 3. The incidence of primary brain tumors was found to be: glioma 64 cases (61.6%) among the GM, the most frequent 17 cases (16.3%), followed by meningioma 12 cases (11.5%), pituitary adenoma 10 cases (9.6%), craniopharyngioma 6 cases (5.8%), pinealoma and germinoma 3 cases (2.9%) respectively, and dermoid cyst 2 cases (1.9%) in that order. 4. The location of the primary brain tumors were as follows: cb. hemisphere (49%) of these 24.5% in parietal region, 11.9% in temporal region, 9.7% in frontal region, 3.0% in occipital region: juxtasella area (16.3%), cerebellar hemisphere (8.7%), parapineal and intraventricle (7.7%) respectively, cerebello-pontine angle area (5.8%), vermis and 4th ventricular region (4.8%). 5. There were no remarkable differences in the findings of pre- and post-contrast CT scanning of primary brain tumors computed with others.

  18. Natural circulation under variable primary mass inventories at BETHSY facility

    International Nuclear Information System (INIS)

    Bazin, P.; Clement, P.; Deruaz, R.

    1989-01-01

    BETHSY is a high pressure integral test facility which models a 3 loop Framatome PWR with the intent of studying PWR accidents. The BETHSY programme includes both accident transients and tests under successive steady state conditions. So far, tests of the latter type have been especially devoted to situations where natural circulation takes place in the primary coolant system (PCS). Tests 4.1a and 4.1a TC, the results of which are introduced, deal with PCS natural circulation patterns and related heat transport mechanisms under two different core power levels (2 and 5% of nominal power), variable primary mass inventory (100% to 30-40% according to core power) and at two different steam generator liquid levels (standard value and 1 meter). (orig.)

  19. Metastasis to neck from unknown primary tumor

    International Nuclear Information System (INIS)

    Jose, B.; Bosch, A.; Caldwell, W.L.; Frias, Z.

    1979-01-01

    The records of 54 consecutive patients who were irradiated for metastatic disease in the neck from an unknown primary tumor were reviewed. The overall survival results are comparable to those of other reported series. Patients with high or posterior cervical lymph node involvement were irradiated with fields including the nasopharynx and oropharynx. Patients with high neck nodes had a better survival rate than those with low neck nodes. The size of the neck tumors and the local control after treatment also have prognostic significance. (Auth.)

  20. Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications

    International Nuclear Information System (INIS)

    Tseng, Ju-Yu; Yang, Chih-Yung; Liang, Shu-Ching; Liu, Ren-Shyan; Jiang, Jeng-Kai; Lin, Chi-Hung

    2014-01-01

    Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis

  1. Dynamic Changes in Numbers and Properties of Circulating Tumor Cells and Their Potential Applications

    Energy Technology Data Exchange (ETDEWEB)

    Tseng, Ju-Yu [Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan (China); Yang, Chih-Yung [Department of Education and Research, Taipei City Hospital, Taipei 10629, Taiwan (China); Liang, Shu-Ching [Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan (China); Liu, Ren-Shyan [Molecular and Genetic Imaging Core/Taiwan Mouse Clinic, Taipei 11529, Taiwan (China); Biomedical Imaging Research Center, Institute of Clinical Medicine, School of Medicine, National Yang-Ming University, Taipei 11221, Taiwan (China); National PET/Cyclotron Center, Taipei Veterans General Hospital, Taipei, 11217, Taiwan (China); Jiang, Jeng-Kai, E-mail: jkjiang@vghtpe.gov.tw [Division of Colon & Rectal Surgery, Department of Surgery, Taipei Veterans General Hospital, Taipei 11217, Taiwan (China); Lin, Chi-Hung, E-mail: jkjiang@vghtpe.gov.tw [Institute of Microbiology and Immunology, School of Life Science, National Yang-Ming University, Taipei 11221, Taiwan (China); VGH Yang-Ming Genome Research Center, Taipei 11221, Taiwan (China)

    2014-12-16

    Circulating tumor cells (CTCs) can be detected in the blood of different types of early or advanced cancer using immunology-based assays or nucleic acid methods. The detection and quantification of CTCs has significant clinical utility in the prognosis of metastatic breast, prostate, and colorectal cancers. CTCs are a heterogeneous population of cells and often different from those of their respective primary tumor. Understanding the biology of CTCs may provide useful predictive information for the selection of the most appropriate treatment. Therefore, CTC detection and characterization could become a valuable tool to refine prognosis and serve as a “real-time biopsy” and has the potential to guide precision cancer therapies, monitor cancer treatment, and investigate the process of metastasis.

  2. Review of the clinical applications and technological advances of circulating tumor DNA in cancer monitoring.

    Science.gov (United States)

    Chang, Yi; Tolani, Bhairavi; Nie, Xiuhong; Zhi, Xiuyi; Hu, Mu; He, Biao

    2017-01-01

    Circulating cell-free DNA (cfDNA) released by tumor cells, termed ctDNA, closely reflects the heterogeneity of primary cancers and their metastases. As a noninvasive, real-time monitoring biomarker, ctDNA is a promising tool for detecting driver gene mutations, assessing tumor burden and acquired resistance, and early diagnosis. However, isolation and enrichment of cfDNA is a big challenge due to the high degree of DNA fragmentation and its relatively low abundance in the bloodstream. This review aims to provide insights into the recent technological advances in acquisition of optimal quality cfDNA, the use of preservatives, isolation methods, processing timelines, and detection techniques. It also describes clinical applications of ctDNA in cancer patient management.

  3. Circulating Tumor Cells in the Adenocarcinoma of the Esophagus

    Directory of Open Access Journals (Sweden)

    Giulia Gallerani

    2016-08-01

    Full Text Available Circulating tumor cells (CTCs are elements of indisputable significance as they seem to be responsible for the onset of metastasis. Despite this, research into CTCs and their clinical application have been hindered by their rarity and heterogeneity at the molecular and cellular level, and also by a lack of technical standardization. Esophageal adenocarcinoma (EAC is a highly aggressive cancer that is often diagnosed at an advanced stage. Its incidence has increased so much in recent years that new diagnostic, prognostic and predictive biomarkers are urgently needed. Preliminary findings suggest that CTCs could represent an effective, non-invasive, real-time assessable biomarker in all stages of EAC. This review provides an overview of EAC and CTC characteristics and reports the main research results obtained on CTCs in this setting. The need to carry out further basic and translational research in this area to confirm the clinical usefulness of CTCs and to provide oncologists with a tool to improve therapeutic strategies for EAC patients was herein highlighted.

  4. Quantifying HER-2 expression on circulating tumor cells by ACCEPT.

    Directory of Open Access Journals (Sweden)

    Leonie Zeune

    Full Text Available Circulating tumor cells (CTCs isolated from blood can be probed for the expression of treatment targets. Immunofluorescence is often used for both the enumeration of CTC and the determination of protein expression levels related to treatment targets. Accurate and reproducible assessment of such treatment target expression levels is essential for their use in the clinic. To enable this, an open source image analysis program named ACCEPT was developed in the EU-FP7 CTCTrap and CANCER-ID programs. Here its application is shown on a retrospective cohort of 132 metastatic breast cancer patients from which blood samples were processed by CellSearch® and stained for HER-2 expression as additional marker. Images were digitally stored and reviewers identified a total of 4084 CTCs. CTC's HER-2 expression was determined in the thumbnail images by ACCEPT. 150 of these images were selected and sent to six independent investigators to score the HER-2 expression with and without ACCEPT. Concordance rate of the operators' scoring results for HER-2 on CTCs was 30% and could be increased using the ACCEPT tool to 51%. Automated assessment of HER-2 expression by ACCEPT on 4084 CTCs of 132 patients showed 8 (6.1% patients with all CTCs expressing HER-2, 14 (10.6% patients with no CTC expressing HER-2 and 110 (83.3% patients with CTCs showing a varying HER-2 expression level. In total 1576 CTCs were determined HER-2 positive. We conclude that the use of image analysis enables a more reproducible quantification of treatment targets on CTCs and leads the way to fully automated and reproducible approaches.

  5. Quantifying HER-2 expression on circulating tumor cells by ACCEPT.

    Science.gov (United States)

    Zeune, Leonie; van Dalum, Guus; Decraene, Charles; Proudhon, Charlotte; Fehm, Tanja; Neubauer, Hans; Rack, Brigitte; Alunni-Fabbroni, Marianna; Terstappen, Leon W M M; van Gils, Stephan A; Brune, Christoph

    2017-01-01

    Circulating tumor cells (CTCs) isolated from blood can be probed for the expression of treatment targets. Immunofluorescence is often used for both the enumeration of CTC and the determination of protein expression levels related to treatment targets. Accurate and reproducible assessment of such treatment target expression levels is essential for their use in the clinic. To enable this, an open source image analysis program named ACCEPT was developed in the EU-FP7 CTCTrap and CANCER-ID programs. Here its application is shown on a retrospective cohort of 132 metastatic breast cancer patients from which blood samples were processed by CellSearch® and stained for HER-2 expression as additional marker. Images were digitally stored and reviewers identified a total of 4084 CTCs. CTC's HER-2 expression was determined in the thumbnail images by ACCEPT. 150 of these images were selected and sent to six independent investigators to score the HER-2 expression with and without ACCEPT. Concordance rate of the operators' scoring results for HER-2 on CTCs was 30% and could be increased using the ACCEPT tool to 51%. Automated assessment of HER-2 expression by ACCEPT on 4084 CTCs of 132 patients showed 8 (6.1%) patients with all CTCs expressing HER-2, 14 (10.6%) patients with no CTC expressing HER-2 and 110 (83.3%) patients with CTCs showing a varying HER-2 expression level. In total 1576 CTCs were determined HER-2 positive. We conclude that the use of image analysis enables a more reproducible quantification of treatment targets on CTCs and leads the way to fully automated and reproducible approaches.

  6. Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells

    International Nuclear Information System (INIS)

    Charpentier, Monica; Martin, Stuart

    2013-01-01

    Metastasis, not the primary tumor, is responsible for the majority of breast cancer-related deaths. Emerging evidence indicates that breast cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) cooperate to produce circulating tumor cells (CTCs) that are highly competent for metastasis. CTCs with both CSC and EMT characteristics have recently been identified in the bloodstream of patients with metastatic disease. Breast CSCs have elevated tumorigenicity required for metastatic outgrowth, while EMT may promote CSC character and endows breast cancer cells with enhanced invasive and migratory potential. Both CSCs and EMT are associated with a more flexible cytoskeleton and with anoikis-resistance, which help breast carcinoma cells survive in circulation. Suspended breast carcinoma cells produce tubulin-based extensions of the plasma membrane, termed microtentacles (McTNs), which aid in reattachment. CSC and EMT-associated upregulation of intermediate filament vimentin and increased detyrosination of α-tubulin promote the formation of McTNs. The combined advantages of CSCs and EMT and their associated cytoskeletal alterations increase metastatic efficiency, but understanding the biology of these CTCs also presents new therapeutic targets to reduce metastasis

  7. Detection and cultivation of circulating tumor cells in malignant pleural mesothelioma.

    Science.gov (United States)

    Bobek, Vladimir; Kacprzak, Grzegorz; Rzechonek, Adam; Kolostova, Katarina

    2014-05-01

    Malignant pleural mesothelioma (MPM) is an aggressive disease with very poor prognosis which tends to affect older patients. Progress in the management of this group of patients has been limited by the rarity of the disease and hence, difficulty in conducting randomized trials. The vast majority of cancer deaths occur due to metastasis of the primary tumor to distant sites via circulating tumor cells (CTCs) in the circulation. CTCs are extremely rare and limits in technology used to capture these cells hamper our complete understanding over the metastatic process. In the present study we present a new method for detection and cultivation of CTCs isolated from peripheral blood of MPM patients. Patients with diagnosed MPM were enrolled into this study. A size-based separation method for viable CTC enrichment from unclothed peripheral blood has been introduced; MetaCell. The size-based enrichment process was based on filtration of peripheral blood (PB) through porous polycarbonate membrane. The separated CTCs are cultured on the membrane in vitro under standard cancer cell culture conditions and observed by an inverted microscope. The reported methodology allows for quick and easy enrichment of CTCs and their cultivation. The cultivated cells can be used for next specification of gene expression and histological/biological specificity of concrete mesothelioma.

  8. Interplay of Stem Cell Characteristics, EMT, and Microtentacles in Circulating Breast Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Charpentier, Monica [Program in Molecular Medicine, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-20, Baltimore, MD 21201 (United States); Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States); Martin, Stuart, E-mail: ssmartin@som.umaryland.edu [Marlene and Stewart Greenebaum National Cancer Institute Cancer Center, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States); Department of Physiology, University of Maryland School of Medicine, 655 W. Baltimore St., Bressler Bldg., Rm 10-29, Baltimore, MD 21201 (United States)

    2013-11-14

    Metastasis, not the primary tumor, is responsible for the majority of breast cancer-related deaths. Emerging evidence indicates that breast cancer stem cells (CSCs) and the epithelial-to-mesenchymal transition (EMT) cooperate to produce circulating tumor cells (CTCs) that are highly competent for metastasis. CTCs with both CSC and EMT characteristics have recently been identified in the bloodstream of patients with metastatic disease. Breast CSCs have elevated tumorigenicity required for metastatic outgrowth, while EMT may promote CSC character and endows breast cancer cells with enhanced invasive and migratory potential. Both CSCs and EMT are associated with a more flexible cytoskeleton and with anoikis-resistance, which help breast carcinoma cells survive in circulation. Suspended breast carcinoma cells produce tubulin-based extensions of the plasma membrane, termed microtentacles (McTNs), which aid in reattachment. CSC and EMT-associated upregulation of intermediate filament vimentin and increased detyrosination of α-tubulin promote the formation of McTNs. The combined advantages of CSCs and EMT and their associated cytoskeletal alterations increase metastatic efficiency, but understanding the biology of these CTCs also presents new therapeutic targets to reduce metastasis.

  9. Bronchoplasty for Primary Broncho-Pulmonary Tumors

    International Nuclear Information System (INIS)

    ABDEL RAHMAN, A.M.

    2010-01-01

    Parenchyma-sparing procedures are widely used in patients with low-grade malignancies of the airway when anatomically suited lesions exist. This study was conducted to evaluate the short-term and the long-term results of bronchoplastic procedures for patients with centrally located primary bronchopulmonary tumors. Methods: Between 2000 and 2009, 36 patients with primary lung tumors required bronchoplasty were retrospectively analyzed. Preoperative assessment included computed tomography (CT) of the chest, bronchoscopy, and spirometry. Pre operative diagnosis was achieved by bronchoscopy for all patients, mediastinoscopy was done for patients with primary lung cancer. Neo adjuvant chemotherapy was given for 6 patients with non small cell lung cancer (NSCLC). Results: We had 15 males and 21 female, the mean age was 37 years and the mean hospital stay was 7.2 days. Operative procedures performed were:Sleeve lobectomy in 30 patients (13 right, 17 left), partial sleeve right pneumonectomy in 3 and bronchial resection with re-anastomosis in 3 (2 left, 1 right). Twelve patients (33.3%) suffered post-operative problems. There was one operative related mortality. Post operative pathology revealed: 27 patients with typical carcinoid, 2 with atypical carcinoid, 4 with squamous cell carcinoma, 2 with adenocarcifioma and one with hamartoma. Pathological TNM staging revealed: 17 patients with stage 1A, 11 with IB, 5 with IIA and 2 with stage IIIA. Follow-up data were available for all patients except two. Two patients died with disseminated disease 1.5 year and 2 years after surgery. The patient with hamartoma developed local recurrence 5 years later and re-excision was done. One patient with lung cancer developed bone metastases and was alive with disease, while the remaining 30 patient's were alive and disease free. The overall 5 years survival was 83.3%. Conclusion: Bronchoplastic resections achieve local control and long-term survival comparable to the standard resections in

  10. Primary brain tumor presenting as intracranial hemorrhage

    International Nuclear Information System (INIS)

    Tsunoda, Shigeru; Sakaki, Toshisuke; Miyamoto, Seiji; Kyoi, Kikuo; Utsumi, Shozaburo; Kamada, Kitaro; Inui, Shoji; Masuda, Akio.

    1989-01-01

    Ten cases of primary brain tumor presenting as intracranial hemorrhage were studied in terms of the radiological and histological findings. The cases having hemorrhage in the tumor, as established through CT or histologically, were excluded if their onsets were not sudden due to intracranial hemorrhages. The results obtained may be summarized as follows: 1) From an anatomical point of view, cerebral subcortical hemorrhages account for 80%; hemorrhages in the cerebellopontine angle, 10%, and hemorrhages in the basal ganglia, 10%. 2) Plain CT findings showed perifocal low-density areas within 24 hours after onset in all 10 cases. 3) Enhanced CT findings showed enhanced areas in 4 or 6 cases. 4) Angiographic findings revealed abnormalities besides the mass effect in 5 of the 10 cases. 4) Angiographic findings revealed abnormalities besides the mass effect in 5 of the 10 cases. 5) From a histological point of view, glioblastomas account for 30%; malignant astrocytomas, 20%; astrocytomas, 20%; malignant ependymomas, 10%; hemangioblastoma, 10%, and transitional meningiomas, 10%. In conclusion, a perifocal low-density area on CT within 24 hours after onset is the most meaningful indication of intracranial hemorrhage originating from a brain tumor. A histological 'perinuclear halo' in an astrocytoma as an artifact due to hemorrhage may often be misleading in diagnosing mixed oligo-astrocytomas. (author)

  11. Gene expression profiling of circulating tumor cells and peripheral blood mononuclear cells from breast cancer patients

    Czech Academy of Sciences Publication Activity Database

    Hensler, M.; Vancurova, I.; Becht, E.; Palata, O.; Strnad, P.; Tesarova, P.; Cabinakova, M.; Švec, David; Kubista, Mikael; Bartunkova, J.; Spisek, R.; Sojka, L.

    2016-01-01

    Roč. 5, č. 4 (2016), e1102827 ISSN 2162-402X Institutional support: RVO:86652036 Keywords : Breast cancer * gene expression profiling * circulating tumor cells Subject RIV: FD - Oncology ; Hematology Impact factor: 7.719, year: 2016

  12. Gene profiling and circulating tumor cells as biomarker to prognostic of patients with locoregional breast cancer.

    Science.gov (United States)

    Kuniyoshi, Renata K; Gehrke, Flávia de Sousa; Alves, Beatriz C A; Vilas-Bôas, Viviane; Coló, Anna E; Sousa, Naiara; Nunes, João; Fonseca, Fernando L A; Del Giglio, Auro

    2015-09-01

    The gene profile of primary tumors, as well as the identification of circulating tumor cells (CTCs), can provide important prognostic and predictive information. In this study, our objective was to perform tumor gene profiling (TGP) in combination with CTC characterization in women with nonmetastatic breast cancer. Biological samples (from peripheral blood and tumors) from 167 patients diagnosed with stage I, II, and III mammary carcinoma, who were also referred for adjuvant/neoadjuvant chemotherapy, were assessed for the following parameters: (a) the presence of CTCs identified by the expression of CK-19 and c-erbB-2 in the peripheral blood mononuclear cell (PBMC) fraction by quantitative reverse transcription PCR (RT-PCR) and (b) the TGP, which was determined by analyzing the expression of 21 genes in paraffin-embedded tissue samples by quantitative multiplex RT-PCR with the Plexor® system. We observed a statistically significant correlation between the progression-free interval (PFI) and the clinical stage (p = 0.000701), the TGP score (p = 0.006538), and the presence of hormone receptors in the tumor (p = 0.0432). We observed no correlation between the PFI and the presence or absence of CK-19 or HER2 expression in the PBMC fraction prior to the start of treatment or in the two following readouts. Multivariate analysis revealed that only the TGP score significantly correlated with the PFI (p = 0.029247). The TGP is an important prognostic variable for patients with locoregional breast cancer. The presence of CTCs adds no prognostic value to the information already provided by the TGP.

  13. Relationship between circulating tumor cells and epithelial to mesenchymal transition in early breast cancer

    International Nuclear Information System (INIS)

    Mego, M.; Cierna, Z.; Janega, P.; Karaba, M.; Minarik, G.; Benca, J.; Sedlácková, T.; Sieberova, G.; Gronesova, P.; Manasova, D.; Pindak, D.; Sufliarsky, J.; Danihel, L.; Reuben, JM; Mardiak, J.

    2015-01-01

    Circulating tumor cells (CTCs) play a crucial role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. Epithelial to mesenchymal transition (EMT) is involved in cancer invasion and metastasis. The aim of this study was to assess correlation between CTCs and expression of EMT transcription factors TWIST1 and SLUG in breast tumor tissue. This study included 102 early BC patients treated by primary surgery. Peripheral blood mononuclear cells (PBMC) were depleted of hematopoietic cells using RossetteSep™ negative selection kit. RNA extracted from CD45-depleted PBMC was interrogated for expression of EMT (TWIST1, SNAIL1, SLUG, FOXC2 and ZEB1) and epithelial (KRT19) gene transcripts by qRT-PCR. Expression of TWIST1 and SLUG in surgical specimens was evaluated by immunohistochemistry and quantified by multiplicative score. CTCs were detected in 24.5 % patients. CTCs exhibiting only epithelial markers were present in 8.8 % patients, whereas CTCs with only EMT markers were observed in 12.8 % of pts and CTCs co-expressing both markers were detected in 2.9 % pts. We observed lack of correlation between CTCs and expression of TWIST1 and SLUG in breast cancer cells or cancer associated stroma. Lack of correlation was observed for epithelial CTCs as well as for CTCs with EMT. In this translational study, we showed a lack of association between CTCs and expression of EMT-inducing transcription factors, TWIST1 and SLUG, in breast tumor tissue. Despite the fact that EMT is involved in cancer invasion and metastasis our results suggest, that expression of EMT proteins in unselected tumor tissue is not surrogate marker of CTCs with either mesenchymal or epithelial features

  14. Self-targeting of TNF-releasing cancer cells in preclinical models of primary and metastatic tumors.

    Science.gov (United States)

    Dondossola, Eleonora; Dobroff, Andrey S; Marchiò, Serena; Cardó-Vila, Marina; Hosoya, Hitomi; Libutti, Steven K; Corti, Angelo; Sidman, Richard L; Arap, Wadih; Pasqualini, Renata

    2016-02-23

    Circulating cancer cells can putatively colonize distant organs to form metastases or to reinfiltrate primary tumors themselves through a process termed "tumor self-seeding." Here we exploit this biological attribute to deliver tumor necrosis factor alpha (TNF), a potent antitumor cytokine, directly to primary and metastatic tumors in a mechanism that we have defined as "tumor self-targeting." For this purpose, we genetically engineered mouse mammary adenocarcinoma (TSA), melanoma (B16-F10), and Lewis lung carcinoma cells to produce and release murine TNF. In a series of intervention trials, systemic administration of TNF-expressing tumor cells was associated with reduced growth of both primary tumors and metastatic colonies in immunocompetent mice. We show that these malignant cells home to tumors, locally release TNF, damage neovascular endothelium, and induce massive cancer cell apoptosis. We also demonstrate that such tumor-cell-mediated delivery avoids or minimizes common side effects often associated with TNF-based therapy, such as acute inflammation and weight loss. Our study provides proof of concept that genetically modified circulating tumor cells may serve as targeted vectors to deliver anticancer agents. In a clinical context, this unique paradigm represents a personalized approach to be translated into applications potentially using patient-derived circulating tumor cells as self-targeted vectors for drug delivery.

  15. Rare primary malignant tumors of the liver

    International Nuclear Information System (INIS)

    Dahan, H.; Zoppardo, P.; Chagnon, S.; Vilgrain, V.; Blery, M.

    1991-01-01

    Angiosarcoma, epithelioid hemangio-endothelioma (EHE) and fibrolamellar carcinoma (FLC) are far less frequent malignant primary tumors of the liver than liver-cell carcinoma, and usually do not occur in a chronic liver disease. Their diagnosis is histological but a few radiological criteria are suggestive: in younger subjects, a solitary, hypervascularized mass containing calcifications and/or a central fibrous scar suggests an FLC; nodular lesions merging into patches, scattered about the periphery, containing calcified clusters and showing a low and late contrast enhancement after injections suggest an EHE; lastly, in case of occupational exposure, an heterogeneous, hypervascularized mass with a centripetal blush but containing central areas that are opacified early should suggest angiosarcoma. (4 figs) [fr

  16. Primary cysts and tumors of the mediastinum

    Directory of Open Access Journals (Sweden)

    Pedro Bastos

    2007-09-01

    .0 years. Complementary treatment with chemo and/or radiotherapy was provided in 75 patients. Six patients had to be reoperated on for local recurrence (3 or metastasis (3 of the primary lesion. Fifteen patients died of their disease during the follow-up period. Actuarial survival at five years was 97.6% for benign lesions and 76.4% for malignant tumours. Conclusion: Results support surgical resection for benign lesions and an aggressive multimodal approach for malignant tumours. Resumo: Objectivo: Avaliação dos resultados em doentes com cistos e tumores primários do mediastino submetidos a tratamento cirúrgico. Material e métodos: Efectuado um estudo retrospectivo mono-institucional em doentes com cistos e tumores primários do mediastino submetidos a tratamento cirúrgico entre Janeiro de 1992 e Dezembro de 2004. Analisaram-se os dados demográficos, a apresentação clínica, a via de abordagem, a intervenção cirúrgica efectuada, a localização da lesão e o diagnóstico histológico. Avaliaram-se, ainda, os factores preditivos de malignidade, a morbilidade e mortalidade pós--operatórias e os resultados a médio prazo. Resultados: Ao longo de um período de 13 anos foram operados 171 doentes, 73 (43% do sexo feminino e 98 (57% do sexo masculino. A idade média foi de 40,3±19,7 anos (20 dias-78 anos. Em 15(9% dos doentes existia uma lesão cística primária. Os tumores primários incluíam neoplasias tímicas (31%, linfomas (22%, tumores neurogénicos (16%, tumores de células germinativas (9% e um grupo miscelâneo (13%. Em 78 doentes (46% as lesões eram malignas. O mediastino ântero-superior foi o compartimento mais frequentemente envolvido por um cisto ou tumor primário (58%, seguido do mediastino posterior (24% e do mediastino médio (18%. Em 68% dos doentes existiam sintomas na altura do diagnóstico: dor torácica (20%, febre e arrepios (13%, miastenia grave (11%, tosse (10%, dispneia (10% e síndroma da veia cava superior (7%. A an

  17. Circulating Tumor Cell Detection and Capture by Photoacoustic Flow Cytometry in Vivo and ex Vivo

    Energy Technology Data Exchange (ETDEWEB)

    Galanzha, Ekaterina I. [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Zharov, Vladimir P., E-mail: zharovvladimirp@uams.edu [Phillips Classic Laser and Nanomedicine Laboratories, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States); Arkansas Nanomedicine Center, University of Arkansas for Medical Sciences, 4301 West Markham Street, Little Rock, AR 72205 (United States)

    2013-12-10

    Despite progress in detecting circulating tumor cells (CTCs), existing assays still have low sensitivity (1–10 CTC/mL) due to the small volume of blood samples (5–10 mL). Consequently, they can miss up to 10{sup 3}–10{sup 4} CTCs, resulting in the development of barely treatable metastasis. Here we analyze a new concept of in vivo CTC detection with enhanced sensitivity (up to 10{sup 2}–10{sup 3} times) by the examination of the entire blood volume in vivo (5 L in adults). We focus on in vivo photoacoustic (PA) flow cytometry (PAFC) of CTCs using label-free or targeted detection, photoswitchable nanoparticles with ultrasharp PA resonances, magnetic trapping with fiber-magnetic-PA probes, optical clearance, real-time spectral identification, nonlinear signal amplification, and the integration with PAFC in vitro. We demonstrate PAFC’s capability to detect rare leukemia, squamous carcinoma, melanoma, and bulk and stem breast CTCs and its clusters in preclinical animal models in blood, lymph, bone, and cerebrospinal fluid, as well as the release of CTCs from primary tumors triggered by palpation, biopsy or surgery, increasing the risk of metastasis. CTC lifetime as a balance between intravasation and extravasation rates was in the range of 0.5–4 h depending on a CTC metastatic potential. We introduced theranostics of CTCs as an integration of nanobubble-enhanced PA diagnosis, photothermal therapy, and feedback through CTC counting. In vivo data were verified with in vitro PAFC demonstrating a higher sensitivity (1 CTC/40 mL) and throughput (up to 10 mL/min) than conventional assays. Further developments include detection of circulating cancer-associated microparticles, and super-resolution PAFC beyond the diffraction and spectral limits.

  18. Primary primitive neuroectodermal tumor of the orbit

    Directory of Open Access Journals (Sweden)

    Das Dipankar

    2009-01-01

    Full Text Available Primitive neuroectodermal tumor (PNET is a small round cell malignant tumor of neuroectodermal origin. Most of the PNETs occur in the central nervous system (CNS. PNETs recognized outside of CNS are diagnosed as peripheral PNET (pPNET. This tumor which expresses MIC-2 gene (CD99 seems to be least aggressive after complete tumor resection. We describe a rare case of PNET in a young girl.

  19. Detection and quantitation of circulating tumor cell dynamics by bioluminescence imaging in an orthotopic mammary carcinoma model.

    Directory of Open Access Journals (Sweden)

    Laura Sarah Sasportas

    Full Text Available Circulating tumor cells (CTCs have been detected in the bloodstream of both early-stage and advanced cancer patients. However, very little is know about the dynamics of CTCs during cancer progression and the clinical relevance of longitudinal CTC enumeration. To address this, we developed a simple bioluminescence imaging assay to detect CTCs in mouse models of metastasis. In a 4T1 orthotopic metastatic mammary carcinoma mouse model, we demonstrated that this quantitative method offers sensitivity down to 2 CTCs in 0.1-1mL blood samples and high specificity for CTCs originating from the primary tumor, independently of their epithelial status. In this model, we simultaneously monitored blood CTC dynamics, primary tumor growth, and lung metastasis progression over the course of 24 days. Early in tumor development, we observed low numbers of CTCs in blood samples (10-15 cells/100 µL and demonstrated that CTC dynamics correlate with viable primary tumor growth. To our knowledge, these data represent the first reported use of bioluminescence imaging to detect CTCs and quantify their dynamics in any cancer mouse model. This new assay is opening the door to the study of CTC dynamics in a variety of animal models. These studies may inform clinical decision on the appropriate timing of blood sampling and value of longitudinal CTC enumeration in cancer patients.

  20. Can Biomarker Assessment on Circulating Tumor Cells Help Direct Therapy in Metastatic Breast Cancer?

    Directory of Open Access Journals (Sweden)

    Natalie Turner

    2014-03-01

    Full Text Available Circulating tumor cell (CTC count has prognostic significance in metastatic breast cancer, but the predictive utility of CTCs is uncertain. Molecular studies on CTCs have often been limited by a low number of CTCs isolated from a high background of leukocytes. Improved enrichment techniques are now allowing molecular characterisation of single CTCs, whereby molecular markers on single CTCs may provide a real-time assessment of tumor biomarker status from a blood test or “liquid biopsy”, potentially negating the need for a more invasive tissue biopsy. The predictive ability of CTC biomarker analysis has predominantly been assessed in relation to HER2, with variable and inconclusive results. Limited data exist for other biomarkers, such as the estrogen receptor. In addition to the need to define and validate the most accurate and reproducible method for CTC molecular analysis, the clinical relevance of biomarkers, including gain of HER2 on CTC after HER2 negative primary breast cancer, remains uncertain. This review summarises the currently available data relating to biomarker evaluation on CTCs and its role in directing management in metastatic breast cancer, discusses limitations, and outlines measures that may enable future development of this approach.

  1. Phenotypic and Genetic Characterization of Circulating Tumor Cells by Combining Immunomagnetic Selection and FICTION Techniques

    Science.gov (United States)

    Campos, María; Prior, Celia; Warleta, Fernando; Zudaire, Isabel; Ruíz-Mora, Jesús; Catena, Raúl; Calvo, Alfonso; Gaforio, José J.

    2008-01-01

    The presence of circulating tumor cells (CTCs) in breast cancer patients has been proven to have clinical relevance. Cytogenetic characterization of these cells could have crucial relevance for targeted cancer therapies. We developed a method that combines an immunomagnetic selection of CTCs from peripheral blood with the fluorescence immunophenotyping and interphase cytogenetics as a tool for investigation of neoplasm (FICTION) technique. Briefly, peripheral blood (10 ml) from healthy donors was spiked with a predetermined number of human breast cancer cells. Nucleated cells were separated by double density gradient centrifugation of blood samples. Tumor cells (TCs) were immunomagnetically isolated with an anti-cytokeratin antibody and placed onto slides for FICTION analysis. For immunophenotyping and genetic characterization of TCs, a mixture of primary monoclonal anti-pancytokeratin antibodies was used, followed by fluorescent secondary antibodies, and finally hybridized with a TOP2A/HER-2/CEP17 multicolor probe. Our results show that TCs can be efficiently isolated from peripheral blood and characterized by FICTION. Because genetic amplification of TOP2A and ErbB2 (HER-2) in breast cancer correlates with response to anthracyclines and herceptin therapies, respectively, this novel methodology could be useful for a better classification of patients according to the genetic alterations of CTCs and for the application of targeted therapies. (J Histochem Cytochem 56:667–675, 2008) PMID:18413646

  2. Investigating mechanisms of alkalinization for reducing primary breast tumor invasion.

    Science.gov (United States)

    Robey, Ian F; Nesbit, Lance A

    2013-01-01

    The extracellular pH (pHe) of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs). We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (P cancer where systemic alkalinization slows the rate of invasion.

  3. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Martin, Olga A. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Anderson, Robin L. [The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Russell, Prudence A. [Department of Anatomical Pathology, St. Vincent Hospital, Fitzroy, VIC (Australia); Ashley Cox, R. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ivashkevich, Alesia [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Laboratory of DNA Repair and Genomics, Centre for Innate Immunity and Infectious Disease, Monash Institute for Medical Research, Monash University, Clayton, VIC (Australia); Swierczak, Agnieszka; Doherty, Judy P. [Metastasis Research Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Jacobs, Daphne H.M. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Smith, Jai [Molecular Radiation Biology Laboratory, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Siva, Shankar; Daly, Patricia E. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); Ball, David L. [Division of Radiation Oncology and Cancer Imaging, Peter MacCallum Cancer Centre, East Melbourne, VIC (Australia); The Sir Peter MacCallum Department of Oncology, University of Melbourne, Melbourne, VIC (Australia); and others

    2014-02-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies.

  4. Mobilization of Viable Tumor Cells Into the Circulation During Radiation Therapy

    International Nuclear Information System (INIS)

    Martin, Olga A.; Anderson, Robin L.; Russell, Prudence A.; Ashley Cox, R.; Ivashkevich, Alesia; Swierczak, Agnieszka; Doherty, Judy P.; Jacobs, Daphne H.M.; Smith, Jai; Siva, Shankar; Daly, Patricia E.; Ball, David L.

    2014-01-01

    Purpose: To determine whether radiation therapy (RT) could mobilize viable tumor cells into the circulation of non-small cell lung cancer (NSCLC) patients. Methods and Materials: We enumerated circulating tumor cells (CTCs) by fluorescence microscopy of blood samples immunostained with conventional CTC markers. We measured their DNA damage levels using γ-H2AX, a biomarker for radiation-induced DNA double-strand breaks, either by fluorescence-activated cell sorting or by immunofluorescence microscopy. Results: Twenty-seven RT-treated NSCLC patients had blood samples analyzed by 1 or more methods. We identified increased CTC numbers after commencement of RT in 7 of 9 patients treated with palliative RT, and in 4 of 8 patients treated with curative-intent RT. Circulating tumor cells were also identified, singly and in clumps in large numbers, during RT by cytopathologic examination (in all 5 cases studied). Elevated γ-H2AX signal in post-RT blood samples signified the presence of CTCs derived from irradiated tumors. Blood taken after the commencement of RT contained tumor cells that proliferated extensively in vitro (in all 6 cases studied). Circulating tumor cells formed γ-H2AX foci in response to ex vivo irradiation, providing further evidence of their viability. Conclusions: Our findings provide a rationale for the development of strategies to reduce the concentration of viable CTCs by modulating RT fractionation or by coadministering systemic therapies

  5. Assessment of the role of circulating breast cancer cells in tumor formation and metastatic potential using in vivo flow cytometry

    Science.gov (United States)

    Hwu, Derrick; Boutrus, Steven; Greiner, Cherry; Dimeo, Theresa; Kuperwasser, Charlotte; Georgakoudi, Irene

    2011-04-01

    The identification of breast cancer patients who will ultimately progress to metastatic disease is of significant clinical importance. The quantification and assessment of circulating tumor cells (CTCs) has been proposed as one strategy to monitor treatment effectiveness and disease prognosis. However, CTCs have been an elusive population of cells to study because of their small number and difficulties associated with isolation protocols. In vivo flow cytometry (IVFC) can overcome these limitations and provide insights in the role these cells play during primary and metastatic tumor growth. In this study, we used two-color IVFC to examine, for up to ten weeks following orthotopic implantation, changes in the number of circulating human breast cells expressing GFP and a population of circulating hematopoietic cells with strong autofluorescence. We found that the number of detected CTCs in combination with the number of red autofluorescent cells (650 to 690 nm) during the first seven days following implantation was predictive in development of tumor formation and metastasis eight weeks later. These results suggest that the combined detection of these two cell populations could offer a novel approach in the monitoring and prognosis of breast cancer progression, which in turn could aid significantly in their effective treatment.

  6. Circulating tumor cells and their relationship with clinical and morphological characteristics of colorectal cancer

    Directory of Open Access Journals (Sweden)

    O I Kit

    2018-02-01

    Full Text Available Aim. To investigate the dependence of the number of circulating tumor cells in peripheral blood of colorectal cancer patients on the clinical and morphological characteristics of underlying disease. Methods. 91 patients with verified metastatic colorectal cancer Т3-4N1-2М1 were included in the study. The average age of the patients was 61.5±1.7 years. The patients were divided into the study group (laparoscopic surgical treatment, n=44 and control group (open surgical intervention, n=47. The number of circulating tumor cells was determined in CellSearch™ system in the peripheral blood drawn before the intervention. The study of the association of attributes by constructing contingency tables consisted in calculating Pearson’s contingency coefficient c2 with Mantel-Haenszel correction for likelihood (nonparametric correction, estimating statistical significance of contingency and analyzing the tightness of the association by A. Chuprov’s mutual contingency coefficient. Results. We found contingency of the number of circulating tumor cells with clinical and morphological parameters of patients with colorectal cancer. The relationship between potential risk factors and increase of the number of circulating tumor cells in the peripheral blood was observed in all colorectal cancer patients, regardless of the surgical intervention method. The most pronounced association of the number of circulating tumor cells in the peripheral blood of metastatic colorectal cancer patients before surgery according to the mutual contingency coefficient (K was shown to be with present distant metastases (status M1b; K=0.63, p=0.0001 and stage T4 (K=0.56, p=0.0009. Conclusion. The obtained results emphasize the important predictive significance of the circulating tumor cells level in peripheral blood for assessment of the potential for colorectal cancer progression.

  7. Nanostructure Embedded Microchips for Detection, Isolation, and Characterization of Circulating Tumor Cells

    Science.gov (United States)

    2015-01-01

    Conspectus Circulating tumor cells (CTCs) are cancer cells that break away from either a primary tumor or a metastatic site and circulate in the peripheral blood as the cellular origin of metastasis. With their role as a “tumor liquid biopsy”, CTCs provide convenient access to all disease sites, including that of the primary tumor and the site of fatal metastases. It is conceivable that detecting and analyzing CTCs will provide insightful information in assessing the disease status without the flaws and limitations encountered in performing conventional tumor biopsies. However, identifying CTCs in patient blood samples is technically challenging due to the extremely low abundance of CTCs among a large number of hematologic cells. To address this unmet need, there have been significant research endeavors, especially in the fields of chemistry, materials science, and bioengineering, devoted to developing CTC detection, isolation, and characterization technologies. Inspired by the nanoscale interactions observed in the tissue microenvironment, our research team at UCLA pioneered a unique concept of “NanoVelcro” cell-affinity substrates, in which CTC capture agent-coated nanostructured substrates were utilized to immobilize CTCs with high efficiency. The working mechanism of NanoVelcro cell-affinity substrates mimics that of Velcro: when the two fabric strips of a Velcro fastener are pressed together, tangling between the hairy surfaces on two strips leads to strong binding. Through continuous evolution, three generations (gens) of NanoVelcro CTC chips have been established to achieve different clinical utilities. The first-gen NanoVelcro chip, composed of a silicon nanowire substrate (SiNS) and an overlaid microfluidic chaotic mixer, was created for CTC enumeration. Side-by-side analytical validation studies using clinical blood samples suggested that the sensitivity of first-gen NanoVelcro chip outperforms that of FDA-approved CellSearch. In conjunction with

  8. Primary tumors of the patella. A review of 42 cases

    Energy Technology Data Exchange (ETDEWEB)

    Kransdorf, M.J. (Walter Reed Army Medical Center, Washington, DC (USA). Dept. of Radiology; University of the Health Sciences, Bethesda, MD (USA). Dept. of Radiology and Nuclear Medicine); Moser, R.P. Jr. (Armed Forces Inst. of Pathology, Washington, DC (USA). Dept. of Radiologic Pathology; University of the Health Sciences, Bethesda, MD (USA). Dept. of Radiology and Nuclear Medicine); Vinh, T.N. (Armed Forces Inst. of Pathology, Washington, DC (USA). Dept. of Orthopaedic Surgery); Aoki, J. (Armed Forces Inst. of Pathology, Washington, DC (USA). Dept. of Radiologic Pathology); Callaghan, J.J. (Duke Univ., Durham, NC (USA). Dept. of Orthopaedic Surgery)

    1989-08-01

    This study reports 42 cases of histologically proven and radiographically correlated primary patellar tumors. Despite diverse histologic diagnoses, the radiographic appearanaces of benign as opposed to malignant patellar neoplasms are essentially indistinguishable. Although the literature suggests that giant cell tumor is the most frequent benign tumor of the patella, the most common benign neoplasm in this series is chondroblastoma (16 cases). Only four primary malignant lesions were encountered, three cases of lymphoma and one case of hemangioendothelioma. Since 38 (90%) of the 42 cases were benign, a benign etiology should be strongly favored, notwithstanding the radiographic appearance, whenever a primary patellar tumor is encountered. (orig.).

  9. Circulating Tumor Cells in Breast Cancer Patients Treated by Neoadjuvant Chemotherapy: A Meta-analysis.

    Science.gov (United States)

    Bidard, François-Clément; Michiels, Stefan; Riethdorf, Sabine; Mueller, Volkmar; Esserman, Laura J; Lucci, Anthony; Naume, Bjørn; Horiguchi, Jun; Gisbert-Criado, Rafael; Sleijfer, Stefan; Toi, Masakazu; Garcia-Saenz, Jose A; Hartkopf, Andreas; Generali, Daniele; Rothé, Françoise; Smerage, Jeffrey; Muinelo-Romay, Laura; Stebbing, Justin; Viens, Patrice; Magbanua, Mark Jesus M; Hall, Carolyn S; Engebraaten, Olav; Takata, Daisuke; Vidal-Martínez, José; Onstenk, Wendy; Fujisawa, Noriyoshi; Diaz-Rubio, Eduardo; Taran, Florin-Andrei; Cappelletti, Maria Rosa; Ignatiadis, Michail; Proudhon, Charlotte; Wolf, Denise M; Bauldry, Jessica B; Borgen, Elin; Nagaoka, Rin; Carañana, Vicente; Kraan, Jaco; Maestro, Marisa; Brucker, Sara Yvonne; Weber, Karsten; Reyal, Fabien; Amara, Dominic; Karhade, Mandar G; Mathiesen, Randi R; Tokiniwa, Hideaki; Llombart-Cussac, Antonio; Meddis, Alessandra; Blanche, Paul; d'Hollander, Koenraad; Cottu, Paul; Park, John W; Loibl, Sibylle; Latouche, Aurélien; Pierga, Jean-Yves; Pantel, Klaus

    2018-04-12

    We conducted a meta-analysis in nonmetastatic breast cancer patients treated by neoadjuvant chemotherapy (NCT) to assess the clinical validity of circulating tumor cell (CTC) detection as a prognostic marker. We collected individual patient data from 21 studies in which CTC detection by CellSearch was performed in early breast cancer patients treated with NCT. The primary end point was overall survival, analyzed according to CTC detection, using Cox regression models stratified by study. Secondary end points included distant disease-free survival, locoregional relapse-free interval, and pathological complete response. All statistical tests were two-sided. Data from patients were collected before NCT (n = 1574) and before surgery (n = 1200). CTC detection revealed one or more CTCs in 25.2% of patients before NCT; this was associated with tumor size (P < .001). The number of CTCs detected had a detrimental and decremental impact on overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P < .001), but not on pathological complete response. Patients with one, two, three to four, and five or more CTCs before NCT displayed hazard ratios of death of 1.09 (95% confidence interval [CI] = 0.65 to 1.69), 2.63 (95% CI = 1.42 to 4.54), 3.83 (95% CI = 2.08 to 6.66), and 6.25 (95% CI = 4.34 to 9.09), respectively. In 861 patients with full data available, adding CTC detection before NCT increased the prognostic ability of multivariable prognostic models for overall survival (P < .001), distant disease-free survival (P < .001), and locoregional relapse-free interval (P = .008). CTC count is an independent and quantitative prognostic factor in early breast cancer patients treated by NCT. It complements current prognostic models based on tumor characteristics and response to therapy.

  10. Circulating tumor cells in patients with breast cancer: monitoring chemotherapy success.

    Science.gov (United States)

    Ušiaková, Zuzana; Mikulová, Veronika; Pintérová, Daniela; Brychta, Milan; Valchář, Josef; Kubecová, Martina; Tesařová, Petra; Bobek, Vladimír; Kološtová, Katarína

    2014-01-01

    Circulating tumor cells (CTCs) are an independent prognostic factor for patients with metastatic breast cancer (MBC). However, the role of CTCs in early breast cancer management is not yet clearly defined. The aim of this study was to assess the CTC-positivity rate in patients undergoing chemotherapy depending on breast cancer stage in the adjuvant and neoadjuvant setting. We evaluated the ability to confirm therapy response by CTC analysis. CTCs isolated from blood by means of immunomagnetic separation were further characterized by means of reverse transcriptase - polymerase chain reaction (RT-PCR) for epithelial cell adhesion molecule (EPCAM), mucin 1 (MUC1) and v-erb-b2 avian erythroblastic leukemia viral oncogene homolog 2 (HER2) transcripts with the AdnaTest™. This prospective study included 179 patients; altogether 419 blood samples were evaluated. Patients with primary tumors were divided into neoadjuvant (n=38), and adjuvant (n=100) groups. Forty-one patients with MBC were evaluated under palliative treatment. CTC positivity was described in 35% of patients with early breast cancer without detected metastases before neoadjuvant chemotherapy; similarly, a 26% positivity rate was found in the adjuvant group. In patients with MBC, we detected CTCs in 43% of them. After completing the therapy, the CTC positivity rate decreased to 5% in the neoadjuvant group, to 13% in the adjuvant group and to 12% in the MBC group. CTC positivity after the therapy may classify a subgroup of patients at high risk of developing metastatic disease. This was even true when a patient was evaluated as being CTC-negative before chemotherapy. The multivariate analysis evaluating the correlation of CTC positivity with clinicopathological characteristics such as tumor size, nodal involvement, hormone receptor status, HER2 expression and number of metastatic sites revealed no statistically significant relationships. CTC status may have a significant impact on early BC management

  11. A novel approach for the detection and genetic analysis of live melanoma circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Melody J Xu

    Full Text Available Circulating tumor cell (CTC detection and genetic analysis may complement currently available disease assessments in patients with melanoma to improve risk stratification and monitoring. We therefore sought to establish the feasibility of a telomerase-based assay for detecting and isolating live melanoma CTCs.The telomerase-based CTC assay utilizes an adenoviral vector that, in the presence of elevated human telomerase activity, drives the amplification of green fluorescent protein. Tumor cells are then identified via an image processing system. The protocol was tested on melanoma cells in culture or spiked into control blood, and on samples from patients with metastatic melanoma. Genetic analysis of the isolated melanoma CTCs was then performed for BRAF mutation status.The adenoviral vector was effective for all melanoma cell lines tested with sensitivity of 88.7% (95%CI 85.6-90.4% and specificity of 99.9% (95%CI 99.8-99.9%. In a pilot trial of patients with metastatic disease, CTCs were identified in 9 of 10 patients, with a mean of 6.0 CTCs/mL. At a cutoff of 1.1 CTCs/mL, the telomerase-based assay exhibits test performance of 90.0% sensitivity and 91.7% specificity. BRAF mutation analysis of melanoma cells isolated from culture or spiked control blood, or from pilot patient samples was found to match the known BRAF mutation status of the cell lines and primary tumors.To our knowledge, this is the first report of a telomerase-based assay effective for detecting and isolating live melanoma CTCs. These promising findings support further studies, including towards integrating into the management of patients with melanoma receiving multimodality therapy.

  12. Primary Neuroendocrine Tumor of the Breast: Imaging Features

    International Nuclear Information System (INIS)

    Chang, Eun Deok; Kim, Min Kyun; Kim, Jeong Soo; Whang, In Yong

    2013-01-01

    Focal neuroendocrine differentiation can be found in diverse histological types of breast tumors. However, the term, neuroendocrine breast tumor, indicates the diffuse expression of neuroendocrine markers in more than 50% of the tumor cell population. The imaging features of neuroendocrine breast tumor have not been accurately described due to extreme rarity of this tumor type. We present a case of a pathologically confirmed, primary neuroendocrine breast tumor in a 42-year-old woman, with imaging findings difficult to be differentiated from that of invasive ductal carcinoma

  13. Intensity-Modulated Radiation Therapy for Primary Brain Tumors

    Institute of Scientific and Technical Information of China (English)

    Zhong-min Wang

    2004-01-01

    Radiation therapy has been used to treat primary brain tumors as standard primary and/or adjunctive therapies for decades. It is difficult for conventional radiotherapy to deliver a lethal dose of radiation to the tumors while sparing surrounding normal brain due to complicated structures and multifunction in human brain. With the understanding of radiation physics and computer technology, a number of novel and more precise radiotherapies have been developed in recent years. Intensity modulated radiotherapy (IMRT) is one of these strategies. The use of IMRT in the treatment of primary brain tumors is being increasing nowadays. It shows great promise for some of primary brain tumors and also presents some problems, This review highlights current IMRT in the treatment of mainly primary brain tumors.

  14. Nanoroughened adhesion-based capture of circulating tumor cells with heterogeneous expression and metastatic characteristics

    International Nuclear Information System (INIS)

    Chen, Weiqiang; Allen, Steven G.; Reka, Ajaya Kumar; Qian, Weiyi; Han, Shuo; Zhao, Jianing; Bao, Liwei; Keshamouni, Venkateshwar G.; Merajver, Sofia D.; Fu, Jianping

    2016-01-01

    Circulating tumor cells (CTCs) have shown prognostic relevance in many cancer types. However, the majority of current CTC capture methods rely on positive selection techniques that require a priori knowledge about the surface protein expression of disseminated CTCs, which are known to be a dynamic population. We developed a microfluidic CTC capture chip that incorporated a nanoroughened glass substrate for capturing CTCs from blood samples. Our CTC capture chip utilized the differential adhesion preference of cancer cells to nanoroughened etched glass surfaces as compared to normal blood cells and thus did not depend on the physical size or surface protein expression of CTCs. The microfluidic CTC capture chip was able to achieve a superior capture yield for both epithelial cell adhesion molecule positive (EpCAM+) and EpCAM- cancer cells in blood samples. Additionally, the microfluidic CTC chip captured CTCs undergoing transforming growth factor beta-induced epithelial-to-mesenchymal transition (TGF-β-induced EMT) with dynamically down-regulated EpCAM expression. In a mouse model of human breast cancer using EpCAM positive and negative cell lines, the number of CTCs captured correlated positively with the size of the primary tumor and was independent of their EpCAM expression. Furthermore, in a syngeneic mouse model of lung cancer using cell lines with differential metastasis capability, CTCs were captured from all mice with detectable primary tumors independent of the cell lines’ metastatic ability. The microfluidic CTC capture chip using a novel nanoroughened glass substrate is broadly applicable to capturing heterogeneous CTC populations of clinical interest independent of their surface marker expression and metastatic propensity. We were able to capture CTCs from a non-metastatic lung cancer model, demonstrating the potential of the chip to collect the entirety of CTC populations including subgroups of distinct biological and phenotypical properties. Further

  15. Primary Tumor Thickness is a Prognostic Factor in Stage IV Melanoma: A Retrospective Study of Primary Tumor Characteristics.

    Science.gov (United States)

    Luen, Stephen; Wong, Siew Wei; Mar, Victoria; Kelly, John W; McLean, Catriona; McArthur, Grant A; Haydon, Andrew

    2018-01-01

    Stage IV melanoma exhibits a diverse range of tumor biology from indolent to aggressive disease. Many important prognostic factors have already been identified. Despite this, the behavior of metastatic melanoma remains difficult to predict. We sought to determine if any primary tumor characteristics affect survival following the diagnosis of stage IV melanoma. All patients diagnosed with stage IV melanoma between January 2003 and December 2012 were identified from the Victorian Melanoma Service database. Retrospective chart review was performed to collect data on primary tumor characteristics (thickness, ulceration, mitotic rate, melanoma subtype, or occult primary). Known and suspected prognostic factors were additionally collected (time to diagnosis of stage IV disease, age, sex, stage, receipt of chemotherapy, and era of recurrence). The effect of primary tumor characteristics on overall survival from the date of diagnosis of stage IV disease was assessed. A total of 227 patients with a median follow-up of 5 years from diagnosis of stage IV disease were identified. Median overall survival of the cohort was 250 days.Of the primary tumor characteristics assessed, only tumor thickness affected survival from diagnosis of stage IV disease, hazard ratio=1.09 (1.02 to 1.16), P=0.008. This remained significant in multivariate analysis, P=0.007. Other primary tumor characteristics did not significantly influence survival. Primary tumor thickness is a significant prognostic factor in stage IV melanoma. Our data suggest that the biology of the primary melanoma may persist to influence the behavior of metastatic disease.

  16. Evaluation of primary neck tumors by computed tomography

    International Nuclear Information System (INIS)

    Suzuki, Keiko

    1983-01-01

    Application of computed tomography (CT) to neck tumors has received little attention. 40 CT scans of primary neck tumors were reviewed, and CT was proved to be extremely useful in the diagnosis and definition of extension of primary neck tumors. In the carotid triangle and sternocleidomastoid region 2nd branchial cysts, cystic hygromas and tuberculous lymphadenitis are included in the differential diagnosis of cystic tumors. In the carotid triangle markedly enhanced solid tumors must be paragangliomas, i.e. carotid body tumors, if they are located posteromedial to the carotid artery. And moderately enhanced tumors are neurilemmomas arising from sympathetic or vagus nerve. It is easy to define enlarged deep jugular lymph nodes because they are located lateral to the carotid artery. In the supraclavicular fossa enlarged lymph nodes can be differentiated from neurilemmomas of branchial plexus because enlarged lymph nodes are located anterior to subclavian vessels or anterior scalene muscle and branchial neurilemmomas are located superoposterior to them. (author)

  17. Primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy

    Directory of Open Access Journals (Sweden)

    Cem Gundogdu

    2011-07-01

    Full Text Available Cancer complicates approximately 0.1% of all pregnancies. Primary tracheal carcinoma is one of very rarely seen tumors and the rate of its being seen makes up approximately % 0,2 of all tumors of respiratory tract. The patient, 28 years old, who has 28-weeks-pregnant, was diagnosed with primary tracheal adenocystic carcinoma. Patient was made operation as thoracotomy and tracheal tumor was removed at the 28th week of pregnancy. Patient was delivered with sectio abdominale at the 39th week of pregnancy. Primary tracheal adenocystic carcinoma is very rarely seen tumors and it is the first tracheal ACC with pregnancy case in literature to have been detected and surgically treated during pregnancy. We discussed primary tracheal adenocystic carcinoma and tracheal tumors during pregnancy with literature.

  18. International study on inter-reader variability for circulating tumor cells in breast cancer

    NARCIS (Netherlands)

    Ignatiadis, Michail; Riethdorf, Sabine; Bidard, François-Clement; Vaucher, Isabelle; Khazour, Mustapha; Rothe, Francoise; Metallo, Jessica; Rouas, Ghizlane; Payne, Rachel E.; Coombes, Raoul Charles; Teufel, Ingrid; Andergassen, Ulrich; Apostolaki, Stella; Politaki, Eleni; Mavroudis, Dimitris; Bessi, Silvia; Pestrin, Martta; di Leo, Angelo; Campion, Michael; Reinholz, Monica; Perez, Edith; Piccart, Martine; Borgen, Elin; Naume, Bjorn; Jimenez, Jose; Aura, Claudia Monica; Zorzino, Laura; Cassatella, Maria Cristina; Sandri, Maria Teresa; Mostert, Bianca; Sleijfer, Stefan; Kraan, Jaco; Janni, Wolfgang; Fehm, Tanja; Rack, Brigitte; Terstappen, Leonardus Wendelinus Mathias Marie; Repollet, Madeline; Pierga, Jean-Yves; Miller, Craig; Sotiriou, Christos; Michiels, Stefan; Pantel, Klaus

    2014-01-01

    IntroductionCirculating tumor cells (CTCs) have been studied in breast cancer with the CellSearch® system. Given the low CTC counts in non-metastatic breast cancer, it is important to evaluate the inter-reader agreement. MethodsCellSearch® images (N = 272) of either CTCs or white blood cells or

  19. Circulating tumor cells, disease recurrence and survival in newly diagnosed breast cancer

    NARCIS (Netherlands)

    Franken, Bas; De Groot, Marco R.; Mastboom, Walter J.B.; Vermes, I.; van der Palen, Jacobus Adrianus Maria; Tibbe, Arjan G.J.; Terstappen, Leonardus Wendelinus Mathias Marie

    2012-01-01

    Introduction The presence of circulating tumor cells (CTC) is an independent prognostic factor for progression-free survival and breast cancer-related death (BRD) for patients with metastatic breast cancer beginning a new line of systemic therapy. The current study was undertaken to explore whether

  20. Molecular profiling of circulating tumor cells links plasticity to the metastatic process in endometrial cancer

    NARCIS (Netherlands)

    Alonso-Alconada, Lorena; Muinelo-Romay, Laura; Madissoo, Kadri; Diaz-Lopez, Antonio; Krakstad, Camilla; Trovik, Jone; Wik, Elisabeth; Hapangama, Dharani; Coenegrachts, Lieve; Cano, Amparo; Gil-Moreno, Antonio; Chiva, Luis; Cueva, Juan; Vieito, Maria; Ortega, Eugenia; Mariscal, Javier; Colas, Eva; Castellvi, Josep; Cusido, Maite; Dolcet, Xavier; Nijman, Hans W.; Bosse, Tjalling; Green, John A.; Romano, Andrea; Reventos, Jaume; Lopez-Lopez, Rafael; Salvesen, Helga B.; Amant, Frederic; Matias-Guiu, Xavier; Moreno-Bueno, Gema; Abal, Miguel

    2014-01-01

    Background: About 20% of patients diagnosed with endometrial cancer (EC) are considered high-risk with unfavorable prognosis. In the framework of the European Network for Individualized Treatment in EC (ENITEC), we investigated the presence and phenotypic features of Circulating Tumor Cells (CTC) in

  1. Primary cardiac and pericardial tumors, imaging approach

    Energy Technology Data Exchange (ETDEWEB)

    Yu-Qing Liu, M D [Chinese Academy of Medical Sciences, Beijing, BJ (China). Dept. of Radiology, Fu Wai Hospital and Cardiovascular Inst.

    1996-12-31

    The incidence of cardiac tumor and its classification was discussed. Imaging study i.e. conventional radiology, echocardiagoaphy (echo), magnetic resonance imaging (MRI), angiography and computed tomography (CT) used also discussed briefly. (8 refs.).

  2. Primary cardiac and pericardial tumors, imaging approach

    International Nuclear Information System (INIS)

    Yu-Qing Liu, M.D.

    1995-01-01

    The incidence of cardiac tumor and its classification was discussed. Imaging study i.e. conventional radiology, echocardiagoaphy (echo), magnetic resonance imaging (MRI), angiography and computed tomography (CT) used also discussed briefly. (8 refs.)

  3. Anti-epithelial cell adhesion molecule antibodies and the detection of circulating normal-like breast tumor cells

    NARCIS (Netherlands)

    A.M. Sieuwerts (Anieta); J. Kraan (Jaco); J. Bolt (Joan); P. van der Spoel (Petra); F. Elstrodt (Fons); A.E.M. Schutte (Mieke); J.W.M. Martens (John); J.W. Gratama (Jan-Willem); S. Sleijfer (Stefan); J.A. Foekens (John)

    2009-01-01

    textabstractIdentification of specific subtypes of circulating tumor cells in peripheral blood of cancer patients can provide information about the biology of metastasis and improve patient management. However, to be effective, the method used to identify circulating tumor cells must detect all

  4. A Case Report of Primary Cardiac Tumor in A Neonate

    Directory of Open Access Journals (Sweden)

    Sh. Rejaei

    2008-04-01

    Full Text Available Introduction: Primary cardiac tumors are extremely rare in infants and children . Most primary cardiac tumors in pediatric age group are benign, and less than 10% of such tumors are malignant. Many of these tumors are asymptomatic and incidentally diagnosed. The clinical manifestations are very different and includes direct cardiac effect, systemic effect , and embolic phenomena. Every infant or child with an unusual cardiac murmur, unexplained congestive heart failure, or arrhythmia should be evaluated for cardiac tumors. Echocardiography has contributed significantly to the evaluation of these patients. Surgery is the only treatment for primary cardiac tumors that require intervention with a relatively good prognosis. Case Report: The patient was a 20 days old neonate presented with severe congestive heart failure. Evaluation of the patient showed primary cardiac tumor in the left atrium and ventricle. We recommended surgical removal of the tumor but her parents denied surgical intervention at all. Conclusion: After about one year follow up, congestive heart failure symptoms were controlled and the tumor size was decreased.

  5. Multiple primary tumor (TPM) in Uruguay - 2008

    International Nuclear Information System (INIS)

    Musetti, C; Garau, M; Alonso, R; Barrios, E.

    2010-01-01

    Objective: To evaluate the incidence of TPM in Uruguay through the RNC data. Materials and Methods: Of the incident cases registered in 2008, they were selected those presented in the database prior cancer registry. The are excluded in situ of the cervix and non-melanoma skin carcinomas. Results: At the present time are entered to the the base of the RNC 11859 new cases of cancer incidents in 2008. Of these 566 (4.7%) had a prior record of criteria selection where 308 were women and 258 men. Of these, 450 met the IACR / IARC criteria (*). (Two topographies and / or different histologies). The median age of first tumor presentation was 65 years (22-89). The second 71 years (27-94). The median of the difference was about 4 years Analyzed by gender: Breast cancer (CM) was the most frequent tumor in women, cancer as first (142) and as second (85). The most common associations (excluding Bilateral) CM, CM with gynecological tumors were (TG: ovarian and corpus uteri) 11% CM and colo-rectum (CCR) (9.4%), TG and CCR (5%). 26% of female cases occurred in two hormone-dependent tumors (CM and CM bilateral or TG). In men prostate cancer (PC) is the most common tumor as first cancer (76) but the CCR is the most frequent and second (56). The association comprises CP-CCR 15% of cases and CP association and transitional tumors (TT) 10%. The association of two or more snuff-dependent tumors was observed in 8% of cases. When discriminated by sex in men is 13%, amounting to 19% if taking into account the multiple TT, while in women corresponds to 2%. Conclusions: The profile presentation of TPM in the RNC of Uruguay is similar to that reported other records in both frequency (depending on the criteria that defined) and associated type of tumors. The most frequent associations also They are similar to those observed by other authors: CCR, CM and TG women and CCR, and CP TT in men. The association of tumors are also observed with risk common factors: in women hormonal factors linked to

  6. Nanostructured Surfaces to Target and Kill Circulating Tumor Cells While Repelling Leukocytes

    Directory of Open Access Journals (Sweden)

    Michael J. Mitchell

    2012-01-01

    Full Text Available Hematogenous metastasis, the process of cancer cell migration from a primary to distal location via the bloodstream, typically leads to a poor patient prognosis. Selectin proteins hold promise in delivering drug-containing nanocarriers to circulating tumor cells (CTCs in the bloodstream, due to their rapid, force-dependent binding kinetics. However, it is challenging to deliver such nanocarriers while avoiding toxic effects on healthy blood cells, as many possess ligands that adhesively interact with selectins. Herein, we describe a nanostructured surface to capture flowing cancer cells, while preventing human neutrophil adhesion. Microtube surfaces with immobilized halloysite nanotubes (HNTs and E-selectin functionalized liposomal doxorubicin (ES-PEG L-DXR significantly increased the number of breast adenocarcinoma MCF7 cells captured from flow, yet also significantly reduced the number of captured neutrophils. Neutrophils firmly adhered and projected pseudopods on surfaces coated only with liposomes, while neutrophils adherent to HNT-liposome surfaces maintained a round morphology. Perfusion of both MCF7 cells and neutrophils resulted in primarily cancer cell adhesion to the HNT-liposome surface, and induced significant cancer cell death. This work demonstrates that nanostructured surfaces consisting of HNTs and ES-PEG L-DXR can increase CTC recruitment for chemotherapeutic delivery, while also preventing healthy cell adhesion and uptake of therapeutic intended for CTCs.

  7. Circulating tumor DNA for triple-negative breast cancer diagnosis and treatment decisions.

    Science.gov (United States)

    Saliou, Adrien; Bidard, François-Clément; Lantz, Olivier; Stern, Marc-Henri; Vincent-Salomon, Anne; Proudhon, Charlotte; Pierga, Jean-Yves

    2016-01-01

    Triple-negative breast cancer (TNBC) is a highly aggressive disease characterized by a high number of relapses and poor overall survival. The heterogeneity of the disease and the limited treatment options compared to other breast cancer subtypes mainly explain these clinical outcomes. New biomarkers are urgently needed to improve the management of TNBC. Circulating tumor DNA, identified by tumor-related molecular alterations, could be used in the context of non-invasive "liquid biopsy" and help in TNBC diagnosis and treatment decisions. In this review, we discuss the key issues related to the potential of circulating tumor DNA to improve the management of this disease and the future steps to overcome before its implementation into clinical routine within the next 5 years.

  8. Androgen receptor expression on circulating tumor cells in metastatic breast cancer.

    Directory of Open Access Journals (Sweden)

    Takeo Fujii

    Full Text Available Androgen receptor (AR is frequently detected in breast cancers, and AR-targeted therapies are showing activity in AR-positive (AR+ breast cancer. However, the role of AR in breast cancers is still not fully elucidated and the biology of AR in breast cancer remains incompletely understood. Circulating tumor cells (CTCs can serve as prognostic and diagnostic tools, prompting us to measure AR protein expression and conduct genomic analyses on CTCs in patients with metastatic breast cancer.Blood samples from patients with metastatic breast cancer were deposited on glass slides, subjected to nuclear staining with DAPI, and reacted with fluorescent-labeled antibodies to detect CD45, cytokeratin (CK, and biomarkers of interest (AR, estrogen receptor [ER], and HER2 on all nucleated cells. The stained slides were scanned and enumerated by non-enrichment-based non-biased approach independent of cell surface epithelial cell adhesion molecule (EpCAM using the Epic Sciences CTC platform. Data were analyzed using established digital pathology algorithms.Of 68 patients, 51 (75% had at least 1 CTC, and 49 of these 51 (96% had hormone-receptor-positive (HR+/HER2-negative primary tumors. AR was expressed in CK+ CTCs in 10 patients. Of these 10 patients, 3 also had ER expression in CK+ CTCs. Single cell genomic analysis of 78 CTCs from 1 of these 3 patients identified three distinct copy number patterns. AR+ cells had a lower frequency of chromosomal changes than ER+ and HER2+ cells.CTC enumeration and analysis using no enrichment or selection provides a non-biased approach to detect AR expression and chromosomal aberrations in CTCs in patients with metastatic breast cancer. The heterogeneity of intrapatient AR expression in CTCs leads to the new hypothesis that patients with AR+ CTCs have heterogeneous disease with multiple drivers. Further studies are warranted to investigate the clinical applicability of AR+ CTCs and their heterogeneity.

  9. Investigating Mechanisms of Alkalinization for Reducing Primary Breast Tumor Invasion

    Directory of Open Access Journals (Sweden)

    Ian F. Robey

    2013-01-01

    Full Text Available The extracellular pH (pHe of many solid tumors is acidic as a result of glycolytic metabolism and poor perfusion. Acidity promotes invasion and enhances metastatic potential. Tumor acidity can be buffered by systemic administration of an alkaline agent such as sodium bicarbonate. Tumor-bearing mice maintained on sodium bicarbonate drinking water exhibit fewer metastases and survive longer than untreated controls. We predict this effect is due to inhibition of tumor invasion. Reducing tumor invasion should result in fewer circulating tumor cells (CTCs. We report that bicarbonate-treated MDA-MB-231 tumor-bearing mice exhibited significantly lower numbers of CTCs than untreated mice (. Tumor pHe buffering may reduce optimal conditions for enzymes involved in tumor invasion such as cathepsins and matrix metalloproteases (MMPs. To address this, we tested the effect of transient alkalinization on cathepsin and MMP activity using enzyme activatable fluorescence agents in mice bearing MDA-MB-231 mammary xenografts. Transient alkalinization significantly reduced the fluorescent signal of protease-specific activatable agents in vivo (. Alkalinization, however, did not affect expression of carbonic anhydrase IX (CAIX. The findings suggest a possible mechanism in a live model system for breast cancer where systemic alkalinization slows the rate of invasion.

  10. Molecular detection of peripheral blood breast cancer mRNA transcripts as a surrogate biomarker for circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Adriana Lasa

    Full Text Available Circulating tumor cells (CTCs are becoming a scientifically recognized indicator of primary tumors and/or metastasis. These cells can now be accurately detected and characterized as the result of technological advances. We analyzed the presence of CTCs in the peripheral blood of patients with metastatic breast cancer by real-time reverse-transcription PCR (RT-qPCR using a panel of selected genes. The analysis of a single marker, without an EpCAM based enrichment approach, allowed the positive identification of 35% of the metastatic breast cancer patients. The analysis of five genes (SCGB2, TFF1, TFF3, Muc1, KRT20 performed in all the samples increased the detection to 61%. We describe a sensitive, reproducible and easy to implement approach to characterize CTC in patients with metastasic breast cancer.

  11. Epilepsy in primary intracranial tumors in a neurosurgical hospital in ...

    African Journals Online (AJOL)

    Background: Seizures may be manifestation of intracranial tumor (IT) and demand thorough neurological evaluation. This paper examines epidemiology, lesion characteristics and outcome of seizures associated with primary IT. Methods: Retrospective analysis of medical records, computed tomography and magnetic ...

  12. Primary intraspinal extradural primitive neuroectodermal tumor: A rare case.

    Science.gov (United States)

    Rege, Shrikant V; Tadghare, Jitendra; Patil, Harshad; Narayan, Sharadendu

    2016-01-01

    Primitive neuroectodermal tumors (PNETs) are aggressive childhood malignancies and are difficult to treat. Primary intraspinal PNETs are rare. These patients have poor prognosis with short survival time even after surgery and chemoradiation. As there are no standard guidelines exist for the management of these tumors, a multidisciplinary approach has been employed with varying success. According to the review of literature, only few cases of primary intraspinal extradural PNETs have been reported. Herein, author has described a case of intraspinal, extradural PNET.

  13. Preoperative tumor localization of primary hyperparathyroidism

    International Nuclear Information System (INIS)

    Morita, Yutaka; Shinohara, Masahiro; Ito, Kazuo; Imamura, Fumimoto; Kasai, Yoichi; Ishizuka, Reiki.

    1983-01-01

    The diagnostic rate of each methods were discussed in thirty six cases and following conclusions were made. 1. The diagnostic rate of US, RI, AG and VS was 64.7%, 50%, 57.9%, 60.7% respectively. 2. Ultrasonography and subtruction-scintigraphy were useful screening examination for localization of parathyroid tumor. 3. The reasonable diagnostic procedures were as follows. 1) In the cases of palpable, reno-uretrolithiasic type, and biochemical type: US → RI → VS 2) In the cases of nonpalpable osteolytic type, and previous neck surgery: US → RI → AG → VS These results indicate that the systemic diagnosis are useful to predict localization of parathyroid tumors. (author)

  14. Quantitation of circulating tumor cells in blood samples from ovarian and prostate cancer patients using tumor-specific fluorescent ligands.

    Science.gov (United States)

    He, Wei; Kularatne, Sumith A; Kalli, Kimberly R; Prendergast, Franklyn G; Amato, Robert J; Klee, George G; Hartmann, Lynn C; Low, Philip S

    2008-10-15

    Quantitation of circulating tumor cells (CTCs) can provide information on the stage of a malignancy, onset of disease progression and response to therapy. In an effort to more accurately quantitate CTCs, we have synthesized fluorescent conjugates of 2 high-affinity tumor-specific ligands (folate-AlexaFluor 488 and DUPA-FITC) that bind tumor cells >20-fold more efficiently than fluorescent antibodies. Here we determine whether these tumor-specific dyes can be exploited for quantitation of CTCs in peripheral blood samples from cancer patients. A CTC-enriched fraction was isolated from the peripheral blood of ovarian and prostate cancer patients by an optimized density gradient centrifugation protocol and labeled with the aforementioned fluorescent ligands. CTCs were then quantitated by flow cytometry. CTCs were detected in 18 of 20 ovarian cancer patients (mean 222 CTCs/ml; median 15 CTCs/ml; maximum 3,118 CTCs/ml), whereas CTC numbers in 16 gender-matched normal volunteers were negligible (mean 0.4 CTCs/ml; median 0.3 CTCs/ml; maximum 1.5 CTCs/ml; p < 0.001, chi(2)). CTCs were also detected in 10 of 13 prostate cancer patients (mean 26 CTCs/ml, median 14 CTCs/ml, maximum 94 CTCs/ml) but not in 18 gender-matched healthy donors (mean 0.8 CTCs/ml, median 1, maximum 3 CTC/ml; p < 0.0026, chi(2)). Tumor-specific fluorescent antibodies were much less efficient in quantitating CTCs because of their lower CTC labeling efficiency. Use of tumor-specific fluorescent ligands to label CTCs in peripheral blood can provide a simple, accurate and sensitive method for determining the number of cancer cells circulating in the bloodstream.

  15. Radiation therapy for primary spinal cord tumors in adults

    International Nuclear Information System (INIS)

    Jeremic, B.; Grujicic, D.; Jovanovic, D.; Djuric, L.; Mijatovic, L.

    1990-01-01

    This paper evaluates the role of radiation therapy in management of primary spinal cord tumors in adults. Records of 21 patients with primary spinal cord tumors treated with radiation therapy after surgery were retrospectively reviewed. Histologic examination showed two diffuse and 10 localized ependymomas, six low-grade gliomas, and three malignant gliomas. Surgery consisted of gross tumor resection in six patients, subtotal resection in three patients, and biopsy in 12 patients. Three patients also received chemotherapy. Radiation dose range from 45 to 55 Cy

  16. FFTF primary system transition to natural circulation from low reactor power

    International Nuclear Information System (INIS)

    Bouchey, G.D.; Additon, S.L.; Nutt, W.T.

    1980-01-01

    Plans for reactor and primary loop natural circulation testing in the Fast Flux Test Facility (FFTF) are summarized. Detailed pretest planning with an emphasis on understanding the implications of process noise and model uncertainties for model verification and test acceptance are discussed for a transition to natural circulation in the reactor core and primary heat transport loops from initial conditions of 5% of rated reactor power and 75% of full flow

  17. Tumor-Associated Macrophages Derived from Circulating Inflammatory Monocytes Degrade Collagen through Cellular Uptake

    DEFF Research Database (Denmark)

    Madsen, Daniel Hargbøl; Jürgensen, Henrik Jessen; Siersbæk, Majken Storm

    2017-01-01

    -associated macrophage (TAM)-like cells that degrade collagen in a mannose receptor-dependent manner. Accordingly, mannose-receptor-deficient mice display increased intratumoral collagen. Whole-transcriptome profiling uncovers a distinct extracellular matrix-catabolic signature of these collagen-degrading TAMs. Lineage......-ablation studies reveal that collagen-degrading TAMs originate from circulating CCR2+ monocytes. This study identifies a function of TAMs in altering the tumor microenvironment through endocytic collagen turnover and establishes macrophages as centrally engaged in tumor-associated collagen degradation. Madsen et...

  18. Probing Androgen Receptor Signaling in Circulating Tumor Cells in Prostate Cancer

    Science.gov (United States)

    2013-07-01

    2010). Toxicity and outcomes after chemoradiation for esophageal cancer in patients age 75 or older. Diseases of the Esophagus , 23:316-23. Epub 2009...Circulating Tumor Cells in Prostate Cancer PRINCIPAL INVESTIGATOR: David T. Miyamoto, M.D., Ph.D... Cancer 5b. GRANT NUMBER W81XWH-12-1-0153 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER David T. Miyamoto, M.D., Ph.D. 5e

  19. CCR 20th Anniversary Commentary: Paving the Way for Circulating Tumor Cells.

    Science.gov (United States)

    Allard, W Jeffrey; Terstappen, Leon W M M

    2015-07-01

    Cancer cells can enter the bloodstream, form distant metastases, and ultimately lead to death. A study by Allard and colleagues, which was published in the October 15, 2004, issue of Clinical Cancer Research, concluded that the CellSearch system could be used as a reliable tool to investigate circulating tumor cells and their clinical utility, and it spurred a still-growing interest in the field. ©2015 American Association for Cancer Research.

  20. Droplet digital PCR for detection and quantification of circulating tumor DNA in plasma of head and neck cancer patients.

    Science.gov (United States)

    van Ginkel, Joost H; Huibers, Manon M H; van Es, Robert J J; de Bree, Remco; Willems, Stefan M

    2017-06-19

    During posttreatment surveillance of head and neck cancer patients, imaging is insufficiently accurate for the early detection of relapsing disease. Free circulating tumor DNA (ctDNA) may serve as a novel biomarker for monitoring tumor burden during posttreatment surveillance of these patients. In this exploratory study, we investigated whether low level ctDNA in plasma of head and neck cancer patients can be detected using Droplet Digital PCR (ddPCR). TP53 mutations were determined in surgically resected primary tumor samples from six patients with high stage (II-IV), moderate to poorly differentiated head and neck squamous cell carcinoma (HNSCC). Subsequently, mutation specific ddPCR assays were designed. Pretreatment plasma samples from these patients were examined on the presence of ctDNA by ddPCR using the mutation-specific assays. The ddPCR results were evaluated alongside clinicopathological data. In all cases, plasma samples were found positive for targeted TP53 mutations in varying degrees (absolute quantification of 2.2-422 mutational copies/ml plasma). Mutations were detected in wild-type TP53 background templates of 7667-156,667 copies/ml plasma, yielding fractional abundances of down to 0.01%. Our results show that detection of tumor specific TP53 mutations in low level ctDNA from HNSCC patients using ddPCR is technically feasible and provide ground for future research on ctDNA quantification for the use of diagnostic biomarkers in the posttreatment surveillance of HNSCC patients.

  1. Rapid decrease of circulating tumor DNA predicted the treatment effect of nivolumab in a lung cancer patient within only 5 days

    Directory of Open Access Journals (Sweden)

    Yuki Iijima

    2017-01-01

    Full Text Available A 77-year-old Japanese man presented to our hospital with a 1-month history of low back pain and was diagnosed as having stage IV EGFR mutation-positive lung adenocarcinoma. After treatment with EGFR tyrosine kinase inhibitor and cytotoxic chemotherapy, nivolumab was started as fourth-line therapy. Remarkable regression of the primary tumor was observed, suggesting high anti-tumor activity of nivolumab. We retrospectively investigated the change in circulating tumor DNA (ctDNA variant allele fractions in serial plasma samples before and after the nivolumab therapy. Targeted sequencing analysis showed tumor-derived TP53R249S and EGFRL858R mutations detectable in plasma, and the timing of decrease was only 5 days, much earlier than the appearance of radiological changes. Overall, these results suggest that ctDNA might reflect tumor burden and might be a surrogate marker of the therapeutic efficacy of immune checkpoint therapy.

  2. Microfluidic flow fractionation device for label-free isolation of circulating tumor cells (CTCs) from breast cancer patients.

    Science.gov (United States)

    Hyun, Kyung-A; Kwon, Kiho; Han, Hyunju; Kim, Seung-Il; Jung, Hyo-Il

    2013-02-15

    Circulating tumor cells (CTCs) are dissociated from primary tumor and circulate in peripheral blood. They are regarded as the genesis of metastasis. Isolation and enumeration of CTCs serve as valuable tools for cancer prognosis and diagnosis. However, the rarity and heterogeneity of CTCs in blood makes it difficult to separate intact CTCs without loss. In this paper, we introduce a parallel multi-orifice flow fractionation (p-MOFF) device in which a series of contraction/expansion microchannels are placed parallel on a chip forming four identical channels. CTCs were continuously isolated from the whole blood of breast cancer patients by hydrodynamic forces and cell size differences. Blood samples from 24 breast cancer patients were analyzed (half were from metastatic breast cancer patients and the rest were from adjuvant breast cancer patients). The number of isolated CTCs varied from 0 to 21 in 7.5 ml of blood. Because our devices do not require any labeling processes (e.g., EpCAM antibody), heterogeneous CTCs can be isolated regardless of EpCAM expression. Copyright © 2012 Elsevier B.V. All rights reserved.

  3. A cell transportation solution that preserves live circulating tumor cells in patient blood samples.

    Science.gov (United States)

    Stefansson, Steingrimur; Adams, Daniel L; Ershler, William B; Le, Huyen; Ho, David H

    2016-05-06

    Circulating tumor cells (CTCs) are typically collected into CellSave fixative tubes, which kills the cells, but preserves their morphology. Currently, the clinical utility of CTCs is mostly limited to their enumeration. More detailed investigation of CTC biology can be performed on live cells, but obtaining live CTCs is technically challenging, requiring blood collection into biocompatible solutions and rapid isolation which limits transportation options. To overcome the instability of CTCs, we formulated a sugar based cell transportation solution (SBTS) that stabilizes cell viability at ambient temperature. In this study we examined the long term viability of human cancer cell lines, primary cells and CTCs in human blood samples in the SBTS for transportation purposes. Four cell lines, 5 primary human cells and purified human PBMCs were tested to determine the viability of cells stored in the transportation solution at ambient temperature for up to 7 days. We then demonstrated viability of MCF-7 cells spiked into normal blood with SBTS and stored for up to 7 days. A pilot study was then run on blood samples from 3 patients with metastatic malignancies stored with or without SBTS for 6 days. CTCs were then purified by Ficoll separation/microfilter isolation and identified using CTC markers. Cell viability was assessed using trypan blue or CellTracker™ live cell stain. Our results suggest that primary/immortalized cell lines stored in SBTS remain ~90% viable for > 72 h. Further, MCF-7 cells spiked into whole blood remain viable when stored with SBTS for up to 7 days. Finally, live CTCs were isolated from cancer patient blood samples kept in SBTS at ambient temperature for 6 days. No CTCs were isolated from blood samples stored without SBTS. In this proof of principle pilot study we show that viability of cell lines is preserved for days using SBTS. Further, this solution can be used to store patient derived blood samples for eventual isolation of viable CTCs after

  4. A cell transportation solution that preserves live circulating tumor cells in patient blood samples

    International Nuclear Information System (INIS)

    Stefansson, Steingrimur; Adams, Daniel L.; Ershler, William B.; Le, Huyen; Ho, David H.

    2016-01-01

    Circulating tumor cells (CTCs) are typically collected into CellSave fixative tubes, which kills the cells, but preserves their morphology. Currently, the clinical utility of CTCs is mostly limited to their enumeration. More detailed investigation of CTC biology can be performed on live cells, but obtaining live CTCs is technically challenging, requiring blood collection into biocompatible solutions and rapid isolation which limits transportation options. To overcome the instability of CTCs, we formulated a sugar based cell transportation solution (SBTS) that stabilizes cell viability at ambient temperature. In this study we examined the long term viability of human cancer cell lines, primary cells and CTCs in human blood samples in the SBTS for transportation purposes. Four cell lines, 5 primary human cells and purified human PBMCs were tested to determine the viability of cells stored in the transportation solution at ambient temperature for up to 7 days. We then demonstrated viability of MCF-7 cells spiked into normal blood with SBTS and stored for up to 7 days. A pilot study was then run on blood samples from 3 patients with metastatic malignancies stored with or without SBTS for 6 days. CTCs were then purified by Ficoll separation/microfilter isolation and identified using CTC markers. Cell viability was assessed using trypan blue or CellTracker™ live cell stain. Our results suggest that primary/immortalized cell lines stored in SBTS remain ~90 % viable for > 72 h. Further, MCF-7 cells spiked into whole blood remain viable when stored with SBTS for up to 7 days. Finally, live CTCs were isolated from cancer patient blood samples kept in SBTS at ambient temperature for 6 days. No CTCs were isolated from blood samples stored without SBTS. In this proof of principle pilot study we show that viability of cell lines is preserved for days using SBTS. Further, this solution can be used to store patient derived blood samples for eventual isolation of viable CTCs

  5. Transarterial chemoembolization for primary and metastatic liver tumors

    Directory of Open Access Journals (Sweden)

    Popov M.V.

    2016-12-01

    Full Text Available The literature review presents the methodology of transarterial chemoembolization (TACE — widely used method of treatment of primary and secondary liver tumors. The TACE role as a neoadjuvant therapy and the role in the management of unresectable primary and secondary liver tumors are shown. The morphofunctional basis of TACE, benefits of superselective intra-arterial administration of cytostatic agents especially in combination with ischemic impact on a tumor are described. The subject of the choice of the chemotherapeutic agent is also touched; modern drug-loaded microspheres which allow the use of higher doses of the chemotherapeutic drug without increasing systemic effect and prolong its effect on tumor are described. Lack of correlation of presence and severity of a post-embolization syndrome with success of the procedure is noted.

  6. Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells

    KAUST Repository

    Malara, Natalia

    2014-07-01

    Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor\\'s stadiation, therapy, and early relapsing lesions. Within surface\\'s bio-functionalization and cell\\'s isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient\\'s blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  7. Digital PCR analysis of circulating tumor DNA: a biomarker for chondrosarcoma diagnosis, prognostication, and residual disease detection.

    Science.gov (United States)

    Gutteridge, Alice; Rathbone, Victoria M; Gibbons, Rebecca; Bi, Mark; Archard, Nicholas; Davies, Kate E J; Brown, Jake; Plagnol, Vincent; Pillay, Nischalan; Amary, Fernanda; O'Donnell, Paul; Gupta, Manu; Tirabosco, Roberto; Flanagan, Adrienne M; Forshew, Tim

    2017-10-01

    Conventional chondrosarcoma is the most common primary bone tumor in adults. Prognosis corresponds with tumor grade but remains variable, especially for individuals with grade (G) II disease. There are currently no biomarkers available for monitoring or prognostication of chondrosarcoma. Circulating tumor DNA (ctDNA) has recently emerged as a promising biomarker for a broad range of tumor types. To date, little has been done to study the presence of ctDNA and its potential utility in the management of sarcomas, including chondrosarcoma. In this study, we have assessed ctDNA levels in a cohort of 71 patients, 32 with sarcoma, including 29 individuals with central chondrosarcoma (CS) and 39 with locally aggressive and benign bone and soft tissue tumors, using digital PCR. In patients with CS, ctDNA was detected in pretreatment samples in 14/29 patients, which showed clear correlation with tumor grade as demonstrated by the detection of ctDNA in all patients with GIII and dedifferentiated disease (n = 6) and in 8/17 patients with GII disease, but never associated with GI CS. Notably detection of ctDNA preoperatively in GII disease was associated with a poor outcome. A total of 14 patients with CS had ctDNA levels assessed at multiple time points and in most patients there was a clear reduction following surgical removal. This research lays the foundation for larger studies to assess the utility of ctDNA for chondrosarcoma diagnosis, prognostication, early detection of residual disease and monitoring disease progression. © 2017 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  8. The potential diagnostic power of circulating tumor cell analysis for non-small-cell lung cancer.

    Science.gov (United States)

    Ross, Kirsty; Pailler, Emma; Faugeroux, Vincent; Taylor, Melissa; Oulhen, Marianne; Auger, Nathalie; Planchard, David; Soria, Jean-Charles; Lindsay, Colin R; Besse, Benjamin; Vielh, Philippe; Farace, Françoise

    2015-01-01

    In non-small-cell lung cancer (NSCLC), genotyping tumor biopsies for targetable somatic alterations has become routine practice. However, serial biopsies have limitations: they may be technically difficult or impossible and could incur serious risks to patients. Circulating tumor cells (CTCs) offer an alternative source for tumor analysis that is easily accessible and presents the potential to identify predictive biomarkers to tailor therapies on a personalized basis. Examined here is our current knowledge of CTC detection and characterization in NSCLC and their potential role in EGFR-mutant, ALK-rearranged and ROS1-rearranged patients. This is followed by discussion of the ongoing issues such as the question of CTC partnership as diagnostic tools in NSCLC.

  9. Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

    International Nuclear Information System (INIS)

    Stolpe, Anja van de; Toonder, Jaap M. J. den

    2014-01-01

    Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics

  10. Circulating Tumor Cells: What Is in It for the Patient? A Vision towards the Future

    Energy Technology Data Exchange (ETDEWEB)

    Stolpe, Anja van de, E-mail: Anja.van.de.stolpe@philips.com [Fellow, Precision and Decentralized Diagnostics, Philips Research, Eindhoven 5656 AE (Netherlands); Toonder, Jaap M. J. den [Chair Microsystems, Eindhoven University of Technology, Postbox 513, Eindhoven 5600 MB (Netherlands)

    2014-05-28

    Knowledge on cellular signal transduction pathways as drivers of cancer growth and metastasis has fuelled development of “targeted therapy” which “targets” aberrant oncogenic signal transduction pathways. These drugs require nearly invariably companion diagnostic tests to identify the tumor-driving pathway and the cause of the abnormal pathway activity in a tumor sample, both for therapy response prediction as well as for monitoring of therapy response and emerging secondary drug resistance. Obtaining sufficient tumor material for this analysis in the metastatic setting is a challenge, and circulating tumor cells (CTCs) may provide an attractive alternative to biopsy on the premise that they can be captured from blood and the companion diagnostic test results are correctly interpreted. We discuss novel companion diagnostic directions, including the challenges, to identify the tumor driving pathway in CTCs, which in combination with a digital pathology platform and algorithms to quantitatively interpret complex CTC diagnostic results may enable optimized therapy response prediction and monitoring. In contrast to CTC-based companion diagnostics, CTC enumeration is envisioned to be largely replaced by cell free tumor DNA measurements in blood for therapy response and recurrence monitoring. The recent emergence of novel in vitro human model systems in the form of cancer-on-a-chip may enable elucidation of some of the so far elusive characteristics of CTCs, and is expected to contribute to more efficient CTC capture and CTC-based diagnostics.

  11. Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castrationresistant prostate cancer: a report from the PETRUS prospective study

    Science.gov (United States)

    Massard, Christophe; Oulhen, Marianne; Le Moulec, Sylvestre; Auger, Nathalie; Foulon, Stéphanie; Abou-Lovergne, Aurélie; Billiot, Fanny; Valent, Alexander; Marty, Virginie; Loriot, Yohann; Fizazi, Karim; Vielh, Philippe; Farace, Francoise

    2016-01-01

    Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs. Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients. PMID:27391263

  12. Phenotypic and genetic heterogeneity of tumor tissue and circulating tumor cells in patients with metastatic castration-resistant prostate cancer: A report from the PETRUS prospective study.

    Science.gov (United States)

    Massard, Christophe; Oulhen, Marianne; Le Moulec, Sylvestre; Auger, Nathalie; Foulon, Stéphanie; Abou-Lovergne, Aurélie; Billiot, Fanny; Valent, Alexander; Marty, Virginie; Loriot, Yohann; Fizazi, Karim; Vielh, Philippe; Farace, Francoise

    2016-08-23

    Molecular characterization of cancer samples is hampered by tumor tissue availability in metastatic castration-resistant prostate cancer (mCRPC) patients. We reported the results of prospective PETRUS study of biomarker assessment in paired primary prostatic tumors, metastatic biopsies and circulating tumor cells (CTCs). Among 54 mCRPC patients enrolled, 38 (70%) had biopsies containing more than 50% tumour cells. 28 (52%) patients were analyzed for both tissue samples and CTCs. FISH for AR-amplification and TMPRSS2-ERG translocation were successful in 54% and 32% in metastatic biopsies and primary tumors, respectively. By comparing CellSearch and filtration (ISET)-enrichment combined to four color immunofluorescent staining, we showed that CellSearch and ISET isolated distinct subpopulations of CTCs: CTCs undergoing epithelial-to-mesenchymal transition, CTC clusters and large CTCs with cytomorphological characteristics but no detectable markers were isolated using ISET. Epithelial CTCs detected by the CellSearch were mostly lost during the ISET-filtration. AR-amplification was detected in CellSearch-captured CTCs, but not in ISET-enriched CTCs which harbor exclusively AR gain of copies. Eighty-eight percent concordance for ERG-rearrangement was observed between metastatic biopsies and CTCs even if additional ERG-alteration patterns were detected in ISET-enriched CTCs indicating a higher heterogeneity in CTCs.Molecular screening of metastatic biopsies is achievable in a multicenter context. Our data indicate that CTCs detected by the CellSearch and the ISET-filtration systems are not only phenotypically but also genetically different. Close attention must be paid to CTC characterization since neither approach tested here fully reflects the tremendous phenotypic and genetic heterogeneity present in CTCs from mCRPC patients.

  13. Metastasis in the subcarinal lymph node with unknown primary tumor

    DEFF Research Database (Denmark)

    Eckardt, J.; Olsen, K. E.; Petersen, H.

    2011-01-01

    -differentiated squamous cell carcinoma but no primary tumor was visible on PET-computed tomography. Because of his previous lymphoma the patient was scheduled for mediastinoscopy where the diagnosis was confirmed. Subsequent gastroscopy was normal and a right-sided thoracotomy showed no evidence of cancer elsewhere, only...... an inoperable metastasis in a subcarinal lymph node which infiltrated the trachea, esophagus and aorta. Such isolated squamous cell carcinoma in a subcarinal lymph node without a primary tumor despite invasive work-up has not been reported before....

  14. Highly efficient capture and harvest of circulating tumor cells on a microfluidic chip integrated with herringbone and micropost arrays.

    Science.gov (United States)

    Xue, Peng; Wu, Yafeng; Guo, Jinhong; Kang, Yuejun

    2015-04-01

    Circulating tumor cells (CTCs), which are derived from primary tumor site and transported to distant organs, are considered as the major cause of metastasis. So far, various techniques have been applied for CTC isolation and enumeration. However, there exists great demand to improve the sensitivity of CTC capture, and it remains challenging to elute the cells efficiently from device for further biomolecular and cellular analyses. In this study, we fabricate a dual functional chip integrated with herringbone structure and micropost array to achieve CTC capture and elution through EpCAM-based immunoreaction. Hep3B tumor cell line is selected as the model of CTCs for processing using this device. The results demonstrate that the capture limit of Hep3B cells can reach up to 10 cells (per mL of sample volume) with capture efficiency of 80% on average. Moreover, the elution rate of the captured Hep3B cells can reach up to 69.4% on average for cell number ranging from 1 to 100. These results demonstrate that this device exhibits dual functions with considerably high capture rate and elution rate, indicating its promising capability for cancer diagnosis and therapeutics.

  15. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Directory of Open Access Journals (Sweden)

    Laura Sarah Sasportas

    Full Text Available Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  16. Folic acid functionalized surface highlights 5-methylcytosine-genomic content within circulating tumor cells

    KAUST Repository

    Malara, Natalia; Coluccio, Maria Laura; Limongi, Tania; Asande, Monica; Trunzo, Valentina; Cojoc, Gheorghe; Raso, Cinzia; Candeloro, Patrizio; Perozziello, Gerardo; Raimondo, Raffaella; De Vitis, Stefania; Roveda, Laura; Renne, Maria; Prati, Ubaldo; Mollace, Vincenzo; Di Fabrizio, Enzo M.

    2014-01-01

    Although the detection of methylated cell free DNA represents one of the most promising approaches for relapse risk assessment in cancer patients, the low concentration of cell-free circulating DNA constitutes the biggest obstacle in the development of DNA methylation-based biomarkers from blood. This paper describes a method for the measurement of genomic methylation content directly on circulating tumor cells (CTC), which could be used to deceive the aforementioned problem. Since CTC are disease related blood-based biomarkers, they result essential to monitor tumor's stadiation, therapy, and early relapsing lesions. Within surface's bio-functionalization and cell's isolation procedure standardization, the presented approach reveals a singular ability to detect high 5-methylcytosine CTC-subset content in the whole CTC compound, by choosing folic acid (FA) as transducer molecule. Sensitivity and specificity, calculated for FA functionalized surface (FA-surface), result respectively on about 83% and 60%. FA-surface, allowing the detection and characterization of early metastatic dissemination, provides a unique advance in the comprehension of tumors progression and dissemination confirming the presence of CTC and its association with high risk of relapse. This functionalized surface identifying and quantifying high 5-methylcytosine CTC-subset content into the patient's blood lead significant progress in cancer risk assessment, also providing a novel therapeutic strategy.© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  17. Imaging circulating tumor cells in freely moving awake small animals using a miniaturized intravital microscope.

    Science.gov (United States)

    Sasportas, Laura Sarah; Gambhir, Sanjiv Sam

    2014-01-01

    Metastasis, the cause for 90% of cancer mortality, is a complex and poorly understood process involving the invasion of circulating tumor cells (CTCs) into blood vessels. These cells have potential prognostic value as biomarkers for early metastatic risk. But their rarity and the lack of specificity and sensitivity in measuring them render their interrogation by current techniques very challenging. How and when these cells are circulating in the blood, on their way to potentially give rise to metastasis, is a question that remains largely unanswered. In order to provide an insight into this "black box" using non-invasive imaging, we developed a novel miniature intravital microscopy (mIVM) strategy capable of real-time long-term monitoring of CTCs in awake small animals. We established an experimental 4T1-GL mouse model of metastatic breast cancer, in which tumor cells express both fluorescent and bioluminescent reporter genes to enable both single cell and whole body tumor imaging. Using mIVM, we monitored blood vessels of different diameters in awake mice in an experimental model of metastasis. Using an in-house software algorithm we developed, we demonstrated in vivo CTC enumeration and computation of CTC trajectory and speed. These data represent the first reported use we know of for a miniature mountable intravital microscopy setup for in vivo imaging of CTCs in awake animals.

  18. Primary desmoplastic small round cell tumor of the femur

    Energy Technology Data Exchange (ETDEWEB)

    Yoshida, Akihiko; Garcia, Joaquin [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Edgar, Mark A. [Memorial Sloan-Kettering Cancer Center, Department of Pathology, New York, NY (United States); Weill Medical College of Cornell University, New York, NY (United States); Meyers, Paul A. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Pediatrics, New York, NY (United States); Morris, Carol D. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Surgery, Orthopaedic Service, New York, NY (United States); Panicek, David M. [Weill Medical College of Cornell University, New York, NY (United States); Memorial Sloan-Kettering Cancer Center, Department of Radiology, New York, NY (United States)

    2008-09-15

    Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm typically involving the abdominal cavity of a young male. Extra-abdominal occurrence of this tumor is very rare. We report a 10-year-old girl with primary DSRCT arising within the left femur. The patient presented with knee pain, and radiological findings were strongly suggestive of osteogenic sarcoma. In addition to the typical microscopic appearance and immunophenotype, RT-PCR demonstrated the chimeric transcript of EWS-WT1, which is diagnostic of DSRCT. Pulmonary metastases were present at initial staging studies, but no abdominal or pelvic lesion was present. Despite chemotherapy and complete tumor excision, the patient developed progressive lung and bone metastases and died 3 years after initial presentation. This is the second reported case of primary DSRCT of bone with genetic confirmation. (orig.)

  19. Primary desmoplastic small round cell tumor of the femur

    International Nuclear Information System (INIS)

    Yoshida, Akihiko; Garcia, Joaquin; Edgar, Mark A.; Meyers, Paul A.; Morris, Carol D.; Panicek, David M.

    2008-01-01

    Desmoplastic small round cell tumor (DSRCT) is a rare malignant neoplasm typically involving the abdominal cavity of a young male. Extra-abdominal occurrence of this tumor is very rare. We report a 10-year-old girl with primary DSRCT arising within the left femur. The patient presented with knee pain, and radiological findings were strongly suggestive of osteogenic sarcoma. In addition to the typical microscopic appearance and immunophenotype, RT-PCR demonstrated the chimeric transcript of EWS-WT1, which is diagnostic of DSRCT. Pulmonary metastases were present at initial staging studies, but no abdominal or pelvic lesion was present. Despite chemotherapy and complete tumor excision, the patient developed progressive lung and bone metastases and died 3 years after initial presentation. This is the second reported case of primary DSRCT of bone with genetic confirmation. (orig.)

  20. Fetal antigen 2 in primary and secondary brain tumors

    DEFF Research Database (Denmark)

    Rasmussen, H Boje; Teisner, B; Schrøder, H D

    1991-01-01

    Immunohistochemical deposition and distribution of fetal antigen 2 (FA2) was examined in normal brain tissue and in primary and metastatic tumors of the brain. In normal brain tissue FA2 was exclusively found linearly around the vessels, along pia and in arachnoidea. A similar localization was seen...

  1. Malignancy risk prediction for primary jejunum-ileal tumors

    Directory of Open Access Journals (Sweden)

    MARQUES Ruy Garcia

    2000-01-01

    Full Text Available This work is aimed at identifying factors associated with primary jejunum-ileal tumors malignancy, defining a prediction model with sensitivity, specificity and accuracy to distinguish malign from benign neoplasms. These tumors are rare, have highly unspecific presentation and, frequently, are diagnosed late. We reviewed the charts of 42 patients with primary jejunum-ileal tumors treated in the Department of General Surgery of Rio de Janeiro State University Hospital, Rio de Janeiro, RJ, Brazil, from 1969 to 1998. We performed bivariate analyses, based on chi² test, searching associations between tumors malignancy and demographic and clinical variables. Then logistic regression was employed to consider the independent effect of variables previously identified on malignancy risk. The malign tumors included 11 adenocarcinomas, 7 leiomyosarcomas, 5 carcinoids and 4 lymphomas; the benign tumors included 10 leiomyomas, 2 hamartomas, and single cases of adenoma, multiple neurilemoma and choristoma. The bivariate analyses indicated the association between malignancy and palpable abdominal mass (P = 0.003, period from signs and symptoms onset to diagnosis (P = 0.016, anemia (P = 0.020, anorexia (P = 0.003, abdominal pain (P = 0.031, weight loss (P = 0.001, nausea and vomit (P = 0.094, and intestinal obstruction (P = 0.066; no association with patients demographic characteristics were found. In the final logistic regression model, weight loss, anemia and intestinal obstruction were statistically associated with the dependent variable of interest. Based only on three variables -- weight loss, anemia and intestinal obstruction -- the model defined was able to predict primary jejunum-ileal tumors malignancy with sensitivity of 85.2%, specificity of 80.0%, and accuracy of 83.3%.

  2. Impact of endoscopic stent insertion on detection of viable circulating tumor cells from obstructive colorectal cancer.

    Science.gov (United States)

    Yamashita, Shinya; Tanemura, Masahiro; Sawada, Genta; Moon, Jeongho; Shimizu, Yosuke; Yamaguchi, Toshiki; Kuwai, Toshio; Urata, Yasuo; Kuraoka, Kazuya; Hatanaka, Nobutaka; Yamashita, Yoshinori; Taniyama, Kiyomi

    2018-01-01

    The placement of a self-expanding metallic stent (SEMS) in obstructive colorectal cancer (OCRC) is acknowledged to be a safe and effective procedure for the relief of obstruction. However, there is concern that shear forces acting on the tumor during stent expansion may release cancer cells into the circulation, resulting in a poor prognosis. The aim of the present study was to determine whether colonic stent insertion increases viable circulating tumor cells (v-CTCs). A telomerase-specific replication-selective adenovirus-expressing GFP (TelomeScanF35) detection system was used to detect v-CTCs in 8 OCRC patients with a SEMS before and after stent insertion and after surgical resection. In 7 patients, a SEMS was inserted as a bridge to surgery (BTS), and in one patient, a SEMS was inserted for palliation. Surgical resection (R0) was performed in 7 patients. Four patients had no v-CTCs before SEMS placement, two of four measurable patients had an increased number of v-CTCs after SEMS placement (1-3 v-CTCs), and one of two patients with increased v-CTCs developed distant lymphatic metastasis despite curative resection. Four patients had v-CTCs (1-19 cells) before SEMS placement, and two of these four patients had an increase in the number of v-CTCs (20-21 cells) after SEMS placement, while one of the four patients died early with distant metastasis. The present study demonstrated that endoscopic stent insertion for OCRC may result in tumor cell dissemination into the peripheral circulation and may induce distant metastases.

  3. Quantification of radionuclide uptake levels for primary bone tumors

    Directory of Open Access Journals (Sweden)

    Hasford Francis

    2015-04-01

    Full Text Available The purpose of the study is to quantify the level of uptake of administered radionuclide in primary bone tumors for patients undergoing bone scintigraphy. Retrospective study on 48 patient's scintigrams to quantify the uptake levels of administered radiopharmaceuticals was performed in a nuclear medicine unit in Ghana. Patients were administered with activity ranging between 0.555 and 1.110 MBq (15–30 mCi, and scanned on Siemens e.cam SPECT system. Analyses on scintigrams were performed with Image J software by drawing regions of interest (ROIs over identified hot spots (pathologic sites. Nine skeletal parts namely cranium, neck, shoulder, sacrum, sternum, vertebra, femur, ribcage, and knee were considered in the study, which involved 96 identified primary tumors. Radionuclide uptakes were quantified in terms of the estimated counts of activity per patient for identified tumor sites. Average normalized counts of activity (nGMC per patient ranged from 5.2759 ± 0.6590 cts/mm2/MBq in the case of cranium tumors to 72.7569 ± 17.8786 cts/mm2/MBq in the case of ribcage tumors. The differences in uptake levels could be attributed to different mechanisms of Tc-99m MDP uptake in different types of bones, which is directly related to blood flow and degree of osteoblastic activity. The overall normalized count of activity for the 96 identified tumors was estimated to be 23.0350 ± 19.5424 cts/mm2/MBq. The study revealed highest uptake of activity in ribcage and least uptake in cranium. Quantification of radionuclide uptakes in tumors is important and recommended in assessing patient's response to therapy, doses to critical organs and in diagnosing tumors.

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

    Science.gov (United States)

    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.

  5. Multiple primary tumors in patients with uterine cancer

    International Nuclear Information System (INIS)

    Velikova, N.; Parvanova, V.; Dimitrova, N.

    2013-01-01

    Full text: Introduction: The aging population and improved medical care lead to increased likelihood for patients experienced a tumor to develop at least one more in the course of his life. The aim of the study was to analyze the clinical and biological characteristics and survival of patients with primary tumor multiplicity in which a tumor is cancer of the uterine body. Materials and Methods: For the period 1997-2007, in the department of radiotherapy were treated 191 women with carcinoma of the uterine body (in a group of moderate and high risk) with invasion of the myometrium more than one third. Patients ranged in age from 36 to 77 (average age 59.9) and were followed until 31.03.2013 with an average follow-up period 126 months. Postoperatively, all were carried intravaginal brachytherapy with high dose rate 3x5 Gy once a week, followed by percutaneous radiotherapy 22x2 Gy daily to the area of the pelvic lymph nodes. Data to diagnose combined tumors were obtained from the National Cancer Registry. Survival analysis was made by the method of Kaplan - Meier with Lograng test. Results: In 26 (13.6 %) of the analyzed patients a tumor multiplicity is find in 22 (84,6%) tumors are two in 3 (11.5 %)- three , and in 1 (3.8%) - four . A detailed analysis of 14 (53.8%) patients whose cancer of the uterine body is the first tumor and is followed by another. The distribution of the tumor according to the second location is: breast cancer 5 (35.7%) skin malignant melanoma without 4 (28.5%) of the column 3 (21.4 %) of stomach 1 (7.1%) , MALT lymphoma, 1 (7.1% ) . Evaluate and compare the 5 - and 10-year overall survival of patients whose cancer of the uterine body only, and those who are diagnosed with a malignant tumor following - in those without a second tumor is 85.3% and 81.4 %, and in the presence of such a - 78, 6% and 69.3% respectively. Conclusion: The matched tumors are the most common among the so-called hormone dependent cancers such as breast cancer, uterine

  6. Primary duodenal adenocarcinoma: case report of an infrequent tumor

    Directory of Open Access Journals (Sweden)

    Óscar Moreno-Loaíza

    2013-10-01

    Full Text Available Introduction. Primary duodenal adenocarcinoma is an infrequent tumor both in our environment and in the world. There is no conclusive evidence on its epidemiology, diagnostic criteria, treatment or prognosis. Clinical case. We report a 77 year-old female patient, of mixed racial origin, native of Cusco (Peru who consulted for abdominal pain, weight loss, nausea, postprandial vomiting and bloating of three months course. At the time of examination she had second to third degree protein malnutrition with a BMI of 16.88 kg/m2, signs of moderate to severe chronic anemia and an 8 cm abdominal tumor in the epigastrium and right hypochondrium. The multislice spiral abdominal CT and ultrasonography revealed the presence of a solid tumor in the second portion of the duodenum. The patient was submitted to a gastroenterostomy without tumor resection. Biopsy confirmed tubular adenocarcinoma. Furthermore, no other primary tumors were found in the stomach, pancreas, biliary tree and colon. The patient was stabilized and was treated with 5-fluorouracil, irinotecan and leucovorin. Literature review. The article includes a brief review on the diagnosis, treatment and prognosis of this condition. Discussion. Management is not straightforward. There is little literature on the subject leaving decisions up to the attending physician’s criteria. We believe that all cases of rare diseases should be studied in depth, give rise to a thorough review of literature and, above all, be brought to the attention of the medical community.

  7. A case of multiple brown tumors with primary hyperparathyroidism.

    Science.gov (United States)

    Mori, Hiroko; Okada, Yosuke; Arao, Tadashi; Shimaziri, Shohei; Tanaka, Yoshiya

    2013-01-01

    We report a case of large multiple brown tumors in a patient with primary hyperparathyroidism. A 52-year-old woman suffered from pain in the ribs and developed left facial swelling and deformity. CT showed a large destructive osteolytic lesion in the left maxillary sinus. Biopsy showed a lesion with newly formed bone tissue, diffuse giant cells and deposits of hemosiderin. In addition, similar lesions were also observed in the ribs, iliac bones and pelvis. The laboratory data showed hypercalcemia and hyperparathyroidism. Cervical echo and (201)Tl-(99m)TcO(4-) scintigraphy demonstrated a right lower swollen parathyroid adenoma. The diagnosis was multiple brown tumors with primary hyperparathyroidism and parathyroidectomy was performed. Follow-up CT showed marked decreases in the size of osteolytic lesions with calcification in the brown tumors compared to pre-treatment findings. These changes were associated with marked improvement in pain and facial deformity. We described a rare case of multiple brown tumors appeared in the maxilla associated with primary hyperparathyroidism.

  8. [Colorectal cancer the importance of primary tumor location].

    Science.gov (United States)

    Ryska, M; Bauer, J

    2017-01-01

    Retrospective evaluations of the relevance of primary colorectal cancer (CRC) location consistently indicate that right-sided tumors, arising in the cecum, ascending colon, hepatic bend, transverse colon and splenic flexure, are clinically, biologically and genetically different from left-sided tumors - those located in the descending colon, sigmoid colon or rectum. Location in the right-sided colon represents a negative prognostic indicator, particularly for stage III and IV carcinomas. Irrespective of treatment, the rightward location is associated with a significantly increased risk of death when compared to the left side.Key words: colorectal cancer - location - therapy - prognosis.

  9. Biphasic Malignant Pleural Mesothelioma Masquerading as a Primary Skeletal Tumor

    Directory of Open Access Journals (Sweden)

    James Benjamin Gleason

    2016-01-01

    Full Text Available Biphasic malignant pleural mesothelioma is a rare malignant tumor, usually presenting as a pleural-based mass in a patient with history of chronic asbestos exposure. We herein report a case of a 41-year-old man who presented with chest pain and had a chest computed tomography (CT scan suggestive of a primary skeletal tumor originating from the ribs (chondrosarcoma or osteosarcoma, with no history of asbestos exposure. CT-guided core needle biopsies were diagnosed as malignant sarcomatoid mesothelioma. Surgical resection and chest wall reconstruction were performed, confirming the diagnosis and revealing a secondary histologic component (epithelioid, supporting the diagnosis of biphasic malignant mesothelioma.

  10. Primary Testicular Carcinoid Tumor presenting as Carcinoid Heart Disease

    Directory of Open Access Journals (Sweden)

    Manjunath L Chikkaraddi

    2015-01-01

    Full Text Available Primary carcinoid tumors of the testis are very rare, and they seldom present with carcinoid syndrome. We report a hereto unreported instance, where a patient with a long-standing testicular mass presented with carcinoid heart disease, an uncommon form of carcinoid syndrome. He presented with symptoms of right heart failure, episodic facial flushing and was found to have severe right-sided valvular heart disease. His urinary 5-hydroxy indole acetic acid level was elevated. He underwent orchidectomy and the histopathology confirmed a testicular carcinoid tumor.

  11. Patient-Specific Circulating Tumor DNA Detection during Neoadjuvant Chemotherapy in Triple-Negative Breast Cancer.

    Science.gov (United States)

    Riva, Francesca; Bidard, Francois-Clement; Houy, Alexandre; Saliou, Adrien; Madic, Jordan; Rampanou, Aurore; Hego, Caroline; Milder, Maud; Cottu, Paul; Sablin, Marie-Paule; Vincent-Salomon, Anne; Lantz, Olivier; Stern, Marc-Henri; Proudhon, Charlotte; Pierga, Jean-Yves

    2017-03-01

    In nonmetastatic triple-negative breast cancer (TNBC) patients, we investigated whether circulating tumor DNA (ctDNA) detection can reflect the tumor response to neoadjuvant chemotherapy (NCT) and detect minimal residual disease after surgery. Ten milliliters of plasma were collected at 4 time points: before NCT; after 1 cycle; before surgery; after surgery. Customized droplet digital PCR (ddPCR) assays were used to track tumor protein p53 ( TP53 ) mutations previously characterized in tumor tissue by massively parallel sequencing (MPS). Forty-six patients with nonmetastatic TNBC were enrolled. TP53 mutations were identified in 40 of them. Customized ddPCR probes were validated for 38 patients, with excellent correlation with MPS ( r = 0.99), specificity (≥2 droplets/assay), and sensitivity (at least 0.1%). At baseline, ctDNA was detected in 27/36 patients (75%). Its detection was associated with mitotic index ( P = 0.003), tumor grade ( P = 0.003), and stage ( P = 0.03). During treatment, we observed a drop of ctDNA levels in all patients but 1. No patient had detectable ctDNA after surgery. The patient with rising ctDNA levels experienced tumor progression during NCT. Pathological complete response (16/38 patients) was not correlated with ctDNA detection at any time point. ctDNA positivity after 1 cycle of NCT was correlated with shorter disease-free ( P < 0.001) and overall ( P = 0.006) survival. Customized ctDNA detection by ddPCR achieved a 75% detection rate at baseline. During NCT, ctDNA levels decreased quickly and minimal residual disease was not detected after surgery. However, a slow decrease of ctDNA level during NCT was strongly associated with shorter survival. © 2016 American Association for Clinical Chemistry.

  12. Assessment of basal-like breast cancer by circulating tumor DNA analysis.

    Science.gov (United States)

    Wei, Wei; Zhang, Xianyu; Sun, Shanshan; Xia, Bingshu; Liang, Xiaoshuan; Cui, Yan; Gao, Song; Pang, Da

    2018-05-01

    Standardized methods for the detection and assessment of circulating tumor DNA (ctDNA) in breast cancer are not sufficient. In the present study, the method and the potential application of ctDNA in the diagnosis of breast cancer were explored. DNA was extracted from the tumor tissues, plasma and peripheral blood cells of 11 patients with early-stage invasive breast cancer. Primers were designed against the exons of phosphatidylinositol-4,5-biphosphate 3-kinase catalytic subunit α, p53, epidermal growth factor receptor, Akt and phosphatase and tensin homolog. The amplicon-based method for whole-exon sequencing was performed. The associations between the ctDNA mutant frequency with the tumor DNA mutant frequency, and the ctDNA concentration with clinical data were analyzed. A linear association was identified between the concentration of ctDNA and the tumor volume for the 3 patients with basal-like breast cancer, and not in other subtypes. The mutation frequency differed the least between ctDNA and tissue DNA in basal-like breast cancer. ctDNA retained the constituent ratio of gene mutations identified in the corresponding tumor tissue. The ctDNA detection rate depended to a certain extent on the mutation frequency in tumor tissue; for example, a mutant locus with a mutation frequency of >30% in tissues presented a detection rate of >40% in plasma samples, whereas a locus with a mutation frequency of <10% in tissue was associated with a detection rate of ≤1% in the plasma. Therefore, ctDNA may reflect the mutations observed in cancer. Compared with other subtypes, ctDNA may be a more sensitive biomarker for the assessment of mutation and cancer burden in basal-like breast cancer relative to other subtypes.

  13. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  15. Extensive screening for primary tumor is redundant in melanoma of unknown primary

    DEFF Research Database (Denmark)

    Tos, Tina; Klyver, Helle; Drzewiecki, Krzysztof T

    2011-01-01

    For decades, patients in our institution with metastastic melanoma of unknown primary have been subjected to extensive examinations in search of the primary tumor. This retrospective study questions the results, and thus the feasibility of these examinations. Of 103 patients diagnosed with unknow......, for patients referred with metastastic melanoma of unknown primary, we recommend that a detailed history is obtained, and a standard physical examination performed, in addition to a histopathological review and CT/PET for staging....

  16. Poor Prognosis Indicated by Venous Circulating Tumor Cell Clusters in Early-Stage Lung Cancers.

    Science.gov (United States)

    Murlidhar, Vasudha; Reddy, Rishindra M; Fouladdel, Shamileh; Zhao, Lili; Ishikawa, Martin K; Grabauskiene, Svetlana; Zhang, Zhuo; Lin, Jules; Chang, Andrew C; Carrott, Philip; Lynch, William R; Orringer, Mark B; Kumar-Sinha, Chandan; Palanisamy, Nallasivam; Beer, David G; Wicha, Max S; Ramnath, Nithya; Azizi, Ebrahim; Nagrath, Sunitha

    2017-09-15

    Early detection of metastasis can be aided by circulating tumor cells (CTC), which also show potential to predict early relapse. Because of the limited CTC numbers in peripheral blood in early stages, we investigated CTCs in pulmonary vein blood accessed during surgical resection of tumors. Pulmonary vein (PV) and peripheral vein (Pe) blood specimens from patients with lung cancer were drawn during the perioperative period and assessed for CTC burden using a microfluidic device. From 108 blood samples analyzed from 36 patients, PV had significantly higher number of CTCs compared with preoperative Pe ( P ontology analysis revealed enrichment of cell migration and immune-related pathways in CTC clusters, suggesting survival advantage of clusters in circulation. Clusters display characteristics of therapeutic resistance, indicating the aggressive nature of these cells. Thus, CTCs isolated from early stages of lung cancer are predictive of poor prognosis and can be interrogated to determine biomarkers predictive of recurrence. Cancer Res; 77(18); 5194-206. ©2017 AACR . ©2017 American Association for Cancer Research.

  17. Small cell lung cancer: Recruitment of macrophages by circulating tumor cells.

    Science.gov (United States)

    Hamilton, Gerhard; Rath, Barbara; Klameth, Lukas; Hochmair, Maximilan J

    2016-03-01

    Tumor-associated macrophages (TAMs) play an important role in tumor progression, suppression of antitumor immunity and dissemination. Blood monocytes infiltrate the tumor region and are primed by local microenvironmental conditions to promote tumor growth and invasion. Although many of the interacting cytokines and factors are known for the tumor-macrophage interactions, the putative contribution of circulating tumor cells (CTCs) is not known so far. These specialized cells are characterized by increased mobility, ability to degrade the extracellular matrix (ECM) and to enter the blood stream and generate secondary lesions which is a leading cause of death for the majority of tumor patients. The first establishment of two permanent CTC lines, namely BHGc7 and 10, from blood samples of advanced stage small cell lung cancer (SCLC) patients allowed us to investigate the CTC-immune cell interaction. Cocultures of peripheral blood mononuclear cells (PBMNCs) with CTCs or addition of CTC-conditioned medium (CTC-CM) in vitro resulted in monocyte-macrophage differentiation and appearance of CD14 + , CD163 weak and CD68 + macrophages expressing markers of TAMs. Furthermore, we screened the supernatants of CTC-primed macrophages for presence of approximately 100 cytokines and compared the expression with those induced by the local metastatic SCLC26A cell line. Macrophages recruited by SCLC26A-CM showed expression of osteopontin (OPN), monocyte chemoattractant protein-1 (MCP-1), IL-8, chitinase3-like 1 (CHI3L1), platelet factor (Pf4), IL-1ra and matrix metalloproteinase-9 (MMP-9) among other minor cytokines/chemokines. In contrast, BHGc7-CM induced marked overexpression of complement factor D (CFD)/adipsin and vitamin D-BP (VDBP), as well as increased secretion of OPN, lipocalin-2 (LCN2), CHI3L1, uPAR, MIP-1 and GDF-15/MIC-1. BHGc10, derived independently from relapsed SCLC, revealed an almost identical pattern with added expression of ENA-78/CXCL5. CMs of the non-tumor HEK293

  18. Detection of mycoplasma infection in circulating tumor cells in patients with hepatocellular carcinoma

    Energy Technology Data Exchange (ETDEWEB)

    Choi, Hong Seo; Lee, Hyun Min; Kim, Won-Tae; Kim, Min Kyu [Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul (Korea, Republic of); Chang, Hee Jin [Center for Colorectal Cancer, Research Institute and Hospital of National Cancer Center, Goyang-si (Korea, Republic of); Lee, Hye Ran [Department of Internal Medicine, Inje University Ilsan Paik Hospital, Goyang-si (Korea, Republic of); Joh, Jae-Won [Department of Surgery, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Kim, Dae Shick, E-mail: oncorkim@skku.edu [Department of Pathology, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul (Korea, Republic of); Ryu, Chun Jeih, E-mail: cjryu@sejong.ac.kr [Department of Bioscience and Biotechnology, Institute of Bioscience, Sejong University, Seoul (Korea, Republic of)

    2014-04-04

    Highlights: • This study generates a monoclonal antibody CA27 against the mycoplasmal p37 protein. • CA27 isolates circulating tumor cells (CTCs) from the blood of liver cancer patients. • Results show the first evidence for mycoplasma infected-CTCs in cancer patients. - Abstract: Many studies have shown that persistent infections of bacteria promote carcinogenesis and metastasis. Infectious agents and their products can modulate cancer progression through the induction of host inflammatory and immune responses. The presence of circulating tumor cells (CTCs) is considered as an important indicator in the metastatic cascade. We unintentionally produced a monoclonal antibody (MAb) CA27 against the mycoplasmal p37 protein in mycoplasma-infected cancer cells during the searching process of novel surface markers of CTCs. Mycoplasma-infected cells were enriched by CA27-conjugated magnetic beads in the peripheral blood mononuclear cells in patients with hepatocellular carcinoma (HCC) and analyzed by confocal microscopy with anti-CD45 and CA27 antibodies. CD45-negative and CA27-positive cells were readily detected in three out of seven patients (range 12–30/8.5 ml blood), indicating that they are mycoplasma-infected circulating epithelial cells. CA27-positive cells had larger size than CD45-positive hematological lineage cells, high nuclear to cytoplasmic ratios and irregular nuclear morphology, which identified them as CTCs. The results show for the first time the existence of mycoplasma-infected CTCs in patients with HCC and suggest a possible correlation between mycoplasma infection and the development of cancer metastasis.

  19. Primary Yolk Sac Tumor of the Omentum: Case Report

    International Nuclear Information System (INIS)

    Baek, Chang Kyu; Oh, Young Taik; Jung, Dae Chul; Bae, Yoon Sung

    2012-01-01

    A 32-year-old woman had been referred to our hospital for lower abdominal pain. Pelvic ultrasonography and magnetic resonance imaging revealed a huge solid mass with an internal cystic portion. The patient underwent a staging laparotomy and subsequent total abdominal hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic lymph nodes sampling, and total omentectomy. At staging laparotomy, a large omental mass was found. The tumor displayed the typical histological patterns observed in the yolk sac tumor. The alpha-fetoprotein (AFP) serum value on the 10th day after surgery was 11,576.67 IU/mL and decreased to 6.46 IU/mL after chemotherapy. At the end of the treatment, all the findings, including the AFP level, were normal. We report a case of primary yolk sac tumor of the omentum in a 32-year-old woman.

  20. Primary Yolk Sac Tumor of the Omentum: Case Report

    Energy Technology Data Exchange (ETDEWEB)

    Baek, Chang Kyu; Oh, Young Taik; Jung, Dae Chul [Dept. of Radiology, Research Institue of Radiological Science, Yensei University College of Medicine, Seoul (Korea, Republic of); Bae, Yoon Sung [Dept. of Pathology, Yensei University College of Medicine, Seoul (Korea, Republic of)

    2012-01-15

    A 32-year-old woman had been referred to our hospital for lower abdominal pain. Pelvic ultrasonography and magnetic resonance imaging revealed a huge solid mass with an internal cystic portion. The patient underwent a staging laparotomy and subsequent total abdominal hysterectomy with bilateral salpingo-oophorectomy, bilateral pelvic lymph nodes sampling, and total omentectomy. At staging laparotomy, a large omental mass was found. The tumor displayed the typical histological patterns observed in the yolk sac tumor. The alpha-fetoprotein (AFP) serum value on the 10th day after surgery was 11,576.67 IU/mL and decreased to 6.46 IU/mL after chemotherapy. At the end of the treatment, all the findings, including the AFP level, were normal. We report a case of primary yolk sac tumor of the omentum in a 32-year-old woman.

  1. Deterministic Evolutionary Trajectories Influence Primary Tumor Growth: TRACERx Renal

    DEFF Research Database (Denmark)

    Turajlic, Samra; Xu, Hang; Litchfield, Kevin

    2018-01-01

    The evolutionary features of clear-cell renal cell carcinoma (ccRCC) have not been systematically studied to date. We analyzed 1,206 primary tumor regions from 101 patients recruited into the multi-center prospective study, TRACERx Renal. We observe up to 30 driver events per tumor and show...... that subclonal diversification is associated with known prognostic parameters. By resolving the patterns of driver event ordering, co-occurrence, and mutual exclusivity at clone level, we show the deterministic nature of clonal evolution. ccRCC can be grouped into seven evolutionary subtypes, ranging from tumors...... outcome. Our insights reconcile the variable clinical behavior of ccRCC and suggest evolutionary potential as a biomarker for both intervention and surveillance....

  2. Imaging of primary bone tumors in veterinary medicine: Which differences?

    Energy Technology Data Exchange (ETDEWEB)

    Vanel, Maïa, E-mail: maiavanel@yahoo.fr [Diagnostic Imaging Department, Faculty of Veterinary Medicine, University of Montreal, 3200 Rue Sicotte, PO Box 5000, Saint-Hyacinthe, QC (Canada); Blond, Laurent [Diagnostic Imaging Department, Faculty of Veterinary Medicine, University of Montreal, 3200 Rue Sicotte, PO Box 5000, Saint-Hyacinthe, QC (Canada); Vanel, Daniel [The Rizzoli Institute, Via del Barbiano 1-10, 40136, Bologna (Italy)

    2013-12-01

    Veterinary medicine is most often a mysterious world for the human doctors. However, animals are important for human medicine thanks to the numerous biological similarities. Primary bone tumors are not uncommon in veterinary medicine and especially in small domestic animals as dogs and cats. As in human medicine, osteosarcoma is the most common one and especially in the long bones extremities. In the malignant bone tumor family, chondrosarcoma, fibrosarcoma and hemangiosarcoma are following. Benign bone tumors as osteoma, osteochondroma and bone cysts do exist but are rare and of little clinical significance. Diagnostic modalities used depend widely on the owner willing to treat his animal. Radiographs and bone biopsy are the standard to make a diagnosis but CT, nuclear medicine and MRI are more an more used. As amputation is treatment number one in appendicular bone tumor in veterinary medicine, this explains on the one hand why more recent imaging modalities are not always necessary and on the other hand, that pronostic on large animals is so poor that it is not much studied. Chemotherapy is sometimes associated with the surgery procedure, depending on the agressivity of the tumor. Although, the strakes differs a lot between veterinary and human medicine, biological behavior are almost the same and should led to a beneficial team work between all.

  3. Imaging of primary bone tumors in veterinary medicine: Which differences?

    International Nuclear Information System (INIS)

    Vanel, Maïa; Blond, Laurent; Vanel, Daniel

    2013-01-01

    Veterinary medicine is most often a mysterious world for the human doctors. However, animals are important for human medicine thanks to the numerous biological similarities. Primary bone tumors are not uncommon in veterinary medicine and especially in small domestic animals as dogs and cats. As in human medicine, osteosarcoma is the most common one and especially in the long bones extremities. In the malignant bone tumor family, chondrosarcoma, fibrosarcoma and hemangiosarcoma are following. Benign bone tumors as osteoma, osteochondroma and bone cysts do exist but are rare and of little clinical significance. Diagnostic modalities used depend widely on the owner willing to treat his animal. Radiographs and bone biopsy are the standard to make a diagnosis but CT, nuclear medicine and MRI are more an more used. As amputation is treatment number one in appendicular bone tumor in veterinary medicine, this explains on the one hand why more recent imaging modalities are not always necessary and on the other hand, that pronostic on large animals is so poor that it is not much studied. Chemotherapy is sometimes associated with the surgery procedure, depending on the agressivity of the tumor. Although, the strakes differs a lot between veterinary and human medicine, biological behavior are almost the same and should led to a beneficial team work between all

  4. Visual findings as primary manifestations in patients with intracranial tumors

    Directory of Open Access Journals (Sweden)

    Nazife Sefi-Yurdakul

    2015-08-01

    Full Text Available AIM:To evaluate the visual findings as primary manifestations in patients with intracranial tumors.METHODS:The medical charts of the patients with intracranial tumors who initially admitted to the Neuro-ophthalmology and Strabismus Department with ocular complaints between August 1999 and December 2012 were reviewed retrospectively. The detailed clinical history and the findings of neuro-ophthalmologic examination were recorded. Ocular symptoms and signs, the types and locations of intracranial tumors, and the duration of symptoms before the diagnosis were evaluated.RESULTS:The mean age of 11 women (61.1% and 7 men (38.9% was 42.2±11.0 (range 20-66y at the time of intracranial tumor diagnosis. Initial symptoms were transient visual obscurations, visual loss or visual field defect in 16 cases (88.9%, and diplopia in 2 cases (11.1%. Neuro-ophthalmologic examination revealed normal optic discs in both eyes of 6 patients (33.3%, paleness, atrophy or edema of optic disc in 12 patients (66.7%, and sixth cranial nerve palsy in 2 patients (11.1%. Visual acuity ranged between normal vision and loss of light perception. Cranial imaging demonstrated craniopharyngioma (n=1, plasmacytoma (n=1, meningioma (n=6; olfactory groove and tuberculum sellae, pontocerebellar angle, anterior cranial fossa, frontal vertex, suprasellar region, and pituitary macroadenoma (n=10. The mean duration between the onset of visual disturbances and the diagnosis of intracranial tumor was 9.8±18mo (range 3d-6y.CONCLUSION:The ophthalmologist is frequently the first physician to encounter a patient with clinical manifestations of intracranial tumors that may cause neurological and ocular complications. Neuro-ophthalmologic findings should be carefully evaluated to avoid a delay in the diagnosis of intracranial tumors.

  5. Visual findings as primary manifestations in patients with intracranial tumors

    Institute of Scientific and Technical Information of China (English)

    Nazife; Sefi-Yurdakul

    2015-01-01

    · AIM: To evaluate the visual findings as primary manifestations in patients with intracranial tumors.·METHODS: The medical charts of the patients with intracranial tumors who initially admitted to the Neuro-ophthalmology and Strabismus Department with ocular complaints between August 1999 and December 2012 were reviewed retrospectively. The detailed clinical history and the findings of neuro-ophthalmologic examination were recorded. Ocular symptoms and signs,the types and locations of intracranial tumors, and the duration of symptoms before the diagnosis were evaluated.·RESULTS: The mean age of 11 women(61.1%) and 7men(38.9%) was 42.2±11.0(range 20-66y) at the time of intracranial tumor diagnosis. Initial symptoms were transient visual obscurations, visual loss or visual field defect in 16 cases(88.9%), and diplopia in 2 cases(11.1%). Neuro-ophthalmologic examination revealed normal optic discs in both eyes of 6 patients(33.3%),paleness, atrophy or edema of optic disc in 12 patients(66.7%), and sixth cranial nerve palsy in 2 patients(11.1%). Visual acuity ranged between normal vision and loss of light perception. Cranial imaging demonstrated craniopharyngioma(n =1), plasmacytoma(n =1),meningioma(n =6; olfactory groove and tuberculum sellae, pontocerebellar angle, anterior cranial fossa,frontal vertex, suprasellar region), and pituitary macroadenoma(n =10). The mean duration between the onset of visual disturbances and the diagnosis of intracranial tumor was 9.8±18mo(range 3d-6y).·CONCLUSION: The ophthalmologist is frequently the first physician to encounter a patient with clinical manifestations of intracranial tumors that may cause neurological and ocular complications. Neuro-ophthalmologic findings should be carefully evaluated to avoid a delay in the diagnosis of intracranial tumors.

  6. Early circulating tumor DNA dynamics and clonal selection with palbociclib and fulvestrant for breast cancer.

    Science.gov (United States)

    O'Leary, Ben; Hrebien, Sarah; Morden, James P; Beaney, Matthew; Fribbens, Charlotte; Huang, Xin; Liu, Yuan; Bartlett, Cynthia Huang; Koehler, Maria; Cristofanilli, Massimo; Garcia-Murillas, Isaac; Bliss, Judith M; Turner, Nicholas C

    2018-03-01

    CDK4/6 inhibition substantially improves progression-free survival (PFS) for women with advanced estrogen receptor-positive breast cancer, although there are no predictive biomarkers. Early changes in circulating tumor DNA (ctDNA) level may provide early response prediction, but the impact of tumor heterogeneity is unknown. Here we use plasma samples from patients in the randomized phase III PALOMA-3 study of CDK4/6 inhibitor palbociclib and fulvestrant for women with advanced breast cancer and show that relative change in PIK3CA ctDNA level after 15 days treatment strongly predicts PFS on palbociclib and fulvestrant (hazard ratio 3.94, log-rank p = 0.0013). ESR1 mutations selected by prior hormone therapy are shown to be frequently sub clonal, with ESR1 ctDNA dynamics offering limited prediction of clinical outcome. These results suggest that early ctDNA dynamics may provide a robust biomarker for CDK4/6 inhibitors, with early ctDNA dynamics demonstrating divergent response of tumor sub clones to treatment.

  7. Multispectral Imaging Analysis of Circulating Tumor Cells in Negatively Enriched Peripheral Blood Samples.

    Science.gov (United States)

    Miller, Brandon; Lustberg, Maryam; Summers, Thomas A; Chalmers, Jeffrey J

    2017-01-01

    A variety of biomarkers are present on cells in peripheral blood of patients with a variety of disorders, including solid tumor malignancies. While rare, characterization of these cells for specific protein levels with the advanced technology proposed, will lead to future validation studies of blood samples as "liquid biopsies" for the evaluation of disease status and therapeutic response. While circulating tumor cells (CTCs) have been isolated in the blood samples of patients with solid tumors, the exact role of CTCs as clinically useful predictive markers is still debated. Current commercial technology has significant bias in that a positive selection technology is used that preassumes specific cell surface markers (such as EpCAM) are present on CTCs. However, CTCs with low EpCAM expression have been experimentally demonstrated to be more likely to be missed by this method. In contrast, this application uses a previously developed, technology that performs a purely negative enrichment methodology on peripheral blood, yielding highly enriched blood samples that contain CTCs as well as other, undefined cell types. The focus of this contribution is the use of multispectral imaging of epifluorescent, microscopic images of these enriched cells in order to help develop clinically relevant liquid biopsies from peripheral blood samples.

  8. Reverse primary-side flow in steam generators during natural circulation cooling

    International Nuclear Information System (INIS)

    Stumpf, H.; Motley, F.; Schultz, R.; Chapman, J.; Kukita, Y.

    1987-01-01

    A TRAC model of the Large Scale Test Facility with a 3-tube steam-generator model was used to analyze natural-circulation test ST-NC-02. For the steady state at 100% primary mass inventory, TRAC was in excellent agreement with the natural-circulation flow rate, the temperature distribution in the steam-generator tubes, and the temperature drop from the hot leg to the steam-generator inlet plenum. TRAC also predicted reverse flow in the long tubes. At reduced primary mass inventories, TRAC predicted the three natural-circulation flow regimes: single phase, two phase, and reflux condensation. TRAC did not predict the cyclic fill-and-dump phenomenon seen briefly in the test. TRAC overpredicted the two-phase natural-circulation flow rate. Since the core is well cooled at this time, the result is conservative. An important result of the analysis is that TRAC was able to predict the core dryout and heatup at approximately the same primary mass inventory as in the test. 4 refs., 8 figs., 2 tabs

  9. Management of primary malignant germ cell tumor of the mediastinum

    International Nuclear Information System (INIS)

    Sakurai, Hiroyuki; Asamura, Hisao; Suzuki, Kenji; Watanabe, Shun-ichi; Tsuchiya, Ryosuke

    2004-01-01

    Primary mediastinal malignant germ cell tumors (GCTs) are rare and have a worse prognosis than their gonadal counterparts. Although multimodality treatment is a standard therapeutic strategy in mediastinal GCTs, the clinical implications of surgical intervention remain unclear. Forty-eight patients with primary mediastinal malignant GCT who were treated at the National Cancer Center Hospital, Tokyo, from 1962 to 2002 were studied retrospectively with regard to their histology and clinical profile. Mediastinal GCT occurred predominantly in young males, with a mean age of 28.8 years at the time of diagnosis. There were 46 males (96%) and two females (4%). Histologically, seven patients (15%) were diagnosed as having pure seminoma and 41 (85%) had nonseminomatous GCT. Treatment consisted of surgery alone in nine patients, surgery followed by chemotherapy in two, and chemotherapy followed by surgery in 20. The other 17 patients received chemotherapy and/or radiotherapy without surgery. Of these latter 17 patients, 14 developed progressive disease and three were followed up with a sustained partial response. Among the 31 patients who underwent surgery, complete resection was performed in 27 (87%) and incomplete resection was performed in four (13%). Twelve (41%) patients had elevated serum tumor marker levels preoperatively. Among the 20 patients who received preoperative chemotherapy, viable cells were found in the resected specimen in six (30%). With regard to tumor recurrence in patients with surgical intervention, the preoperative serum tumor marker levels and the presence of viable cells in the resected specimen were significantly associated with recurrence. There was no significant association between surgical curability and recurrence. The 5-year overall survival rate in all 48 patients was 45.5%. Surgical intervention for mediastinal GCT may be needed to remove a chemotherapy-refractory tumor or to assess the pathological response to chemotherapy to determine

  10. Factors affecting the local control of stereotactic body radiotherapy for lung tumors including primary lung cancer and metastatic lung tumors

    International Nuclear Information System (INIS)

    Hamamoto, Yasushi; Kataoka, Masaaki; Yamashita, Motohiro

    2012-01-01

    The purpose of this study was to identify factors affecting local control of stereotactic body radiotherapy (SBRT) for lung tumors including primary lung cancer and metastatic lung tumors. Between June 2006 and June 2009, 159 lung tumors in 144 patients (primary lung cancer, 128; metastatic lung tumor, 31) were treated with SBRT with 48-60 Gy (mean 50.1 Gy) in 4-5 fractions. Higher doses were given to larger tumors and metastatic tumors in principle. Assessed factors were age, gender, tumor origin (primary vs. metastatic), histological subtype, tumor size, tumor appearance (solid vs. ground glass opacity), maximum standardized uptake value of positron emission tomography using 18 F-fluoro-2-deoxy-D-glucose, and SBRT doses. Follow-up time was 1-60 months (median 18 months). The 1-, 2-, and 3-year local failure-free rates of all lesions were 90, 80, and 77%, respectively. On univariate analysis, metastatic tumors (p<0.0001), solid tumors (p=0.0246), and higher SBRT doses (p=0.0334) were the statistically significant unfavorable factors for local control. On multivariate analysis, only tumor origin was statistically significant (p=0.0027). The 2-year local failure-free rates of primary lung cancer and metastatic lung tumors were 87 and 50%, respectively. A metastatic tumor was the only independently significant unfavorable factor for local control after SBRT. (author)

  11. Plasma circulating tumor DNA as an alternative to metastatic biopsies for mutational analysis in breast cancer.

    Science.gov (United States)

    Rothé, F; Laes, J-F; Lambrechts, D; Smeets, D; Vincent, D; Maetens, M; Fumagalli, D; Michiels, S; Drisis, S; Moerman, C; Detiffe, J-P; Larsimont, D; Awada, A; Piccart, M; Sotiriou, C; Ignatiadis, M

    2014-10-01

    Molecular screening programs use next-generation sequencing (NGS) of cancer gene panels to analyze metastatic biopsies. We interrogated whether plasma could be used as an alternative to metastatic biopsies. The Ion AmpliSeq™ Cancer Hotspot Panel v2 (Ion Torrent), covering 2800 COSMIC mutations from 50 cancer genes was used to analyze 69 tumor (primary/metastases) and 31 plasma samples from 17 metastatic breast cancer patients. The targeted coverage for tumor DNA was ×1000 and for plasma cell-free DNA ×25 000. Whole blood normal DNA was used to exclude germline variants. The Illumina technology was used to confirm observed mutations. Evaluable NGS results were obtained for 60 tumor and 31 plasma samples from 17 patients. When tumor samples were analyzed, 12 of 17 (71%, 95% confidence interval (CI) 44% to 90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1 or IDH2 gene. When plasma samples were analyzed, 12 of 17 (71%, 95% CI: 44-90%) patients had ≥1 mutation (median 1 mutation per patient, range 0-2 mutations) in either p53, PIK3CA, PTEN, AKT1, IDH2 and SMAD4. All mutations were confirmed. When we focused on tumor and plasma samples collected at the same time-point, we observed that, in four patients, no mutation was identified in either tumor or plasma; in nine patients, the same mutations was identified in tumor and plasma; in two patients, a mutation was identified in tumor but not in plasma; in two patients, a mutation was identified in plasma but not in tumor. Thus, in 13 of 17 (76%, 95% CI 50% to 93%) patients, tumor and plasma provided concordant results whereas in 4 of 17 (24%, 95% CI 7% to 50%) patients, the results were discordant, providing complementary information. Plasma can be prospectively tested as an alternative to metastatic biopsies in molecular screening programs. © The Author 2014. Published by Oxford University Press on behalf of the European Society for Medical Oncology

  12. Primary hyperparathyroidism, adrenal tumors and neuroendocrine tumors of the pancreas - clinical diagnosis and imaging requirements

    International Nuclear Information System (INIS)

    Auernhammer, C.J.; Engelhardt, D.; Goeke, B.

    2003-01-01

    Diseases of the parathyroids, the adrenals and of neuroendocrine tumors of the pancreas are primarily diagnosed by clinical and endocrinological evaluation.The requirements concerning various imaging techniques and their relative importance in localization strategies of the different tumors are complex. Current literature search, using PubMed. Evaluation of primary hyperparathyroidism requires bone densitometry by DXA and search for nephrolithiasis by ultrasound or native CT examination.While ultrasound of the thyroid and parathyroids seems useful before any parathyroid surgery,more extensive preoperative localization strategies (sestamibi scintigraphy, MRI) should be restricted to minimal invasive parathyroid surgery or re-operations.For adrenal tumors CT and MRI are of similar diagnostic value. Imaging of pheochromocytomas should be completed by MIBG scintigraphy. Each adrenal incidentaloma requires an endocrinological work-up.A fine-needle aspiration or core needle biopsy of an adrenal tumor is rarely indicated.Before adrenal biopsy a pheochromocytoma has to be excluded.Successful localization strategies for neuroendocrine tumors of the pancreas include somatostatin receptor scintigraphy, endoscopic ultrasound and MRI.Discussion Specific localization strategies have been established for the aforementioned tumors.The continuous progress of different imaging techniques requires a regular reevaluation of these localization strategies. (orig.) [de

  13. Circulating and tumor-infiltrating Tim-3 in patients with colorectal cancer

    Science.gov (United States)

    Gao, Quanli; Yuan, Peng; Zhao, Peng; Yuan, Huijuan; Fan, Huijie; Li, Tiepeng; Qin, Peng; Han, Lu; Fang, Weijia; Suo, Zhenhe

    2015-01-01

    T-cell exhaustion represents a progressive loss of T-cell function. The inhibitory receptor PD-1 is known to negatively regulate CD8+ T cell responses directed against tumor antigen, but the blockades of PD-1 pathway didn't show the objective responses in patients with colorectal cancer (CRC). Thus, further exploring the molecular mechanism responsible for inducing T-cell dysfunction in CRC patients may reveal effective strategies for immune therapy. This study aims to characterize co-inhibitory receptors on T cells in CRC patients to identify novel targets for immunotherapy. In this study, peripheral blood samples from 20 healthy controls and 54 consented CRC patients, and tumor and matched paraneoplastic tissues from 7 patients with advanced CRC, subjected to multicolor flow cytometric analysis of the expression of PD-1 and Tim-3 receptors on CD8+ T cells. It was found that CRC patients presented with significantly higher levels of circulating Tim-3+PD-1+CD8+ T cells compared to the healthy controls (medians of 3.12% and 1.99%, respectively, p = 0.0403). A similar increase of Tim-3+PD-1+CD8+ T cells was also observed in the tumor tissues compared to paraneoplastic tussues. Tim-3+PD-1+CD8+ T cells in tumor tissues produced even less cytokine than that in paraneoplastic tissues. Functional ex vivo experiments showed that Tim-3+PD-1+CD8+ T cells produced significantly less IFN-γ than Tim-3−PD-1−CD8+ T cells, followed by Tim-3+PD-1−CD8+ T cells, and Tim-3−PD-1+CD8+ T cells, indicating a stronger inhibition of IFN-γ production of Tim-3+CD8+ T cells. It is also found in this study that Tim-3+PD-1+CD8+ T cell increase in circulation was correlated with clinical cancer stage but not histologic grade and serum concentrations of cancer biomarker CEA. Our results indicate that upregulation of the inhibitory receptor Tim-3 may restrict T cell responses in CRC patients, and therefore blockage of Tim-3 and thus restoring T cell responses may be a potential

  14. Circulating Tumor Cells and Cardiac Metastasis from Esophageal Cancer: A Case Report

    Directory of Open Access Journals (Sweden)

    Francesca Consoli

    2011-05-01

    Full Text Available We report the case of a 67-year-old man affected by metastatic esophageal cancer. The patient developed a symptomatic heart metastasis presenting as mimicking ST-segment elevation myocardial infarction. Cardiac magnetic resonance imaging (MRI documented the presence of a mass in the apex and septum of the left ventriculum. The dissemination of cancer was confirmed by the detection of circulating tumor cells (CTCs in the peripheral blood, measured by the CellSearch System (Veridex, LLC, Raritan, N.J., USA. The blood sample drawn at cardiac disease progression revealed the presence of 2 CTCs per 7.5 ml of blood. This report highlights the potential role of CTCs as markers of metastatic spread.

  15. CCR 20th Anniversary Commentary: Circulating Tumor Cells in Prostate Cancer.

    Science.gov (United States)

    Mehra, Niven; Zafeiriou, Zafeiris; Lorente, David; Terstappen, Leon W M M; de Bono, Johann S

    2015-11-15

    Circulating tumor cells (CTC) have substantial promise for multipurpose biomarker studies in prostate cancer. The IMMC-38 trial conducted by de Bono and colleagues, which was published in the October 1, 2008, issue of Clinical Cancer Research, demonstrated for the first time that CTCs are the most accurate and independent predictor of overall survival in metastatic prostate cancer. Since the publication of prospective trials demonstrating prognostic utility, CTCs have been utilized for nucleic acid analyses, for protein analyses, and in intermediate endpoint studies. CTC studies are also now facilitating the analysis of intrapatient heterogeneity. See related article by de Bono et al., Clin Cancer Res 2008;14(19) October 1, 2008;6302-9. ©2015 American Association for Cancer Research.

  16. Circulating Tumor Cell Analysis: Technical and Statistical Considerations for Application to the Clinic

    Directory of Open Access Journals (Sweden)

    Alison L. Allan

    2010-01-01

    Full Text Available Solid cancers are a leading cause of death worldwide, primarily due to the failure of effective clinical detection and treatment of metastatic disease in distant sites. There is growing evidence that the presence of circulating tumor cells (CTCs in the blood of cancer patients may be an important indicator of the potential for metastatic disease and poor prognosis. Technological advances have now facilitated the enumeration and characterization of CTCs using methods such as PCR, flow cytometry, image-based immunologic approaches, immunomagnetic techniques, and microchip technology. However, the rare nature of these cells requires that very sensitive and robust detection/enumeration methods be developed and validated in order to implement CTC analysis for widespread use in the clinic. This review will focus on the important technical and statistical considerations that must be taken into account when designing and implementing CTC assays, as well as the subsequent interpretation of these results for the purposes of clinical decision making.

  17. Considerations in the development of circulating tumor cell technology for clinical use

    Directory of Open Access Journals (Sweden)

    Parkinson David R

    2012-07-01

    Full Text Available Abstract This manuscript summarizes current thinking on the value and promise of evolving circulating tumor cell (CTC technologies for cancer patient diagnosis, prognosis, and response to therapy, as well as accelerating oncologic drug development. Moving forward requires the application of the classic steps in biomarker development–analytical and clinical validation and clinical qualification for specific contexts of use. To that end, this review describes methods for interactive comparisons of proprietary new technologies, clinical trial designs, a clinical validation qualification strategy, and an approach for effectively carrying out this work through a public-private partnership that includes test developers, drug developers, clinical trialists, the US Food & Drug Administration (FDA and the US National Cancer Institute (NCI.

  18. [Echocardiography in diagnosis of primary cardiac tumors in pediatrics].

    Science.gov (United States)

    Erdmenger Orellana, Julio; Vázquez, Clara; Ortega Maldonado, Jesús

    2005-01-01

    We report the experience in the diagnosis of primary cardiac tumor during the period from 1999 to 2004, 8500 studies were revised echocardiographic carried out. We found 21 patients, 11 of female sex (55%). In 15/21 (71%), the age of presentation was less than 1 year. In 9/21 the tumor was multiple (42.8%), lodged in the ventricle right in 2/21 (9.5%), in the ventricle left 3 (14.2%), 8 in the septum interventricular (38%) and 4 compromised the auriculas. They were classified like rabdomiomas 14 (66%), 5 associates with sclerosis tuberosa, 4 mixomas (19%), 2 fibromas (9.5%) and 1 rabdomiosarcoma (4.7%). In five patients the diagnosis was prenatal. The global mortality went of 9.5%. The echocardiograpy is a good diagnosis method in our series the rabdomioma occupied the first place in frequency.

  19. Relationship of circulating tumor cells to tumor response, progression-free survival, and overall survival in patients with metastatic colorectal cancer

    NARCIS (Netherlands)

    Cohen, Steven J.; Punt, Cornelis J. A.; Iannotti, Nicholas; Saidman, Bruce H.; Sabbath, Kert D.; Gabrail, Nashat Y.; Picus, Joel; Morse, Michael; Mitchell, Edith; Miller, M. Craig; Doyle, Gerald V.; Tissing, Henk; Terstappen, Leon W. M. M.; Meropol, Neal J.

    2008-01-01

    As treatment options expand for metastatic colorectal cancer (mCRC), a blood marker with a prognostic and predictive role could guide treatment. We tested the hypothesis that circulating tumor cells (CTCs) could predict clinical outcome in patients with mCRC. In a prospective multicenter study, CTCs

  20. Experience with surgical treatment for primary malignant adrenal tumors

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    V. R. Latypov

    2016-01-01

    Full Text Available Background. Adrenal tumors occur in 3–10 % of the population and are mostly benign adrenal cortical tumors. Adrenocortical carcinoma is a very rare tumor and has an annual incidence of 1–2 cases per million people. The U.S. National Cancer Data Base registered 4275 patients with adrenocortical carcinoma in 1985 to 2007. It is extremely difficult to assess Russia’s epidemiological data, as reports on adrenocortical carcinoma are not presented separately.Materials and methods. A total of 133 patients (49 men and 84 women (1:1.7 with adrenal tumors were operated on at the clinics of the Siberian State Medical University in the period December 1998 to March 2015. The patients’ mean age was 51.3 (16–80 years (median age 51.0 years. The right and left adrenal glands were affected in 49 (36.9 % and 77 (57.9 % patients, respectively; both adrenal glands were involved in 7 (5.3 %. A group of 21 (15.8 % people with primary malignant adrenal tumors was identified among all the patients. The clinical manifestations of the disease were evaluated from the presence of hormonal activity, gastrointestinal symptoms, pain syndrome, and hypertension. All the patients were operated on under endotracheal anesthesia. The data were statistically processed using the program package Statistica 6.0. Survival rates were analyzed by the Kaplan–Meier method. The Gehan–Wilcoxon test was used to compare the groups.Results. The investigation analyzed treatment results in 21 (15.8 % patients with primary malignant adrenal lesions (Group 1. The most common morphological form was adrenocortical carcinoma in 15 (11.3 % patients (5 men and 10 women (1:2; their mean age was 48.1 years. The right, left, and both adrenal glands were affected in 4, 9, and 2 cases, respectively. In Group 2, other malignant adrenal involvements were identified from 1 case of rare malignant adrenal tumors: malignant pheochromocytoma, sarcoma, melanoma, squamous cell

  1. Integration of biomimicry and nanotechnology for significantly improved detection of circulating tumor cells (CTCs).

    Science.gov (United States)

    Myung, Ja Hye; Park, Sin-Jung; Wang, Andrew Z; Hong, Seungpyo

    2017-12-13

    Circulating tumor cells (CTCs) have received a great deal of scientific and clinical attention as a biomarker for diagnosis and prognosis of many types of cancer. Given their potential significance in clinics, a variety of detection methods, utilizing the recent advances in nanotechnology and microfluidics, have been introduced in an effort of achieving clinically significant detection of CTCs. However, effective detection and isolation of CTCs still remain a tremendous challenge due to their extreme rarity and phenotypic heterogeneity. Among many approaches that are currently under development, this review paper focuses on a unique, promising approach that takes advantages of naturally occurring processes achievable through application of nanotechnology to realize significant improvement in sensitivity and specificity of CTC capture. We provide an overview of successful outcome of this biomimetic CTC capture system in detection of tumor cells from in vitro, in vivo, and clinical pilot studies. We also emphasize the clinical impact of CTCs as biomarkers in cancer diagnosis and predictive prognosis, which provides a cost-effective, minimally invasive method that potentially replaces or supplements existing methods such as imaging technologies and solid tissue biopsy. In addition, their potential prognostic values as treatment guidelines and that ultimately help to realize personalized therapy are discussed. Copyright © 2017. Published by Elsevier B.V.

  2. Development of a cell microarray chip for detection of circulating tumor cells

    Science.gov (United States)

    Yamamura, S.; Yatsushiro, S.; Abe, K.; Baba, Y.; Kataoka, M.

    2012-03-01

    Detection of circulating tumor cells (CTCs) in the peripheral blood of metastatic cancer patients has clinical significance in earlier diagnosis of metastases. In this study, a novel cell microarray chip for accurate and rapid detection of tumor cells from human leukocytes was developed. The chip with 20,944 microchambers (105 μm diameter and 50 μm depth) was made from polystyrene, and the surface was rendered to hydrophilic by means of reactive-ion etching, which led to the formation of mono-layers of leukocytes on the microchambers. As the model of CTCs detection, we spiked human bronchioalveolar carcinoma (H1650) cells into human T lymphoblastoid leukemia (CEM) cells suspension and detected H1650 cells using the chip. A CEM suspension contained with H1650 cells was dispersed on the chip surface, followed by 10 min standing to allow the cells to settle down into the microchambers. About 30 CEM cells were accommodated in each microchamber, over 600,000 CEM cells in total being on a chip. We could detect 1 H1650 cell per 106 CEM cells on the microarray by staining with fluorescence-conjugated antibody (Anti-Cytokeratin) and cell membrane marker (DiD). Thus, this cell microarray chip has highly potential to be a novel tool of accurate and rapid detection of CTCs.

  3. Cultured circulating tumor cells and their derived xenografts for personalized oncology

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    Ruoxiang Wang

    2016-10-01

    Full Text Available Recent cancer research has demonstrated the existence of circulating tumor cells (CTCs in cancer patient's blood. Once identified, CTC biomarkers will be invaluable tools for clinical diagnosis, prognosis and treatment. In this review, we propose ex vivo culture as a rational strategy for large scale amplification of the limited numbers of CTCs from a patient sample, to derive enough CTCs for accurate and reproducible characterization of the biophysical, biochemical, gene expressional and behavioral properties of the harvested cells. Because of tumor cell heterogeneity, it is important to amplify all the CTCs in a blood sample for a comprehensive understanding of their role in cancer metastasis. By analyzing critical steps and technical issues in ex vivo CTC culture, we developed a cost-effective and reproducible protocol directly culturing whole peripheral blood mononuclear cells, relying on an assumed survival advantage in CTCs and CTC-like cells over the normal cells to amplify this specified cluster of cancer cells.

  4. Clinical Utility of Circulating Tumor Cells in ALK-Positive Non-Small-Cell Lung Cancer.

    Science.gov (United States)

    Faugeroux, Vincent; Pailler, Emma; Auger, Nathalie; Taylor, Melissa; Farace, Françoise

    2014-01-01

    The advent of rationally targeted therapies such as small-molecule tyrosine kinase inhibitors (TKIs) has considerably transformed the therapeutic management of a subset of patients with non-small-cell lung cancer (NSCLC) harboring defined molecular abnormalities. When such genetic molecular alterations are detected the use of specific TKI has demonstrated better results (overall response rate, progression free survival) compared to systemic therapy. However, the detection of such molecular abnormalities is complicated by the difficulty in obtaining sufficient tumor material, in terms of quantity and quality, from a biopsy. Here, we described how circulating tumor cells (CTCs) can have a clinical utility in anaplastic lymphoma kinase (ALK) positive NSCLC patients to diagnose ALK-EML4 gene rearrangement and to guide therapeutic management of these patients. The ability to detect genetic abnormalities such ALK rearrangement in CTCs shows that these cells could offer new perspectives both for the diagnosis and the monitoring of ALK-positive patients eligible for treatment with ALK inhibitors.

  5. Circulating tumor cells predict survival benefit from chemotherapy in patients with lung cancer.

    Science.gov (United States)

    Wu, Zhuo-Xuan; Liu, Zhen; Jiang, Han-Ling; Pan, Hong-Ming; Han, Wei-Dong

    2016-10-11

    This meta-analysis was to explore the clinical significance of circulating tumor cells (CTCs) in predicting the tumor response to chemotherapy and prognosis of patients with lung cancer. We searched PubMed, Embase, Cochrane Database, Web of Science and reference lists of relevant articles. Our meta-analysis was performed by Stata software, version 12.0, with a random effects model. Risk ratio (RR), hazard ratio (HR) and 95% confidence intervals (CI) were used as effect measures. 8 studies, including 453 patients, were eligible for analyses. We showed that the disease control rate (DCR) in CTCs-negative patients was significantly higher than CTCs-positive patients at baseline (RR = 2.56, 95%CI [1.36, 4.82], p chemotherapy (RR = 9.08, CI [3.44, 23.98], p chemotherapy had a worse disease progression than those with CTC-positive to negative or persistently negative (RR = 8.52, CI [1.66, 43.83], p chemotherapy also indicated poor overall survival (OS) (baseline: HR = 3.43, CI [2.21, 5.33], pchemotherapy: HR = 3.16, CI [2.23, 4.48], p chemotherapy: HR = 3.78, CI [2.33, 6.13], p chemotherapy and poor prognosis in patients with lung cancer.

  6. Assessment of γ-H2AX levels in circulating tumor cells from patients receiving chemotherapy

    Energy Technology Data Exchange (ETDEWEB)

    Garcia-Villa, Alejandra; Balasubramanian, Priya; Miller, Brandon L. [William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH (United States); Lustberg, Maryam B.; Ramaswamy, Bhuvaneswari [Department of Internal Medicine, Breast Medical Oncology, James Cancer Hospital and Ohio State University Comprehensive Cancer Center, Columbus, OH (United States); Chalmers, Jeffrey J., E-mail: chalmers.1@osu.edu [William G. Lowrie Department of Chemical and Biomolecular Engineering, The Ohio State University, Columbus, OH (United States)

    2012-10-25

    Circulating tumor cells (CTCs) are prognostic markers in a variety of solid tumor malignancies. The potential of CTCs to be used as a “liquid biopsy” to monitor a patient’s condition and predict drug response and resistance is currently under investigation. Using a negative depletion, enrichment methodology, CTCs isolated from the peripheral blood of breast cancer patients with stage IV breast cancer undergoing DNA damaging therapy with platinum-based therapy were enriched. The enriched cell suspensions were stained with an optimized labeling protocol targeting: nuclei, cytokeratins 8, 18, and 19, the surface marker CD45, and the presence of the protein γ-H2AX. As a direct or indirect result of platinum therapy, double-strand break of DNA initiates phosphorylation of the histone H2AX, at serine 139; this phosphorylated form is referred to as γ-H2AX. In addition to γ-H2AX staining in specific locations with the cell nuclei, consistent with previous reports and referred to as foci, more general staining in the cell cytoplasm was also observed in some cells suggesting the potential of cell apoptosis. Our study underscores the utility and the complexity of investigating CTCs as predictive markers of response to various therapies. Additional studies are ongoing to evaluate the diverse γ-H2AX staining patterns we report here which needs to be further correlated with patient outcomes.

  7. A SYSTEM AND A DEVICE FOR ISOLATING CIRCULATING TUMOR CELLS FROM THE PERIPHERAL BLOOD IN VIVO

    Directory of Open Access Journals (Sweden)

    Michal Mego

    2015-08-01

    Full Text Available Circulating tumor cells (CTC play a crucial role in disseminating tumors and in the metastatic cascade. CTCs are found only in small numbers, and the limited amount of isolated CTCs makes it impossible to characterize them closely. This paper presents a proposal for a new system for isolating CTCs from the peripheral blood in vivo. The system enables CTCs to be isolated from the whole blood volume for further research and applications. The proposed system consists of magnetic nanoparticles covered by monoclonal antibodies against a common epithelial antigen, large supermagnets, which are used to control the position of the nanoparticles within the human body, and a special wire made of a magnetic core wrapped in a non-magnetic shell. The system could be used not only for isolating CTCs, but also for in vivo isolation of other rare cells from the peripheral blood, including hematopoietic and/or mesenchymal stem cells, with applications in regenerative medicine and/or in stem cell transplantation.

  8. Isolation of circulating tumor cells by a magnesium-embedded filter

    International Nuclear Information System (INIS)

    Liu, Yang; Kang, Dongyang; Xu, Lei; Park, Jungwook; Zhang, Xiaoxiao; Tai, Yu-Chong; Xu, Tong; Xu, Yucheng; Chang, Jay Han-Chieh; Goldkorn, Amir

    2015-01-01

    Circulating tumor cells (CTCs) are rare cancer cells that are shed by tumors into the bloodstream and that can be valuable biomarkers for various types of cancers. However, CTCs captured on the filter could not be released easily using the existing CTC analysis platforms based on size. To address this limitation, we have developed a novel magnesium (Mg)-embedded cell filter for capture, release and isolation of CTCs. The CTC-filter consists of a thin Ebeam-deposited Mg layer embedded between two parylene-C (PA-C) layers with designed slots for filtration and CTC capture. Thin Mg film has proved highly biocompatible and can be etched in saline, PBS and Dulbecco’s modified eagle medium (DMEM) etc, properties that are of great benefit to help dissociate the filter and thus release the cells. The finite element method (FEM) analysis was performed on the Mg etching process in DMEM for the structure design. After the filtration process, the filter was submerged in DMEM to facilitate Mg etching. The top PA-C filter pieces break apart from the bottom after Mg completely dissolves, enabling captured CTCs to detach. The released CTC can be easily aspirated into a micropipette for further analysis. Thus, the Mg-embedded cell filter provides a new and effective approach for CTCs isolation from the filter, making this a promising new strategy for cancer detection. (paper)

  9. Development of the automated circulating tumor cell recovery system with microcavity array.

    Science.gov (United States)

    Negishi, Ryo; Hosokawa, Masahito; Nakamura, Seita; Kanbara, Hisashige; Kanetomo, Masafumi; Kikuhara, Yoshihito; Tanaka, Tsuyoshi; Matsunaga, Tadashi; Yoshino, Tomoko

    2015-05-15

    Circulating tumor cells (CTCs) are well recognized as useful biomarker for cancer diagnosis and potential target of drug discovery for metastatic cancer. Efficient and precise recovery of extremely low concentrations of CTCs from blood has been required to increase the detection sensitivity. Here, an automated system equipped with a microcavity array (MCA) was demonstrated for highly efficient and reproducible CTC recovery. The use of MCA allows selective recovery of cancer cells from whole blood on the basis of differences in size between tumor and blood cells. Intra- and inter-assays revealed that the automated system achieved high efficiency and reproducibility equal to the assay manually performed by well-trained operator. Under optimized assay workflow, the automated system allows efficient and precise cell recovery for non-small cell lung cancer cells spiked in whole blood. The automated CTC recovery system will contribute to high-throughput analysis in the further clinical studies on large cohort of cancer patients. Copyright © 2014 Elsevier B.V. All rights reserved.

  10. Assessing Clinical Outcomes in Colorectal Cancer with Assays for Invasive Circulating Tumor Cells.

    Science.gov (United States)

    Zhang, Yue; Zarrabi, Kevin; Hou, Wei; Madajewicz, Stefan; Choi, Minsig; Zucker, Stanley; Chen, Wen-Tien

    2018-06-06

    Colorectal carcinoma (CRC) is the second leading cause of cancer-related mortality. The goals of this study are to evaluate the association between levels of invasive circulating tumor cells (iCTCs) with CRC outcomes and to explore the molecular characteristics of iCTCs. Peripheral blood from 93 patients with Stage I⁻IV CRC was obtained and assessed for the detection and characterization of iCTCs using a functional collagen-based adhesion matrix (CAM) invasion assay. Patients were followed and assessed for overall survival. Tumor cells isolated by CAM were characterized using cell culture and microarray analyses. Of 93 patients, 88 (95%) had detectable iCTCs, ranging over 0⁻470 iCTCs/mL. Patients with Stage I⁻IV disease exhibited median counts of 0.0 iCTCs/mL ( n = 6), 13.0 iCTCs/mL ( n = 12), 41.0 iCTCs/mL ( n = 12), and 133.0 iCTCs/mL ( n = 58), respectively ( p < 0.001). Kaplan⁻Meier curve analysis demonstrated a significant survival benefit in patients with low iCTC counts compared with in patients with high iCTC counts (log-rank p < 0.001). Multivariable Cox model analysis revealed that iCTC count was an independent prognostic factor of overall survival ( p = 0.009). Disease stage ( p = 0.01, hazard ratio 1.66; 95% confidence interval: 1.12⁻2.47) and surgical intervention ( p = 0.03, HR 0.37; 95% CI: 0.15⁻0.92) were also independent prognostic factors. Gene expression analysis demonstrated the expression of both endothelial and tumor progenitor cell biomarkers in iCTCs. CAM-based invasion assay shows a high detection sensitivity of iCTCs that inversely correlated with overall survival in CRC patients. Functional and gene expression analyses showed the phenotypic mosaics of iCTCs, mimicking the survival capability of circulating endothelial cells in the blood stream.

  11. Magnetic resonance imaging of primary intracranial tumors: a review

    International Nuclear Information System (INIS)

    Holland, B.A.; Brant-Zawadzki, M.; Norman, D.; Newton, T.H.

    1985-01-01

    The experience in magnetic resonance (MR) imaging of primary intracranial neoplasia at University of California, San Francisco is reviewed. Seventy patients have been evaluated by MR and computerized tomography (CT). MR scans were performed using a multi-slice spin echo technique with a long pulse repetition time (TR = 2000 msec), and long echo sampling delay (TE = 56 msec). This method was most sensitive in differentiating normal gray and white matter and in detecting both cerebral edema and abnormal tissue with prolonged T 2 characteristics. More sensitive to slight alterations in normal tissue, MR may detect a focal lesion in cases in which CT shows only mass effect. Moreover, MR may demonstrate more thoroughly the extent of tumor infiltration and broaden the characterization of abnormal tissue. Posterior fossa and brainstem anatomy are invariably better depicted by MR. The major limitations of MR include its inability to detect foci of tumor calcification, demonstrate the severity of bone destruction, or reliably distinguish tumor nidus from surrounding edema

  12. Classification of large circulating tumor cells isolated with ultra-high throughput microfluidic Vortex technology

    Science.gov (United States)

    Che, James; Yu, Victor; Dhar, Manjima; Renier, Corinne; Matsumoto, Melissa; Heirich, Kyra; Garon, Edward B.; Goldman, Jonathan; Rao, Jianyu; Sledge, George W.; Pegram, Mark D.; Sheth, Shruti; Jeffrey, Stefanie S.; Kulkarni, Rajan P.; Sollier, Elodie; Di Carlo, Dino

    2016-01-01

    Circulating tumor cells (CTCs) are emerging as rare but clinically significant non-invasive cellular biomarkers for cancer patient prognosis, treatment selection, and treatment monitoring. Current CTC isolation approaches, such as immunoaffinity, filtration, or size-based techniques, are often limited by throughput, purity, large output volumes, or inability to obtain viable cells for downstream analysis. For all technologies, traditional immunofluorescent staining alone has been employed to distinguish and confirm the presence of isolated CTCs among contaminating blood cells, although cells isolated by size may express vastly different phenotypes. Consequently, CTC definitions have been non-trivial, researcher-dependent, and evolving. Here we describe a complete set of objective criteria, leveraging well-established cytomorphological features of malignancy, by which we identify large CTCs. We apply the criteria to CTCs enriched from stage IV lung and breast cancer patient blood samples using the High Throughput Vortex Chip (Vortex HT), an improved microfluidic technology for the label-free, size-based enrichment and concentration of rare cells. We achieve improved capture efficiency (up to 83%), high speed of processing (8 mL/min of 10x diluted blood, or 800 μL/min of whole blood), and high purity (avg. background of 28.8±23.6 white blood cells per mL of whole blood). We show markedly improved performance of CTC capture (84% positive test rate) in comparison to previous Vortex designs and the current FDA-approved gold standard CellSearch assay. The results demonstrate the ability to quickly collect viable and pure populations of abnormal large circulating cells unbiased by molecular characteristics, which helps uncover further heterogeneity in these cells. PMID:26863573

  13. Mutant KRAS Circulating Tumor DNA Is an Accurate Tool for Pancreatic Cancer Monitoring.

    Science.gov (United States)

    Perets, Ruth; Greenberg, Orli; Shentzer, Talia; Semenisty, Valeria; Epelbaum, Ron; Bick, Tova; Sarji, Shada; Ben-Izhak, Ofer; Sabo, Edmond; Hershkovitz, Dov

    2018-05-01

    Many new pancreatic cancer treatment combinations have been discovered in recent years, yet the prognosis of pancreatic ductal adenocarcinoma (PDAC) remains grim. The advent of new treatments highlights the need for better monitoring tools for treatment response, to allow a timely switch between different therapeutic regimens. Circulating tumor DNA (ctDNA) is a tool for cancer detection and characterization with growing clinical use. However, currently, ctDNA is not used for monitoring treatment response. The high prevalence of KRAS hotspot mutations in PDAC suggests that mutant KRAS can be an efficient ctDNA marker for PDAC monitoring. Seventeen metastatic PDAC patients were recruited and serial plasma samples were collected. CtDNA was extracted from the plasma, and KRAS mutation analysis was performed using next-generation sequencing and correlated with serum CA19-9 levels, imaging, and survival. Plasma KRAS mutations were detected in 5/17 (29.4%) patients. KRAS ctDNA detection was associated with shorter survival (8 vs. 37.5 months). Our results show that, in ctDNA positive patients, ctDNA is at least comparable to CA19-9 as a marker for monitoring treatment response. Furthermore, the rate of ctDNA change was inversely correlated with survival. Our results confirm that mutant KRAS ctDNA detection in metastatic PDAC patients is a poor prognostic marker. Additionally, we were able to show that mutant KRAS ctDNA analysis can be used to monitor treatment response in PDAC patients and that ctDNA dynamics is associated with survival. We suggest that ctDNA analysis in metastatic PDAC patients is a readily available tool for disease monitoring. Avoiding futile chemotherapy in metastatic pancreatic ductal adenocarcinoma (PDAC) patients by monitoring response to treatment is of utmost importance. A novel biomarker for monitoring treatment response in PDAC, using mutant KRAS circulating tumor DNA (ctDNA), is proposed. Results, although limited by small sample numbers

  14. CUP Syndrome-Metastatic Malignancy with Unknown Primary Tumor.

    Science.gov (United States)

    Zaun, Gregor; Schuler, Martin; Herrmann, Ken; Tannapfel, Andrea

    2018-03-09

    2-4% of newly diagnosed cases of malignant disease involve cancer of unknown primary (CUP). This mixed entity is one of the 6 most common types of malignant disease in Germany. Highly refined treatment strategies can now be offered to patients with CUP. This review is based on pertinent publications retrieved by a selective search in PubMed with an emphasis on articles from the past decade. The current guidelines and recommendations of specialty societies were also considered in the evaluation. CUP most commonly manifests itself as metastases to the lymph nodes, lungs, liver, or bones. With the aid of imaging studies, including functional hybrid imaging and further medical examination, a primary tumor can be discovered in up to 40% of patients initially diagnosed with CUP. Immunohistochemistry guided by histomorphology often enables precise characterization of the lesion and can be supplemented, in selected cases, by molecular-genetic diagnostic evaluation. The most commonly detected types of primary tumor are cancers of the lung, pancreas, liver, and biliary system. For patients with local metastases, surgical resection or radiotherapy with curative intent is usually indicated, sometimes in the framework of a multimodal treatment concept. The median 2-year survival of patients with disseminated CUP is only 20%. For such patients, specific types of systemic therapy are recommended on the basis of the diagnostic characterization of the disease. Immune-modulatory antibodies can be effective, particularly in the treatment of CUP that has been characterized with biomarkers, but should still be considered experimental at present. A combination of conventional and innovative diagnostic methods enables the provision of highly refined therapeutic strategies to patients with CUP who are undergoing treatment in interdisciplinary cancer centers.

  15. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    International Nuclear Information System (INIS)

    Cha, Zhanshan; Qian, Guangfang; Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua; Song, Haihan; Qian, Baohua

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5"+ CD4"+ T cells, in DLBCL. Data showed that compared to CXCR5"- CD4"+ T cells, CXCR5"+ CD4"+ T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5"+ CD4"+ T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5"- CD4"+ T cells, while the level of IL-10 secretion was significant elevated in the CXCR5"+ compartment compared to the CXCR5"- compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5"+ CD4"+ T cell coculture compromised the CXCR5"+ CD4"+ T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5"+ compartment also contained significantly lower frequencies of cytotoxic CD4"+ T cells than the CXCR5"- compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4"+ T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  16. Myeloid cells in circulation and tumor microenvironment of breast cancer patients.

    Science.gov (United States)

    Toor, Salman M; Syed Khaja, Azharuddin Sajid; El Salhat, Haytham; Faour, Issam; Kanbar, Jihad; Quadri, Asif A; Albashir, Mohamed; Elkord, Eyad

    2017-06-01

    Pathological conditions including cancers lead to accumulation of a morphological mixture of highly immunosuppressive cells termed as myeloid-derived suppressor cells (MDSC). The lack of conclusive markers to identify human MDSC, due to their heterogeneous nature and close phenotypical and functional proximity with other cell subsets, made it challenging to identify these cells. Nevertheless, expansion of MDSC has been reported in periphery and tumor microenvironment of various cancers. The majority of studies on breast cancers were performed on murine models and hence limited literature is available on the relation of MDSC accumulation with clinical settings in breast cancer patients. The aim of this study was to investigate levels and phenotypes of myeloid cells in peripheral blood (n = 23) and tumor microenvironment of primary breast cancer patients (n = 7), compared with blood from healthy donors (n = 21) and paired non-tumor normal breast tissues from the same patients (n = 7). Using multicolor flow cytometric assays, we found that breast cancer patients had significantly higher levels of tumor-infiltrating myeloid cells, which comprised of granulocytes (P = 0.022) and immature cells that lack the expression of markers for fully differentiated monocytes or granulocytes (P = 0.016). Importantly, this expansion was not reflected in the peripheral blood. The immunosuppressive potential of these cells was confirmed by expression of Arginase 1 (ARG1), which is pivotal for T-cell suppression. These findings are important for developing therapeutic modalities to target mechanisms employed by immunosuppressive cells that generate an immune-permissive environment for the progression of cancer.

  17. A magnetic micropore chip for rapid (<1 hour) unbiased circulating tumor cell isolation and in situ RNA analysis.

    Science.gov (United States)

    Ko, Jina; Bhagwat, Neha; Yee, Stephanie S; Black, Taylor; Redlinger, Colleen; Romeo, Janae; O'Hara, Mark; Raj, Arjun; Carpenter, Erica L; Stanger, Ben Z; Issadore, David

    2017-09-12

    The use of microtechnology for the highly selective isolation and sensitive detection of circulating tumor cells has shown enormous promise. One challenge for this technology is that the small feature sizes - which are the key to this technology's performance - can result in low sample throughput and susceptibility to clogging. Additionally, conventional molecular analysis of CTCs often requires cells to be taken off-chip for sample preparation and purification before analysis, leading to the loss of rare cells. To address these challenges, we have developed a microchip platform that combines fast, magnetic micropore based negative immunomagnetic selection (>10 mL h -1 ) with rapid on-chip in situ RNA profiling (>100× faster than conventional RNA labeling). This integrated chip can isolate both rare circulating cells and cell clusters directly from whole blood and allow individual cells to be profiled for multiple RNA cancer biomarkers, achieving sample-to-answer in less than 1 hour for 10 mL of whole blood. To demonstrate the power of this approach, we applied our device to the circulating tumor cell based diagnosis of pancreatic cancer. We used a genetically engineered lineage-labeled mouse model of pancreatic cancer (KPCY) to validate the performance of our chip. We show that in a cohort of patient samples (N = 25) that this device can detect and perform in situ RNA analysis on circulating tumor cells in patients with pancreatic cancer, even in those with extremely sparse CTCs (<1 CTC mL -1 of whole blood).

  18. Primary renal carcinoid tumor mimicking non-clear cell renal cell carcinoma: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Joo, Lee Hi; Kim, See Hyung; Kim, Mi Jeong; Choe, Mi Sun [Keimyung University School of Medicine, Dongsan Medical Center, Daegu (Korea, Republic of)

    2016-07-15

    Carcinoid tumors are neoplasms with neuroendocrine differentiation, and they are most commonly found in the gastrointestinal and respiratory systems. Primary renal carcinoid tumor has rarely been reported. Here, we present a case of primary renal carcinoid tumor manifesting as a small but a gradually enhancing mass with calcification and a cystic component.

  19. Tumores primarios de la pared torácica Primary tumors of the thorax wall

    Directory of Open Access Journals (Sweden)

    Bárbaro Agustín Armas Pérez

    2011-09-01

    Full Text Available Introducción: se revisan aspectos teóricos en los tumores primarios de la pared torácica, sobre todo en la clasificación y en aspectos clínicos, diagnósticos y terapéuticos, con el propósito de conocer los resultados del tratamiento en el centro. Métodos: se realizó un estudio retrospectivo descriptivo para analizar los resultados del tratamiento quirúrgico en 22 pacientes (muestra con tumores primarios de la pared torácica, en un período de 15 años (enero de 1993 a diciembre de 2008, en los servicios de cirugía general y ortopedia del Hospital "Amalia Simoni" de Camagüey. Resultados: hubo ligero predominio del sexo femenino y del grupo de edad entre 17 a 44 años (media 39,4, la comorbilidad que predominó fue la hipertensión arterial, el hemitórax derecho fue el más afectado, y las costillas de la 1 a la 4 las más lesionadas, y predominaron las afecciones benignas, entre ellas, el osteocondroma. El tratamiento más utilizado fue la resección quirúrgica, y la complicación posoperatoria que predominó fue la bronconeumonía. El índice de recidiva tumoral fue alto, no siempre por cáncer. Hubo 4 fallecidos por enfermedad maligna avanzada, y no se presentaron muertes perioperatorias. Conclusiones: fueron comparados los resultados con los de otros reportes y se hallaron puntos de coincidencia en diversos aspectos, pero también discrepantes, se trata de unificar criterios para mejorar el diagnóstico y los resultados del tratamiento en estos enfermos. La mayoría de los pacientes no presentaron complicaciones, y la recidiva tumoral estuvo por encima de lo esperado. La resección tumoral siempre debe ser amplia. El resultado global fue satisfactorio.Introduction: the theoretical features in the primary tumors of the thorax wall, especially in the classification and clinical, diagnostic y therapeutical features were reviewed to know the results of treatment in our institution. Methods: a descriptive and retrospective study was

  20. Experimental Study on the Natural Circulation Characteristics in the Primary Loop of the SMART Reactor by using the VISTA Facility

    International Nuclear Information System (INIS)

    Park, Hyun-Sik; Choi, Ki-Yong; Cho, Seok; Yi, Sung-Jae; Park, Choon-Kyung; Chung, Moon-Ki

    2007-01-01

    The SMART uses a two-phase natural circulation in the PRHRS loop to remove the heat from the steam generators to the PRHRS heat exchangers, while a single phase natural circulation occurs in the primary loop to transfer the decay heat from the core to the steam generator. Natural circulation operation with a power range of 20 ∼ 25% was considered for SMART and nowadays the possibility of increasing the power level during the natural circulation operation is being investigated. Previously Park et al. performed several experiments by using the VISTA facility on the thermal-hydraulic characteristics of the PRHRS for the SMART-P, which includes a single-phase natural circulation in the primary loop. From the analysis with the TASS-SMR code it was shown that the reference temperature for the primary steam generator inlet temperature should be increased in order to compensate for the decreased core flow. To investigate the possibility of an increase of the power and reference temperature, it is necessary to get experimental data to characterize the natural circulation phenomena in the primary loop of the SMART. In this paper, the characteristics of natural circulation in the primary loop are experimentally investigated during various operational conditions by using the VISTA facility

  1. Long-circulating DNA lipid nanocapsules as new vector for passive tumor targeting.

    Science.gov (United States)

    Morille, Marie; Montier, Tristan; Legras, Pierre; Carmoy, Nathalie; Brodin, Priscille; Pitard, Bruno; Benoît, Jean-Pierre; Passirani, Catherine

    2010-01-01

    Systemic gene delivery systems are needed for therapeutic application to organs that are inaccessible by percutaneous injection. Currently, the main objective is the development of a stable and non-toxic vector that can encapsulate and deliver foreign genetic material to target cells. To this end, DNA, complexed with cationic lipids i.e. DOTAP/DOPE, was encapsulated into lipid nanocapsules (LNCs) leading to the formation of stable nanocarriers (DNA LNCs) with a size inferior to 130 nm. Amphiphilic and flexible poly (ethylene glycol) (PEG) polymer coatings [PEG lipid derivative (DSPE-mPEG(2000)) or F108 poloxamer] at different concentrations were selected to make DNA LNCs stealthy. Some of these coated lipid nanocapsules were able to inhibit complement activation and were not phagocytized in vitro by macrophagic THP-1 cells whereas uncoated DNA LNCs accumulated in the vacuolar compartment of THP-1 cells. These results correlated with a significant increase of in vivo circulation time in mice especially for DSPE-mPEG(2000) 10 mm and an early half-life time (t(1/2) of distribution) 5-fold greater than for non-coated DNA LNCs (7.1 h vs 1.4 h). Finally, a tumor accumulation assessed by in vivo fluorescence imaging system was evidenced for these coated LNCs as a passive targeting without causing any hepatic damage.

  2. Size-amplified acoustofluidic separation of circulating tumor cells with removable microbeads

    Science.gov (United States)

    Liu, Huiqin; Ao, Zheng; Cai, Bo; Shu, Xi; Chen, Keke; Rao, Lang; Luo, Changliang; Wang, Fu-Bin; Liu, Wei; Bondesson, Maria; Guo, Shishang; Guo, Feng

    2018-06-01

    Isolation and analysis of rare circulating tumor cells (CTCs) is of great interest in cancer diagnosis, prognosis, and treatment efficacy evaluation. Acoustofluidic cell separation becomes an attractive method due to its contactless, noninvasive, simple, and versatile features. However, the indistinctive physical difference between CTCs and normal blood cells limits the purity of CTCs using current acoustic methods. Herein, we demonstrate a size-amplified acoustic separation and release of CTCs with removable microbeads. CTCs selectively bound to size-amplifiers (40 μm-diameter anti-EpCAM/gelatin-coated SiO2 microbeads) have significant physical differences (size and mechanics) compared to normal blood cells, resulting in an amplification of acoustic radiation force approximately a hundredfold over that of bare CTCs or normal blood cells. Therefore, CTCs can be efficiently sorted out with size-amplifiers in a traveling surface acoustic wave microfluidic device and released from size-amplifiers by enzymatic degradation for further purification or downstream analysis. We demonstrate a cell separation from blood samples with a total efficiency (E total) of ∼ 77%, purity (P) of ∼ 96%, and viability (V) of ∼83% after releasing cells from size-amplifiers. Our method substantially improves the emerging application of rare cell purification for translational medicine.

  3. Three-Dimensional Inverse Opal Photonic Crystal Substrates toward Efficient Capture of Circulating Tumor Cells.

    Science.gov (United States)

    Xu, Hongwei; Dong, Biao; Xiao, Qiaoqin; Sun, Xueke; Zhang, Xinran; Lyu, Jiekai; Yang, Yudan; Xu, Lin; Bai, Xue; Zhang, Shuang; Song, Hongwei

    2017-09-13

    Artificial fractal structures have attracted considerable scientific interest in circulating tumor cells (CTCs) detection and capture, which plays a pivotal role in the diagnosis and prognosis of cancer. Herein, we designed a bionic TiO 2 inverse opal photonic crystal (IOPC) structure for highly efficient immunocapture of CTCs by combination of a magnetic Fe 3 O 4 @C6@silane nanoparticles with anti-EpCAM (antiepithelial cell adhesion molecule) and microchannel structure. Porous structure and dimension of IOPC TiO 2 can be precisely controlled for mimicking cellular components, and anti-EpCAM antibody was further modified on IOPC interface by conjugating with polydopamine (PDA). The improvement of CTCs capture efficiency reaches a surprising factor of 20 for the IOPC interface compared to that on flat glass, suggesting that the IOPCs are responsible for the dramatic enhancement of the capture efficiency of MCF-7 cells. IOPC substrate with pore size of 415 nm leads to the optimal CTCs capture efficiency of 92% with 1 mL/h. Besides the cell affinity, IOPCs also have the advantage of light scattering property which can enhance the excitation and emission light of fluorescence labels, facilitating the real-time monitoring of CTCs capture. The IOPC-based platform demonstrates excellent performance in CTCs capture, which will take an important step toward specific recognition of disease-related rare cells.

  4. Velocity effect on aptamer-based circulating tumor cell isolation in microfluidic devices.

    Science.gov (United States)

    Wan, Yuan; Tan, Jifu; Asghar, Waseem; Kim, Young-tae; Liu, Yaling; Iqbal, Samir M

    2011-12-01

    The isolation and detection of rare circulating tumor cells (CTCs) has been one of the focuses of intense research recently. In a microfluidic device, a number of factors can influence the enrichment capability of surface-bound probe molecules. This article analyzes the important factor of flow velocity in a microfluidic channel. The competition of surface-grafted anti-EGFR aptamers to bind the overexpressed EGFR on cell membranes against the drag force from the fluid flow is an important efficiency determining factor. The flow rate variations are applied both in experiments and in simulation models to study their effects on CTC capture efficiency. A mixture of mononuclear cells and human Glioblastoma cells is used to isolate cancer cells from the cellular flow. The results show interdependence between the adhesion probability, isolation efficiency, and flow rate. This work can help in designing flow-through lab-on-chip devices that use surface-bound probe affinities against overexpressed biomarkers for cell isolation. This work demonstrates that microfluidic based approaches have strong potential applications in CTC detection and isolation. © 2011 American Chemical Society

  5. Perioperative Search for Circulating Tumor Cells in Patients Undergoing Prostate Brachytherapy for Clinically Nonmetastatic Prostate Cancer

    Directory of Open Access Journals (Sweden)

    Hideyasu Tsumura

    2017-01-01

    Full Text Available Despite the absence of local prostate cancer recurrence, some patients develop distant metastases after prostate brachytherapy. We evaluate whether prostate brachytherapy procedures have a potential risk for hematogenous spillage of prostate cancer cells. Fifty-nine patients who were undergoing high-dose-rate (HDR or low-dose-rate (LDR brachytherapy participated in this prospective study. Thirty patients with high-risk or locally advanced cancer were treated with HDR brachytherapy after neoadjuvant androgen deprivation therapy (ADT. Twenty-nine patients with clinically localized cancer were treated with LDR brachytherapy without neoadjuvant ADT. Samples of peripheral blood were drawn in the operating room before insertion of needles (preoperative and again immediately after the surgical manipulation (intraoperative. Blood samples of 7.5 mL were analyzed for circulating tumor cells (CTCs using the CellSearch System. While no preoperative samples showed CTCs (0%, they were detected in intraoperative samples in 7 of the 59 patients (11.8%; preoperative vs. intraoperative, p = 0.012. Positive CTC status did not correlate with perioperative variables, including prostate-specific antigen (PSA at diagnosis, use of neoadjuvant ADT, type of brachytherapy, Gleason score, and biopsy positive core rate. We detected CTCs from samples immediately after the surgical manipulation. Further study is needed to evaluate whether those CTCs actually can survive and proliferate at distant sites.

  6. Development of Coagulation Factor Probes for the Identification of Procoagulant Circulating Tumor Cells

    Energy Technology Data Exchange (ETDEWEB)

    Tormoen, Garth W.; Cianchetti, Flor A. [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Bock, Paul E. [Department of Pathology, Microbiology and Immunology, Vanderbilt University School of Medicine, Nashville, TN (United States); McCarty, Owen J. T., E-mail: tormoeng@ohsu.edu [Department of Biomedical Engineering, Oregon Health and Science University, Portland, OR (United States); Department of Cell and Developmental Biology, Oregon Health and Science University, Portland, OR (United States); Division of Hematology and Medical Oncology, Department of Medicine, Oregon Health and Science University, Portland, OR (United States)

    2012-09-06

    Metastatic cancer is associated with a hypercoagulable state, and pathological venous thromboembolic disease is a significant source of morbidity and the second leading cause of death in patients with cancer. Here we aimed to develop a novel labeling strategy to detect and quantify procoagulant circulating tumor cells (CTCs) from patients with metastatic cancer. We hypothesize that the enumeration of procoagulant CTCs may be prognostic for the development of venous thrombosis in patients with cancer. Our approach is based on the observation that cancer cells are capable of initiating and facilitating cell-mediated coagulation in vitro, whereby activated coagulation factor complexes assemble upon cancer cell membrane surfaces. Binding of fluorescently labeled, active site-inhibited coagulation factors VIIa, Xa, and IIa to the metastatic breast cancer cell line, MDA-MB-231, non-metastatic colorectal cell line, SW480, or metastatic colorectal cell line, SW620, was characterized in a purified system, in anticoagulated blood and plasma, and in plasma under conditions of coagulation. We conclude that a CTC labeling strategy that utilizes coagulation factor-based fluorescent probes may provide a functional assessment of the procoagulant potential of CTCs, and that this strategy is amenable to current CTC detection platforms.

  7. Paper-Based MicroRNA Expression Profiling from Plasma and Circulating Tumor Cells.

    Science.gov (United States)

    Leong, Sai Mun; Tan, Karen Mei-Ling; Chua, Hui Wen; Huang, Mo-Chao; Cheong, Wai Chye; Li, Mo-Huang; Tucker, Steven; Koay, Evelyn Siew-Chuan

    2017-03-01

    Molecular characterization of circulating tumor cells (CTCs) holds great promise for monitoring metastatic progression and characterizing metastatic disease. However, leukocyte and red blood cell contamination of routinely isolated CTCs makes CTC-specific molecular characterization extremely challenging. Here we report the use of a paper-based medium for efficient extraction of microRNAs (miRNAs) from limited amounts of biological samples such as rare CTCs harvested from cancer patient blood. Specifically, we devised a workflow involving the use of Flinders Technology Associates (FTA) ® Elute Card with a digital PCR-inspired "partitioning" method to extract and purify miRNAs from plasma and CTCs. We demonstrated the sensitivity of this method to detect miRNA expression from as few as 3 cancer cells spiked into human blood. Using this method, background miRNA expression was excluded from contaminating blood cells, and CTC-specific miRNA expression profiles were derived from breast and colorectal cancer patients. Plasma separated out during purification of CTCs could likewise be processed using the same paper-based method for miRNA detection, thereby maximizing the amount of patient-specific information that can be derived from a single blood draw. Overall, this paper-based extraction method enables an efficient, cost-effective workflow for maximized recovery of small RNAs from limited biological samples for downstream molecular analyses. © 2016 American Association for Clinical Chemistry.

  8. Circulating tumor cell detection: A direct comparison between negative and unbiased enrichment in lung cancer.

    Science.gov (United States)

    Xu, Yan; Liu, Biao; Ding, Fengan; Zhou, Xiaodie; Tu, Pin; Yu, Bo; He, Yan; Huang, Peilin

    2017-06-01

    Circulating tumor cells (CTCs), isolated as a 'liquid biopsy', may provide important diagnostic and prognostic information. Therefore, rapid, reliable and unbiased detection of CTCs are required for routine clinical analyses. It was demonstrated that negative enrichment, an epithelial marker-independent technique for isolating CTCs, exhibits a better efficiency in the detection of CTCs compared with positive enrichment techniques that only use specific anti-epithelial cell adhesion molecules. However, negative enrichment techniques incur significant cell loss during the isolation procedure, and as it is a method that uses only one type of antibody, it is inherently biased. The detection procedure and identification of cell types also relies on skilled and experienced technicians. In the present study, the detection sensitivity of using negative enrichment and a previously described unbiased detection method was compared. The results revealed that unbiased detection methods may efficiently detect >90% of cancer cells in blood samples containing CTCs. By contrast, only 40-60% of CTCs were detected by negative enrichment. Additionally, CTCs were identified in >65% of patients with stage I/II lung cancer. This simple yet efficient approach may achieve a high level of sensitivity. It demonstrates a potential for the large-scale clinical implementation of CTC-based diagnostic and prognostic strategies.

  9. eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood

    Directory of Open Access Journals (Sweden)

    Jinfeng Zou

    2017-04-01

    Full Text Available With the technology development on detecting circulating tumor cells (CTCs and cell-free DNAs (cfDNAs in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86–0.96 and high recall rates (0.79–0.92 for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78–0.92 and recall rates (0.58–0.95 have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs.

  10. Tumor-selective replication herpes simplex virus-based technology significantly improves clinical detection and prognostication of viable circulating tumor cells

    DEFF Research Database (Denmark)

    Zhang, Wen; Bao, Li; Yang, Shaoxing

    2016-01-01

    Detection of circulating tumor cells remains a significant challenge due to their vast physical and biological heterogeneity. We developed a cell-surface-marker-independent technology based on telomerase-specific, replication-selective oncolytic herpes-simplex-virus-1 that targets telomerase......-reverse-transcriptase-positive cancer cells and expresses green-fluorescent-protein that identifies viable CTCs from a broad spectrum of malignancies. Our method recovered 75.5-87.2% of tumor cells spiked into healthy donor blood, as validated by different methods, including single cell sequencing. CTCs were detected in 59-100% of 326...

  11. Primary hepatic neuroendocrine tumor after 4 years tumor-free follow-up.

    Science.gov (United States)

    Lambrescu, Ioana Maria; Martin, Sorina; Cima, Luminita; Herlea, Vlad; Badiu, Corin; Fica, Simona

    2015-06-01

    A primary hepatic neuroendocrine tumour (PHNET) is a very rare disease. The liver represents the preferential site for neuroendocrine tumors' metastases. A 45-year old Caucasian female who presented with nausea, vomiting, diarrhea, accompanied by diffuse abdominal pain was found to have on contrast-enhanced computer tomography an encapsulated, partially cystic liver mass. The patient underwent an uneventful left atypical hepatic resection. Histopatological and immunohistochemical examination revealed a slowly growing (G1) hepatic neuroendocrine tumour. Post surgery, the specific neuroendocrine markers (serum Chromogranin A and 24h urinary 5 hydroxy-indolacetic acid) were within normal range. Further functional imaging investigations were performed. No other lesions were found making probable the diagnosis of PHNET. The patient is presently after 4 years of follow-up with no local recurrence or distant metastases. The diagnosis of PHNET is a medical challenge that requires a thorough long term follow-up in order to exclude an occult primary neuroendocrine tumour.

  12. Assessment of a six gene panel for the molecular detection of circulating tumor cells in the blood of female cancer patients

    International Nuclear Information System (INIS)

    Obermayr, Eva; Heinze, Georg; Tong, Dan; Zeillinger, Robert; Sanchez-Cabo, Fatima; Tea, Muy-Kheng M; Singer, Christian F; Krainer, Michael; Fischer, Michael B; Sehouli, Jalid; Reinthaller, Alexander; Horvat, Reinhard

    2010-01-01

    The presence of circulating tumor cells (CTC) in the peripheral blood of cancer patients has been described for various solid tumors and their clinical relevance has been shown. CTC detection based on the analysis of epithelial antigens might be hampered by the genetic heterogeneity of the primary tumor and loss of epithelial antigens. Therefore, we aimed to identify new gene markers for the PCR-based detection of CTC in female cancer patients. Gene expression of 38 cancer cell lines (breast, ovarian, cervical and endometrial) and of 10 peripheral blood mononuclear cell (PBMC) samples from healthy female donors was measured using microarray technology (Applied Biosystems). Differentially expressed genes were identified using the maxT test and the 50% one-sided trimmed maxT-test. Confirmatory RT-qPCR was performed for 380 gene targets using the AB TaqMan ® Low Density Arrays. Then, 93 gene targets were analyzed using the same RT-qPCR platform in tumor tissues of 126 patients with primary breast, ovarian or endometrial cancer. Finally, blood samples from 26 healthy women and from 125 patients (primary breast, ovarian, cervical, or endometrial cancer, and advanced breast cancer) were analyzed following OncoQuick enrichment and RNA pre-amplification. Likewise, hMAM and EpCAM gene expression was analyzed in the blood of breast and ovarian cancer patients. For each gene, a cut-off threshold value was set at three standard deviations from the mean expression level of the healthy controls to identify potential markers for CTC detection. Six genes were over-expressed in blood samples from 81% of patients with advanced and 29% of patients with primary breast cancer. EpCAM gene expression was detected in 19% and 5% of patients, respectively, whereas hMAM gene expression was observed in the advanced group (39%) only. Multimarker analysis using the new six gene panel positively identified 44% of the cervical, 64% of the endometrial and 19% of the ovarian cancer patients. The

  13. Enrichment of circulating tumor cells from a large blood volume using leukapheresis and elutriation: proof of concept.

    Science.gov (United States)

    Eifler, Robert L; Lind, Judith; Falkenhagen, Dieter; Weber, Viktoria; Fischer, Michael B; Zeillinger, Robert

    2011-03-01

    The aim of this study was to determine the applicability of a sequential process using leukapheresis, elutriation, and fluorescence-activated cell sorting (FACS) to enrich and isolate circulating tumor cells from a large blood volume to allow further molecular analysis. Mononuclear cells were collected from 10 L of blood by leukapheresis, to which carboxyfluorescein succinimidyl ester prelabeled CaOV-3 tumor cells were spiked at a ratio of 26 to 10⁶ leukocytes. Elutriation separated the spiked leukapheresates primarily by cell size into distinct fractions, and leukocytes and tumor cells, characterized as carboxyfluorescein succinimidyl ester positive, EpCAM positive and CD45 negative events, were quantified by flow cytometry. Tumor cells were isolated from the last fraction using FACS or anti-EpCAM coupled immunomagnetic beads, and their recovery and purity determined by fluorescent microscopy and real-time PCR. Leukapheresis collected 13.5 x 10⁹ mononuclear cells with 87% efficiency. In total, 53 to 78% of spiked tumor cells were pre-enriched in the last elutriation fraction among 1.6 x 10⁹ monocytes. Flow cytometry predicted a circulating tumor cell purity of ~90% giving an enrichment of 100,000-fold following leukapheresis, elutriation, and FACS, where CaOV-3 cells were identified as EpCAM positive and CD45 negative events. FACS confirmed this purity. Alternatively, immunomagnetic bead adsorption recovered 10% of tumor cells with a median purity of 3.5%. This proof of concept study demonstrated that elutriation and FACS following leukapheresis are able to enrich and isolate tumor cells from a large blood volume for molecular characterization. Copyright © 2010 International Clinical Cytometry Society.

  14. Radionuclide analyses taken during primary coolant decontamination at Three Mile Island indicate general circulation

    International Nuclear Information System (INIS)

    Hofstetter, K.J.; Baston, V.F.; Hitz, C.G.; Malinauskas, A.P.

    1983-01-01

    Radionuclide concentration data taken during decontamination of the primary reactor coolant system at Three Mile Island by a feed-and-bleed process have provided information on future defueling operations. Analysis of the radiocesium concentrations in samples taken at the letdown point indicates general circulation within the primary system, including the reactor vessel and both steam generators. A standard dilution model with parameters consistent with engineering estimates (volume, flow rate, etc.) accurately predicts the radiocesium decontamination rates. Unlike cesium, the behavior of other principal soluble radionuclides ( 90 Sr and 3 H) cannot be readily described by dilution theory. A significant appearance rate is observed for 90 Sr suggesting a chemical solubility mechanism. The use of processed water containing high 3 H for makeup causes uncertainty in the interpretation of the 3 H analysis

  15. Trans arterial embolization of primary and secondary tumors of the skeletal system

    International Nuclear Information System (INIS)

    Radeleff, B.; Eiers, M.; Lopez-Benitez, R.; Noeldge, G.; Hallscheidt, P.; Grenacher, L.; Libicher, M.; Zeifang, F.; Meeder, P.J.; Kauffmann, G.W.; Richter, G.M.

    2006-01-01

    Percutaneous transcatheter al embolization s of primary and secondary bone tumors are important minimal invasive angiographic interventions of the skeletal system. In most of the cases embolization is performed for preoperative devascularization or as a palliative measure to treat tumor-associated pain or other tumor bulk symptoms. The transarterial embolization of primary and secondary tumors of the skeletal system has been developed to a safe and very effective method. Indications, techniques, results and complications of this minimal invasive interventional therapy for treatment of primary and secondary bone tumors are described and discussed and compared with the newer literature and our own results

  16. Modeling tissue contamination to improve molecular identification of the primary tumor site of metastases

    DEFF Research Database (Denmark)

    Vincent, Martin; Perell, Katharina; Nielsen, Finn Cilius

    2014-01-01

    with any predictor model. The usability of the model is illustrated on primary tumor site identification of liver biopsies, specifically, on a human dataset consisting of microRNA expression measurements of primary tumor samples, benign liver samples and liver metastases. For a predictor trained on primary...... tumor and benign liver samples, the contamination model decreased the test error on biopsies from liver metastases from 77 to 45%. A further reduction to 34% was obtained by including biopsies in the training data....

  17. Method for semi-automated microscopy of filtration-enriched circulating tumor cells.

    Science.gov (United States)

    Pailler, Emma; Oulhen, Marianne; Billiot, Fanny; Galland, Alexandre; Auger, Nathalie; Faugeroux, Vincent; Laplace-Builhé, Corinne; Besse, Benjamin; Loriot, Yohann; Ngo-Camus, Maud; Hemanda, Merouan; Lindsay, Colin R; Soria, Jean-Charles; Vielh, Philippe; Farace, Françoise

    2016-07-14

    Circulating tumor cell (CTC)-filtration methods capture high numbers of CTCs in non-small-cell lung cancer (NSCLC) and metastatic prostate cancer (mPCa) patients, and hold promise as a non-invasive technique for treatment selection and disease monitoring. However filters have drawbacks that make the automation of microscopy challenging. We report the semi-automated microscopy method we developed to analyze filtration-enriched CTCs from NSCLC and mPCa patients. Spiked cell lines in normal blood and CTCs were enriched by ISET (isolation by size of epithelial tumor cells). Fluorescent staining was carried out using epithelial (pan-cytokeratins, EpCAM), mesenchymal (vimentin, N-cadherin), leukocyte (CD45) markers and DAPI. Cytomorphological staining was carried out with Mayer-Hemalun or Diff-Quik. ALK-, ROS1-, ERG-rearrangement were detected by filter-adapted-FISH (FA-FISH). Microscopy was carried out using an Ariol scanner. Two combined assays were developed. The first assay sequentially combined four-color fluorescent staining, scanning, automated selection of CD45(-) cells, cytomorphological staining, then scanning and analysis of CD45(-) cell phenotypical and cytomorphological characteristics. CD45(-) cell selection was based on DAPI and CD45 intensity, and a nuclear area >55 μm(2). The second assay sequentially combined fluorescent staining, automated selection of CD45(-) cells, FISH scanning on CD45(-) cells, then analysis of CD45(-) cell FISH signals. Specific scanning parameters were developed to deal with the uneven surface of filters and CTC characteristics. Thirty z-stacks spaced 0.6 μm apart were defined as the optimal setting, scanning 82 %, 91 %, and 95 % of CTCs in ALK-, ROS1-, and ERG-rearranged patients respectively. A multi-exposure protocol consisting of three separate exposure times for green and red fluorochromes was optimized to analyze the intensity, size and thickness of FISH signals. The semi-automated microscopy method reported here

  18. Method for semi-automated microscopy of filtration-enriched circulating tumor cells

    International Nuclear Information System (INIS)

    Pailler, Emma; Oulhen, Marianne; Billiot, Fanny; Galland, Alexandre; Auger, Nathalie; Faugeroux, Vincent; Laplace-Builhé, Corinne; Besse, Benjamin; Loriot, Yohann; Ngo-Camus, Maud; Hemanda, Merouan; Lindsay, Colin R.; Soria, Jean-Charles; Vielh, Philippe; Farace, Françoise

    2016-01-01

    Circulating tumor cell (CTC)-filtration methods capture high numbers of CTCs in non-small-cell lung cancer (NSCLC) and metastatic prostate cancer (mPCa) patients, and hold promise as a non-invasive technique for treatment selection and disease monitoring. However filters have drawbacks that make the automation of microscopy challenging. We report the semi-automated microscopy method we developed to analyze filtration-enriched CTCs from NSCLC and mPCa patients. Spiked cell lines in normal blood and CTCs were enriched by ISET (isolation by size of epithelial tumor cells). Fluorescent staining was carried out using epithelial (pan-cytokeratins, EpCAM), mesenchymal (vimentin, N-cadherin), leukocyte (CD45) markers and DAPI. Cytomorphological staining was carried out with Mayer-Hemalun or Diff-Quik. ALK-, ROS1-, ERG-rearrangement were detected by filter-adapted-FISH (FA-FISH). Microscopy was carried out using an Ariol scanner. Two combined assays were developed. The first assay sequentially combined four-color fluorescent staining, scanning, automated selection of CD45 − cells, cytomorphological staining, then scanning and analysis of CD45 − cell phenotypical and cytomorphological characteristics. CD45 − cell selection was based on DAPI and CD45 intensity, and a nuclear area >55 μm 2 . The second assay sequentially combined fluorescent staining, automated selection of CD45 − cells, FISH scanning on CD45 − cells, then analysis of CD45 − cell FISH signals. Specific scanning parameters were developed to deal with the uneven surface of filters and CTC characteristics. Thirty z-stacks spaced 0.6 μm apart were defined as the optimal setting, scanning 82 %, 91 %, and 95 % of CTCs in ALK-, ROS1-, and ERG-rearranged patients respectively. A multi-exposure protocol consisting of three separate exposure times for green and red fluorochromes was optimized to analyze the intensity, size and thickness of FISH signals. The semi-automated microscopy method reported here

  19. A New Size-based Platform for Circulating Tumor Cell Detection in Colorectal Cancer Patients.

    Science.gov (United States)

    Oh, Bo Young; Kim, Jhingook; Lee, Woo Yong; Kim, Hee Cheol

    2017-09-01

    Circulating tumor cells (CTCs) might play a significant role in cancer progression and metastasis. However, the ability to detect CTCs is limited, especially in cells undergoing epithelial-mesenchymal transition. In this study, we evaluated a new size-based CTC detection platform and its clinical efficacy in colorectal cancer. Blood samples were obtained from 76 patients with colorectal cancer and 20 healthy control subjects for CTC analysis. CTCs were enriched using a high-density microporous chip filter and were detected using a 4-color staining protocol including 4',6-diamidino-2-phenylindole (DAPI) for nucleated cells, CD45 monoclonal antibody (mAb) as a leukocyte marker, and epithelial cell adhesion molecule (EpCAM) mAb or cytokeratin (CK) mAb as an epithelial cell marker. CTC positivity was defined as DAPI-positive (DAPI + )/CD45 - /EpCAM + or CK + cells and clinical outcomes of patients were analyzed according to CTC counts. CTCs were detected in 50 patients using this size-based filtration platform. CTC + patients were more frequently identified with a high level of carcinoembryonic antigen and advanced stage cancer (P = .038 and P = .017, respectively). CTC counts for patients with stage IV cancer (12.47 ± 24.00) were significantly higher than those for patients with cancers that were stage I to III (2.84 ± 5.29; P = .005) and healthy control subjects (0.25 ± 0.55; P colorectal cancer patients. Our results suggest that this new size-based platform has potential for determining prognosis and therapeutic response in colorectal cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  20. The Potential of Circulating Tumor Cells in Personalized Management of Breast Cancer: A Systematic Review

    Directory of Open Access Journals (Sweden)

    Fatemeh Khatami

    2017-03-01

    Full Text Available Circulating tumor cells (CTCs recognition and characterization in the peripheral blood of patients with breast cancer have proven practical and predictive value in different studies. However, the clinical significance of CTCs enumeration and molecular characterization in thepersonalization of breast cancer diagnosis and treatment remains under the debate. A literature search in PubMed, Web of Science and Scopus was performed from October 1990 to June 2016 for studies which evaluating CTCs and its association with clinical and pathological characteristics and medical outcome in the field of breast cancer personalization for both diagnosis and treatment categories. The treatment outcomes were progression-free survival (PFS and overall survival (OS or relapse in different patients. Sixty-nine studies met the inclusion criteria. The sample size varies from 1 to 2026. Median follow-up was 15 months (range 3-27. Different molecular techniques have been applied toresearch, but they mostly are based on CTCs enrichment and then detection by using FDA-approved Cell SearchTM. By far the most studies define CTCs as cytokeratins (CK positive and CD45 negative cells. Despite the differences in methodology, twenty-eight studies for breast cancer diagnosis and prognosis were mainly focused on CTCs isolation and enumeration.Forty-threeresearches were about CTCs count and exact molecular characterization. In the way of precision treatment, CTCs detection before starting the first-line of therapy or during therapy in breast cancer patients is extremely valuable, but in the way of precision medicine it should be supported with some molecular characteristics of CTCs like CTCs phenotypic changes, gene expression analysis of CTCs and molecular characteristics of CTCs.

  1. Impact of Emergent Circulating Tumor DNA RAS Mutation in Panitumumab-Treated Chemoresistant Metastatic Colorectal Cancer.

    Science.gov (United States)

    Kim, Tae Won; Peeters, Marc; Thomas, Anne L; Gibbs, Peter; Hool, Kristina; Zhang, Jianqi; Ang, Agnes; Bach, Bruce Allen; Price, Timothy

    2018-06-13

    The accumulation of emergent RAS mutations during anti-epidermal growth factor receptor (EGFR) therapy is of interest as a mechanism for acquired resistance to anti-EGFR treatment. Plasma analysis of circulating tumor (ct) DNA is a minimally invasive and highly sensitive method to determine RAS mutational status. This biomarker analysis of the global phase III ASPECCT study used next-generation sequencing to detect expanded RAS ctDNA mutations in panitumumab-treated patients. Plasma samples collected at baseline and posttreatment were analyzed categorically for the presence of RAS mutations by the Plasma Select -R™ 64-gene panel at 0.1% sensitivity. Among panitumumab-treated patients with evaluable plasma samples at baseline (n = 238), 188 (79%) were wild-type (WT) RAS, and 50 (21%) were mutant RAS Of the 188 patients with baseline ctDNA WT RAS status, 164 had evaluable posttreatment results with a 32% rate of emergent RAS mutations. The median overall survival (OS) for WT and RAS mutant status by ctDNA at baseline was 13.7 (95% confidence interval: 11.5-15.4) and 7.9 months (6.4-9.6), respectively ( P < 0.0001). Clinical outcomes were not significantly different between patients with and without emergent ctDNA RAS mutations. Although patients with baseline ctDNA RAS mutations had worse outcomes than patients who were WT RAS before initiating treatment, emergent ctDNA RAS mutations were not associated with less favorable patient outcomes in panitumumab-treated patients. Further research is needed to determine a clinically relevant threshold for baseline and emergent ctDNA RAS mutations. Copyright ©2018, American Association for Cancer Research.

  2. Optical Aptamer Probes of Fluorescent Imaging to Rapid Monitoring of Circulating Tumor Cell

    Directory of Open Access Journals (Sweden)

    Ji Yeon Hwang

    2016-11-01

    Full Text Available Fluorescence detecting of exogenous EpCAM (epithelial cell adhesion molecule or muc1 (mucin1 expression correlated to cancer metastasis using nanoparticles provides pivotal information on CTC (circulating tumor cell occurrence in a noninvasive tool. In this study, we study a new skill to detect extracellular EpCAM/muc1 using quantum dot-based aptamer beacon (QD-EpCAM/muc1 ALB (aptamer linker beacon. The QD-EpCAM/muc1 ALB was designed using QDs (quantum dots and probe. The EpCAM/muc1-targeting aptamer contains a Ep-CAM/muc1 binding sequence and BHQ1 (black hole quencher 1 or BHQ2 (black hole quencher2. In the absence of target EpCAM/muc1, the QD-EpCAM/muc1 ALB forms a partial duplex loop-like aptamer beacon and remained in quenched state because the BHQ1/2 quenches the fluorescence signal-on of the QD-EpCAM/muc1 ALB. The binding of EpCAM/muc1 of CTC to the EpCAM/muc1 binding aptamer sequence of the EpCAM/muc1-targeting oligonucleotide triggered the dissociation of the BHQ1/2 quencher and subsequent signal-on of a green/red fluorescence signal. Furthermore, acute inflammation was stimulated by trigger such as caerulein in vivo, which resulted in increased fluorescent signal of the cy5.5-EpCAM/muc1 ALB during cancer metastasis due to exogenous expression of EpCAM/muc1 in Panc02-implanted mouse model.

  3. Comparative study on antibody immobilization strategies for efficient circulating tumor cell capture.

    Science.gov (United States)

    Ates, Hatice Ceren; Ozgur, Ebru; Kulah, Haluk

    2018-03-23

    Methods for isolation and quantification of circulating tumor cells (CTCs) are attracting more attention every day, as the data for their unprecedented clinical utility continue to grow. However, the challenge is that CTCs are extremely rare (as low as 1 in a billion of blood cells) and a highly sensitive and specific technology is required to isolate CTCs from blood cells. Methods utilizing microfluidic systems for immunoaffinity-based CTC capture are preferred, especially when purity is the prime requirement. However, antibody immobilization strategy significantly affects the efficiency of such systems. In this study, two covalent and two bioaffinity antibody immobilization methods were assessed with respect to their CTC capture efficiency and selectivity, using an anti-epithelial cell adhesion molecule (EpCAM) as the capture antibody. Surface functionalization was realized on plain SiO 2 surfaces, as well as in microfluidic channels. Surfaces functionalized with different antibody immobilization methods are physically and chemically characterized at each step of functionalization. MCF-7 breast cancer and CCRF-CEM acute lymphoblastic leukemia cell lines were used as EpCAM positive and negative cell models, respectively, to assess CTC capture efficiency and selectivity. Comparisons reveal that bioaffinity based antibody immobilization involving streptavidin attachment with glutaraldehyde linker gave the highest cell capture efficiency. On the other hand, a covalent antibody immobilization method involving direct antibody binding by N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC)-N-hydroxysuccinimide (NHS) reaction was found to be more time and cost efficient with a similar cell capture efficiency. All methods provided very high selectivity for CTCs with EpCAM expression. It was also demonstrated that antibody immobilization via EDC-NHS reaction in a microfluidic channel leads to high capture efficiency and selectivity.

  4. Effects of Flowing RBCs on Adhesion of a Circulating Tumor Cell in Microvessels

    Science.gov (United States)

    Xiao, L.L.; Liu, Y.; Chen, S.; Fu, B.M.

    2016-01-01

    Adhesion of circulating tumor cells (CTCs) to the microvessel wall largely depends on the blood hydrodynamic conditions, one of which is the blood viscosity. Since blood is a non-Newtonian fluid, whose viscosity increases with hematocrit, in the microvessels at low shear rate. In this study, the effects of hematocrit, vessel size, flow rate and red blood cells (RBCs) aggregation on adhesion of a CTC in the microvessels were numerically investigated using dissipative particle dynamics. The membrane of cells was represented by a spring-based network connected by elastic springs to characterize its deformation. RBCs aggregation was modelled by a Morse potential function based on depletion-mediated assumption and the adhesion of the CTC to the vessel wall was achieved by the interactions between receptors and ligands at the CTC and those at the endothelial cells forming the vessel wall. The results demonstrated that in the microvessel of 15μm diameter, the CTC has an increasing probability of adhesion with the hematocrit due to a growing wall-directed force, resulting in a larger number of receptor-ligand bonds formed on the cell surface. However, with the increase in microvessel size, an enhanced lift force at higher hematocrit detaches the initial adherent CTC quickly. If the microvessel is comparable to the CTC in diameter, CTC adhesion is independent of Hct. In addition, the velocity of CTC is larger than the average blood flow velocity in smaller microvessels and the relative velocity of CTC decreases with the increase in microvessel size. An increased blood flow resistance in the presence of CTC was also found. Moreover, it was found that the large deformation induced by high flow rate and the presence of aggregation promote the adhesion of CTC. PMID:27738841

  5. Neuroblastoma: treatment outcome after incomplete resection of primary tumors.

    Science.gov (United States)

    Moon, Suk-Bae; Park, Kwi-Won; Jung, Sung-Eun; Youn, Woong-Jae

    2009-09-01

    For International Neuroblastoma Staging System (INSS) stages III or IV neuroblastoma (intermediate or high risk), complete excision of the primary tumor is not always feasible. Most current studies on the treatment outcome of these patients have reported on the complete excision status. The aim of this study is to review the treatment outcome after the incomplete resection. The medical records of 37 patients that underwent incomplete resection between January 1986 and December 2005 were reviewed retrospectively. Incomplete resection was assessed by review of the operative notes and postoperative computerized tomography. Age, gender, tumor location, INSS stage, N-myc gene copy number, pre- and postoperative therapy, and treatment outcome were reviewed. The treatment outcome was evaluated according to the postoperative treatment protocol in the high-risk group. Intermediate-risk patients were treated with conventional chemotherapy, isotretinoin (ITT) and interleukin-2 (IL-2). High-risk patients were treated with peripheral blood stem cell transplantation (PBSCT), ITT, and IL-2 (N = 11). Before the introduction of PBSCT, the high-risk patients were also treated with the conventional chemotherapy (N = 19). Intermediate-risk patients (N = 5) currently have no evidence of disease (NED). For the high-risk patients (N = 32), 19 patients were treated with chemotherapy alone; 15 patients died of their disease while four patients currently have an NED status. Eight of 11 patients that underwent PBSCT are currently alive. For intermediate risk, conventional chemotherapy appears to be acceptable treatment. However, for high-risk patients, every effort should be made to control residual disease including the use of myeloablative chemotherapy, differentiating agents and immune-modulating agents.

  6. Primary Carcinosarcoma of Ovary an Unusual Tumor Case Report ...

    African Journals Online (AJOL)

    radiotherapy and chemotherapy or chemotherapy alone.[2]. These tumors are .... stage of disease.[6]. The adverse prognostic factors as enumerated by various ... The effect of epithelial and stromal tumor components on. FIGO stages III and IV ...

  7. Modulation of Tumor Tolerance in Primary Central Nervous System Malignancies

    Directory of Open Access Journals (Sweden)

    Theodore S. Johnson

    2012-01-01

    Full Text Available Central nervous system tumors take advantage of the unique immunology of the CNS and develop exquisitely complex stromal networks that promote growth despite the presence of antigen-presenting cells and tumor-infiltrating lymphocytes. It is precisely this immunological paradox that is essential to the survival of the tumor. We review the evidence for functional CNS immune privilege and the impact it has on tumor tolerance. In this paper, we place an emphasis on the role of tumor-infiltrating myeloid cells in maintaining stromal and vascular quiescence, and we underscore the importance of indoleamine 2,3-dioxygenase activity as a myeloid-driven tumor tolerance mechanism. Much remains to be discovered regarding the tolerogenic mechanisms by which CNS tumors avoid immune clearance. Thus, it is an open question whether tumor tolerance in the brain is fundamentally different from that of peripheral sites of tumorigenesis or whether it simply stands as a particularly strong example of such tolerance.

  8. Feedback control of primary circulation pump of PIUS-Type reactor

    International Nuclear Information System (INIS)

    Fujii, Mikiya; Anoda, Yoshinari; Murata, Hideo; Yonomoto, Taisuke; Kukita, Yutaka; Tasaka, Kanji.

    1991-05-01

    In operating the PIUS-Type reactor, it is required to keep stationary density interfaces between the primary loop hot water and the poison tank cold, borated water by maintaining pressure balance between the primary-loop and the poison-tank. The authors have developed a primary circulation pump speed control system and tested it in small-scale experiments. This control system regulates the pump speed based on measurements of the density lock differential pressure which is proportional to the elevation of the interface in the density lock. This pump speed control facilitated the normal plant operation which included core power changes. However, the elevation of the density interface indicated oscillatory behavior when the pump speed was regulated as a linear function of the density lock differential pressure. The mechanism responsible for such oscillatory behavior was found to be manometric oscillations that could be eliminated by adding a damping term to compensate for the mechanical delay of the primary pump speed. The passive shutdown function of the reactor was retained by setting an upper limit to the pump speed. This was confirmed in a loss-of-feedwater abnormal transient test. (author)

  9. Malignant primary germ-cell tumor of the brain

    International Nuclear Information System (INIS)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh

    1983-01-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported.FThe first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe.FTotal removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule.FHistological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma.FPrimary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma.FIn this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy. (author)

  10. PRIMARY PREVENTION OF MALIGNANT SKIN TUMORS – PHOTOPROTECTION

    Directory of Open Access Journals (Sweden)

    Ana Benedičič - Pilih

    2001-12-01

    Full Text Available Background. The incidence of skin cancer is increasing in the world as well as in our country. Decades of research have increased the understanding of the ethiopathogenetic influences and risk factors for development of malignant skin tumors and stimulated efforts to promote their prevention. There are successes of prevention programs in some places in the world expressing with the reduction of mortality because of the cutaneous malignant melanoma. A primary prevention of a skin cancer attempts to change population knowledge, attitudes and beliefs about sunlight, leading to reduce of sunlight exposure.Conclusions. In this article we are discussing guidelines for photoprevention. The best approach to it is a reduction in the overall exposure to sunlight. The natural protection with the use of shade, clothing and hats is promoted as the best protection. Sunscreens are assumed as an important component of adjuvant photoprotection based on their convenience of use and also on their widespread promotion. While it has been argued that all tanning is a manifestation of skin injury, avoiding of artificial tanning devices is proposed also.

  11. Cistos e tumores primários do mediastino Primary cysts and tumors of the mediastinum

    Directory of Open Access Journals (Sweden)

    Pedro Bastos

    2007-09-01

    Full Text Available Objectivo: Avaliação dos resultados em doentes com cistos e tumores primários do mediastino submetidos a tratamento cirúrgico. Material e métodos: Efectuado um estudo retrospectivo mono-institucional em doentes com cistos e tumores primários do mediastino submetidos a tratamento cirúrgico entre Janeiro de 1992 e Dezembro de 2004. Analisaram-se os dados demográficos, a apresentação clínica, a via de abordagem, a intervenção cirúrgica efectuada, a localização da lesão e o diagnóstico histológico. Avaliaram-se, ainda, os factores preditivos de malignidade, a morbilidade e mortalidade pós-operatórias e os resultados a médio prazo. Resultados: Ao longo de um período de 13 anos foram operados 171 doentes, 73 (43% do sexo feminino e 98 (57% do sexo masculino. A idade média foi de 40,3±19,7 anos (20 dias-78 anos. Em 15(9% dos doentes existia uma lesão cística primária. Os tumores primários incluíam neoplasias tímicas (31%, linfomas (22%, tumores neurogénicos (16%, tumores de células germinativas (9% e um grupo miscelâneo (13%. Em 78 doentes (46% as lesões eram malignas. O mediastino ântero-superior foi o compartimento mais frequentemente envolvido por um cisto ou tumor primário (58%, seguido do mediastino posterior (24% e do mediastino médio (18%. Em 68% dos doentes existiam sintomas na altura do diagnóstico: dor torácica (20%, febre e arrepios (13%, miastenia grave (11%, tosse (10%, dispneia (10% e síndroma da veia cava superior (7%. A análise unifactorial identificou a existência de sintomas como factor preditivo de malignidade (pObjective: To assess results in patients with primary cysts and tumours of the mediastinum who underwent surgery. Methods: A retrospective single-centre study was undertaken into patients with primary cysts and tumours of the mediastinum who underwent surgery between January 1992 and December 2004. We analysed demographic data, clinical presentation, type of surgery carried out and

  12. [Regression and therapy-resistance of primary liver tumors and liver metastases after regional chemotherapy and local tumor ablation].

    Science.gov (United States)

    Fischer, H-P

    2005-05-01

    High dosage regional chemotherapy, chemoembolization and other methods of regional treatment are commonly used to treat unresectable primary liver malignancies and liver metastases. In liver malignancies of childhood neoadjuvant chemotherapy is successfully combined with surgical treatment. Chemotherapy and local tumor ablation lead to characteristic histomorphologic changes: Complete destruction of the tumor tissue and its vascular bed is followed by encapsulated necroses. After selective eradication of the tumor cells under preservation of the fibrovasular bed the tumor is replaced by hypocellular edematous and fibrotic tissue. If completely damaged tumor tissue is absorbed quickly, the tumor area is replaced by regenerating liver tissue. Obliterating fibrohyalinosis of tumor vessels, and perivascular edema or necrosis indicate tissue damage along the vascular bed. Degenerative pleomorphism of tumor cells, steatosis, hydropic swelling and Malloryhyalin in HCC can represent cytologic findings of cytotoxic cellular damage. Macroscopic type of HCC influences significantly the response to treatment. Multinodular HCC often contain viable tumor nodules close to destroyed nodules after treatment. Encapsulated uninodular tumors undergo complete necrosis much easier. Large size and a tumor capsule limitate the effect of percutaneous injection of ethanol into HCC. In carcinomas with an infiltrating border, especially in metastases of adenocarcinomas and hepatic cholangiocarcinoma cytostatic treatment damages the tumor tissue mainly in the periphery. Nevertheless the infiltrating rim, portal veins, lymphatic spaces and bile ducts as well as the angle between liver capsule, tumor nodule and bordering parenchyma are the main refugees of viable tumor tissue even after high dosage regional chemotherapy. This local resistance is caused by special local conditions of vascularization and perfusion. These residues are the source of local tumor progression and distant metastases

  13. eTumorType, An Algorithm of Discriminating Cancer Types for Circulating Tumor Cells or Cell-free DNAs in Blood.

    Science.gov (United States)

    Zou, Jinfeng; Wang, Edwin

    2017-04-01

    With the technology development on detecting circulating tumor cells (CTCs) and cell-free DNAs (cfDNAs) in blood, serum, and plasma, non-invasive diagnosis of cancer becomes promising. A few studies reported good correlations between signals from tumor tissues and CTCs or cfDNAs, making it possible to detect cancers using CTCs and cfDNAs. However, the detection cannot tell which cancer types the person has. To meet these challenges, we developed an algorithm, eTumorType, to identify cancer types based on copy number variations (CNVs) of the cancer founding clone. eTumorType integrates cancer hallmark concepts and a few computational techniques such as stochastic gradient boosting, voting, centroid, and leading patterns. eTumorType has been trained and validated on a large dataset including 18 common cancer types and 5327 tumor samples. eTumorType produced high accuracies (0.86-0.96) and high recall rates (0.79-0.92) for predicting colon, brain, prostate, and kidney cancers. In addition, relatively high accuracies (0.78-0.92) and recall rates (0.58-0.95) have also been achieved for predicting ovarian, breast luminal, lung, endometrial, stomach, head and neck, leukemia, and skin cancers. These results suggest that eTumorType could be used for non-invasive diagnosis to determine cancer types based on CNVs of CTCs and cfDNAs. Copyright © 2017 Beijing Institute of Genomics, Chinese Academy of Sciences and Genetics Society of China. Production and hosting by Elsevier B.V. All rights reserved.

  14. Near-Infrared Neodymium Tag for Quantifying Targeted Biomarker and Counting Its Host Circulating Tumor Cells.

    Science.gov (United States)

    Liu, Chunlan; Lu, Shu; Yang, Limin; Chen, Peijie; Bai, Peiming; Wang, Qiuquan

    2017-09-05

    Quantitative information on a targeted analyte in a complex biological system is the most basic premise for understanding its involved mechanisms, and thus precise diagnosis of a disease if it is a so-called biomarker. Here, we designed and synthesized a neodymium (Nd)-cored tag [1,4,7,10-tetraazacyclododecane-1,4,7-trisacetic acid (DOTA)-Nd complex together with a light-harvesting antenna aminofluorescein (AMF, λ ex/em = 494/520 nm), AMF-DOTA-Nd] with duplex signals, second near-infrared (NIR) window luminescence (λ em = 1065 nm, 2.5 μs), and stable isotopic mass ( 142 Nd). AMF-DOTA-Nd covalently linked with a urea-based peptidomimetic targeting group, 2-[3-(1,3-dicarboxypropyl)-ureido]pentanedioic acid (DUPA)-8-Aoc-Phe-Phe-Cys (DUPAaFFC) (DUPAaFFC-AMF-DOTA-Nd), allowing us to detect and quantify prostate-specific membrane antigen (PSMA) and its splice variants (total PSMA, tPSMA), which was set as an example of targeted biomarkers in this study, using NIR and inductively coupled plasma mass spectrometry (ICPMS) with the limit of detection (LOD) (3σ) of 0.3 ng/mL. When it was applied to the analysis of 80 blood samples from prostate cancer (PCa) and benign prostatic hyperplasia (BPH) patients as well as healthy volunteers, we found that 320 and 600 ng/mL tPSMA could be recommended as the threshold values to differentiate BPH from PCa and for the diagnosis of PCa. Moreover, PSMA-positive circulating tumor cells (CTCs) were counted using ICPMS being from 134 to 773 CTCs in the PCa blood samples of the Gleason score from 6 to 9 when the cell membrane-spanning mPSMA was tagged. Such a methodology developed could be expected to be applicable to other clinic-meaningful biomolecules and their host CTCs in liquid biopsy, when other specific targeting groups are modified to the NIR Nd tag.

  15. A rare case of extremely high counts of circulating tumor cells detected in a patient with an oral squamous cell carcinoma

    International Nuclear Information System (INIS)

    Wu, Xianglei; Mastronicola, Romina; Tu, Qian; Faure, Gilbert Charles; De Carvalho Bittencourt, Marcelo; Dolivet, Gilles

    2016-01-01

    Despite aggressive regimens, the clinical outcome of head and neck squamous cell carcinoma remains poor. The detection of circulating tumor cells could potentially improve the management of patients with disseminated cancer, including diagnosis, treatment strategies, and surveillance. Currently, CellSearch ® is the most widely used and the only Food and Drug Administration-cleared system for circulating tumor cells detection in patients with metastatic breast, colorectal, or prostate cancer. In most cases of head and neck squamous cell carcinoma, only low counts of circulating tumor cells have been reported. A 56-year-old white male with no particular medical history, was diagnosed with a squamous cell carcinoma of oral cavity. According to the imaging results (computed tomography and 18 F-fluorodeoxyglucose positron emission tomography / computed tomography) and panendoscopy, the TNM staging was classified as T4N2M0. A non-interruptive pelvimandibulectomy was conducted according to the multidisciplinary meeting advices and the postoperative observations were normal. The patient complained of a painful cervical edema and a trismus 6 weeks after the surgery. A relapse was found by computed tomography and the patient died two weeks later. The search for circulating tumor cells in peripheral venous blood by using the CellSearch ® system revealed a very high count compared with published reports at three time points (pre-operative: 400; intra-operative: 150 and post-operative day 7: 1400 circulating tumor cells). Of note, all detected circulating tumor cells were epidermal growth factor receptor negative. We report here for the first time a rare case of oral squamous cell carcinoma with extremely high circulating tumor cells counts using the CellSearch ® system. The absolute number of circulating tumor cells might predict a particular phase of cancer development as well as a poor survival, potentially contributing to a personalized healthcare

  16. Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

    Science.gov (United States)

    Ellsworth, Rachel E.; Field, Lori A.; Love, Brad; Kane, Jennifer L.; Hooke, Jeffrey A.; Shriver, Craig D.

    2011-01-01

    Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n = 41) and positive (n = 35) lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (P 1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis. PMID:22295210

  17. Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

    International Nuclear Information System (INIS)

    Ellsworth, R.E.; Field, L.A.; Kane, J.L.; Love, B.; Hooke, J.A.; Shriver, C.D.

    2011-01-01

    Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (n=41) and positive (n=35) lymph node status matched for possible confounding factors were subjected to laser micro dissection and gene expression data generated. Although ANOVA analysis (P 1.5) revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis

  18. Differential Gene Expression in Primary Breast Tumors Associated with Lymph Node Metastasis

    Directory of Open Access Journals (Sweden)

    Rachel E. Ellsworth

    2011-01-01

    Full Text Available Lymph node status remains one of the most useful prognostic indicators in breast cancer; however, current methods to assess nodal status disrupt the lymphatic system and may lead to secondary complications. Identification of molecular signatures discriminating lymph node-positive from lymph node-negative primary tumors would allow for stratification of patients requiring surgical assesment of lymph nodes. Primary breast tumors from women with negative (=41 and positive (=35 lymph node status matched for possible confounding factors were subjected to laser microdissection and gene expression data generated. Although ANOVA analysis (1.5 revealed 13 differentially expressed genes, hierarchical clustering classified 90% of node-negative but only 66% of node-positive tumors correctly. The inability to derive molecular profiles of metastasis in primary tumors may reflect tumor heterogeneity, paucity of cells within the primary tumor with metastatic potential, influence of the microenvironment, or inherited host susceptibility to metastasis.

  19. (18)F-Fluorodeoxyglucose PET/Computed Tomography for Primary Brain Tumors

    DEFF Research Database (Denmark)

    Antonsen Segtnan, Eivind; Hess, Søren; Grupe, Peter

    2015-01-01

    Structural imaging with computed tomography (CT) and MR imaging is the mainstay in primary diagnosis of primary brain tumors, but these modalities depend on morphologic appearance and an intact blood-brain barrier, and important aspects of tumor biology are not addressed. Such issues may...

  20. Differentiation between tuberculosis and primary tumors in the adrenal gland: evaluation with contrast-enhanced CT

    International Nuclear Information System (INIS)

    Yang, Zhi-Gang; Guo, Ying-Kun; Li, Yuan; Min, Peng-Qiu; Yu, Jian-Qun; Ma, En-Sen

    2006-01-01

    The aim of the present study is to determine imaging criteria for differentiating tuberculosis from primary tumors in the adrenal gland on contrast-enhanced CT. Non-contrast and contrast-enhanced CT features in 108 patients with adrenal tuberculosis (n=34) and primary tumor (n=74) were retrospectively assessed for the location, size, calcification and enhancement patterns. The primary tumors included 41 adenomas, 11 pheochromocytomas, 4 carcinomas, 3 lymphomas, 6 myelolipomas, 6 ganglioneuromas, 2 neurilemmomas and 1 ganglioneuroblastoma. Biochemical investigation was performed for all patients. Of the tuberculosis cases, 31 (91%) invaded with bilateral involvement, while 7 (9%) of the primary tumors invaded with bilateral involvement (P<0.001). Tuberculosis often showed calcification (20 of 34; 59%), whereas primary tumors infrequently showed calcification (6 of 74; 8%; P<0.001). Low attenuation in the center with peripheral rim enhancement was more commonly seen in tuberculosis (16 of 34; 47%) than in primary tumors (7 of 74; 9%; P<0.001). In the determination of tuberculosis, the highest sensitivity (91%) and accuracy (91%) were obtained with bilateral involvement, and the highest specificity (99%) was obtained with the contour preserved. In the determination of primary tumors using a combination of having unilateral involvement and being mass-like, the outcome was a sensitivity of 91%, specificity of 94% and accuracy of 92%. CT findings can differentiate tuberculosis from a primary tumor of the adrenal glands with high sensitivity and an acceptable specificity when combined with the endocrinological examination. (orig.)

  1. EpCAM-Independent Enrichment of Circulating Tumor Cells in Metastatic Breast Cancer

    Science.gov (United States)

    Schneck, Helen; Gierke, Berthold; Uppenkamp, Frauke; Behrens, Bianca; Niederacher, Dieter; Stoecklein, Nikolas H.; Templin, Markus F.; Pawlak, Michael; Fehm, Tanja; Neubauer, Hans

    2015-01-01

    Circulating tumor cells (CTCs) are the potential precursors of metastatic disease. Most assays established for the enumeration of CTCs so far–including the gold standard CellSearch—rely on the expression of the cell surface marker epithelial cell adhesion molecule (EpCAM). But, these approaches may not detect CTCs that express no/low levels of EpCAM, e.g. by undergoing epithelial-to-mesenchymal transition (EMT). Here we present an enrichment strategy combining different antibodies specific for surface proteins and extracellular matrix (ECM) components to capture an EpCAMlow/neg cell line and EpCAMneg CTCs from blood samples of breast cancer patients depleted for EpCAM-positive cells. The expression of respective proteins (Trop2, CD49f, c-Met, CK8, CD44, ADAM8, CD146, TEM8, CD47) was verified by immunofluorescence on EpCAMpos (e.g. MCF7, SKBR3) and EpCAMlow/neg (MDA-MB-231) breast cancer cell lines. To test antibodies and ECM proteins (e.g. hyaluronic acid (HA), collagen I, laminin) for capturing EpCAMneg cells, the capture molecules were first spotted in a single- and multi-array format onto aldehyde-coated glass slides. Tumor cell adhesion of EpCAMpos/neg cell lines was then determined and visualized by Coomassie/MitoTracker staining. In consequence, marginal binding of EpCAMlow/neg MDA-MB-231 cells to EpCAM-antibodies could be observed. However, efficient adhesion/capturing of EpCAMlow/neg cells could be achieved via HA and immobilized antibodies against CD49f and Trop2. Optimal capture conditions were then applied to immunomagnetic beads to detect EpCAMneg CTCs from clinical samples. Captured CTCs were verified/quantified by immunofluorescence staining for anti-pan-Cytokeratin (CK)-FITC/anti-CD45 AF647/DAPI. In total, in 20 out of 29 EpCAM-depleted fractions (69%) from 25 metastatic breast cancer patients additional EpCAMneg CTCs could be identified [range of 1–24 CTCs per sample] applying Trop2, CD49f, c-Met, CK8 and/or HA magnetic enrichment. Ep

  2. Multiple brown tumors of the jaws in primary hyperparathyroidism

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Kyoung A; Koh, Kwang Joon [School of Dentisity, Chonbuk National University, Jeonju (Korea, Republic of)

    2010-09-15

    Brown tumor is usually diagnosed at the terminal stage of hyperparathyroidism. Diagnosis of this tumor is confirmed by endocrinologic investigations along with clinical and radiographic examination. Radiographical differential diagnosis of this tumor includes central giant cell granuloma, aneurysmal bone cyst, metastatic tumor, multiple myeloma, and Paget disease. This report presents a rare case of multiple brown tumors occurring at the maxilla and mandible, which was initially misdiagnosed as central giant cell granuloma. Plain radiographs demonstrated multiple well-defined multilocular radiolucency. CT images showed soft tissue mass with low attenuated lesions, perforation of the lingual cortical plate, and a heterogeneous mass at the right thyroid lobe. These findings were consistent with parathyroid adenoma. The patient had hypercalcemia, hypophosphatemia, and elevated alkaline phosphatase level. Surgical excision of the tumor was performed. No recurrence was observed during a 28-month follow-up.

  3. Bone-metastasizing primary renal tumors in children

    International Nuclear Information System (INIS)

    Lamego, C.M.B.; Zerbini, M.C.N.

    1984-01-01

    Seven cases of childhood renal tumor with extensive bone involvement are reported. These neoplasms had been classified originally as wills tumors with atypical clinical and pathologic features. Subsequent to a retrospective histologic analysis, the lesions were reclassified as follows: three cases as bone-metastasizing renal tumors of childhood, one as rhabdomyosarcoma, two as indifferentiated Sarcomas and one case as indifferentiated malignant neoplasm. (Author) [pt

  4. Primary cardiac tumors associated with genetic syndromes. A comprehensive review

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Elizabeth; Agarwal, Prachi P. [University of Michigan Health System, University Hospital Division of Cardiothoracic Radiology, Department of Radiology, Ann Arbor, MI (United States); Mahani, Maryam Ghadimi [University of Michigan Health System, University Hospital Division of Cardiothoracic Radiology, Department of Radiology, Ann Arbor, MI (United States); University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); Lu, Jimmy C.; Dorfman, Adam L. [University of Michigan Health System, Section of Pediatric Radiology, C.S. Mott Children' s Hospital, Department of Radiology, Ann Arbor, MI (United States); C.S. Mott Children' s Hospital, University of Michigan Health System, Section of Pediatric Cardiology, Department of Pediatrics, Ann Arbor, MI (United States); Srinivasan, Ashok [University of Michigan Health System, Division of Neuroradiology, Department of Radiology, Ann Arbor, MI (United States)

    2018-02-15

    Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be different in syndromic forms, and on imaging children sometimes demonstrate additional manifestations of the underlying syndrome. We discuss the imaging appearance of cardiac tumors occurring in the framework of a genetic syndrome, the findings that suggest an underlying syndrome, and the impact on management. (orig.)

  5. Primary cardiac tumors associated with genetic syndromes. A comprehensive review

    International Nuclear Information System (INIS)

    Lee, Elizabeth; Agarwal, Prachi P.; Mahani, Maryam Ghadimi; Lu, Jimmy C.; Dorfman, Adam L.; Srinivasan, Ashok

    2018-01-01

    Various cardiac tumors occur in the setting of a genetic syndrome such as myxomas in Carney complex and rhabdomyomas in tuberous sclerosis. Tumor biology can be different in syndromic forms, and on imaging children sometimes demonstrate additional manifestations of the underlying syndrome. We discuss the imaging appearance of cardiac tumors occurring in the framework of a genetic syndrome, the findings that suggest an underlying syndrome, and the impact on management. (orig.)

  6. Advising potential recipients on the use of organs from donors with primary central nervous system tumors.

    Science.gov (United States)

    Warrens, Anthony N; Birch, Rhiannon; Collett, David; Daraktchiev, Maren; Dark, John H; Galea, George; Gronow, Katie; Neuberger, James; Hilton, David; Whittle, Ian R; Watson, Christopher J E

    2012-02-27

    Deciding to use an organ from a donor with a primary central nervous system (CNS) tumor necessitates offsetting the risk of tumor transmission with the chances of survival if the patient waits for another offer of a transplant. Published data vary in the quoted risk of tumor transmission. We used data obtained by reviewing 246 UK recipients of organs taken from donors with CNS tumors and found no evidence of a difference in overall patient mortality for recipients of a kidney, liver, or cardiothoracic organ, compared with recipients of organs from donors without a CNS tumor. Recent publication of the UK experience of transplanting organs from CNS tumor donors found no transmission in 448 recipients of organs from 177 donors with a primary CNS tumor (Watson et al., Am J Transplant 2010; 10: 1437). This 0% transmission rate is associated with an upper 95% confidence interval limit of 1.5%. Using a series of assumptions of risk, we compared the risks of dying as a result of the transmission of a primary brain tumor with the risks of dying if not transplanted. On this basis, the use of kidneys from a donor with a primary CNS tumor provides a further 8 years of life over someone who waited for a donor who did not have a primary CNS tumor, in addition to the life years gained by the transplant itself. The benefits for the recipients of livers and cardiothoracic organs were less, but there was no disadvantage in the impact on life expectancy.

  7. Primary Germ Cell Tumors of the Mediastinum: 10 Years of Experience in a Tertiary Teaching Hospital

    Directory of Open Access Journals (Sweden)

    Chih-Jen Yang

    2005-09-01

    Full Text Available Germ cell tumors occur mostly in the gonad. Extragonadal germ cell tumors are rare, and most occur in the retroperitoneum and mediastinum. Primary mediastinal germ cell tumors are often found in the anterior portion of the mediastinum and include teratomas and non-teratomatous tumors. Non-teratomatous tumors include seminomas and malignant non-seminomatous germ cell tumors (MNSGCTs. MNSGCTs include yolk sac tumors, choriocarcinomas, embryonal carcinomas, and mixed type germ cell tumors. Teratomas are the most common germ cell tumors of the mediastinum, and seminomas are the most common non-teratomatous germ cell tumors of the mediastinum. Cases of primary mediastinal MNSGCT reported in the literature are rare. In this report, we review all primary mediastinal germ cell tumors from a 10-year period at the Chung-Ho Memorial Hospital of Kaohsiung Medical University. A total of 14 cases were reviewed, including 11 patients with mature teratomas, two with yolk sac tumors, and one with seminoma. We discuss the differences in clinical presentation, histopathologic characteristics, treatment, and prognosis.

  8. Intra-Arterial Treatment of Primary and Metastatic Liver Tumors

    NARCIS (Netherlands)

    Buijs, M.A.M.; Vossen, J.A.

    2009-01-01

    The aims of this thesis were, first, to investigate the toxicities associated with trans-arterial chemoembolization (TACE) of liver tumors and to evaluate the use of MR imaging in characterizing tumor response after this locoregional therapy, second, to further develop intra-arterial therapy of

  9. Epilepsy in primary intracranial tumors in a neurosurgical hospital in ...

    African Journals Online (AJOL)

    2015-04-06

    Apr 6, 2015 ... with epilepsy have a brain tumor,[2,3] as many as 30–50% of patients with ... and another 10–30% develop seizures in the further course of .... Percentage. 46.3 .... tumors,[32] the prophylactic use of AEDs are still common. We.

  10. Primary extraskeletal Ewing's sarcoma/primitive neuroectodermal tumor of breast

    Directory of Open Access Journals (Sweden)

    Smita Srivastava

    2016-01-01

    Full Text Available Extraskeletal Ewing's sarcoma (EES is a rare soft tissue tumor that is morphologically indistinguishable from skeletal ES. We report a case of a 25-year-old female with recurrent EES/primitive neuroectodermal tumor of right breast with imaging findings on mammogram, ultrasound, magnetic resonance imaging breast, and positron emission tomography–computed tomography.

  11. A Primary Pulmonary Glomus Tumor: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Yasushi Ariizumi

    2012-01-01

    Full Text Available A case of a glomus tumor originating from the lung is reported. A 43-year-old female had undergone resection of a right lung tumor following a clinical diagnosis of carcinoid, sclerosing hemangioma, or other sarcoma. Histologically, the tumor comprised uniform small round to oval cells with centrally located nucleus, a clear cytoplasm, and apparent cell borders. The tumor also showed a focally hemangiopericytomatous pattern with irregularly branching or dilated vessels. Electron microscopy revealed smooth muscle differentiation of the tumor cells. Immunostaining further revealed that the tumor cells expressed smooth muscle actin, h-caldesmon, muscle specific actin (HHF-35, but not cytokeratin, epithelial membrane antigen, synaptophysin, or chromogranin A. Based on these findings, a diagnosis of primary pulmonary glomus tumor was established. Glomus tumors of the lung are very rare and only 21 cases have been reported to date. The histological features of the present tumor and the relevant literature are discussed.

  12. The Faroe shelf circulation and its potential impact on the primary production

    Science.gov (United States)

    Rasmussen, Till A. S.; Olsen, Steffen M.; Hansen, Bogi; Hátún, Hjálmar; Larsen, Karin M. H.

    2014-10-01

    The ecosystem on the Faroe shelf has been shown to be tightly controlled by the primary production. It has been suggested that the primary production is governed by the physical processes controlling this water mass. The objective of this study is to identify the physical control mechanisms that control this water mass, link these to the interannual variability of the chlorophyll content on the Faroe shelf and through this discuss the influence on the primary production. In order to achieve this, a 10 year hindcast (2000-2009) with a regional ocean circulation model has been set up for the focus area. Results are compared with measurements on the Faroe shelf. The model reproduces the clockwise residual circulation around the Faroe Islands. The vertical velocity profile is validated using observations at a location west of the Islands. Observations show a logarithmic profile in the entire water column indicating a fully developed boundary layer. The modeled profile matches the observations in the bottom part of the water column, however the thickness of the bottom boundary layer is underestimated, which results in a constant profile in the upper part of the water column. As a consequence, the modeled velocity in the upper part of the water column is up to 20% lower than the observed velocity. The direction of the modeled velocity profile compares well with observations. The model realistically forms the partly isolated unique shelf water mass. Years with anomalously early and persistent modeled spring stratification correspond with years with a high on-shelf chlorophyll concentration. An integration of the exchange across the 120 m isobath shows intense water mass exchange across this depth contour. The major part of this includes tidal shifting of the front between on-shelf and off-shelf waters and is associated with little effective water mass exchange. The result is a shelf water mass that is relatively isolated. The modeled net exchange is constituted by an on

  13. 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)

  14. Detection of circulating tumor cells harboring a unique ALK rearrangement in ALK-positive non-small-cell lung cancer.

    Science.gov (United States)

    Pailler, Emma; Adam, Julien; Barthélémy, Amélie; Oulhen, Marianne; Auger, Nathalie; Valent, Alexander; Borget, Isabelle; Planchard, David; Taylor, Melissa; André, Fabrice; Soria, Jean Charles; Vielh, Philippe; Besse, Benjamin; Farace, Françoise

    2013-06-20

    The diagnostic test for ALK rearrangement in non-small-cell lung cancer (NSCLC) for crizotinib treatment is currently done on tumor biopsies or fine-needle aspirations. We evaluated whether ALK rearrangement diagnosis could be performed by using circulating tumor cells (CTCs). The presence of an ALK rearrangement was examined in CTCs of 18 ALK-positive and 14 ALK-negative patients by using a filtration enrichment technique and filter-adapted fluorescent in situ hybridization (FA-FISH), a FISH method optimized for filters. ALK-rearrangement patterns were determined in CTCs and compared with those present in tumor biopsies. ALK-rearranged CTCs and tumor specimens were characterized for epithelial (cytokeratins, E-cadherin) and mesenchymal (vimentin, N-cadherin) marker expression. ALK-rearranged CTCs were monitored in five patients treated with crizotinib. All ALK-positive patients had four or more ALK-rearranged CTCs per 1 mL of blood (median, nine CTCs per 1 mL; range, four to 34 CTCs per 1 mL). No or only one ALK-rearranged CTC (median, one per 1 mL; range, zero to one per 1 mL) was detected in ALK-negative patients. ALK-rearranged CTCs harbored a unique (3'5') split pattern, and heterogeneous patterns (3'5', only 3') of splits were present in tumors. ALK-rearranged CTCs expressed a mesenchymal phenotype contrasting with heterogeneous epithelial and mesenchymal marker expressions in tumors. Variations in ALK-rearranged CTC levels were detected in patients being treated with crizotinib. ALK rearrangement can be detected in CTCs of patients with ALK-positive NSCLC by using a filtration technique and FA-FISH, enabling both diagnostic testing and monitoring of crizotinib treatment. Our results suggest that CTCs harboring a unique ALK rearrangement and mesenchymal phenotype may arise from clonal selection of tumor cells that have acquired the potential to drive metastatic progression of ALK-positive NSCLC.

  15. [Identification of Circulating Tumor Cell(CTC)in Breast Cancer Patients Using a Newly Established CTC Detecting System].

    Science.gov (United States)

    Nagata, Takuya; Ohnaga, Takashi; Lu, Xiao Long; Watanabe, Toru; Hirano, Katsuhisa; Okumura, Tomoyuki; Tsukada, Kazuhiro

    2015-10-01

    We developed a new circulating tumor cell (CTC) chip in order to identify CTCs in the peripheral blood of cancer patients. In this study, we aimed to identify CTCs in the blood of breast cancer patients by using this CTC detecting system. In addition, we used this system to evaluate the response to anticancer agents. We were able to identify CTCs in 5 of 6 patients. In addition, the system showed that the number of CTCs had decreased after chemotherapy. Thus, the CTC detecting system was useful in the identification of CTCs in the breast cancer patients and in the early prediction of response to anticancer agents.

  16. Application of detecting cerebrospinal fluid circulating tumor cells in the diagnosis of meningeal metastasis of non-small cell lung cancer

    Directory of Open Access Journals (Sweden)

    Rong JIANG

    2014-08-01

    Full Text Available Objective To observe a new technology for the detection and enumeration of cerebrospinal fluid (CSF circulating tumor cells (CTCs in the diagnosis of non-small cell lung cancer (NSCLC with meningeal metastasis (MM.  Methods Five cases of NSCLC with MM that were diagnosed by CSF cytology were selected, and 20 ml CSF samples were obtained by lumbar puncture for every patient. The tumor marker immunostaining-fluorescence in situ hybridization (TM-iFISH technology was adapted to detect enrichment and enumeration of circulating tumor cells in 7.50 ml CSF samples; CSF cytology was checked in 10 ml CSF samples; CSF tumor markers were detected in 2.50 ml CSF samples. All of 5 cases were examined by MRI enhancement scan.  Results TM-iFISH detection found circulating tumor cells numbers ranging 18-1823/7.50 ml. Only 2 cases of patients with CSF cytology examination showed the tumor cells. The results of CSF tumor markers in all samples were higher than normal serum tumor markers detection results. The enhanced MRI scan of 5 cases revealed typical signs of MM.  Conclusions The TM-iFISH test showed certain advantages in the detection of malignant tumor cells in CSF. This technology may be a new method of detection and enumeration of tumor cells in CSF, but more studies are needed to prove its sensitivity and specificity. doi: 10.3969/j.issn.1672-6731.2014.08.011

  17. Circulating CXCR5+CD4+ T cells assist in the survival and growth of primary diffuse large B cell lymphoma cells through interleukin 10 pathway

    Energy Technology Data Exchange (ETDEWEB)

    Cha, Zhanshan [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Qian, Guangfang [Department of Endocrinology, Zhangqiu Municipal Hospital of Traditional Chinese Medicine, Zhangqiu, Shandong 250200 (China); Zang, Yan; Gu, Haihui; Huang, Yanyan; Zhu, Lishuang; Li, Jinqi; Liu, Yang; Tu, Xiaohua [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China); Song, Haihan [Emergency Center, East Hospital, Shanghai 200120 (China); Qian, Baohua, E-mail: qianbhl963@163.com [Department of Transfusion, Changhai Hospital, Second Military Medical University, Shanghai 200433 (China)

    2017-01-01

    Diffuse large B cell lymphoma (DLBCL) is a common and aggressive cancer caused by the malignant transformation of B cells. Although it has been established that the follicular helper T (Tfh) cells play a central role in B cell development, little information is available on their involvement in DLBCL pathogenesis. We studied the role of the peripheral Tfh equivalent, the CXCR5{sup +} CD4{sup +} T cells, in DLBCL. Data showed that compared to CXCR5{sup -} CD4{sup +} T cells, CXCR5{sup +} CD4{sup +} T cells were significantly more effective at promoting the proliferation as well as inhibiting the apoptosis of primary autologous DLBCL tumor cells. Surprisingly, we found that at equal cell numbers, CXCR5{sup +} CD4{sup +} T cells in DLBCL patients secreted significantly less interleukin (IL)-21 than CXCR5{sup -} CD4{sup +} T cells, while the level of IL-10 secretion was significant elevated in the CXCR5{sup +} compartment compared to the CXCR5{sup -} compartment. Neutralization of IL-10 in the primary DLBCL-CXCR5{sup +} CD4{sup +} T cell coculture compromised the CXCR5{sup +} CD4{sup +} T cell-mediated pro-tumor effects, in a manner that was dependent on the concentration of anti-IL-10 antibodies. The CXCR5{sup +} compartment also contained significantly lower frequencies of cytotoxic CD4{sup +} T cells than the CXCR5{sup -} compartment. In conclusion, our investigations discovered a previously unknown pro-tumor role of CXCR5-expressing circulating CD4{sup +} T cells, which assisted the survival and proliferation of primary DLBCL cells through IL-10. - Highlights: • We studied the role of the peripheral Tfh in DLBCL. • Tfh were effective at promoting the proliferation of primary DLBCL tumor cells. • Tfh were effective at inhibiting the apoptosis of primary DLBCL tumor cells. • IL-10 secretion in Tfh was significant elevated in DLBCL. • Neutralization of IL-10 compromised Tfh-mediated pro-tumor effects.

  18. Filter-Adapted Fluorescent In Situ Hybridization (FA-FISH) for Filtration-Enriched Circulating Tumor Cells.

    Science.gov (United States)

    Oulhen, Marianne; Pailler, Emma; Faugeroux, Vincent; Farace, Françoise

    2017-01-01

    Circulating tumor cells (CTCs) may represent an easily accessible source of tumor material to assess genetic aberrations such as gene-rearrangements or gene-amplifications and screen cancer patients eligible for targeted therapies. As the number of CTCs is a critical parameter to identify such biomarkers, we developed fluorescent in situ hybridization (FISH) for CTCs enriched on filters (filter-adapted-FISH, FA-FISH). Here, we describe the FA-FISH protocol, the combination of immunofluorescent staining (DAPI/CD45) and FA-FISH techniques, as well as the semi-automated microscopy method that we developed to improve the feasibility and reliability of FISH analyses in filtration-enriched CTC.

  19. Prognostic significance of maximum primary tumor diameter in nasopharyngeal carcinoma

    International Nuclear Information System (INIS)

    Liang, Shao-Bo; Deng, Yan-Ming; Zhang, Ning; Lu, Rui-Liang; Zhao, Hai; Chen, Hai-Yang; Li, Shao-En; Liu, Dong-Sheng; Chen, Yong

    2013-01-01

    To evaluate the prognostic value of maximum primary tumor diameter (MPTD) in nasopharyngeal carcinoma (NPC). Three hundred and thirty-three consecutive, newly-diagnosed NPC patients were retrospectively reviewed. Kaplan-Meier analysis and the log-rank test were used to estimate overall survival (OS), failure-free survival (FFS), distant metastasis-free survival (DMFS) and local relapse-free survival (LRFS). Cox proportional hazards regression analysis was used to assess the prognostic value of MPTD. Median follow-up was 66 months (range, 2–82 months). Median MPTD in stage T1, T2, T3 and T4 was 27.9, 37.5, 45.0 and 61.3 mm, respectively. The proportion of T1 patients with a MPTD ≤ 30 mm was 62.3%; 72% and 62.9% of T2 and T3 patients had a MPTD > 30–50 mm, and 83.5% of T4 patients had a MPTD > 50 mm. For patients with a MPTD ≤ 30 mm, > 30–50 mm and > 50 mm, the 5-year OS, FFS, DMFS and LRFS rates were 85.2%, 74.2% and 56.3% (P < 0.001); 87%, 80.7% and 62.8% (P < 0.001); 88.7%, 86.4% and 72.5% (P = 0.003); and 98.2%, 93.2% and 86.3% (P = 0.012), respectively. In multivariate analysis, MPTD was a prognostic factor for OS, FFS and DMFS, and the only independent prognostic factor for LRFS. For T3-T4 patients with a MPTD ≤ 50 mm and > 50 mm, the 5-year OS, FFS and DMFS rates were 70.4% vs. 58.4% (P = 0.010), 77.5% vs. 65.2% (P = 0.013) and 83.6% vs. 73.6% (P = 0.047), respectively. In patients with a MPTD ≤ 30 mm, 5-year LRFS in T1, T2, T3 and T4 was 100%, 100%, 88.9% and 100% (P = 0.172). Our data suggest that MPTD is an independent prognostic factor in NPC, and incorporation of MPTD might lead to a further refinement of T staging

  20. Calcitonin-negative primary neuroendocrine tumor of the thyroid ...

    African Journals Online (AJOL)

    nonmedullary" in humans is a rare tumor that arises primarily in the thyroid gland and may be mistaken for medullary thyroid carcinoma; it is characterized by the immunohistochemical (IHC) expression of neuroendocrine markers and the absence of ...

  1. Incidentally diagnosed simultaneous second primary tumor of the sphenoid sinus in a patient with lung cancer

    DEFF Research Database (Denmark)

    Yigit, Ozgur; Taskin, Umit; Demir, Ahmet

    2009-01-01

    Synchronous tumors are described as multiple primary malignancies presenting within 6 months of diagnosis of index tumors. Synchronous tumors of the lung and the head and neck region is frequently seen. However, isolated sphenoid sinus and lung cancers are not reported yet. Here, we reported...... an incidentally diagnosed simultaneous second primary sphenoid sinus tumor in a patient with lung cancer. Radiological evaluation results demonstrated a significant contrast-enhanced mass in the sphenoid sinus extending through the nasopharynx because of the destruction of the sphenoid sinus. The decision...

  2. Shared liver-like transcriptional characteristics in liver metastases and corresponding primary colorectal tumors.

    Science.gov (United States)

    Cheng, Jun; Song, Xuekun; Ao, Lu; Chen, Rou; Chi, Meirong; Guo, You; Zhang, Jiahui; Li, Hongdong; Zhao, Wenyuan; Guo, Zheng; Wang, Xianlong

    2018-01-01

    Background & Aims : Primary tumors of colorectal carcinoma (CRC) with liver metastasis might gain some liver-specific characteristics to adapt the liver micro-environment. This study aims to reveal potential liver-like transcriptional characteristics associated with the liver metastasis in primary colorectal carcinoma. Methods: Among the genes up-regulated in normal liver tissues versus normal colorectal tissues, we identified "liver-specific" genes whose expression levels ranked among the bottom 10% ("unexpressed") of all measured genes in both normal colorectal tissues and primary colorectal tumors without metastasis. These liver-specific genes were investigated for their expressions in both the primary tumors and the corresponding liver metastases of seven primary CRC patients with liver metastasis using microdissected samples. Results: Among the 3958 genes detected to be up-regulated in normal liver tissues versus normal colorectal tissues, we identified 12 liver-specific genes and found two of them, ANGPTL3 and CFHR5 , were unexpressed in microdissected primary colorectal tumors without metastasis but expressed in both microdissected liver metastases and corresponding primary colorectal tumors (Fisher's exact test, P colorectal tumors may express some liver-specific genes which may help the tumor cells adapt the liver micro-environment.

  3. LOH at 6q and 10q in fractionated circulating DNA of ovarian cancer patients is predictive for tumor cell spread and overall survival

    Directory of Open Access Journals (Sweden)

    Kuhlmann Jan

    2012-07-01

    Full Text Available Abstract Background We recently showed that LOH proximal to M6P/IGF2R locus (D6S1581 in primary ovarian tumors is predictive for the presence of disseminated tumor cells (DTC in the bone marrow (BM. For therapy-monitoring, it would be highly desirable to establish a blood-based biomarker. Therefore, we quantified circulating DNA (cirDNA in sera of 63 ovarian cancer patients before surgery and after chemotherapy, measured incidence of LOH at four cancer-relevant chromosomal loci, correlated LOH with tumor cell spread to the BM and evaluated prognostic significance of LOH. Methods cirDNA was fractionated into high- and low molecular-weight fraction (HMWF, LMWF for LOH-profiling, utilizing PCR-based fluorescence microsatellite analysis. BM aspirates were analyzed for DTC by immunocytochemistry using the pan-cytokeratin antibody A45-B/B3. Results cirDNA levels in the HMWF before surgery were predictive for residual tumor load (p = 0.017. After chemotherapy, we observed a significant decline of cirDNA in the LMWF (p = 0.0001 but not in the HMWF. LOH was prevalently detected in the LMWF with an overall frequency of 67%, only moderately ablating after chemotherapy (45%. Before surgery, LOH in the LMWF at marker D10S1765 and D13S218 significantly correlated with tumor grading and FIGO stage (p = 0.033, p = 0.004, respectively. In both combined fractions, LOH at D6S1581 additionally associated with overall survival (OS (p = 0.030. Moreover, solely LOH at D10S1765 in LMWF after therapy correlated with DTC in BM after therapy (p = 0.017. Conclusion We demonstrate the applicability and necessity of DNA-fractionation prior to analyzing circulating LOH and identify LOH at D10S1765 and D6S1581 as novel blood-based biomarkers for ovarian cancer, being relevant for therapy-monitoring.

  4. Pitfalls in the MR diagnosis of primary malignant bone tumors

    International Nuclear Information System (INIS)

    Bader, T.R.

    1998-01-01

    MRI has gained an undisputed place in the evaluation of malignant bone tumors, not only for verifying results of conventional radiography and clarifying differential diagnoses; it has also become increasingly important for the assessment of the malignant/benign nature of the tumor, its growth rate, definition of adequate sites for biopsy, local preoperative staging, and evaluation of the response to chemotherapy. However, several pitfalls have to be observed regarding choice of technical parameters (coils, sequences, imaging planes), tissue differentiation, and tumor staging. When staging malignant tumors, critical aspects which have to be observed are tumor extension, integrity of the cortical bone, soft tissue components, infiltration of a joint or neurovascular bundle. The use of contrast agents provides important additional information but can also give rise to misinterpretations. Thus, all features of a tumor have to be observed in order to establish a final diagnosis. Particular difficulties can occur with the interpretation of MR images of osteomyelitis, osteoid osteoma, stress and insufficiency fractures, bone infarcts, myositis ossificans, hemangiomas, and aneurysmal bone cysts. (orig.) [de

  5. Phenotypic and Functional Alterations in Circulating Memory CD8 T Cells with Time after Primary Infection.

    Directory of Open Access Journals (Sweden)

    Matthew D Martin

    2015-10-01

    Full Text Available Memory CD8 T cells confer increased protection to immune hosts upon secondary viral, bacterial, and parasitic infections. The level of protection provided depends on the numbers, quality (functional ability, and location of memory CD8 T cells present at the time of infection. While primary memory CD8 T cells can be maintained for the life of the host, the full extent of phenotypic and functional changes that occur over time after initial antigen encounter remains poorly characterized. Here we show that critical properties of circulating primary memory CD8 T cells, including location, phenotype, cytokine production, maintenance, secondary proliferation, secondary memory generation potential, and mitochondrial function change with time after infection. Interestingly, phenotypic and functional alterations in the memory population are not due solely to shifts in the ratio of effector (CD62Llo and central memory (CD62Lhi cells, but also occur within defined CD62Lhi memory CD8 T cell subsets. CD62Lhi memory cells retain the ability to efficiently produce cytokines with time after infection. However, while it is was not formally tested whether changes in CD62Lhi memory CD8 T cells over time occur in a cell intrinsic manner or are due to selective death and/or survival, the gene expression profiles of CD62Lhi memory CD8 T cells change, phenotypic heterogeneity decreases, and mitochondrial function and proliferative capacity in either a lymphopenic environment or in response to antigen re-encounter increase with time. Importantly, and in accordance with their enhanced proliferative and metabolic capabilities, protection provided against chronic LCMV clone-13 infection increases over time for both circulating memory CD8 T cell populations and for CD62Lhi memory cells. Taken together, the data in this study reveal that memory CD8 T cells continue to change with time after infection and suggest that the outcome of vaccination strategies designed to elicit

  6. Fascin and EMMPRIN expression in primary mucinous tumors of ovary: a tissue microarray study.

    Science.gov (United States)

    Alici, Omer; Kefeli, Mehmet; Yildiz, Levent; Baris, Sancar; Karagoz, Filiz; Kandemir, Bedri

    2014-12-01

    The aim of this study was to compare the expressions of fascin and EMMPRIN in primary malignant, borderline and benign mucinous ovarian tumors, and to investigate the relationship of these markers with tumor progression and their applicability to differential diagnosis. An immunohistochemical study was performed for fascin and EMMPRIN using the tissue microarray technique. Eighty-one cases were included in the study; there were 37 benign, 25 borderline and 19 malignant primary mucinous ovarian tumors. For each case, a total staining score was determined, consisting of scores for extent of staining and intensity of staining. The cases were allocated to negative, weakly positive and strongly positive staining categories, according to the total staining score. Both of the markers were significantly negative in benign tumors as compared with borderline and malignant tumors. There was no significant difference between borderline and malignant groups for both markers. Sixty-eight percent of malignant tumors were stained positive by fascin, while this rate was 40% for borderline mucinous tumors. All malignant tumors were strongly stained positive for EMMPRIN, while this rate was 92% for borderline mucinous tumors. The rest of the cases stained weakly positive. No significant difference in staining score was found between fascin and EMMPRIN expression. In ovarian primary mucinous tumors, fascin and EMMPRIN may play an important role in tumor progression from benign tumor to carcinoma. In that context, EMMPRIN and fascin expression may have potential application in the differential diagnosis of some diagnostically problematic mucinous ovarian tumors. However, the differential diagnostic applicability of EMMPRIN appears to be more limited than that of fascin due to its wide spectrum of staining in mucinous ovarian tumors. Copyright © 2014 Elsevier GmbH. All rights reserved.

  7. High level of chromosomal instability in circulating tumor cells of ROS1-rearranged non-small-cell lung cancer.

    Science.gov (United States)

    Pailler, E; Auger, N; Lindsay, C R; Vielh, P; Islas-Morris-Hernandez, A; Borget, I; Ngo-Camus, M; Planchard, D; Soria, J-C; Besse, B; Farace, F

    2015-07-01

    Genetic aberrations affecting the c-ros oncogene 1 (ROS1) tyrosine kinase gene have been reported in a small subset of patients with non-small-cell lung cancer (NSCLC). We evaluated whether ROS1-chromosomal rearrangements could be detected in circulating tumor cells (CTCs) and examined tumor heterogeneity of CTCs and tumor biopsies in ROS1-rearranged NSCLC patients. Using isolation by size of epithelial tumor cells (ISET) filtration and filter-adapted-fluorescence in situ hybridization (FA-FISH), ROS1 rearrangement was examined in CTCs from four ROS1-rearranged patients treated with the ROS1-inhibitor, crizotinib, and four ROS1-negative patients. ROS1-gene alterations observed in CTCs at baseline from ROS1-rearranged patients were compared with those present in tumor biopsies and in CTCs during crizotinib treatment. Numerical chromosomal instability (CIN) of CTCs was assessed by DNA content quantification and chromosome enumeration. ROS1 rearrangement was detected in the CTCs of all four patients with ROS1 rearrangement previously confirmed by tumor biopsy. In ROS1-rearranged patients, median number of ROS1-rearranged CTCs at baseline was 34.5 per 3 ml blood (range, 24-55). In ROS1-negative patients, median background hybridization of ROS1-rearranged CTCs was 7.5 per 3 ml blood (range, 7-11). Tumor heterogeneity, assessed by ROS1 copy number, was significantly higher in baseline CTCs compared with paired tumor biopsies in the three patients experiencing PR or SD (P < 0.0001). Copy number in ROS1-rearranged CTCs increased significantly in two patients who progressed during crizotinib treatment (P < 0.02). CTCs from ROS1-rearranged patients had a high DNA content and gain of chromosomes, indicating high levels of aneuploidy and numerical CIN. We provide the first proof-of-concept that CTCs can be used for noninvasive and sensitive detection of ROS1 rearrangement in NSCLC patients. CTCs from ROS1-rearranged patients show considerable heterogeneity of ROS1-gene

  8. Design and Selection of Innovative Primary Circulation Pumps for GEN-IV Lead Fast Reactors

    Directory of Open Access Journals (Sweden)

    Walter Borreani

    2017-12-01

    Full Text Available Although Lead-cooled Fast Reactor (LFR is not a new concept, it continues to be an example of innovation in the nuclear field. Recently, there has been strong interest in liquid lead (Pb or liquid lead–bismuth eutectic (LBE both critical and subcritical systems in a relevant number of Countries, including studies performed in the frame of GENERATION-IV initiative. In this paper, the theoretical and computational findings for three different designs of Primary Circulation Pump (PCP evolving liquid lead (namely the jet pump, the Archimedean pump and the blade pump are presented with reference to the ALFRED (Advanced Lead Fast Reactor European Demonstrator design. The pumps are first analyzed from the theoretical point of view and then modeled with a 3D CFD code. Required design performance of the pumps are approximatively around an effective head of 2 bar with a mass flow rate of 5000 kg/s. Taking into account the geometrical constraints of the reactor and the fluid dynamics characteristics of the molten lead, the maximum design velocity for molten lead fluid flow of 2 m/s may be exceeded giving rise to unacceptable erosion phenomena of the blade or rotating component of the primary pumping system. For this reason a deep investigation of non-conventional axial pumps has been performed. The results presented shows that the design of the jet pump looks like beyond the current technological feasibility while, once the mechanical challenges of the Archimedean (screw pump and the fluid-dynamic issues of the blade pump will be addressed, both could represent viable solutions as PCP for ALFRED. Particularly, the blade pump shows the best performance in terms of pressure head generated in normal operation conditions as well as pressure drop in locked rotor conditions. Further optimizations (mainly for what the geometrical configuration is concerned are still necessary.

  9. Feasibility analysis of the Primary Loop of Pool-Type Natural Circulating Nuclear Reactor Dedicated to Seawater Desalination

    Energy Technology Data Exchange (ETDEWEB)

    Jeong, Woonho; Jeong, Yong Hoon [KAIST, Daejeon (Korea, Republic of)

    2016-05-15

    In this study, the feasibility of natural circulation was evaluated for the reference plant AHR400 (Advanced Heating Reactor 400MWth). AHR400 is a pool-type desalination-dedicated nuclear reactor. As a consequence, AHR400 has low operating pressure and temperature which provides large safety margin. Removal of the reactor coolant pump from the AHR400 will enforce integrity of the reactor vessel and passive safety feature. Therefore, the study also tried to find out optimized primary loop design to achieve total natural circulation of the coolant. Natural circulation capacity of the primary loop of the desalination dedicated nuclear reactor AHR400 was evaluated. It was concluded that to remove RCP from the AHR400 and operates the reactor only by natural circulation of the coolant is impossible. Decreased core power as half make removal of RCP possible with 15m central height difference between the core and IHXs. Furthermore, validation and modification of pressure loss coefficients by small-scaled natural circulation experiment at a pool-type reactor would provide more accurate results.

  10. Preoperative measurement of canine primary bone tumors, using radiography and bone scintigraphy

    International Nuclear Information System (INIS)

    Lamb, C.R.; Berg, J.; Bengston, A.E.

    1990-01-01

    Specimens of 20 canine primary bone tumors (18 osteosarcoma, 2 fibrosarcoma) were examined to compare the maximal axial length of gross tumor with the length of the lesion seen on preoperative radiographs and 99mTc methylene diphosphonate bone scintigraphic images. Radiographs defined the length of the tumor to within +/- 10% of the gross measurement for 6 (30%), underestimated it for 12 (60%), and overestimated it for 2 (10%) specimens. Bone scintigraphy defined tumor length within +/- 10% for 8 (40%), underestimated it for 1 (5%), and overestimated it for the remaining 11 (55%) specimens. Use of radiographic evaluation alone could result in underestimation of the diaphyseal extent of a primary bone tumor, with risk of incomplete resection. Bone scan images tend to overestimate tumor length and, therefore, may provide safer resection guidelines

  11. Stromal Gene Expression and Function in Primary Breast Tumors that Metastasize to Bone Cancer

    Science.gov (United States)

    2006-07-01

    surrounding bone microenvironment were investigated by purifying endothelial cells from tumor-burdened and non-tumor burdened spines . 4T1...of Balb/c mice. Fresh resected tissue (normal fat pad, primary tumor tissue or the metastatic sites spine , femur and lung) was obtained and cell... Hedgehog signalling pathway: Lasp1, CREBBP/EP300 inhibitory protein 1 and FoxP1. Of interest as well are a number of differentially regulated ESTs

  12. Brown tumor of the patella caused by primary hyperparathyroidism: A case report

    Energy Technology Data Exchange (ETDEWEB)

    Irie, Tomoko; Mawatari, Taro; Ikemura, Satoshi; Matsui, Gen; Iguchi, Takahiro; Mitsuyasu, Hiroaki [Orthopaedic Surgery, Hamanomachi Hospital, Fukuoka (Japan)

    2015-06-15

    It has been reported that the common sites of brown tumors are the jaw, pelvis, ribs, femurs and clavicles. We report our experience in a case of brown tumor of the patella caused by primary hyperparathyroidism. An initial radiograph and CT showed an osteolytic lesion and MR images showed a mixed solid and multiloculated cystic tumor in the right patella. One month after the parathyroidectomy, rapid bone formation was observed on both radiographs and CT images.1.

  13. Pulmonary emphysema and tumor microenvironment in primary lung cancer.

    Science.gov (United States)

    Murakami, Junichi; Ueda, Kazuhiro; Sano, Fumiho; Hayashi, Masataro; Nishimoto, Arata; Hamano, Kimikazu

    2016-02-01

    To clarify the relationship between the presence of pulmonary emphysema and tumor microenvironment and their significance for the clinicopathologic aggressiveness of non-small cell lung cancer. The subjects included 48 patients with completely resected and pathologically confirmed stage I non-small cell lung cancer. Quantitative computed tomography was used to diagnose pulmonary emphysema, and immunohistochemical staining was performed to evaluate the matrix metalloproteinase (MMP) expression status in the intratumoral stromal cells as well as the microvessel density (MVD). Positive MMP-9 staining in the intratumoral stromal cells was confirmed in 17 (35%) of the 48 tumors. These 17 tumors were associated with a high MVD, frequent lymphovascular invasion, a high proliferative activity, and high postoperative recurrence rate (all, P pulmonary emphysema (P = 0.02). Lung cancers arising from pulmonary emphysema were also associated with a high MVD, proliferative activity, and postoperative recurrence rate (all, P < 0.05). The MMP-9 expression in intratumoral stromal cells is associated with the clinicopathologic aggressiveness of lung cancer and is predominantly identified in tumors arising in emphysematous lungs. Further studies regarding the biological links between the intratumoral and extratumoral microenvironment will help to explain why lung cancers originating in emphysematous lung tissues are associated with a poor prognosis. Copyright © 2016 Elsevier Inc. All rights reserved.

  14. Endoscopic Management of a Primary Duodenal Carcinoid Tumor

    Directory of Open Access Journals (Sweden)

    Albin Abraham

    2012-03-01

    Full Text Available Carcinoids are rare, slow-growing tumors originating from a variety of different neuroendocrine cell types. They are identified histologically by their affinity for silver salts and by positive reactions to neuroendocrine markers such as neuron-specific enolase, synaptophysin and chromogranin. They can present with various clinical symptoms and are difficult to diagnose. We present the case of a 43-year-old woman who was referred for evaluation of anemia. Upper endoscopy showed a duodenal bulb mass around 1 cm in size. Histopathological and immunohistochemistry staining were consistent with the diagnosis of a carcinoid tumor. Further imaging and endoscopic studies showed no other synchronous carcinoid lesions. Endoscopic ultrasound (EUS revealed a 1 cm lesion confined to the mucosa and no local lymphadenopathy. Successful endoscopic mucosal resection of the mass was performed. Follow-up surveillance 6 months later with EUS and Octreoscan revealed no new lesions suggestive of recurrence. No consensus guidelines exist for the endoscopic management of duodenal carcinoid tumors. However, endoscopic resection is safe and preferred for tumors measuring 1 cm or less with no evidence of invasion of the muscularis layer.

  15. Primary Ewing Sarcoma/Primitive Neuroectodermal Tumor of the Stomach

    Directory of Open Access Journals (Sweden)

    Safi Khuri

    2016-11-01

    Full Text Available Ewing sarcoma/primitive neuroectodermal tumor (ES/PNET is a tumor of small round cells arising in skeletal tissues. These tumors rarely arise in the stomach. We present a 31-year-old healthy female patient who was admitted to our surgical ward due to upper gastrointestinal hemorrhage. Upper endoscopy revealed a large ulcerated bleeding mass originating from the lesser curvature. Biopsy revealed tumor cell immunoreactivity positive for CD99, vimentin, and Ki67 (an index of proliferation. These findings were compatible with gastric ES/PNET. The fluorescence in situ hybridization analysis result for the EWSR1 gene rearrangement (11: 22 translocation was positive. The patient refused neoadjuvant treatment and thus underwent an operation during which a mass at the lesser curvature of the stomach was found. The mass was adhering to the pancreatic tail and to the mesentery of the transverse and descending colon. Total gastrectomy, distal pancreatectomy, splenectomy, and left adrenalectomy were done. The patient refused adjuvant treatment. She is free of disease 3 years after surgery.

  16. Primary benign brachial plexus tumors: an experience of 115 operated cases.

    Science.gov (United States)

    Desai, Ketan I

    2012-01-01

    Primary benign brachial plexus tumors are rare. They pose a great challenge to the neurosurgeon, because the majority of patients present with minimal or no neurological deficits. Radical to complete excision of the tumor with preservation of neurological function of the involved nerve is an ideal surgical treatment option with benign primary brachial plexus tumor surgery. We present a review article of our 10-year experience with primary benign brachial plexus tumors surgically treated at King Edward Memorial Hospital and P.D. Hinduja National Hospital from 2000 to 2009. The clinical presentations, radiological features, surgical strategies, and the eventual outcome following surgery are analyzed, discussed, and compared with available series in the world literature. Various difficulties and problems faced in the management of primary benign brachial plexus tumors are analyzed. Irrespective of the tumor size, the indications for surgical intervention are also discussed. The goal of our study was to optimize the treatment of patients with benign brachial plexus tumors with minimal neurological deficits. It is of paramount importance that brachial plexus tumors be managed by a peripheral nerve surgeon with expertise and experience in this field to minimize the neurological insult following surgery.

  17. A FISH-based method for assessment of HER-2 amplification status in breast cancer circulating tumor cells following CellSearch isolation

    Directory of Open Access Journals (Sweden)

    Frithiof H

    2016-11-01

    Full Text Available Henrik Frithiof,1 Kristina Aaltonen,1 Lisa Rydén2,3 1Division of Oncology and Pathology, 2Division of Surgery, Department of Clinical Sciences Lund, Lund University, Lund, 3Department of Surgery, Skåne University Hospital, Malmö, Sweden Introduction: Amplification of the HER-2/neu (HER-2 proto-oncogene occurs in 10%–15% of primary breast cancer, leading to an activated HER-2 receptor, augmenting growth of cancer cells. Tumor classification is determined in primary tumor tissue and metastatic biopsies. However, malignant cells tend to alter their phenotype during disease progression. Circulating tumor cell (CTC analysis may serve as an alternative to repeated biopsies. The Food and Drug Administration-approved CellSearch system allows determination of the HER-2 protein, but not of the HER-2 gene. The aim of this study was to optimize a fluorescence in situ hybridization (FISH-based method to quantitatively determine HER-2 amplification in breast cancer CTCs following CellSearch-based isolation and verify the method in patient samples. Methods: Using healthy donor blood spiked with human epidermal growth factor receptor 2 (HER-2-positive breast cancer cell lines, SKBr-3 and BT-474, and a corresponding negative control (the HER-2-negative MCF-7 cell line, an in vitro CTC model system was designed. Following isolation in the CellSearch system, CTC samples were further enriched and fixed on microscope slides. Immunocytochemical staining with cytokeratin and 4',6-diamidino-2'-phenylindole dihydrochloride identified CTCs under a fluorescence microscope. A FISH-based procedure was optimized by applying the HER2 IQFISH pharmDx assay for assessment of HER-2 amplification status in breast cancer CTCs. Results: A method for defining the presence of HER-2 amplification in single breast cancer CTCs after CellSearch isolation was established using cell lines as positive and negative controls. The method was validated in blood from breast cancer patients

  18. Radiographically determined growth kinetics of primary lung tumors in the dog

    International Nuclear Information System (INIS)

    Perry, R.E.; Weller, R.E.; Buschbom, R.L.; Dagle, G.E.; Park, J.F.

    1989-10-01

    Tumor growth rate patterns especially tumor doubling time (TDT), have been extensively evaluated in man. Studies involving the determination of TDT in humans are limited, however, by the number of cases, time consistent radiographic tumor measurements, and inability to perform experimental procedures. In animals similar constraints do not exist. Lifespan animal models lend themselves well to tumor growth pattern analysis. Experimental studies have been designed to evaluate both the biological effects and growth patterns of induced and spontaneous tumors. The purpose of this study was to calculate the tumor volume doubling times (TCDT) for radiation-induced and spontaneous primary pulmonary neoplasms in dogs to see if differences existed due to etiology, sex or histologic cell type, and to determine if the time of tumor onset could be extrapolated from the TVDT. 3 refs

  19. Cytogenetic and molecular-genetic aberrations in malignant primary bone tumors

    International Nuclear Information System (INIS)

    Zoubek, A.; Kovar, H.; Gadner, H.

    1998-01-01

    Osteosarcoma, chondrosarcoma and tumors of the Ewing group are the most frequently observed primary malignant bone tumors. In an Internet homepage recently constructed for the Orthopedic Hospital Rizzoli Bologna, Italy, these tumors have represented the majority of 4423 malignant bone tumors in the archives of this institution since 1920 (http://www.tizeta.it/rizzoli). Malignant fibrous histiocytoma, fibrosarcoma, hemangioendothelioma, malignant hemangiopericytoma and giant-cell tumors are diagnosed less frequently. Since the introduction of modern molecular and cytogenic techniques, knowledge of genetic aberrations in malginant bone tumors has steadily increased. However, so far only for the group of Ewing tumors has a recurrent chromosomal marker, the translocation t(11; 22)(q24; q12), been identified. (orig.) [de

  20. Temporalis Myofascial Flap for Primary Cranial Base Reconstruction after Tumor Resection

    OpenAIRE

    Eldaly, Ahmed; Magdy, Emad A.; Nour, Yasser A.; Gaafar, Alaa H.

    2008-01-01

    Objective: To evaluate the use of the temporalis myofascial flap in primary cranial base reconstruction following surgical tumor ablation and to explain technical issues, potential complications, and donor site consequences along with their management. Design: Retrospective case series. Setting: Tertiary referral center. Participants: Forty-one consecutive patients receiving primary temporalis myofascial flap reconstructions following cranial base tumor resections in a 4-year period. Main Out...

  1. MicroRNA signature characterizes primary tumors that metastasize in an esophageal adenocarcinoma rat model.

    Directory of Open Access Journals (Sweden)

    Ali H Zaidi

    Full Text Available To establish a miRNA signature for metastasis in an animal model of esophageal adenocarcinoma (EAC.The incidence of esophageal adenocarcinoma (EAC has dramatically increased and esophageal cancer is now the sixth leading cause of cancer deaths worldwide. Mortality rates remain high among patients with advanced stage disease and esophagectomy is associated with high complication rates. Hence, early identification of potentially metastatic disease would better guide treatment strategies.The modified Levrat's surgery was performed to induce EAC in Sprague-Dawley rats. Primary EAC and distant metastatic sites were confirmed via histology and immunofluorescence. miRNA profiling was performed on primary tumors with or without metastasis. A unique subset of miRNAs expressed in primary tumors and metastases was identified with Ingenuity Pathway Analysis (IPA along with upstream and downstream targets. miRNA-linked gene expression analysis was performed on a secondary cohort of metastasis positive (n=5 and metastasis negative (n=28 primary tumors.The epithelial origin of distant metastasis was established by IF using villin (VIL1 and mucin 5AC (MUC5AC antibodies. miRNome analysis identified four down-regulated miRNAs in metastasis positive primary tumors compared to metastasis negative tumors: miR-92a-3p (p=0.0001, miR-141-3p (p=0.0022, miR-451-1a (p=0.0181 and miR133a-3p (p=0.0304. Six target genes identified in the top scoring networks by IPA were validated as significantly, differentially expressed in metastasis positive primary tumors: Ago2, Akt1, Kras, Bcl2L11, CDKN1B and Zeb2.In vivo metastasis was confirmed in the modified Levrat's model. Analysis of the primary tumor identified a distinctive miRNA signature for primary tumors that metastasized.

  2. Malignant primary germ-cell tumor of the brain: case report

    Energy Technology Data Exchange (ETDEWEB)

    Yamamoto, Toyoshiro; Sato, Shinichi; Nakao, Satoshi; Ban, Sadahiko; Namba, Koh (Kobe Municipal Central Hospital (Japan))

    1983-04-01

    The unusual case of a 15 year old boy with three discrete paraventricular germ-cell tumors is reported. The first tumor was located just lateral to the left thalamus and included a massive cystic part around it, the second tumor in the paraventricular region above the head of the left caudate nucleus and the third tumor in the medial part of the left parietal lobe. Total removal of all tumors was successfully accomplished in stages at four separate operations, namely, the first tumor was removed through the left transsylvian approach, the second tumor via left superior frontal gyrus and the third tumor via left superior frontal gyrus and left superior parietal lobule. Histological examination revealed that the first tumor was teratoma, the second was choriocarcinoma and the third was germinoma. Primary germ-cell tumors of the brain can be divided into 5 groups: 1) germinoma; 2) embryonal carcinoma; 3) choriocarcinoma; 4) yolk-sac tumor; or 5) teratoma. In this case, a combination of three different histological patterns was seen. If malignant germ-cell tumor is supected on CT, aggressive extirpation should be done, not only to determine the exact diagnosis, but also to provide the basis for subsequent adjunctive therapy.

  3. RNA-Sequencing of Primary Retinoblastoma Tumors Provides New Insights and Challenges Into Tumor Development

    Directory of Open Access Journals (Sweden)

    Sailaja V. Elchuri

    2018-05-01

    Full Text Available Retinoblastoma is rare tumor of the retina caused by the homozygous loss of the Retinoblastoma 1 tumor suppressor gene (RB1. Loss of the RB1 protein, pRB, results in de-regulated activity of the E2F transcription factors, chromatin changes and developmental defects leading to tumor development. Extensive microarray profiles of these tumors have enabled the identification of genes sensitive to pRB disruption, however, this technology has a number of limitations in the RNA profiles that they generate. The advent of RNA-sequencing has enabled the global profiling of all of the RNA within the cell including both coding and non-coding features and the detection of aberrant RNA processing events. In this perspective, we focus on discussing how RNA-sequencing of rare Retinoblastoma tumors will build on existing data and open up new area’s to improve our understanding of the biology of these tumors. In particular, we discuss how the RB-research field may be to use this data to determine how RB1 loss results in the expression of; non-coding RNAs, causes aberrant RNA processing events and how a deeper analysis of metabolic RNA changes can be utilized to model tumor specific shifts in metabolism. Each section discusses new opportunities and challenges associated with these types of analyses and aims to provide an honest assessment of how understanding these different processes may contribute to the treatment of Retinoblastoma.

  4. Extratumoral Heme Oxygenase-1 (HO-1 Expressing Macrophages Likely Promote Primary and Metastatic Prostate Tumor Growth.

    Directory of Open Access Journals (Sweden)

    Sofia Halin Bergström

    Full Text Available Aggressive tumors induce tumor-supporting changes in the benign parts of the prostate. One factor that has increased expression outside prostate tumors is hemoxygenase-1 (HO-1. To investigate HO-1 expression in more detail, we analyzed samples of tumor tissue and peritumoral normal prostate tissue from rats carrying cancers with different metastatic capacity, and human prostate cancer tissue samples from primary tumors and bone metastases. In rat prostate tumor samples, immunohistochemistry and quantitative RT-PCR showed that the main site of HO-1 synthesis was HO-1+ macrophages that accumulated in the tumor-bearing organ, and at the tumor-invasive front. Small metastatic tumors were considerably more effective in attracting HO-1+ macrophages than larger non-metastatic ones. In clinical samples, accumulation of HO-1+ macrophages was seen at the tumor invasive front, almost exclusively in high-grade tumors, and it correlated with the presence of bone metastases. HO-1+ macrophages, located at the tumor invasive front, were more abundant in bone metastases than in primary tumors. HO-1 expression in bone metastases was variable, and positively correlated with the expression of macrophage markers but negatively correlated with androgen receptor expression, suggesting that elevated HO-1 could be a marker for a subgroup of bone metastases. Together with another recent observation showing that selective knockout of HO-1 in macrophages reduced prostate tumor growth and metastatic capacity in animals, the results of this study suggest that extratumoral HO-1+ macrophages may have an important role in prostate cancer.

  5. The prognostic value of circulating tumor cells in patients with melanoma: a systematic review and meta-analysis.

    Science.gov (United States)

    Mocellin, Simone; Hoon, Dave; Ambrosi, Alessandro; Nitti, Donato; Rossi, Carlo Riccardo

    2006-08-01

    The detection of circulating tumor cells (CTC) in patients with melanoma represents an appealing prognostic tool, but no consensus exists on this topic. We aimed to comprehensively and quantitatively summarize the evidence for the use of CTC to predict patients' clinical outcome. Fifty-three studies enrolling 5,433 patients were reviewed. Correlation of CTC status with tumor-node-metastasis disease stage and patients' overall (OS) and progression-free (PFS) survival was assessed by means of association statistics and meta-analysis, respectively. CTC status correlated with both tumor-node-metastasis stage (stage I, 32%; stage II, 41.7%; stage III, 41.1%; stage IV, 47.4%; P(trend) < 0.0001) and survival (OS: hazard ratio, 2.42; 95% confidence interval, 1.7-3.45, P < 0.0001; PFS: hazard ratio, 2.45; 95% confidence interval, 1.78-3.38; P < 0.0001). However, statistical heterogeneity was significant for both OS and PFS, likely underscoring the wide variability in study design. Furthermore, CTC positivity rates in early stages were higher and in the metastatic setting were lower than expected, which indicates an unsatisfactory accuracy of currently available CTC detection assays. Our findings suggest that CTC might have a clinically valuable prognostic power in patients with melanoma. However, the heterogeneity of the studies thus far published warrants caution not to overestimate the favorable results of pooled data.

  6. [What future for circulating tumor DNA? Current data and prospects in colorectal, non-small cell lung and pancreatic cancers].

    Science.gov (United States)

    Pietrasz, Daniel; Pécuchet, Nicolas; Fabre, Elizabeth; Blons, Hélène; Chevalier, Line; Taly, Valérie; Laurent-Puig, Pierre; Bachet, Jean-Baptiste

    2016-01-01

    Ten years after the discovery of the predictive value of KRAS status for anti-EGFR antibodies, other genes involved in oncogenesis and therapeutic responses were identified and are now systematically sought. Molecular diagnosis often requires invasive procedures, sometimes iatrogenic, and is limited by feasibility problems, quantity and quality of samples. Identifying these mutations from blood biomarkers would reduce costs and diagnostic delay. The circulating tumor DNA (ctDNA) is one of the most promising blood biomarkers. In this review, we report and discuss the latest results obtained with ctDNA in colorectal cancer, non-small cell lung cancer, and adenocarcinoma of the pancreas. If the methods highlighting appear very heterogeneous, the correlation between mutations found in tumor and those identified in the blood exceeds 95 % specificity in numerous studies. The detection sensitivity is in turn strongly related to tumor stage patients. The presence of ctDNA appears as a prognostic factor for progression-free survival and overall survival. Finally, recent studies have shown that the changing rate ctDNA during systemic treatments had a predictive value for therapeutic efficacy. These results allow to consider the use of ctDNA in monitoring patients to identify early recurrence or progression. Copyright © 2015 Société Française du Cancer. Published by Elsevier Masson SAS. All rights reserved.

  7. Epithelial-mesenchymal transition: a hallmark in metastasis formation linking circulating tumor cells and cancer stem cells.

    Science.gov (United States)

    Książkiewicz, Magdalena; Markiewicz, Aleksandra; Zaczek, Anna J

    2012-01-01

    The occurrence of either regional or distant metastases is an indicator of poor prognosis for cancer patients. The mechanism of their formation has not yet been fully uncovered, which limits the possibility of developing new therapeutic strategies. Nevertheless, the discovery of circulating tumor cells (CTCs), which are responsible for tumor dissemination, and cancer stem cells (CSCs), required for tumor growth maintenance, shed light on the metastatic cascade. It seems that CTCs and CSCs are not necessarily separate populations of cancer cells, as CTCs generated in the process of epithelial-mesenchymal transition (EMT) can bear features characteristic of CSCs. This article describes the mechanisms of CTC and CSC formation and characterizes their molecular hallmarks. Moreover, we present different types of EMT occurring in physiological and pathological conditions, and we demonstrate its crucial role in providing CTCs with a CSC phenotype. The article delineates molecular changes acquired by cancer cells undergoing EMT that facilitate metastasis formation. Deeper understanding of those processes is of fundamental importance for the development of new strategies of early cancer detection and effective cancer treatment approaches that will be translated into clinical practice. Copyright © 2012 S. Karger AG, Basel.

  8. Primary malignant peripheral nerve sheath tumor at unusual location

    Directory of Open Access Journals (Sweden)

    Souvagya Panigrahi

    2013-01-01

    Full Text Available Malignant peripheral nerve sheath tumor (MPNST is a rare soft tissue sarcoma. Most arise in association with major nerve trunks. Their most common anatomical sites are the proximal portions of the upper and lower extremities and the trunk. MPNSTs have rarely been reported in literature to occur in other unusual body parts. We review all such cases reported till now in terms of site of origin, surgical treatment, adjuvant therapy and outcome and shortly describe our experience with two of these cases. Both of our case presented with lump at unusual sites resembling neurofibroma, one at orbitotemporal area and other in the paraspinal region with characteristic feature of neurofibroma with the exception that both had very short history of progression. They underwent gross total removal of the tumor with adjuvant radiotherapy postoperatively. At 6-month follow-up both are doing well with no evidence of recurrence.

  9. Telomerase Activity in Breast Tumor Tissues and its Possible use for Detection of Circulating Carcinoma Cells

    Czech Academy of Sciences Publication Activity Database

    Šimíčková, M.; Nekulová, M.; Pecen, Ladislav; Vagundová, M.; Maláska, J.; Obermannová, R.; Lauerová, L.

    2002-01-01

    Roč. 5, - (2002), s. 98 ISSN 1211-8869. [Central European Conference on Human Tumor Markers /4./. 13.02.2003-16.02.2003, Karlovy Vary] Institutional research plan: CEZ:AV0Z1030915 Keywords : telomerase activity * early detection of distant metastases * cancer reccurence Subject RIV: BB - Applied Statistics, Operational Research

  10. Direct detection of early-stage cancers using circulating tumor DNA

    DEFF Research Database (Denmark)

    Phallen, Jillian; Sausen, Mark; Adleff, Vilmos

    2017-01-01

    Early detection and intervention are likely to be the most effective means for reducing morbidity and mortality of human cancer. However, development of methods for noninvasive detection of early-stage tumors has remained a challenge. We have developed an approach called targeted error correction...

  11. Clinical implications of monitoring circulating tumor DNA in patients with colorectal cancer

    DEFF Research Database (Denmark)

    Schøler, Lone V; Reinert, Thomas; Ørntoft, Mai-Britt W

    2017-01-01

    .007). Changes in ctDNA levels induced by relapse intervention (n = 19) showed good agreement with changes in tumor volume (κ = 0.41; Spearman ρ = 0.4).Conclusions: Postoperative ctDNA detection provides evidence of residual disease and identifies patients at very high risk of relapse. Longitudinal surveillance...

  12. Correlation of primary tumor FDG uptake with histopathologic features of advanced gastric cancer

    International Nuclear Information System (INIS)

    Kim, Hae Won; Won, Kyoung Sook; Song, Bong Il; Kang, Yu Na

    2015-01-01

    Histopathologic features could affect the FDG uptake of primary gastric cancer and detection rate on FDG PET/CT. The aim of this study was to evaluate the FDG uptake of primary gastric cancer by correlating it with the histopathologic features of the tumors. Fifty patients with locally advanced gastric adenocarcinoma who were referred for preoperative FDG-PET/CT scans were enrolled in this study. The detection rate of PET/CT and maximum standardized uptake values (SUV max ) of the primary tumor were compared using the WHO, Lauren, Ming and Borrmann classifications and tumor size and location. In 45 of the 50 patients (90 %), the primary gastric tumors were detected by FDG PET/CT. On comparison using the WHO classification, the detection rate and SUV max of the tubular type were significantly higher than those of the poorly cohesive type. On comparison using the Lauren and Ming classifications, the SUV maxs of the intestinal type and expanding type were significantly higher than those of the diffuse and infiltrative type, respectively. On comparison using the Borrmann classification and tumor size and location, there was no significant difference in the detection rate and SUV max of primary gastric tumors. This study demonstrates that the poorly cohesive type according to the WHO classification, diffuse type according to the Lauren classification and infiltrative type according to the Ming classification have low FDG uptake in patients with locally advanced gastric carcinoma. Understanding the relationship between primary tumor FDG uptake and histopathologic features would be helpful in detecting the primary tumor by FDG PET/CT in patients with gastric cancer

  13. Interactions between atmospheric circulation, nutrient deposition, and tropical forest primary production (Invited)

    Science.gov (United States)

    Randerson, J. T.; Chen, Y.; Rogers, B. M.; Morton, D. C.; van der Werf, G.; Mahowald, N. M.

    2010-12-01

    Tropical forests influence regional and global climate by means of several pathways, including by modifying surface energy exchange and by forming clouds. High levels of precipitation, leaching, and soil weathering limit nutrient availability in these ecosystems. Phosphorus (P) is a key element limiting net primary production, and in some areas, including forests recovering from prior disturbance, nitrogen (N) also may limit some components of production. Here we quantified atmospheric P and N inputs to these forests from fires using satellite-derived estimates of emissions and atmospheric models. In Africa and South America, cross-biome transport of fire-emitted aerosols and reactive N gases from savannas and areas near the deforestation frontier increased deposition of P and N in interior forests. Equatorward atmospheric transport during the dry (fire) season in one hemisphere was linked with surface winds moving toward the inter-tropical convergence zone (ITCZ) in the other hemisphere. Deposition levels were higher in tropical forests in Africa than in South America because of large savanna areas with high levels of fire emissions in both southern and northern Africa. We conclude by describing a potential feedback loop by which equatorward transport of fire emissions, dust, and spores sustains the productivity of tropical forests. We specifically assessed evidence that savanna-to-forest atmospheric transport of nutrients increases forest productivity, height, and rates of evapotranspiration (ET). In parallel, we examined the degree to which increases in ET and surface roughness in tropical forests have the potential to strengthen several components of the Hadley circulation, including deep convection, equatorward return flow (near the surface), and the intensity of seasonal drought in the subtropics (thereby increasing fires). These interactions are important for understanding biogeochemical - climate interactions on millennial timescales and for quantifying how

  14. Surgical outcome of primary clipping for anterior circulation aneurysms of size 2 centimeters or larger.

    Science.gov (United States)

    Furtado, Sunil V; Saikiran, Narayanam A; Thakar, Sumit; Dadlani, Ravi; Mohan, Dilip; Aryan, Saritha; Hegde, Alangar S

    2014-07-01

    Aneurysms of the anterior circulation larger than 2cm have a complex relationship to the anterior skull base, requiring a multi-modality management approach. This retrospective study of 54 patients with such aneurysms who underwent clipping between 2001 and 2012 analyzes clinical and surgical data, aneurysm characteristics and correlates them with respect to the Glasgow outcome score at follow-up and immediate post-operative clinical status. Patients with an outcome score of 5 or 4 were categorized as "good", while those with score 3-1 were "poor". Fisher's exact test and paired T-test (p<0.5) were used to test statistical significance for discrete and continuous variables respectively. 44 (81.4%) patients had a good outcome. Patients with non-ophthalmic/paraclinoid aneurysms had significantly lower incidence of adverse intra-operative events (p=0.035). Patients older than 50 years (p=0.045), with adverse intra-operative events (p=0.015) and post-operative infarction (p<0.001) had a poor outcome compared to those younger than 50 years age and those without adverse intra-operative events or infarctions. The grouped age variable had maximum influence on patient outcome. Location and size of aneurysm did not have an overall impact on surgical outcome. There were 4 mortalities. Primary clipping of proximal non-cavernous aneurysms on the internal carotid artery is associated with adverse intra-operative events. A multi-modality treatment approach in these aneurysms should be individualized, more so in patients older than 50 years. Copyright © 2014 Elsevier B.V. All rights reserved.

  15. Gamma-knife radiosurgery for metastatic brain tumors from primary lung cancer

    International Nuclear Information System (INIS)

    Uchiyama, Bine; Satoh, Ken; Saijo, Yasuo

    1998-01-01

    Forty patients with metastatic brain tumors from primary lung cancer underwent radiosurgery (γ-knife). We retrospectively compared their prior treatment history, number of metastatic foci, and performance status, to evaluate the effects of, and indications for, γ-knife therapy. After both the primary and the metastatic tumors were controlled, performance status could be used as an index in the choice of γ-knife therapy. Our results demonstrate that repeated γ-knife radiosurgeries prolonged survival time. Gamma-knife radiosurgery improves quality of life and prognosis of patients with metastatic brain tumors. (author)

  16. Classification of primary lung tumors in dogs: 210 cases (1975-1985)

    International Nuclear Information System (INIS)

    Ogilvie, G.K.; Haschek, W.M.; Withrow, S.J.; Richardson, R.C.; Harvey, H.J.; Henderson, R.A.; Fowler, J.D.; Norris, A.M.; Tomlinson, J.; McCaw, D.

    1989-01-01

    Two hundred ten dogs that had primary lung tumors diagnosed between 1975 and 1985 were evaluated. The majority of the tumors were classified as adenocarcinoma (74.8%) and alveolar carcinoma (20%). The most common clinical signs of disease were cough (52%), dyspnea (23.8%), lethargy (18.1%), weight loss (12.4%), and tachypnea (4.8%). The clinical methods that were most successful in directly or indirectly leading to a diagnosis of primary lung tumor were thoracic radiography (77.1%) and cytologic examination of fine-needle aspirate specimens (24.8%)

  17. Brown tumor mimicking maxillary sinus mucocele as the first manifestation of primary hyperparathyroidism

    DEFF Research Database (Denmark)

    Guldfred, Liviu-Adelin; Daugaard, Søren; von Buchwald, Christian

    2012-01-01

    We describe the first case of brown tumor mimicking a maxillary sinus mucocele as the first manifestation of the patient's primary hyperparathyroidism. A 34-year old woman presented with a 14 days history of elevation of the right orbit, retrobulbar pain and cheek anesthesia. The CT and MR evalua...... either giant cell granuloma or brown tumor. The finding of hyperparathyroidism confirmed the diagnosis of brown tumor. To our knowledge, this is the first report of cystic brown tumor mimicking a mucocele of the maxillary sinus....

  18. Surgical Control of a Primary Hepatic Carcinoid Tumor: A Case Report

    Directory of Open Access Journals (Sweden)

    Norio Yokoigawa

    2009-04-01

    Full Text Available We report a primary hepatic carcinoid tumor occurring in a 47-year-old man. The patient consulted our hospital complaining of epigastralgia. Abdominal ultrasonography, computed tomography scanning, and magnetic resonance imaging showed a large mass in the right lobe of the liver. FDG-PET revealed 18F-FDG uptake by the right hepatic lobe. The tumor was a solid mass with cystic components, approximately 15 cm in diameter. We conducted an extended right lobectomy of the liver. The resected specimen was a solid tumor with cystic components and hemorrhagic lesion. Microscopic findings showed that the tumor cells had round nuclei and formed trabecular patterns. Immunohistologically, tumor cells were stained positive for chromogranin A, neuron specific enolase, CD56, and S-100. Careful examinations before and after the operation revealed no other possible origin of the tumor. Based on these findings, the tumor was diagnosed as a primary hepatic carcinoid. This is a report of a rare case of a primary hepatic carcinoid tumor with a discussion of several other relevant reports.

  19. Copy number variation analysis of matched ovarian primary tumors and peritoneal metastasis.

    Directory of Open Access Journals (Sweden)

    Joel A Malek

    Full Text Available Ovarian cancer is the most deadly gynecological cancer. The high rate of mortality is due to the large tumor burden with extensive metastatic lesion of the abdominal cavity. Despite initial chemosensitivity and improved surgical procedures, abdominal recurrence remains an issue and results in patients' poor prognosis. Transcriptomic and genetic studies have revealed significant genome pathologies in the primary tumors and yielded important information regarding carcinogenesis. There are, however, few studies on genetic alterations and their consequences in peritoneal metastatic tumors when compared to their matched ovarian primary tumors. We used high-density SNP arrays to investigate copy number variations in matched primary and metastatic ovarian cancer from 9 patients. Here we show that copy number variations acquired by ovarian tumors are significantly different between matched primary and metastatic tumors and these are likely due to different functional requirements. We show that these copy number variations clearly differentially affect specific pathways including the JAK/STAT and cytokine signaling pathways. While many have shown complex involvement of cytokines in the ovarian cancer environment we provide evidence that ovarian tumors have specific copy number variation differences in many of these genes.

  20. Rearrangement of a common cellular DNA domain on chromosome 4 in human primary liver tumors

    International Nuclear Information System (INIS)

    Pasquinelli, C.; Garreau, F.; Bougueleret, L.; Cariani, E.; Thiers, V.; Croissant, O.; Hadchouel, M.; Tiollais, P.; Brechot, C.; Grzeschik, K.H.

    1988-01-01

    Hepatitis B virus (HBV) DNA integration has been shown to occur frequently in human hepatocellular carcinomas. The authors have investigated whether common cellular DNA domains might be rearranged, possibly by HBV integration, in human primary liver tumors. Unique cellular DNA sequences adjacent to an HBV integration site were isolated from a patient with hepatitis B surface antigen-positive hepatocellular carcinoma. These probes detected rearrangement of this cellular region of chromosomal DNA in 3 of 50 additional primary liver tumors studied. Of these three tumor samples, two contained HBV DNA, without an apparent link between the viral DNA and the rearranged allele; HBV DNA sequences were not detected in the third tumor sample. By use of a panel of somatic cell hybrids, these unique cellular DNA sequences were shown to be located on chromosome 4. Therefore, this region of chromosomal DNA might be implicated in the formation of different tumors at one step of liver cell transformation, possible related to HBV integration

  1. Infratentorial brain tumors in children and adolescents - the significance of MRI in the diagnosis of primary and recurrent tumors

    International Nuclear Information System (INIS)

    Engelbrecht, V.; Kahn, T.; Moedder, U.

    1994-01-01

    MRI is the current method of choice for the diagnosis of infratentorial tumors in children and adolescents. The present article discusses the individual tumor entities on the basis of their magnetic resonance imaging characteristics in the patient pool of 1991/1992. New magnetic resonance imaging procedures are considered for infratentorial vascular anomalies. In addition to its use in the primary diagnosis, the significance of MRI for the detection of recurrences is discussed. Problems arising after prior surgery and irradiation as well as metastasization through CSF pathways are also mentioned. (orig.) [de

  2. Tumor pardo maxilar: Elemento diagnóstico de hiperparatiroidismo primario Maxillary brown tumor: A diagnostic tool for primary hyperparathyroidism

    Directory of Open Access Journals (Sweden)

    S. Gallana Álvarez

    2005-08-01

    Full Text Available El hiperparatiroidismo primario es un transtorno generalizado del metabolismo óseo producido por un aumento de la secreción de hormona paratiroidea (PTH. La etiología de este transtorno es múltiple; en la forma primaria la causa de la hipersecreción de la hormona es la propia glándula, y el motivo más frecuente el adenoma paratiroideo. Los tumores pardos son lesiones óseas focales secundarias a hiperparatiroidismo. El tratamiento de elección de los tumores pardos es la extirpación del adenoma de paratiroides, ya que la normalización de la función paratiroidea debería provocar una reducción del tamaño o desaparición del tumor. Presentamos un caso de tumor pardo mandibular en un paciente con hiperparatiroidismo primario, en el cual el tumor recidivó después de la extirpación del adenoma paratiroideo. La finalidad de la presentación de este caso es recordar el interés que para el cirujano oral y maxilofacial representan las manifestaciones orales de la patología sistémica.The primary hyperparathyroidism is a generalized disorder of the osseous metabolism, caused by hypersecretion of PTH. Hyperparathyroidism has a multiple etiology. In its primary form, the hypersecretion of the hormone is caused by the gland itself, the commonest reason being parathyroid adenoma. The treatment of first choice for brown tumor is the parathyroidectomy because the normalization of parathyroid function should lead to a reduction in size or disappearance of the tumor. We present a case of the brown tumor in the mandible and primary hyperparathyroidism in whom the tumor enlarged after removal of parathyroid adenoma. Upon presentation of this report, our aim is to bring forward the significance oral manifestations of systemic pathology has for oral and maxillofacial surgeons.

  3. The role of imaging for the surgeon in primary malignant bone tumors of the chest wall

    Energy Technology Data Exchange (ETDEWEB)

    Rocca, M., E-mail: michele.rocca@ior.it [General and Thoracic Surgery, The Rizzoli Orthopaedic Institute, Via Pupilli 1, 40136 Bologna (Italy); Salone, M. [General and Thoracic Surgery, The Rizzoli Orthopaedic Institute, Via Pupilli 1, 40136 Bologna (Italy); Galletti, S. [Ultrasound Unit, The Rizzoli Orthopaedic Institute, Bologna (Italy); Balladelli, A. [Laboratory of Experimental Oncology, The Rizzoli Orthopaedic Institute, Bologna (Italy); Vanel, D. [Research in Imaging Musculo Skeletal Tumors, The Rizzoli Orthopaedic Institute, Bologna (Italy); Briccoli, A. [General and Thoracic Surgery, The Rizzoli Orthopaedic Institute, Via Pupilli 1, 40136 Bologna (Italy)

    2013-12-01

    Primary malignant chest wall tumors are rare. The most frequent primary malignant tumor of the chest wall is chondrosarcoma, less common are primary bone tumors belonging to the Ewing Family Bone Tumors (EFBT), or even rarer are osteosarcomas. They represent a challenging clinical entities for surgeons as the treatment of choice for these neoplasms is surgical resection, excluding EFBT which are normally treated by a multidisciplinary approach. Positive margins after surgical procedure are the principal risk factor of local recurrence, therefore to perform adequate surgery a correct preoperative staging is mandatory. Imaging techniques are used for diagnosis, to determine anatomic site and extension, to perform a guided biopsy, for local and general staging, to evaluate chemotherapy response, to detect the presence of a recurrence. This article will focus on the role of imaging in guiding this often difficult surgery and the different technical possibilities adopted in our department to restore the mechanics of the thoracic cage after wide resections.

  4. [Extracorporeal circulation and hypothermy surgery in tumors with vena cava extension: 20 years experience at the University Clinic of Navarra].

    Science.gov (United States)

    Rioja Zuazu, J; Rodríguez-Rubio Cortadillas, F; Zudaire Bergera, J J; Saiz Sansi, A; Rosell Costa, D; Robles García, J E; Rábago, G; Berián Polo, J M

    2008-04-01

    We present our 20 years experience treating patients with vena cava extension in whom an extracorporeal circulation, hypothermia, cardio circulatory arrest (ECC-H-CCA) in order to perform, together with a tumoral resection, a thrombus resection. From 1985 to 2005 a total of 28 retroperitoneal tumor were treated: 25 renal cancers, a Wilms tumor, a paratesticular rabdomiosarcoma, and a pheocromocitoma. All of them had an extension by means of thrombus above the suprahepatics veins. All of them were treated by means of ECC-H-CCA for thrombus extraction. A descriptive study of the serie is performed as well as a Kaplan Meyer survival study. Surgical complications were present within 10 patients (35%), with a surgical mortality of two patients (7%): one intra-operatively because a massive embolism of the lungs and the other because of a lung embolism on the 4th post-operative day. Global actuarial survival was 29.1+/-10% at three years and 17.5+/-8% at five years. Analyzing only who do not have metastatic lesions, nor lymph nodes at diagnosis their three year survival was 50.9+/-16.3% and 32.2+/-16% at five years. Mean while those who have any metastatic lesion at diagnosis their three and five years survival was 20.8+/-12% and 10.4+/-9% respectively. The employ of surgical techniques with ECC-H-CCA with in oncological pathology associated with vena cava thrombus is justified and its employment does not worsen the survival; it is indicated because its results, allowing a complete tumoral resection in a safe and reproducible fashion.

  5. Primary intracranial tumors among atomic bomb survivors and controls, Hiroshima and Nagasaki, 1961-75

    International Nuclear Information System (INIS)

    Seyama, Shinichi; Ishimaru, Toranosuke; Iijima, Soichi; Mori, Kazuo.

    1980-02-01

    An analysis was made of the relationship of radiation dose to the occurrence of primary intracranial tumors among atomic bomb survivors and nonexposed controls, Hiroshima and Nagasaki, in the fixed cohort of the Life Span Study (LSS) extended sample during the period 1961-75, or 16 to 30 years after the A-bombs. Based on various medical sources, 104 cases of primary intracranial tumors were identified among approximately 99,000 LSS extended sample members who were alive as of 1 January 1961. Of these 104 cases, 45 had manifested clinical signs of brain tumors, but, 59 cases were identified incidentally at postmortem examination. The distributions of morphologic type, age, and size of tumor were quite different for those primary intracranial tumors with and without a clinical sign of brain tumor. Glioma was the most frequent type of tumor with a clinical sign and meningioma was the most frequent type without. In relation to radiation dose the incidence rate of primary intracranial tumors with a clinical sign showed a significant excess risk for males in the high dose group who received 100 rad or more after adjustment for age at the time of the bomb (ATB). The standardized relative risk is around 5 in this group. The data also suggest that the crude relative risk of glioma is greater in the high dose group for younger ages ATB. However, there is no increased risk in females. Among the 5,012 autopsy subjects in the LSS extended sample during 1961-75, there is no relationship between radiation dose and the prevalence rate of primary intracranial tumors in those identified incidentally by autopsy. The relative risk of subclinical adenoma of the pituitary gland between high dose subjects and controls was also examined for a sample of 95 sex- and age-matched pairs using Hiroshima autopsy materials for 1961-74, but no relationship to dose was observed. (author)

  6. Podoplanin expression in primary brain tumors induces platelet aggregation and increases risk of venous thromboembolism.

    Science.gov (United States)

    Riedl, Julia; Preusser, Matthias; Nazari, Pegah Mir Seyed; Posch, Florian; Panzer, Simon; Marosi, Christine; Birner, Peter; Thaler, Johannes; Brostjan, Christine; Lötsch, Daniela; Berger, Walter; Hainfellner, Johannes A; Pabinger, Ingrid; Ay, Cihan

    2017-03-30

    Venous thromboembolism (VTE) is common in patients with brain tumors, and underlying mechanisms are unclear. We hypothesized that podoplanin, a sialomucin-like glycoprotein, increases the risk of VTE in primary brain tumors via its ability to induce platelet aggregation. Immunohistochemical staining against podoplanin and intratumoral platelet aggregates was performed in brain tumor specimens of 213 patients (mostly high-grade gliomas [89%]) included in the Vienna Cancer and Thrombosis Study, a prospective observational cohort study of patients with newly diagnosed cancer or progressive disease aimed at identifying patients at risk of VTE. Platelet aggregation in response to primary human glioblastoma cells was investigated in vitro. During 2-year follow-up, 29 (13.6%) patients developed VTE. One-hundred fifty-one tumor specimens stained positive for podoplanin (33 high expression, 47 medium expression, 71 low expression). Patients with podoplanin-positive tumors had lower peripheral blood platelet counts ( P < .001) and higher D-dimer levels ( P < .001). Podoplanin staining intensity was associated with increasing levels of intravascular platelet aggregates in tumor specimens ( P < .001). High podoplanin expression was associated with an increased risk of VTE (hazard ratio for high vs no podoplanin expression: 5.71; 95% confidence interval, 1.52-21.26; P = 010), independent of age, sex, and tumor type. Podoplanin-positive primary glioblastoma cells induced aggregation of human platelets in vitro, which could be abrogated by an antipodoplanin antibody. In conclusion, high podoplanin expression in primary brain tumors induces platelet aggregation, correlates with hypercoagulability, and is associated with increased risk of VTE. Our data indicate novel insights into the pathogenesis of VTE in primary brain tumors. © 2017 by The American Society of Hematology.

  7. Resveratrol-Loaded Albumin Nanoparticles with Prolonged Blood Circulation and Improved Biocompatibility for Highly Effective Targeted Pancreatic Tumor Therapy

    Science.gov (United States)

    Geng, Tao; Zhao, Xia; Ma, Meng; Zhu, Gang; Yin, Ling

    2017-06-01

    Human serum albumin (HSA) is an intrinsic protein and important carrier that transports endogenous as well as exogenous substances across cell membranes. Herein, we have designed and prepared resveratrol (RV)-loaded HSA nanoparticles conjugating RGD (arginine-glycine-aspartate) via a polyethylene glycol (PEG) "bridge" (HRP-RGD NPs) for highly effective targeted pancreatic tumor therapy. HRP-RGD NPs possess an average size of 120 ± 2.6 nm with a narrow distribution, a homodisperse spherical shape, a RV encapsulation efficiency of 62.5 ± 4.21%, and a maximum RV release ratio of 58.4.2 ± 2.8% at pH 5.0 and 37 °C. In vitro biocompatibility of RV is improved after coating with HSA and PEG. Confocal fluorescence images show that HRP-RGD NPs have the highest cellular uptake ratio of 47.3 ± 4.6% compared to HRP NPs and HRP-RGD NPs with free RGD blocking, attributing to an RGD-mediated effect. A cell counting kit-8 (CCK-8) assay indicates that HRP-RGD NPs without RV (HP-RGD NPs) have nearly no cytotoxicity, but HRP-RGD NPs are significantly more cytotoxic to PANC-1 cells compared to free RV and HRP NPs in a concentration dependent manner, showing apoptotic morphology. Furthermore, with a formulated PEG and HSA coating, HRP-RGD NPs prolong the blood circulation of RV, increasing approximately 5.43-fold (t1/2). After intravenous injection into tumor-bearing mice, the content of HRP-RGD NPs in tumor tissue was proven to be approximately 3.01- and 8.1-fold higher than that of HRP NPs and free RV, respectively. Based on these results, HRP-RGD NPs were used in an in vivo anti-cancer study and demonstrated the best tumor growth suppression effect of all tested drugs with no relapse, high in vivo biocompatibility, and no significant systemic toxicity over 35 days treatment. These results demonstrate that HRP-RGD NPs with prolonged blood circulation and improved biocompatibility have high anti-cancer effects with promising future applications in cancer therapy.

  8. In vitro validation of an ultra-sensitive scanning fluorescence microscope for analysis of Circulating Tumor Cells

    DEFF Research Database (Denmark)

    Hillig, Thore; Nygaard, Ann-Britt; Nekiunaite, Laura

    2014-01-01

    Analysis of circulating tumor cells (CTC) holds promise of providing liquid biopsies from patients with cancer. However, current methods include enrichment procedures. We present a method (CytoTrack), where CTC from 7.5 mL of blood is stained, analyzed and counted by a scanning fluorescence...... microscope. The method was validated by breast cancer cells (MCF-7) spiked in blood from healthy donors. The number of cells spiked in each blood sample was exactly determined by cell sorter and performed in three series of three samples spiked with 10, 33 or 100 cells in addition with three control samples...... detect breast cancer cells in spiking experiments and should be tested on blood samples from breast cancer patients. The method could benefit from automation that could reduce the CV%, and further optimization of the procedure to increase the recovery....

  9. High circulating levels of tumor necrosis factor-alpha in centenarians are not associated with increased production in T lymphocytes

    DEFF Research Database (Denmark)

    Sandmand, Marie; Bruunsgaard, Helle; Kemp, Kåre

    2003-01-01

    BACKGROUND: Aging is characterized by increased inflammatory activity reflected by increased plasma levels of proinflammatory cytokines, concomitant with an altered cytokine profile of T lymphocytes. High plasma levels of tumor necrosis factor (TNF)-alpha are strongly associated with morbidity...... and mortality in elderly humans. However, the cellular source and mechanisms for the increased circulating TNF-alpha levels are unknown. OBJECTIVE: The aim of the present study was to investigate if high plasma levels of TNF-alpha are associated with increased production of TNF-alpha by T lymphocytes in elderly...... humans. METHODS: TNF-alpha production by CD4+ and CD8+ T lymphocytes was measured by flow cytometry following stimulation with phorbol 12-myristate 13-acetate and ionomycin in 28 young controls, 14, 81-year-olds and 25 centenarians. RESULTS: Plasma levels of TNF-alpha increased with increasing age...

  10. High expression of TRF2, SOX10, and CD10 in circulating tumor microemboli detected in metastatic melanoma patients. A potential impact for the assessment of disease aggressiveness.

    Science.gov (United States)

    Long, Elodie; Ilie, Marius; Bence, Coraline; Butori, Catherine; Selva, Eric; Lalvée, Salomé; Bonnetaud, Christelle; Poissonnet, Gilles; Lacour, Jean-Philippe; Bahadoran, Philippe; Brest, Patrick; Gilson, Eric; Ballotti, Robert; Hofman, Véronique; Hofman, Paul

    2016-06-01

    Circulating tumors cells (CTCs) can be detected in the blood of metastatic melanoma patients (MMPs) both as isolated circulating tumor cells (iCTCs) and circulating tumor microemboli (CTMs), but their clinical significance remains unknown. The aim of this work was to evaluate the prognostic impact in metastatic cutaneous melanoma of CTMs and iCTCs identified by a cytomorphological approach using the isolation by size of tumor cell (ISET) method. We characterized the phenotype of CTCs using anti-PS100, anti-SOX10, anti-CD10, and anti-TRF2 antibodies. 128 MMPs and 37 control healthy individuals with benign nevi were included in this study. Results were compared to the follow-up of patients. 109/128 (85%) MMPs showed CTCs, 44/128 (34%) with 2 to 6 CTMs and 65/128 (51%) with 4 to 9 iCTCs. PS100 expression was homogeneous in iCTCs and heterogeneous in CTMs. SOX10, CD10, and TRF2 were mainly expressed in CTMs. None of the control subjects demonstrated circulating malignant tumor cells. Overall survival was significantly decreased in patients with CTMs, independently of the therapeutic strategies. In conclusion, the presence of CTMs is an independent predictor of shorter survival from the time of diagnosis of MMPs. © 2016 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

  11. [Clinical analysis of 138 multiple primary cancers diagnosed of digestive system malignant tumor initially].

    Science.gov (United States)

    Lyu, J M; Xiong, H C; Wu, B; Zhou, X Q; Hu, J

    2018-02-23

    Objective: To study the clinical characteristics, strategy of treatment and prognosis of multiple primary cancers(MPC) diagnosed of digestive system malignant tumor firstly. Methods: From January, 2000 to December, 2015, the clinical, follow-up and prognostic data of 138 MPC patients diagnosed of digestive system malignant tumor firstly were retrospectively analyzed. Results: 138 cases were found in 10 580 cases with malignant tumors, and the incidence was 1.30%. There were 129 cases of duplex primary cancers, 8 cases of triple primary cancers and 1 case of quintuple primary cancers. The repetitive primary cancer was occurred in digestive system (61cases, 44.2%) most frequently, with the next in respiratory system (46 cases, 33.3%). 52.2% (72 cases) suffered second primary cancer in 2 years after first primary cancer diagnosed, and 75.4% (104 cases) in 5 years. The median overall survival in patients with all cancer lesions radically treated was 168 months, better than any other treatment (68 months, P digestive system malignant tumor most frequently occurred in the digestive system and respiratory system. More concern should be attracted in follow-up, especially in the first 5 years. The key to improve patient' prognosis was radical treatment to every primary cancer.

  12. Sensitive and Specific Biomimetic Lipid Coated Microfluidics to Isolate Viable Circulating Tumor Cells and Microemboli for Cancer Detection.

    Directory of Open Access Journals (Sweden)

    Jia-Yang Chen

    Full Text Available Here we presented a simple and effective membrane mimetic microfluidic device with antibody conjugated supported lipid bilayer (SLB "smart coating" to capture viable circulating tumor cells (CTCs and circulating tumor microemboli (CTM directly from whole blood of all stage clinical cancer patients. The non-covalently bound SLB was able to promote dynamic clustering of lipid-tethered antibodies to CTC antigens and minimized non-specific blood cells retention through its non-fouling nature. A gentle flow further flushed away loosely-bound blood cells to achieve high purity of CTCs, and a stream of air foam injected disintegrate the SLB assemblies to release intact and viable CTCs from the chip. Human blood spiked cancer cell line test showed the ~95% overall efficiency to recover both CTCs and CTMs. Live/dead assay showed that at least 86% of recovered cells maintain viability. By using 2 mL of peripheral blood, the CTCs and CTMs counts of 63 healthy and colorectal cancer donors were positively correlated with the cancer progression. In summary, a simple and effective strategy utilizing biomimetic principle was developed to retrieve viable CTCs for enumeration, molecular analysis, as well as ex vivo culture over weeks. Due to the high sensitivity and specificity, it is the first time to show the high detection rates and quantity of CTCs in non-metastatic cancer patients. This work offers the values in both early cancer detection and prognosis of CTC and provides an accurate non-invasive strategy for routine clinical investigation on CTCs.

  13. Clinical significance of circulating tumor cells (CTCs) with respect to optimal cut-off value and tumor markers in advanced/metastatic breast cancer.

    Science.gov (United States)

    Shiomi-Mouri, Yukako; Kousaka, Junko; Ando, Takahito; Tetsuka, Rie; Nakano, Shogo; Yoshida, Miwa; Fujii, Kimihito; Akizuki, Miwa; Imai, Tsuneo; Fukutomi, Takashi; Kobayashi, Katsumasa

    2016-01-01

    Although carcinoembryonic antigen (CEA) and cancer antigen 15-3 (CA15-3) are useful tumor markers (TMs) in metastatic breast cancer (MBC), circulating tumor cells (CTCs) are also detected in patients with advanced or metastatic breast cancer. We analyzed CTCs in MBC patients in order to establish the optimal cut-off value, to evaluate the prognostic utility of CTC count, and to clarify whether CTC count could provide information in addition to CEA and CA15-3. We studied 98 MBC patients enrolled between June 2007 and March 2013. To quantify CTCs, 7.5 ml of blood was collected and CEA and CA15-3 were measured simultaneously. CTCs were counted using the CellSearch™ System. The CTC count was dichotomized as 0 (CTC-negative) or ≥1 (CTC-positive). The clinical significance of CTCs was evaluated in terms of its relationship with levels of CEA and CA15-3. Associations between qualitative variables were evaluated using the chi-square test. In order to evaluate the predictive value of CTCs for advanced or metastatic breast cancer, multivariate Cox proportional hazards modeling was used to calculate hazard ratios. With a CTC cut-off value of 1, there were 53 (54.1 %) CTC-negative patients and 45 (45.9 %) CTC-positive patients. Patients in the CTC-positive group had worse survival than those in the CTC-negative group (p CEA and CA15-3.

  14. Impact of primary metastatic bone disease in germ cell tumors

    DEFF Research Database (Denmark)

    Oing, C; Oechsle, K; Necchi, A

    2017-01-01

    (multivariate Cox regression; HR, 0.32; P=0.011) with respective 2-year PFS and OS rates of 68% and 75% compared with 24% and 36% for non-seminoma patients. Conclusions: Outcome of GCT patients with primary metastatic bone disease is particularly poor in non-seminoma patients, even worse than the expected...

  15. Detection of circulating tumor lysate-reactive CD4+ T cells in melanoma patients

    DEFF Research Database (Denmark)

    Ladekarl, Morten; Agger, Ralf; Fleischer, Charlotte C

    2004-01-01

    PURPOSE: We wanted to study whether an allogeneic melanoma lysate would be a feasible stimulatory antigen source for detection of a peripheral CD4+ T-cell immune response in patients with medically untreated malignant melanoma. The lysate was produced from a melanoma cell line (FM3.29) which...... was found in 1 of 4 patients radically operated for localized disease, whereas no responders were seen among 7 healthy donors. The fraction of circulating lysate-activated T cells ranged from 0.0037% to 0.080% of the CD4+ population. A negative result of the assay was found occasionally, especially...... expresses high amounts of melanoma antigens. METHODS: Fresh peripheral blood was incubated with and without lysate for 6 h in the presence of anti-CD28/anti-CD49d MoAb (for costimulation). After flow cytometric estimation of the frequency of CD69+/IFN-gamma+ cells in the CD4+ population, the response...

  16. Complications Following Primary and Revision Transsphenoidal Surgeries for Pituitary Tumors

    Science.gov (United States)

    Krings, James G.; Kallogjeri, Dorina; Wineland, Andre; Nepple, Kenneth G.; Piccirillo, Jay F.; Getz, Anne E.

    2014-01-01

    Objective This study aimed to determine the incidence of major complications following both primary and revision transsphenoidal pituitary surgery. Major complications included endocrinopathic, skull base, orbital, hemorrhagic and thromboembolic complications, respiratory failure, and death. Secondarily, this study aimed to examine factors associated with the occurrence of complications. Study Design Retrospective cohort analysis of California and Florida all-payer databases from 2005-2008. Methods The major complication rate following both primary and revision transsphenoidal pituitary surgery was calculated. Bivariate analyses were performed to investigate the relationship of patient characteristics with complication occurrence, and a multivariate model was constructed to determine risk factors associated with these complications. Results 5,277 primary cases and 192 revision cases met inclusion criteria. There was a non-significant absolute difference of 3.09% (95% CI −11.00 to 16.14) between the rate of complications following primary (n=443; 8.39%) and revision (n=22; 11.46%) surgeries. Multivariate analyses showed that patients with Medicare (OR=1.74; 95% CI 1.17 to 2.61), Medicaid (OR=2.13; 95% CI 1.59 to 2.86), or a malignant neoplasm (OR=3.10; 95% CI 1.62 to 5.93) were more likely to have complications. Conclusions The rate of major complications following transsphenoidal pituitary surgery is lower than earlier retrospective reports. The overall complication rate following revision surgery was not significantly different from primary surgery. Insurance status and a diagnosis of a malignant neoplasm were associated with a higher rate of complications. PMID:25263939

  17. Application of detecting cerebrospinal fluid circulating tumor cells in the diagnosis of meningeal metastasis of non-small cell lung cancer

    OpenAIRE

    Rong JIANG; Chun-hua MA; Zi-long ZHU; Jin-duo LI; Bin WANG; Li-wei SUN; Yuan LÜ

    2014-01-01

    Objective To observe a new technology for the detection and enumeration of cerebrospinal fluid (CSF) circulating tumor cells (CTCs) in the diagnosis of non-small cell lung cancer (NSCLC) with meningeal metastasis (MM).  Methods Five cases of NSCLC with MM that were diagnosed by CSF cytology were selected, and 20 ml CSF samples were obtained by lumbar puncture for every patient. The tumor marker immunostaining-fluorescence in situ hybridization (TM-iFISH) technology was adapted to detect...

  18. Microarray profiling shows distinct differences between primary tumors and commonly used preclinical models in hepatocellular carcinoma

    International Nuclear Information System (INIS)

    Wang, Weining; Iyer, N. Gopalakrishna; Tay, Hsien Ts’ung; Wu, Yonghui; Lim, Tony K. H.; Zheng, Lin; Song, In Chin; Kwoh, Chee Keong; Huynh, Hung; Tan, Patrick O. B.; Chow, Pierce K. H.

    2015-01-01

    Despite advances in therapeutics, outcomes for hepatocellular carcinoma (HCC) remain poor and there is an urgent need for efficacious systemic therapy. Unfortunately, drugs that are successful in preclinical studies often fail in the clinical setting, and we hypothesize that this is due to functional differences between primary tumors and commonly used preclinical models. In this study, we attempt to answer this question by comparing tumor morphology and gene expression profiles between primary tumors, xenografts and HCC cell lines. Hep G2 cell lines and tumor cells from patient tumor explants were subcutaneously (ectopically) injected into the flank and orthotopically into liver parenchyma of Mus Musculus SCID mice. The mice were euthanized after two weeks. RNA was extracted from the tumors, and gene expression profiling was performed using the Gene Chip Human Genome U133 Plus 2.0. Principal component analyses (PCA) and construction of dendrograms were conducted using Partek genomics suite. PCA showed that the commonly used HepG2 cell line model and its xenograft counterparts were vastly different from all fresh primary tumors. Expression profiles of primary tumors were also significantly divergent from their counterpart patient-derived xenograft (PDX) models, regardless of the site of implantation. Xenografts from the same primary tumors were more likely to cluster together regardless of site of implantation, although heat maps showed distinct differences in gene expression profiles between orthotopic and ectopic models. The data presented here challenges the utility of routinely used preclinical models. Models using HepG2 were vastly different from primary tumors and PDXs, suggesting that this is not clinically representative. Surprisingly, site of implantation (orthotopic versus ectopic) resulted in limited impact on gene expression profiles, and in both scenarios xenografts differed significantly from the original primary tumors, challenging the long

  19. Digit ratio (2D:4D) in primary brain tumor patients: A case-control study.

    Science.gov (United States)

    Bunevicius, Adomas; Tamasauskas, Sarunas; Deltuva, Vytenis Pranas; Tamasauskas, Arimantas; Sliauzys, Albertas; Bunevicius, Robertas

    2016-12-01

    The second-to-fourth digit ratio (2D:4D) reflects prenatal estrogen and testosterone exposure, and is established in utero. Sex steroids are implicated in development and progression of primary brain tumors. To investigate whether there is a link between 2D:4D ratio and primary brain tumors, and age at presentation. Digital images of the right and left palms of 85 primary brain tumor patients (age 56.96±13.68years; 71% women) and 106 (age 54.31±13.68years; 68% women) gender and age matched controls were obtained. The most common brain tumor diagnoses were meningioma (41%), glioblastoma (20%) and pituitary adenoma (16%). Right and left 2D:4D ratios, and right minus left 2D:4D (D r-l ) were compared between patients and controls, and were correlated with age. Right and left 2D:4D ratios were significantly lower in primary brain tumor patients relative to controls (t=-4.28, pbrain tumor patients and controls (p=0.27). In meningioma and glioma patients, age at presentation correlated negatively with left 2D:4D ratio (rho=-0.42, p=0.01 and rho=-0.36, p=0.02, respectively) and positively with D r-l (rho=0.45, p=0.009 and rho=0.65, p=0.04, respectively). Right and left hand 2D:4D ratios are lower in primary brain tumor patients relative to healthy individuals suggesting greater prenatal testosterone and lower prenatal estrogen exposure in brain tumor patients. Greater age at presentation is associated with greater D r-l and with lower left 2D:4D ratio of meningioma and glioma patients. Due to small sample size our results should be considered preliminary and interpreted with caution. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  20. A Cancer Cell-Activatable Aptamer-Reporter System for One-Step Assay of Circulating Tumor Cells

    Directory of Open Access Journals (Sweden)

    Zihua Zeng

    2014-01-01

    Full Text Available The current antibody-mediated numeration assays of circulating tumor cells (CTCs require multiple steps and are time-consuming. To overcome these technical limitations, a cancer cell-activatable aptamer-reporter was formulated by conjugating a biomarker-specific aptamer sequence with paired fluorochrome-quencher molecules. In contrast to the antibody probes, the intact aptamer-reporter was optically silent in the absence of cells of interest. However, when used in an assay, the aptamer selectively targeted cancer cells through interaction with a specific surface biomarker, which triggered internalization of the aptamer-reporter and, subsequently, into cell lysosomes. Rapid lysosomal degradation of the aptamer-reporter resulted in separation of the paired fluorochrome-quencher molecules. The released fluorochrome emitted bright fluorescent signals exclusively within the targeted cancer cells, with no background noise in the assay. Thus, the assays could be completed in a single step within minutes. By using this one-step assay, CTCs in whole blood and marrow aspirate samples of patients with lymphoma tumors were selectively highlighted and rapidly detected with no off-target signals from background blood cells. The development of the cancer cell-activatable aptamer-reporter system allows for the possibility of a simple and robust point-of-care test for CTC detection, which is currently unavailable.

  1. Diagnostic value of circulating tumor cell detection in bladder and urothelial cancer: systematic review and meta-analysis

    International Nuclear Information System (INIS)

    Msaouel, Pavlos; Koutsilieris, Michael

    2011-01-01

    The diagnostic value and prognostic significance of circulating tumor cell (CTC) detection in patients with bladder cancer is controversial. We performed a meta-analysis to consolidate current evidence regarding the use of CTC detection assays to diagnose bladder and other urothelial cancers and the association of CTC positivity with advanced, remote disease. Studies that investigated the presence of CTCs in the peripheral blood of patients with bladder cancer and/or urothelial cancer were identified and reviewed. Sensitivities, specificities, and positive (LR+) and negative likelihood ratios (LR-) of CTC detection in individual studies were calculated and meta-analyzed by random effects model. Overall odds ratio of CTC positivity in patients with advanced disease versus those with organ-confined cancer was also calculated. Overall sensitivity of CTC detection assays was 35.1% (95%CI, 32.4-38%); specificity, LR+, and LR- was 89.4% (95%CI, 87.2-91.3%), 3.77 (95%CI, 1.95-7.30) and 0.72 (95%CI, 0.64-0.81). CTC-positive patients were significantly more likely to have advanced (stage III-IV) disease compared with CTC-negative patients (OR, 5.05; 95%CI, 2.49-10.26). CTC evaluation can confirm tumor diagnosis and identify patients with advanced bladder cancer. However, due to the low overall sensitivity, CTC detection assays should not be used as initial screening tests

  2. Expression of E-selectin ligands on circulating tumor cells: cross-regulation with cancer stem cell regulatory pathways?

    International Nuclear Information System (INIS)

    Burdick, Monica M.; Henson, Karissa A.; Delgadillo, Luis F.; Choi, Young Eun; Goetz, Douglas J.; Tees, David F. J.; Benencia, Fabian

    2012-01-01

    Although significant progress has been made in the fight against cancer, successful treatment strategies have yet to be developed to combat those tumors that have metastasized to distant organs. Poor characterization of the molecular mechanisms of cancer spread is a major impediment to designing predictive diagnostics and effective clinical interventions against late stage disease. In hematogenous metastasis, it is widely suspected that circulating tumor cells (CTCs) express specific adhesion molecules that actively initiate contact with the vascular endothelium lining the vessel walls of the target organ. This “tethering” is mediated by ligands expressed by CTCs that bind to E-selectin expressed by endothelial cells. However, it is currently unknown whether expression of functional E-selectin ligands on CTCs is related to cancer stem cell regulatory or maintenance pathways, particularly epithelial-to-mesenchymal transition and the reverse, mesenchymal-to-epithelial transition. In this hypothesis and theory article, we explore the potential roles of these mechanisms on the dynamic regulation of selectin ligands mediating CTC trafficking during metastasis.

  3. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

    International Nuclear Information System (INIS)

    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen; Haberer, Thomas; Jaekel, Oliver

    2013-01-01

    To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications

  4. Proton and carbon ion radiotherapy for primary brain tumors and tumors of the skull base

    Energy Technology Data Exchange (ETDEWEB)

    Combs, Stephanie E.; Kessel, Kerstin; Habermehl, Daniel; Debus, Jurgen [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany)], e-mail: Stephanie.Combs@med.uni-heidelberg.de; Haberer, Thomas [Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany); Jaekel, Oliver [Univ. Hospital of Heidelberg, Dept. of Radiation Oncology, Heidelberg (Germany); Heidelberger Ionenstrahl Therapiezentrum (HIT), Heidelberg (Germany)

    2013-10-15

    To analyze clinical concepts, toxicity and treatment outcome in patients with brain and skull base tumors treated with photons and particle therapy. Material and methods: In total 260 patients with brain tumors and tumors of the skull base were treated at the Heidelberg Ion Therapy Center (HIT). Patients enrolled in and randomized within prospective clinical trials as well as bony or soft tissue tumors are not included in this analysis. Treatment was delivered as protons, carbon ions, or combinations of photons and a carbon ion boost. All patients are included in a tight follow-up program. The median follow-up time is 12 months (range 2-39 months). Results: Main histologies included meningioma (n = 107) for skull base lesions, pituitary adenomas (n = 14), low-grade gliomas (n = 51) as well as high-grade gliomas (n = 55) for brain tumors. In all patients treatment could be completed without any unexpected severe toxicities. No side effects > CTC Grade III were observed. To date, no severe late toxicities were observed, however, for endpoints such as secondary malignancies or neuro cognitive side effects follow-up time still remains too short. Local recurrences were mainly seen in the group of high-grade gliomas or atypical meningiomas; for benign skull base meningiomas, to date, no recurrences were observed during follow-up. Conclusion: The specific benefit of particle therapy will potentially reduce the risk of secondary malignancies as well as improve neuro cognitive outcome and quality of life (QOL); thus, longer follow-up will be necessary to confirm these endpoints. Indication-specific trials on meningiomas and gliomas are underway to elucidate the role of protons and carbon ions in these indications.

  5. Isolation of circulating tumor cells using photoacoustic flowmetry and two phase flow

    Science.gov (United States)

    O'Brien, Christine M.; Rood, Kyle D.; Gupta, Sagar K.; Mosley, Jeffrey D.; Goldschmidt, Benjamin S.; Sharma, Nikhilesh; Sengupta, Shramik; Viator, John A.

    2011-03-01

    Melanoma is the deadliest form of skin cancer, yet current diagnostic methods are inadequately sensitive. Patients must wait until secondary tumors form before malignancy can be diagnosed and treatment prescribed. Detection of cells that have broken off the original tumor and flow through the blood or lymph system can provide data for diagnosing and monitoring cancer. Our group utilizes the photoacoustic effect to detect metastatic melanoma cells, which contain the pigmented granule melanin. As a rapid laser pulse irradiates melanoma, the melanin undergoes thermo-elastic expansion and ultimately creates a photoacoustic wave. Thus, melanoma patient's blood samples can be enriched, leaving the melanoma in a white blood cell (WBC) suspension. Irradiated melanoma cells produce photoacoustic waves, which are detected with a piezoelectric transducer, while the optically transparent WBCs create no signals. Here we report an isolation scheme utilizing two-phase flow to separate detected melanoma from the suspension. By introducing two immiscible fluids through a t-junction into one flow path, the analytes are compartmentalized. Therefore, the slug in which the melanoma cell is located can be identified and extracted from the system. Two-phase immiscible flow is a label free technique, and could be used for other types of pathological analytes.

  6. 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

  7. Neratinib Efficacy and Circulating Tumor DNA Detection of HER2 Mutations in HER2 Nonamplified Metastatic Breast Cancer.

    Science.gov (United States)

    Ma, Cynthia X; Bose, Ron; Gao, Feng; Freedman, Rachel A; Telli, Melinda L; Kimmick, Gretchen; Winer, Eric; Naughton, Michael; Goetz, Matthew P; Russell, Christy; Tripathy, Debu; Cobleigh, Melody; Forero, Andres; Pluard, Timothy J; Anders, Carey; Niravath, Polly Ann; Thomas, Shana; Anderson, Jill; Bumb, Caroline; Banks, Kimberly C; Lanman, Richard B; Bryce, Richard; Lalani, Alshad S; Pfeifer, John; Hayes, Daniel F; Pegram, Mark; Blackwell, Kimberly; Bedard, Philippe L; Al-Kateb, Hussam; Ellis, Matthew J C

    2017-10-01

    Purpose: Based on promising preclinical data, we conducted a single-arm phase II trial to assess the clinical benefit rate (CBR) of neratinib, defined as complete/partial response (CR/PR) or stable disease (SD) ≥24 weeks, in HER2 mut nonamplified metastatic breast cancer (MBC). Secondary endpoints included progression-free survival (PFS), toxicity, and circulating tumor DNA (ctDNA) HER2 mut detection. Experimental Design: Tumor tissue positive for HER2 mut was required for eligibility. Neratinib was administered 240 mg daily with prophylactic loperamide. ctDNA sequencing was performed retrospectively for 54 patients (14 positive and 40 negative for tumor HER2 mut ). Results: Nine of 381 tumors (2.4%) sequenced centrally harbored HER2 mut (lobular 7.8% vs. ductal 1.6%; P = 0.026). Thirteen additional HER2 mut cases were identified locally. Twenty-one of these 22 HER2 mut cases were estrogen receptor positive. Sixteen patients [median age 58 (31-74) years and three (2-10) prior metastatic regimens] received neratinib. The CBR was 31% [90% confidence interval (CI), 13%-55%], including one CR, one PR, and three SD ≥24 weeks. Median PFS was 16 (90% CI, 8-31) weeks. Diarrhea (grade 2, 44%; grade 3, 25%) was the most common adverse event. Baseline ctDNA sequencing identified the same HER2 mut in 11 of 14 tumor-positive cases (sensitivity, 79%; 90% CI, 53%-94%) and correctly assigned 32 of 32 informative negative cases (specificity, 100%; 90% CI, 91%-100%). In addition, ctDNA HER2 mut variant allele frequency decreased in nine of 11 paired samples at week 4, followed by an increase upon progression. Conclusions: Neratinib is active in HER2 mut , nonamplified MBC. ctDNA sequencing offers a noninvasive strategy to identify patients with HER2 mut cancers for clinical trial participation. Clin Cancer Res; 23(19); 5687-95. ©2017 AACR . ©2017 American Association for Cancer Research.

  8. Primary intraosseous smooth muscle tumor of uncertain malignant potential: original report and molecular characterization

    Directory of Open Access Journals (Sweden)

    Lauren Kropp

    2016-11-01

    Full Text Available We report the first case of primary intraosseous smooth muscle tumor of uncertain malignant potential (STUMP which is analogous to borderline malignant uterine smooth muscle tumors so designated. The tumor presented in the femur of an otherwise healthy 30-year-old woman. Over a 3-year period, the patient underwent 11 biopsies or resections and 2 cytologic procedures. Multiple pathologists reviewed the histologic material including musculoskeletal pathologists but could not reach a definitive diagnosis. However, metastases eventually developed and were rapidly progressive and responsive to gemcitabine and docetaxel. Molecular characterization and ultrastructural analysis was consistent with smooth muscle origin, and amplification of unmutated chromosome 12p and 12q segments appears to be the major genomic driver of this tumor. Primary intraosseous STUMP is thought to be genetically related to leiomyosarcoma of bone, but likely representing an earlier stage of carcinogenesis. Wide excision and aggressive followup is warranted for this potentially life-threatening neoplasm.

  9. Primary Intraosseous Smooth Muscle Tumor of Uncertain Malignant Potential: Original Report and Molecular Characterization.

    Science.gov (United States)

    Kropp, Lauren; Siegal, Gene P; Frampton, Garrett M; Rodriguez, Michael G; McKee, Svetlana; Conry, Robert M

    2016-11-17

    We report the first case of primary intraosseous smooth muscle tumor of uncertain malignant potential (STUMP) which is analogous to borderline malignant uterine smooth muscle tumors so designated. The tumor presented in the femur of an otherwise healthy 30-year-old woman. Over a 3-year period, the patient underwent 11 biopsies or resections and 2 cytologic procedures. Multiple pathologists reviewed the histologic material including musculoskeletal pathologists but could not reach a definitive diagnosis. However, metastases eventually developed and were rapidly progressive and responsive to gemcitabine and docetaxel. Molecular characterization and ultrastructural analysis was consistent with smooth muscle origin, and amplification of unmutated chromosome 12p and 12q segments appears to be the major genomic driver of this tumor. Primary intraosseous STUMP is thought to be genetically related to leiomyosarcoma of bone, but likely representing an earlier stage of carcinogenesis. Wide excision and aggressive follow-up is warranted for this potentially life-threatening neoplasm.

  10. Primary Neuroendocrine Tumor of Vulva: A Case Report

    Directory of Open Access Journals (Sweden)

    Shaghayegh kamian

    2018-02-01

    Full Text Available Vulvar cancer is a rare malignancy representing less than 1% of the cancers, which is diagnosed in women with a high incidence of local recurrence and distant metastasis and carries a poor prognosis. We presented a 51-year-old woman with a lesion in the vulva appeared for three months. The lesion was large, ulcerative, hemorrhagic, tender, and mobile with no lymphadenopathy. Excisional biopsy demonstrated a high-grade malignant neoplasm with lymphovascular invasion. Based on the immunohistochemistry test, the patient was diagnosed with neuroendocrine carcinoma with poorly differentiated tumor. In the diagnostic workup, there were two small lymph nodes on the left inguinal area. The patient was subjected to radical vulvectomy and bilateral illioinguinal lymphadenectomy. In addition, she was prescribed to undergo adjuvant chemotherapy for three cycles. Subsequently, she was given hyperfractionated radiotherapy in the pelvis and bilateral inguinals  concurrently with chemotherapy. In the last follow-up visit in 32 months later, the patient was disease-free in the physical examination, and the laboratory tests and imaging findings were normal.

  11. Protein structure of fetal antigen 1 (FA1). A novel circulating human epidermal-growth-factor-like protein expressed in neuroendocrine tumors and its relation to the gene products of dlk and pG2

    DEFF Research Database (Denmark)

    Jensen, Charlotte Harken; Krogh, Thomas N; Højrup, Peter

    1994-01-01

    The present paper describes the primary structure, glycosylation and tissue localization of fetal antigen 1 (FA1) isolated from second-trimester human amniotic fluid. FA1 is a single-chained, heterogeneous glycoprotein of 225-262 amino acid residues. FA1 has six well conserved epidermal...... extends with minor corrections to the human adrenal-specific mRNA, pG2 as well. Immunohistochemical analysis demonstrated the presence of FA1 in 10 out of 14 lung tumors containing neuroendocrine elements, and in the placental villi where FA1 was exclusively seen in stromal cells in close contact...... to the vascular structure. In the pancreas, FA1 co-localized with insulin in the insulin secretory granules of the beta cells within the islets of Langerhans. Our findings suggest that FA1 is synthesized as a membrane anchored protein and released into the circulation after enzymic cleavage, and that circulating...

  12. Molecular characterization of circulating tumor cells from patients with metastatic breast cancer reflects evolutionary changes in gene expression under the pressure of systemic therapy

    Czech Academy of Sciences Publication Activity Database

    Aaltonen, K. E.; Novosadová, Vendula; Bendahl, P.-O.; Graffman, C.; Larsson, A.-M.; Ryden, L.

    2017-01-01

    Roč. 8, č. 28 (2017), s. 45544-45565 ISSN 1949-2553 Institutional support: RVO:86652036 Keywords : metastatic breast cancer * circulating tumor cells * gene expression Subject RIV: EB - Genetics ; Molecular Biology OBOR OECD: Genetics and heredity (medical genetics to be 3) Impact factor: 5.168, year: 2016

  13. Primary oral and nasal transmissible venereal tumor in a mix-breed dog

    OpenAIRE

    Rezaei, Mahdieh; Azizi, Shahrzad; Shahheidaripour, Shima; Rostami, Sara

    2016-01-01

    Transmissible venereal tumor (TVT) is a coitally transmitted tumor of dogs with widespread distribution. The present study describes the occurrence of the primary oral and nasal TVT in a 10-year-old, female, mix-breed dog. The case was presented with a history of anorexia, inability to swallow and dyspnea. Clinical examinations revealed the emaciation, muzzle deformity due to the presence of a friable, fleshy, cauliflower-like mass in the oral cavity and submandibular lymphadenopathy. TVT was...

  14. Radiological contribution in the treatment of primary and secondary liver tumors

    International Nuclear Information System (INIS)

    Mathias, K.; Hoffmann, G.; Loeffler, T.; Hausamen, T.

    1986-01-01

    The prognosis of patients with primary and secondary liver tumors has been improved recently by more aggressive operative, chemotherapeutic and embolization treatment. In a personal series of 40 patients with liver metastases colorectal cancer, regional intraarterial chemotherapy was superior to systematic intravenous treatment, with a tumor remission rate in 66% in comparison to 48% of the cases. But the benefit of intraarterial chemotherapy is still questionable considering the higher complication rate and the absence of prognostic data of the procedure. (orig.) [de

  15. Primary Neuroendocrine Tumor of the Left Hepatic Duct: A Case Report with Review of the Literature

    Directory of Open Access Journals (Sweden)

    Ajay H. Bhandarwar

    2012-01-01

    Full Text Available Primary Biliary Tract Neuroendocrine tumors (NET are extremely rare tumors with only 77 cases been reported in the literature till now. We describe a case of a left hepatic duct NET and review the literature for this rare malignancy. To the best of our knowledge the present case is the first reported case of a left hepatic duct NET in the literature. In spite of availability of advanced diagnostic tools like Computerized Tomography (CT Scan and Endoscopic Retrograde Cholangio Pancreaticography (ERCP a definitive diagnosis of these tumors is possible only after an accurate histopathologic diagnosis of operative specimens with immunohistochemistry and electron microscopy. Though surgical excision remains the gold standard treatment for such tumors, patients with unresectable tumors have good survival with newer biologic agents like Octreotride.

  16. Pancreatic neuroendocrine tumor - incidental finding during a follow-up CT for primary ovarian carcinoma

    International Nuclear Information System (INIS)

    Ivanova, D.; Balev, B.

    2013-01-01

    Pancreatic neuroendocrine tumors (PNET) are primary, usually we 11-differentiated pancreatic tumors. Their origin is not fully understood, but they are thought to develop from the pluripotent cells in the exocrine part of the pancreas. PNET are a heterogeneous group with different malignant potential. In some of the patients with sporadical forms of PNET there is association with other malignancies such as ovarian cancer, breast cancer, bladder and prostate cancers. We present a case of 50-year-old woman, with incidentally found pancreatic neoplasm, during a follow-up CT for ovarian cancer. Laparotomy and pancreatic biopsy are performed. Histological diagnosis confirms a well- differentiated endocrine tumor of the pancreas. (authors)

  17. Primary dorsal spine primitive neuroectodermal tumor in an adult patient: Case report and literature review

    Directory of Open Access Journals (Sweden)

    Satyashiva Munjal

    2017-01-01

    Full Text Available Primary spinal primitive neuroectodermal tumor (psPNET is a rare entity with few cases reported in literature. We report a case of a 50-year-old female who presented to us with paraplegia and was diagnosed with extradural dorsal spine psPNET. The diagnosis was not suspected at presentation or on radiology but was established on histopathological examination. It is important to distinguish it from central nervous system primitive neuroectodermal tumors and from other spinal tumors since it follows a different clinical course and therapeutic outcome.

  18. The clinical pathological features, diagnosis, treatment and prognosis of small intestine primary malignant tumors.

    Science.gov (United States)

    Guo, Xiaochuan; Mao, Zhiyuan; Su, Dan; Jiang, Zhaocai; Bai, Li

    2014-04-01

    The aim of the study was to describe and analyze the clinicopathological features and diagnosis of Chinese patients with small intestine primary malignant tumors and to explore the best therapy to small bowel adenocarcinoma (SBA). More than 26,000 patients with digestive tract malignant tumors received treatment in PLA hospital from 2000 to 2011, and among them, there were 887 patients who had small intestine primary malignant tumors, and 666 of 887 patients had the completed basic clinical documents. We retrospectively analyzed the correlation between clinical and pathological features of the 666 patients and analyzed the survival and prognosis of 173 SBA patients with follow-up data. Both the number of patients with primary malignant tumors of the small intestine and the number of patients who received chemotherapy showed an increasing trend. The ratio of male to female was 1.58:1. The male patients significantly exceed the female patients with tumors of non-ampullary duodenum, jejunum and duodenal ampulla; and most of the patients are over 60 years of age. For patients burdened with either of the pathological types of tumors, the males exceeded the females, but there was no significant difference. Abdominal pain was the main clinical manifestation for patients with tumors of non-ampullary duodenum, jejunum and ileum, and the most common clinical manifestations were jaundice and abdominal pain for patients with ampullary duodenal tumors, adenocarcinoma, neuroendocrine tumors and sarcoma. In addition, patients with stromal tumors were prone to gastrointestinal bleeding. Gastrointestinal endoscopy was the most common examinational procedure. Patients under 60 years of age were prone to surgery and chemotherapy after surgery, and patients over 60 years of age were prone to supportive treatment and chemotherapy without surgery. The medium overall survival of patients who received surgery without chemotherapy, chemotherapy after surgery, chemotherapy without surgery

  19. A case of primary neuroendcrine tumor of liver with FDG accumulation by PET/CT

    International Nuclear Information System (INIS)

    Okumura, Yoshihiro; Kishi, Ryotaro; Uka, Mayu; Tsuchihashi, Kazuyo; Hyodo, Takeshi; Takakura, Norihisa; Iguchi, Toshihiro; Kanazawa, Susumu

    2014-01-01

    We report an 80's male with primary hepatic neuroendcrine tumor without clinical symptom. dynamic contrast CT showed a hypervascular tumor at S5 of the liver. EOB-MRI showed high intensity on T2WI, low intensity on T1WI, the hepatic phase and the diffusion weighted image. It showed high FDG accumulation. Pathological examination confirmed neuroendcrine tumor of liver, G2 stage, and owing to the CD56 positive, 12.6% at MIB-1 index, with a little necrosis, no capsule and hemorrhage. (author)

  20. Single cells from human primary colorectal tumors exhibit polyfunctional heterogeneity in secretions of ELR+ CXC chemokines.

    Science.gov (United States)

    Adalsteinsson, Viktor A; Tahirova, Narmin; Tallapragada, Naren; Yao, Xiaosai; Campion, Liam; Angelini, Alessandro; Douce, Thomas B; Huang, Cindy; Bowman, Brittany; Williamson, Christina A; Kwon, Douglas S; Wittrup, K Dane; Love, J Christopher

    2013-10-01

    Cancer is an inflammatory disease of tissue that is largely influenced by the interactions between multiple cell types, secreted factors, and signal transduction pathways. While single-cell sequencing continues to refine our understanding of the clonotypic heterogeneity within tumors, the complex interplay between genetic variations and non-genetic factors ultimately affects therapeutic outcome. Much has been learned through bulk studies of secreted factors in the tumor microenvironment, but the secretory behavior of single cells has been largely uncharacterized. Here we directly profiled the secretions of ELR+ CXC chemokines from thousands of single colorectal tumor and stromal cells, using an array of subnanoliter wells and a technique called microengraving to characterize both the rates of secretion of several factors at once and the numbers of cells secreting each chemokine. The ELR+ CXC chemokines are highly redundant, pro-angiogenic cytokines that signal via the CXCR1 and CXCR2 receptors, influencing tumor growth and progression. We find that human primary colorectal tumor and stromal cells exhibit polyfunctional heterogeneity in the combinations and magnitudes of secretions for these chemokines. In cell lines, we observe similar variance: phenotypes observed in bulk can be largely absent among the majority of single cells, and discordances exist between secretory states measured and gene expression for these chemokines among single cells. Together, these measures suggest secretory states among tumor cells are complex and can evolve dynamically. Most importantly, this study reveals new insight into the intratumoral phenotypic heterogeneity of human primary tumors.

  1. Contemporary Role of Radiotherapy in the Management of Primary Penile Tumors and Metastatic Disease.

    Science.gov (United States)

    Crook, Juanita

    2016-11-01

    Squamous cell cancer of the penis is a radiocurable malignancy all too often managed solely by partial or total penectomy. Effective management of the primary tumor while preserving penile morphology and function is a priority. External radiotherapy and brachytherapy have a role to play in the definitive management of the primary tumor. Surgical nodal staging remains a cornerstone of management because it is the strongest predictor of survival, and inguinal status determines pelvic management. Postoperative radiotherapy of the regional nodes for high-risk pathology is indicated. Chemoradiotherapy should be considered as neoadjuvant treatment for unresectable nodes or as definitive management. Copyright © 2016 Elsevier Inc. All rights reserved.

  2. Circulating tumor DNA changes for early monitoring of anti-PD1 immunotherapy: a proof-of-concept study.

    Science.gov (United States)

    Cabel, L; Riva, F; Servois, V; Livartowski, A; Daniel, C; Rampanou, A; Lantz, O; Romano, E; Milder, M; Buecher, B; Piperno-Neumann, S; Bernard, V; Baulande, S; Bieche, I; Pierga, J Y; Proudhon, C; Bidard, F-C

    2017-08-01

    Recent clinical results support the use of new immune checkpoint blockers (ICB), such as anti-PD-1 (e.g. nivolumab and pembrolizumab) and anti-PD-L1 antibodies. Radiological evaluation of ICB efficacy during therapy is challenging due to tumor immune infiltration. Changes of circulating tumor DNA (ctDNA) levels during therapy could be a promising tool for very accurate monitoring of treatment efficacy, but data are lacking with ICB. This prospective pilot study was conducted in patients with nonsmall cell lung cancer, uveal melanoma, or microsatellite-instable colorectal cancer treated by nivolumab or pembrolizumab monotherapy at Institut Curie. ctDNA levels were assessed at baseline and after 8 weeks (w8) by bidirectional pyrophosphorolysis-activated polymerization, droplet digital PCR or next-generation sequencing depending on the mutation type. Radiological evaluation of efficacy of treatment was carried out by using immune-related response criteria. ctDNA was detected at baseline in 10 out of 15 patients. At w8, a significant correlation (r = 0.86; P = 0.002) was observed between synchronous changes in ctDNA levels and tumor size. Patients in whom ctDNA levels became undetectable at w8 presented a marked and lasting response to therapy. ctDNA detection at w8 was also a significant prognostic factor in terms of progression-free survival (hazard ratio = 10.2; 95% confidence interval 2.5-41, P < 0.001) and overall survival (hazard ratio = 15; 95% confidence interval 2.5-94.9, P = 0.004). This proof-of-principle study is the first to demonstrate that quantitative ctDNA monitoring is a valuable tool to assess tumor response in patients treated with anti-PD-1 drugs. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For permissions, please email: journals.permissions@oup.com.

  3. Multi-course PDT of malignant tumors: the influence on primary tumor, metastatic spreading and homeostasis of cancer patients

    Science.gov (United States)

    Sokolov, Victor V.; Chissov, Valery I.; Yakubovskaya, Raisa I.; Filonenko, E. V.; Sukhin, Garry M.; Nemtsova, E. R.; Belous, T. A.; Zharkova, Natalia N.

    1996-12-01

    The first clinical trials of photodynamic therapy (PDT) of cancer with two photosensitizers, PHOTOHEME and PHOTOSENS, were started in P.A. Hertzen Research Oncological Institute (Moscow, Russia) in 1992 and 1994. Up to now, 208 patients with primary, recurrent and metastatic malignant tumors (469) of skin (34 patients/185 tumors), breast cancer (24/101), head and neck (30/31), trachea and bronchus (31/42), esophagus (35/35), stomach (31/32), rectum (4/4), vagina and uterine cervix (7/8) and bladder (12/31) have been treated by PDT. One-hundred-thirty patients were injected with PHOTOHEME, 64 patients were injected with PHOTOSENS, 14 patients were injected with PHOTOHEME and PHOTOSENS. Totally, 302 courses of treatment were performed: 155 patients had one course and 53 patients were subjected to two to nine PDT sources with intervals from 1 to 18 months. A therapeutic effect of a one-course and multi- course PDT of malignant tumors (respiratory, digestive and urogenital systems) was evaluated clinically, histologically, roentgenologically, sonographically and endoscopically. The biochemical, hematological and immunological investigations were performed for all the patients in dynamics. Results of our study showed that a multi-course PDT method seems to be perspective in treatment of malignant tumors of basic localizations.

  4. MiRNA-21 Expression Decreases from Primary Tumors to Liver Metastases in Colorectal Carcinoma.

    Directory of Open Access Journals (Sweden)

    Fabian Feiersinger

    Full Text Available Metastasis is the major cause of death in colorectal cancer patients. Expression of certain miRNAs in the primary tumors has been shown to be associated with progression of colorectal cancer and the initiation of metastasis. In this study, we compared miRNA expression in primary colorectal cancer and corresponding liver metastases in order to get an idea of the oncogenic importance of the miRNAs in established metastases.We analyzed the expression of miRNA-21, miRNA-31 and miRNA-373 in corresponding formalin-fixed paraffin-embedded (FFPE tissue samples of primary colorectal cancer, liver metastasis and healthy tissues of 29 patients by quantitative real-time PCR.All three miRNAs were significantly up-regulated in the primary tumor tissues as compared to healthy colon mucosa of the respective patients (p < 0.01. MiRNA-21 and miRNA-31 were also higher expressed in liver metastases as compared to healthy liver tissues (p < 0.01. No significant difference of expression of miRNA-31 and miRNA-373 was observed between primary tumors and metastases. Of note, miRNA-21 expression was significantly reduced in liver metastases as compared to the primary colorectal tumors (p < 0.01.In the context of previous studies demonstrating increased miRNA-21 expression in metastatic primary tumors, our findings raise the question whether miRNA-21 might be involved in the initiation but not in the perpetuation and growth of metastases.

  5. Ipsilateral Breast Tumor Relapse: Local Recurrence Versus New Primary Tumor and the Effect of Whole-Breast Radiotherapy on the Rate of New Primaries

    International Nuclear Information System (INIS)

    Gujral, Dorothy M.; Sumo, Georges; Owen, John R.; Ashton, Anita; Bliss, Judith M.; Haviland, Joanne; Yarnold, John R.

    2011-01-01

    Purpose: The justification for partial breast radiotherapy after breast conservation surgery assumes that ipsilateral breast tumor relapses (IBTR) outside the index quadrant are mostly new primary (NP) tumors that develop despite radiotherapy. We tested the hypothesis that whole-breast radiotherapy (WBRT) is ineffective in preventing NP by comparing development rates in irradiated and contralateral breasts after tumor excision and WBRT. Methods and Materials: We retrospectively reviewed 1,410 women with breast cancer who were entered into a prospective randomized trial of radiotherapy fractionation and monitored annually for ipsilateral breast tumor relapses (IBTR) and contralateral breast cancer (CLBC). Cases of IBTR were classified into local recurrence (LR) or NP tumors based on location and histology and were subdivided as definite or likely depending on clinical data. Rates of ipsilateral NP and CLBC were compared over a 15-year period of follow-up. Results: At a median follow-up of 10.1 years, there were 150 documented cases of IBTR: 118 (79%) cases were definite or likely LR; 27 (18%) cases were definite or likely NP; and 5 (3%) cases could not be classified. There were 71 cases of CLBC. The crude proportion of definite-plus-likely NP was 1.9% (27/1,410) patients compared with 5% (71/1,410) CLBC patients. Cumulative incidence rates at 5, 10, and 15 years were 0.8%, 2.0%, and 3.5%, respectively, for definite-plus-likely NP and 2.4%, 5.8%, and 7.9%, respectively for CLBC, suggesting a difference in the rates of NP and CLBC. Conclusions: This analysis suggests that WBRT reduces the rate of ipsilateral NP tumors. The late presentation of NP has implications for the reporting of trials that are testing partial breast radiotherapy.

  6. Primary Hyperparathyroidism Misdiagnosed as Giant Cell Bone Tumor of Maxillary Sinus: A Case Report

    International Nuclear Information System (INIS)

    Aghaghazvini, Leila; Sharifian, Hashem; Rasuli, Bahman

    2016-01-01

    Primary hyperparathyroidism is an endocrine disorder recognized by hyperfunction of parathyroid gland, which can result in persistent bone absorption and brown tumor. Facial involvement of brown tumor is rare and usually involves the mandible. Giant cell tumor (GCT) is an expansile osteolytic bone tumor which is very similar in clinical, radiological and histological features to brown tumor. Herein, we present a 35-year-old woman with an 11-month history of gradually swelling of the right maxilla and buccal spaces began during pregnancy two years ago. No other clinical or laboratory problems were detected. Postpartum CT scan demonstrated a lytic expansile multi-septated mass lesion containing enhancing areas, which initially described as GCT of the right maxillary sinus following surgery. Four months later, gradual progressive swelling of the bed of tumor was recurred and revised pathological slices were compatible with GCT. Regarding patient recent paresthesia, repeated laboratory tests were performed. Finally, according to laboratory results (elevation of serum calcium and parathyroid hormone), ultrasonographic findings and radioisotope scan (Sestamibi), probable parathyroid mass and brown tumor of maxilla was diagnosed. Pathology confirmed hyperplasia of right inferior parathyroid gland. Our case was thought-provoking due to its interesting clinical presentation and unusual presentation of brown tumor in parathyroid hyperplasia

  7. Age dependency of primary tumor sites and metastases in patients with Ewing sarcoma.

    Science.gov (United States)

    Worch, Jennifer; Ranft, Andreas; DuBois, Steven G; Paulussen, Michael; Juergens, Heribert; Dirksen, Uta

    2018-06-01

    The median age of patients with Ewing sarcoma (EwS) at diagnosis is around 14-15 years. Older age is associated with a worse outcome. The correlation of age at diagnosis on sites of disease has not been fully described. The goal of this study was to evaluate the differences in sites of primary tumor and metastatic tumor involvement according to age groups. EwS data from the Gesellschaft für Pädiatrische Onkologie und Hämatology (GPOH) database of the Cooperative Ewing Sarcoma Study (CESS) 81/86 and the European Intergroup Cooperative Ewing's Sarcoma Study EICESS 92 and the EUROpean Ewing tumor Working Initiative of National Groups-99-Protocol (EURO-E.W.I.N.G.-99) study were analyzed. Patient and tumor characteristics were evaluated statistically using chi square tests. The study population included 2,635 patients with bone EwS. Sites of primary and metastatic tumors differed according to the age groups of young children (0-9 years), early adolescence (10-14 years), late adolescence (15-19 years), young adults (20-24 years), and adults (more than 24 years). Young children demonstrated the most striking differences in site of disease with a lower proportion of pelvic primary and axial tumors. They presented less often with metastatic disease at diagnosis. Site of primary and metastatic tumor involvement in EwS differs according to patient age. The biological and developmental etiology for these differences requires further investigations. © 2018 Wiley Periodicals, Inc.

  8. Therapeutically targeting cyclin D1 in primary tumors arising from loss of Ini1

    Science.gov (United States)

    Smith, Melissa E.; Cimica, Velasco; Chinni, Srinivasa; Jana, Suman; Koba, Wade; Yang, Zhixia; Fine, Eugene; Zagzag, David; Montagna, Cristina; Kalpana, Ganjam V.

    2011-01-01

    Rhabdoid tumors (RTs) are rare, highly aggressive pediatric malignancies with poor prognosis and with no standard or effective treatment strategies. RTs are characterized by biallelic inactivation of the INI1 tumor suppressor gene. INI1 directly represses CCND1 and activates cyclin-dependent kinase (cdk) inhibitors p16Ink4a and p21CIP. RTs are exquisitely dependent on cyclin D1 for genesis and survival. To facilitate translation of unique therapeutic strategies, we have used genetically engineered, Ini1+/− mice for therapeutic testing. We found that PET can be used to noninvasively and accurately detect primary tumors in Ini1+/− mice. In a PET-guided longitudinal study, we found that treating Ini1+/− mice bearing primary tumors with the pan-cdk inhibitor flavopiridol resulted in complete and stable regression of some tumors. Other tumors showed resistance to flavopiridol, and one of the resistant tumors overexpressed cyclin D1, more than flavopiridol-sensitive cells. The concentration of flavopiridol used was not sufficient to down-modulate the high level of cyclin D1 and failed to induce cell death in the resistant cells. Furthermore, FISH and PCR analyses indicated that there is aneuploidy and increased CCND1 copy number in resistant cells. These studies indicate that resistance to flavopiridol may be correlated to elevated cyclin D1 levels. Our studies also indicate that Ini1+/− mice are valuable tools for testing unique therapeutic strategies and for understanding mechanisms of drug resistance in tumors that arise owing to loss of Ini1, which is essential for developing effective treatment strategies against these aggressive tumors. PMID:21173237

  9. Effect of adrenomedullin on the cerebral circulation: relevance to primary headache disorders

    DEFF Research Database (Denmark)

    Petersen, K A; Birk, S; Kitamura, K

    2009-01-01

    Adrenomedullin (ADM) is closely related to calcitonin gene-related peptide, which has a known causative role in migraine. Animal studies have strongly suggested that ADM has a vasodilatory effect within the cerebral circulation. For these reasons, ADM is also likely to be involved in migraine....... However, the hypothetical migraine-inducing property and effect on human cerebral circulation of ADM have not previously been investigated. Human ADM (0.08 microg kg(-1) min(-1)) or placebo (saline 0.9%) was administered as a 20-min intravenous infusion to 12 patients suffering from migraine without aura...... in a crossover double-blind study. The occurrence of headache and associated symptoms were registered regularly 24 h post infusion. Cerebral blood flow (CBF) was measured by (133)Xenon single-photon emission computed tomography, mean blood flow velocity in the middle cerebral artery (V(MCA)) by transcranial...

  10. Calculation models of pressure wave propagation within the WWER-440 primary circulating loop

    International Nuclear Information System (INIS)

    Adamik, V.; Tkach, A.

    1982-01-01

    Computer codes SHOCK, LOVE, BAREL are described that can be used for the study of pressure wave propagation within the reactor and pipeline system during a LOCA as well as for mechanical loads identification in various parts of the system. SHOCK code is applicable to one-dimensional pressure wave propagation analysis in any hydraulic network containing a compressible nonviscous liquid with a constant (within the considered transient process period) density. LOVE code allows to calculate non-symmetrical mechanical loads on the WWER shaft in case of the main circulation pipeline cold branch rupture. BAREL code is an advanced modification of SHOCK code. It is fitted for two-dimensional pressure wave propagation analysing in the downstream section of a pressurised water reactor in case of the main circulation pipeline cold branch rupture. The calculation results for B-213 type WWER-440 reactor are presented that have been obtained under the assumption of perfect structure rigidity [ru

  11. Local melanoma recurrences in the scar after limited surgery for primary tumor

    DEFF Research Database (Denmark)

    Drzewiecki, K T; Andersson, A P

    1995-01-01

    The clinical and histologic records of 46 consecutive patients were reviewed who during the period 1980-1993 had recurrence from melanoma in the scar after limited surgery for a skin tumor. They constituted about 50% of all patients admitted with local recurrence from melanoma during this period....... At reexamination of the primary tumors, 16 were found to be malignant melanomas and 9 were nevi (four atypical and five benign). Twenty-one were missing, 11 of which had never been set for histologic examination. The median thickness of nine measurable melanomas was 0.66 mm. The recurrences in scar consisted of 34...... recurrences in the form of a new primary in a scar following limited surgery supports the theory of limited field change around a primary melanoma. Furthermore, limited procedures for primary melanoma, if followed by a recurrence in the scar, worsen the prognosis....

  12. Clinical validation of an ultra high-throughput spiral microfluidics for the detection and enrichment of viable circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Bee Luan Khoo

    Full Text Available Circulating tumor cells (CTCs are cancer cells that can be isolated via liquid biopsy from blood and can be phenotypically and genetically characterized to provide critical information for guiding cancer treatment. Current analysis of CTCs is hindered by the throughput, selectivity and specificity of devices or assays used in CTC detection and isolation.Here, we enriched and characterized putative CTCs from blood samples of patients with both advanced stage metastatic breast and lung cancers using a novel multiplexed spiral microfluidic chip. This system detected putative CTCs under high sensitivity (100%, n = 56 (Breast cancer samples: 12-1275 CTCs/ml; Lung cancer samples: 10-1535 CTCs/ml rapidly from clinically relevant blood volumes (7.5 ml under 5 min. Blood samples were completely separated into plasma, CTCs and PBMCs components and each fraction were characterized with immunophenotyping (Pan-cytokeratin/CD45, CD44/CD24, EpCAM, fluorescence in-situ hybridization (FISH (EML4-ALK or targeted somatic mutation analysis. We used an ultra-sensitive mass spectrometry based system to highlight the presence of an EGFR-activating mutation in both isolated CTCs and plasma cell-free DNA (cf-DNA, and demonstrate concordance with the original tumor-biopsy samples.We have clinically validated our multiplexed microfluidic chip for the ultra high-throughput, low-cost and label-free enrichment of CTCs. Retrieved cells were unlabeled and viable, enabling potential propagation and real-time downstream analysis using next generation sequencing (NGS or proteomic analysis.

  13. The Prognostic Role of Circulating Tumor Cells (CTC) in High-risk Non-muscle-invasive Bladder Cancer.

    Science.gov (United States)

    Busetto, Gian Maria; Ferro, Matteo; Del Giudice, Francesco; Antonini, Gabriele; Chung, Benjamin I; Sperduti, Isabella; Giannarelli, Diana; Lucarelli, Giuseppe; Borghesi, Marco; Musi, Gennaro; de Cobelli, Ottavio; De Berardinis, Ettore

    2017-08-01

    The purpose of this study was to evaluate the impact of circulating tumor cells (CTCs) as a prognostic marker in patients with high-risk non-muscle-invasive bladder cancer (NMIBC) and assess the efficacy and reliability of 2 different CTC isolation methods. Globally, 155 patients with a pathologically confirmed diagnosis of high-risk NMIBC were included (pT1G3 with or without carcinoma in situ) and underwent transurethral resection of bladder tumor (TURB) after a blood withdrawal for CTC evaluation. A total of 101 patients (Group A) had their samples analyzed with the CellSearch automated system, and 54 (Group B) had their samples analyzed with the CELLection Dynabeads manual system. Patients were followed for 28 months, and during this interval, there were a total of 65 (41.9%) recurrences, 27 (17.4%) disease progressions, and 9 (5.8%) lymph node and/or bone metastasis. In our CTC analysis, there were 20 (19.8%) positive patients in Group A and 24 in Group B (44.4%). In our analysis, we found a strong correlation between CTC presence and time to first recurrence; in Group A, we observed an incidence of recurrence in 75% of CTC-positive patients and in Group B of 83% of CTC-positive patients. The time to progression was also strongly correlated with CTCs: 65% and 29%, respectively, of those patients who progressed in those with CTCs in Group A and B. The study demonstrates the potential role of CTCs as a prognostic marker for risk stratification in patients with NMIBC, to predict both recurrence and progression. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. 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

  15. 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)

  16. The Findings of 99mTc-MDP Bone Scan in Primary malignant Bone Tumors

    International Nuclear Information System (INIS)

    Hyun, In Young; Lee, Kung Han; Lee, Dong Soo; Chung, June Key; Lee, Myung Chul; Koh, Chang Soon; Kang, Heung Sik; Lee, Sang Hoon; Lee, Han Koo

    1995-01-01

    Tc-99m-MDP bone scan was performed in 31 patients with primary malignant bone tumors, 22 patients with osteogenic sarcoma, 5 patients with chondrosarcoma and 4 patients with Ewing's sarcoma. The findings were classified by isotope intensity of accumulation in tumor as grade 1 to 3, overall pattern of isotope distribution in tumor as grade 1 to 3, and distortion of bony outline as grade 1 to 3. Histologic classifications were correlated with scan findings in 22 patients with osteogenic sarcoma. The results were as follows. 1) In 22 patients with osteogenic sarcoma, markedly increased isotope intensity higher than sacroiliac joint with patchy areas of decreased intensity and severe bony distortion were found in 16 patients. The correlations between histologic classification and scan findings were not discovered. 2) In 5 patients with chondrosarcoma, mildly increased isotope intensity with patchy areas of increased intensity and mild bony distortion were found in 4 patients. 3) In 4 patients with Ewing's sarcoma, markedly increased homogenous intensity with moderate bony distortion were found in 3 patients. Conclusively there were common findings in each 3 primary malignant bone tumors and Tc-99m-MDP bone scan was complemented with radiologic studies in differentiating primary malignant bone tumors.

  17. Gene expression analysis of matched ovarian primary tumors and peritoneal metastasis

    Directory of Open Access Journals (Sweden)

    Malek Joel A

    2012-06-01

    Full Text Available Abstract Background Ovarian cancer is the most deadly gynecological cancer due to late diagnosis at advanced stage with major peritoneal involvement. To date most research has focused on primary tumor. However the prognosis is directly related to residual disease at the end of the treatment. Therefore it is mandatory to focus and study the biology of meatastatic disease that is most frequently localized to the peritoneal caivty in ovarian cancer. Methods We used high-density gene expression arrays to investigate gene expression changes between matched primary and metastatic (peritoneal lesions. Results Here we show that gene expression profiles in peritoneal metastasis are significantly different than their matched primary tumor and these changes are affected by underlying copy number variation differences among other causes. We show that differentially expressed genes are enriched in specific pathways including JAK/STAT pathway, cytokine signaling and other immune related pathways. We show that underlying copy number variations significantly affect gene expression. Indeed patients with important differences in copy number variation displayed greater gene expression differences between their primary and matched metastatic lesions. Conclusions Our analysis shows a very specific targeting at both the genomic and transcriptomic level to upregulate certain pathways in the peritoneal metastasis of ovarian cancer. Moreover, while primary tumors use certain pathways we identify distinct differences with metastatic lesions. The variation between primary and metastatic lesions should be considered in personalized treatment of ovarian cancer.

  18. Clinical utility of circulating tumor cell counting through CellSearch®: the dilemma of a concept suspended in Limbo

    Directory of Open Access Journals (Sweden)

    Raimondi C

    2014-04-01

    Full Text Available Cristina Raimondi,1 Angela Gradilone,1 Giuseppe Naso,2 Enrico Cortesi,2 Paola Gazzaniga1 1Dipartimento Medicina Molecolare, Sapienza Università di Roma, Rome, Italy; 2Dipartimento di Scienze Radiologiche, Oncologiche e Anatomopatologiche, Sapienza Università di Roma, Rome, Italy Abstract: To date, 10 years after the first demonstration of circulating tumor cells (CTCs, prognostic significance in metastatic breast cancer using the US Food and Drug Administration–cleared system CellSearch®, the potential utility of CTCs in early clinical development of drugs, their role as a surrogate marker of response to therapy, and their molecular analysis for patient stratification for targeted therapies are still major unsolved questions. Great expectations are pinned on the ongoing interventional trials aimed to demonstrate that CTCs might be of value for guiding treatment of patients and predicting cancer progression. To fill the gap between theory and practice with regard to the clinical utility of CTCs, a bridge is needed, taking into account innovative design for clinical trials, a revised definition of traditional CTCs, next-generation CTC technology, the potential clinical application of CTC analysis in non-validated settings of disease, and finally, expanding the number of patients enrolled in the studies. In this regard, the results of the first European pooled analysis definitely validated the independent prognostic value of CTC counting in metastatic breast cancer patients. Keywords: CTC, clinical trials, prognosis

  19. Quantitative image cytometry measurements of lipids, DNA, CD45 and cytokeratin for circulating tumor cell identification in a model system

    Science.gov (United States)

    Futia, Gregory L.; Qamar, Lubna; Behbakht, Kian; Gibson, Emily A.

    2016-04-01

    Circulating tumor cell (CTC) identification has applications in both early detection and monitoring of solid cancers. The rarity of CTCs, expected at ~1-50 CTCs per million nucleated blood cells (WBCs), requires identifying methods based on biomarkers with high sensitivity and specificity for accurate identification. Discovery of biomarkers with ever higher sensitivity and specificity to CTCs is always desirable to potentially find more CTCs in cancer patients thus increasing their clinical utility. Here, we investigate quantitative image cytometry measurements of lipids with the biomarker panel of DNA, Cytokeratin (CK), and CD45 commonly used to identify CTCs. We engineered a device for labeling suspended cell samples with fluorescent antibodies and dyes. We used it to prepare samples for 4 channel confocal laser scanning microscopy. The total data acquired at high resolution from one sample is ~ 1.3 GB. We developed software to perform the automated segmentation of these images into regions of interest (ROIs) containing individual cells. We quantified image features of total signal, spatial second moment, spatial frequency second moment, and their product for each ROI. We performed measurements on pure WBCs, cancer cell line MCF7 and mixed samples. Multivariable regressions and feature selection were used to determine combination features that are more sensitive and specific than any individual feature separately. We also demonstrate that computation of spatial characteristics provides higher sensitivity and specificity than intensity alone. Statistical models allowed quantification of the required sensitivity and specificity for detecting small levels of CTCs in a human blood sample.

  20. In vitro detection of circulating tumor cells compared by the CytoTrack and CellSearch methods

    DEFF Research Database (Denmark)

    Hillig, T.; Horn, P.; Nygaard, Ann-Britt

    2015-01-01

    .23/p = 0.09). Overall, the recovery of CytoTrack and CellSearch was 68.8 +/- 3.9 %/71.1 +/- 2.9 %, respectively (p = 0.58). In spite of different methodologies, CytoTrack and CellSearch found similar number of CTCs, when spiking was performed with the EpCAM and pan cytokeratin-positive cell line MCF-7......Comparison of two methods to detect circulating tumor cells (CTC) CytoTrack and CellSearch through recovery of MCF-7 breast cancer cells, spiked into blood collected from healthy donors. Spiking of a fixed number of EpCAM and pan-cytokeratin positive MCF-7 cells into 7.5 mL donor blood...... was performed by FACSAria flow sorting. The samples were shipped to either CytoTrack or CellSearch research facilities within 48 h, where evaluation of MCF-7 recovery was performed. CytoTrack and CellSearch analyses were performed simultaneously. Recoveries of MCF-7 single cells, cells in clusters, and clusters...

  1. Five Simultaneous Primary Tumors in a Single Patient: A Case Report and Review of the Literature

    Directory of Open Access Journals (Sweden)

    Casey W. Williamson

    2015-10-01

    Full Text Available Multiple primary malignancies (MPMs are present when a patient is diagnosed with more than one primary malignancy and when each tumor is histologically unrelated to the others. MPMs are considered synchronous when they present within 6 months of one another. Here, we report the case of a 57-year-old woman with a past medical history significant for melanoma in 1988, who presented in 2014 with 5 distinct tumors within 4 months: malignant melanoma of the right popliteal fossa, invasive lobular breast carcinoma, diffuse large B cell lymphoma, nodular lymphocyte predominant Hodgkin lymphoma, and a giant cell tumor of tendon sheath/pigmented villonodular synovitis. We discuss her treatment and also present a brief review of the literature. The incidence of MPMs appears to be on the rise, which demands an interdisciplinary, multimodal, and personalized approach to care.

  2. Top 50 most cited articles on primary tumors of the spine.

    Science.gov (United States)

    Alan, Nima; Cohen, Jonathan; Ozpinar, Alp; Agarwal, Nitin; Kanter, Adam S; Okonkwo, David O; Hamilton, D Kojo

    2017-08-01

    Citation analysis was performed in order to identify the top 50 most cited articles pertaining to the field of primary spinal tumors. This collection of articles highlights important trends in the neurosurgical literature. We searched the Thomson Reuters Web of Knowledge in order to identify articles pertaining to primary tumors of the spine. Impertinent articles were removed. The top 50 most cited articles were identified. Thereafter, article characteristics were determined including article type, article topic, level of evidence, and citation rate. The selected articles were published between 1951 and 2008. The most productive year was 1997 with 6 publications. The top 50 articles were published in twenty-two different journals, most commonly in Neurosurgery (12), Journal of Neurosurgery (8), and Spine (6). The most frequently cited article was by Tomita et al. written in 1997 which described total en bloc spondylectomy as a novel surgical technique in management of primary tumors of the vertebral column. We identified the 50 most-cited articles in the field of primary spinal tumors. This collection of articles serves as a reference for recognizing impactful studies in the field. Copyright © 2017. Published by Elsevier Ltd.

  3. Immunocytochemical characterization of primary cell culture in canine transmissible venereal tumor

    Directory of Open Access Journals (Sweden)

    Luis M.M. Flórez

    Full Text Available Abstract: Immunochemistry with anti-vimentin, anti-lysozyme, anti-alpha 1 antitrypsin, anti-CD3 and anti-CD79α antibodies has been used for characterization of primary cell culture in the transmissible venereal tumor (TVT. Samples for primary cell culture and immunohistochemistry assays were taken from eight dogs with cytological and clinical diagnosis of TVT. To validate the immunochemical results in the primary cell culture of TVT, a chromosome count was performed. For the statistical analysis, the Mann-Whitney test with p<0.05 was used. TVT tissues and culture cells showed intense anti-vimentin immunoreactivity, lightly to moderate immunoreactivity for anti-lysozyme, and mild for anti-alpha-antitrypsin. No marking was achieved for CD3 and CD79α. All culture cells showed chromosomes variable number of 56 to 68. This is the first report on the use of immunocytochemical characterization in cell culture of TVT. Significant statistic difference between immunochemistry in tissue and culture cell was not established, what suggests that the use of this technique may provide greater certainty for the confirmation of tumors in the primary culture. This fact is particularly important because in vitro culture of tumor tissues has been increasingly used to provide quick access to drug efficacy and presents relevant information to identify potential response to anticancer medicine; so it is possible to understand the behavior of the tumor.

  4. Bone scintigraphy in Ewing's sarcoma during and after treatment - prognostic information from the primary tumor site

    International Nuclear Information System (INIS)

    Piers, D.A.; Veenhoven, R.H.; Kamps, W.A.; Woldring, M.G.

    1988-01-01

    A bone scan can be negative in Ewing's sarcoma. The bone scan during and after treatment can give prognostic information on the primary tumor site: A persisting hot spot strongly suggests the presence of local malignancy, while a hot spot becomming negative points to local cure of Ewing's sarcoma. (orig.)

  5. Circulating DNA as Potential Biomarker for Cancer Individualized Therapy

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    Shaorong Yu

    2013-09-01

    Full Text Available Cancer individualized therapy often requires for gene mutation analysis of tumor tissue. However, tumor tissue is not always available in clinical practice, particularly from patients with refractory and recurrence disease. Even if patients have sufficient tumor tissue for detection, as development of cancer, the gene status and drug sensitivity of tumor tissues could also change. Hence, screening mutations from primary tumor tissues becomes useless, it’s necessary to find a surrogate tumor tissue for individualized gene screening. Circulating DNA is digested rapidly from blood, which could provide real-time information of the released fragment and make the real-time detection possible. Therefore, it’s expected that circulating DNA could be a potential tumor biomarker for cancer individualized therapy. This review focuses on the biology and clinical utility of circulating DNA mainly on gene mutation detection. Besides, its current status and possible direction in this research area is summarized and discussed objectively.

  6. Fibulectomy for primary proximal fibular bone tumors: A functional and clinical outcome in 46 patients

    Directory of Open Access Journals (Sweden)

    Zile Singh Kundu

    2018-01-01

    Full Text Available Background: Primary benign and malignant tumors of the proximal fibula are not very common. Upper fibula being an expendable bone; the majority of the primary bone tumors at this site are usually treated with en bloc proximal fibulectomy. There is scarce literature on functional results, difficulties faced during dissection when to preserve or sacrifice common peroneal nerve and importance of lateral collateral ligament repair after proximal fibulectomy. The present study attempts at assessing these variables. Materials and Methods: This retrospective study included 46 patients; 30 males and 16 females with age ranging from 12 to 44 years (average: 26 years operated between 2003 and 2014. There were 34 benign and 12 malignant tumors. All were treated with proximal en bloc fibulectomy as indicated and decided by the operating surgeon keeping in view its extent on magnetic resonance imaging. Peroneal nerve sacrifice or preservation was decided as per the type (benign/malignant, its involvement by the tumor and the extent of the tumor. In 14 (for 12 malignant and two benign giant cell tumors [GCTs] patients, the peroneal nerve required resection for the margins. Partial upper tibial resection was performed in cases of malignant tumors and three GCTs. The followup ranged between 24 and 120 months (median: 48 months. Results: Patients with peroneal nerve resection had inferior functional outcome than those without peroneal nerve resection. There was no higher risk of tibia fracture in patients with partial tibial resection. Lateral collateral reconstruction yielded better results and should be performed in all cases. Functional outcome was significantly better in patients with benign tumors than in patients with malignant tumors as these required neither resection of the peroneal nerve nor large amount of muscle excision. The functional results were evaluated using Musculoskeletal Tumor Society (MSTS score, and clinical outcomes were evaluated using

  7. 3. Workshop for IAEA ICSP on Integral PWR Design Natural Circulation Flow Stability and Thermo-hydraulic Coupling of Containment and Primary System during Accidents. Presentations

    International Nuclear Information System (INIS)

    2012-04-01

    Most advanced nuclear power plant designs adopted several kinds of passive systems. Natural circulation is used as a key driving force for many passive systems and even for core heat removal during normal operation such as NuScale, CAREM, ESBWR and Indian AHWR designs. Simulation of natural circulation phenomena is very challenging since the driving force of it is weak compared to forced circulation and involves a coupling between primary system and containment for integral type reactor. The IAEA ICSP (International Collaborative Standard Problem) on 'Integral PWR Design Natural Circulation Flow Stability and Thermo-hydraulic Coupling of Containment and Primary System during Accidents' was proposed within the CRP on 'Natural Circulation Phenomena, Modelling, and Reliability of Passive Systems that utilize Natural Circulation'. Oregon State University (OSU) of USA offered to host this ICSP. This ICSP plans to conduct the following experiments and blind/open simulations with system codes: 1. Quasi-steady state operation with different core power levels: Conduct quasi-steady state operation with step-wise increase of core power level in order to observe single phase natural circulation flow according to power level. The experimental facility and operating conditions for an integral PWR will be used. 2. Thermo-hydraulic Coupling between Primary system and Containment: Conduct a loss of feedwater transient with subsequent ADS blowdown and long term cooling to determine the progression of a loss of feedwater transient by natural circulation through primary and containment systems. These tests would examine the blowdown phase as well as the long term cooling using sump natural circulation by coupling the primary to containment systems. This data could be used for the evaluation of system codes to determine if they model specific phenomena in an accurate manner. OSU completed planned two ICSP tests in July 2011 and real initial and boundary conditions measured from the

  8. Detection of circulating tumor cells with CK20 RT-PCR is an independent negative prognostic marker in colon cancer patients - a prospective study.

    Science.gov (United States)

    Hinz, Sebastian; Hendricks, Alexander; Wittig, Amke; Schafmayer, Clemens; Tepel, Jürgen; Kalthoff, Holger; Becker, Thomas; Röder, Christian

    2017-01-13

    Detection of circulating (CTC) or disseminated tumor cells (DTC) has been associated with negative prognosis and outcome in patients with colorectal cancer, though testing for these cells is not yet part of clinical routine. There are several different methodological approaches to detect tumor cells but standardized detection assays are not implemented so far. In this prospective monocentric study 299 patients with colon cancer were included. CTC and DTC were detected using CK20 RT-PCR as well as immunocytochemistry staining with anti-pan-keratin and anti-EpCAM antibodies. The primary endpoints were: Evaluation of CTC and DTC at the time of surgery and correlation with main tumor characteristics and overall (OS) and disease free survival (DFS). Patients with detectable CTC had a 5-year OS rate of 68% compared to a 5-year OS rate of 85% in patients without detectable CTC in the blood (p = 0.002). Detection of DTC in the bone marrow with CK20 RT-PCR was not associated with a worse OS or DFS. Detection of pan-cytokeratin positive DTC in the bone marrow correlated with a significantly reduced 5-year OS rate (p = 0.048), but detection of DTC in the bone marrow with the anti-EpCAM antibody did not significantly influence the 5-year OS rate (p = 0.958). By multivariate analyses only detection of CTC with CK20 RT-PCR in the blood was revealed to be an independent predictor of worse OS (HR1.94; 95% CI 1.0-3.7; p = 0.04) and DFS (HR 1.94; 95% CI 1.1-3.7; p = 0.044). Detection of CTC with CK20 RT-PCR is a highly specific and independent prognostic marker in colon cancer patients. Detection of DTC in the bone marrow with CK20 RT-PCR or immunohistochemistry with anti-EpCAM antibody is not associated with a negative prognostic influence.

  9. Tumor Hypoxia is Independent of Hemoglobin and Prognostic for Loco-regional Tumor Control after Primary Radiotherapy in Advanced Head and Neck Cancer

    International Nuclear Information System (INIS)

    Nordsmark, Marianne; Overgaard, Jens

    2004-01-01

    There is evidence that tumor hypoxia adversely affects loco-regional tumor control and survival in head and neck cancer. The aim of the current study was to compare pretreatment tumor oxygenation measured by Eppendorf pO2 electrodes with known prognostic factors in advanced head and neck tumors after definitive radiotherapy, and to evaluate the prognostic significance of these parameters on loco-regional tumor control. Sixty-seven patients, median age 56 years (22-82), all with primary stage III-IV squamous cell carcinoma were available for survival analysis. Tumor oxygenation was described as the fraction of pO2 values=2.5 mmHg (HP2.5) and the median tumor pO2. By regression analysis HP2.5 was independent of known prognostic factors including stage, pretreatment hemoglobin (Hb) and the largest tumor diameter at the site of pO2 measurement. By Kaplan-Meier analysis loco-regional tumor control at 5 years was in favor of less hypoxic tumors using either HP2.5 or median tumor pO2 as descriptors and stratifying by the median values. Also, Hb was prognostic of loco-regional tumor control at 5 years using the median value as cut off. HP2.5 as continuous parameter was highly significant for loco-regional tumor control in a multivariate analysis. In conclusion both HP2.5 and total Hb were prognostic for loco-regional tumor control, but HP2.5 as continuous variable was independently the strongest prognostic indicator for loco-regional tumor control after definitive primary radiotherapy in advanced head and neck tumors

  10. Mammographic Features of Local Recurrence after Conservative Surgery and Radiation Therapy: Comparison with that of the Primary Tumor

    International Nuclear Information System (INIS)

    Guenhan-Bilgen, I.; Oktay, A.

    2007-01-01

    Purpose: To compare the mammographic features of recurrent breast cancer with those of the primary tumor and to determine whether certain mammographic features are associated with a higher risk of local recurrence after breast-conserving therapy. Material and Methods: A retrospective review of mammograms of 421 patients who were treated with conservative surgery and radiotherapy revealed 41 recurrent tumors. Mammographic findings, location, and histopathologic characteristics were retrospectively compared between primary and recurrent tumors. Results: Recurrent tumors were similar in mammographic appearance to primary tumors in 27 (66%) cases. Of 27 primary tumors that occurred as masses without calcifications, 19 (70%) recurred as a mass, and of the six isolated calcifications, five (83%) recurred with calcifications. Ten (53%) of the 19 recurrent masses and five (100%) of the five recurrent calcifications had morphologic features that were similar to those of the primary tumor. Ninety-two percent (11/12) of the recurrences containing microcalcifications (isolated or associated with a mass) had microcalcifications in their primary tumor. Of 27 masses that recurred, the morphology of the primary tumor was obscured in 13 (48%), ill defined in 10 (37%), and spiculated in four (15%) of the masses. Seventy-six percent (31/41) of recurrences were within the lumpectomy quadrant. In 25 (61%) cases, the histologic findings from the primary tumor and the recurrence were identical. Conclusion: The majority of recurrent tumors appear to be mammographically similar to primary tumors. Therefore, it is important to review preoperative mammograms during follow-up of these patients. Although the study population is small, it was noted that mass with spiculated contour is associated with a lower risk for local recurrence

  11. CFD Analysis of the Primary Cooling System for the Small Modular Natural Circulation Lead Cooled Fast Reactor SNRLFR-100

    Directory of Open Access Journals (Sweden)

    Pengcheng Zhao

    2016-01-01

    Full Text Available Small modular reactor (SMR has drawn wide attention in the past decades, and Lead cooled fast reactor (LFR is one of the most promising advanced reactors which are able to meet the safety economic goals of Gen-IV nuclear energy systems. A small modular natural circulation lead cooled fast reactor-100 MWth (SNRLFR-100 is being developed by University of Science and Technology of China (USTC. In the present work, a 3D CFD model, primary heat exchanger model, fuel pin model, and point kinetic model were established based on some reasonable simplifications and assumptions, the steady-state natural circulation characteristics of SNCLFR-100 primary cooling system were discussed and illustrated, and some reasonable suggestions were proposed for the reactor’s thermal-hydraulic and structural design. Moreover, in order to have a first evaluation of the system behavior in accident conditions, an unprotected loss of heat sink (ULOHS transient simulation at beginning of the reactor cycle (BOC has been analyzed and discussed based on the steady-state simulation results. The key temperatures of the reactor core are all under the safety limits at transient state; the reactor has excellent thermal-hydraulic performance.

  12. Morphological studies in the diagnosis of primary and secondary bone tumors

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    Matveeva O.V.

    2016-12-01

    Full Text Available The aim: to show the possibility of morphological studies in the diagnosis of primary and secondary tumors of bones. Material and Methods. 105 (72% patients with primary bone tumors aged from 15 to 66 years and 42 (28% patients with metastatic bone lesions aged from 42 to 70 years were examined and treated for the period from 2008 till 2015. Material for morphological studies was prepared using an open biopsy tissue slices and a scraping resected tumor during surgery. Soft-tissue component is subjected to cytology. The material for histological study included changes in bone and soft tissue. Results. Giant cell tumor was verified in 45% of cases by histological examination. Multiple myeloma was diagnosed in 15% of patients. Osteogenic sarcoma was diagnosed in 14% of cases. Ewing's sarcoma was diagnosed in 3%, 2% of cases were matched by diagnosed chordoma. According to the data received, cancer metastasis of kidney and lung is mostly diagnosed in men from the group of patients with secondary bone defeat. Metastasis of cancer of the breast in women was predominated. Conclusion. The morphological (histological, cytological study plays an important role in the diagnosis of bone tumors. The coincidence of the cytological and histological diagnoses was 97%.

  13. Tailored antihypertensive drug therapy prescribed to older women attenuates circulating levels of interleukin-6 and tumor necrosis factor-α

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    Toledo JO

    2015-01-01

    Full Text Available Juliana O Toledo,1 Clayton F Moraes,2,3 Vinícius C Souza,2 Audrey C Tonet-Furioso,2 Luís CC Afonso,4 Cláudio Córdova,3 Otávio T Nóbrega1,2 1Graduate Program in Health Sciences, 2Graduate Program in Medical Sciences, University of Brasília, Brasília, 3Graduate Program in Gerontology, Catholic University of Brasília, Brasília, 4Research Center in Biological Sciences, Federal University of Ouro Preto, Ouro Preto, Brazil Objective: To test the hypothesis that antihypertensive drug therapy produces anti-inflammatory effects in clinical practice, this study investigated circulating levels of selected proinflammatory mediators (interleukin-6 [IL-6], tumor necrosis factor-alpha [TNF-α], and interferon-γ [INF-γ] in response to multivariate drug directions for blood pressure (BP control.Methods: Prospective study involving 110 hypertensive, community-dwelling older women with different metabolic disorders. A short-term BP-lowering drug therapy was conducted according to current Brazilian guidelines on hypertension, and basal cytokine levels were measured before and after intervention.Results: Interventions were found to represent current hypertension-management practices in Brazil and corresponded to a significant reduction in systolic and diastolic BP levels in a whole-group analysis, as well as when users and nonusers of the most common therapeutic classes were considered separately. Considering all patients, mean IL-6 and TNF-α levels showed a significant decrease in circulating concentrations (P<0.01 at the endpoint compared with baseline, whereas the mean INF-γ level was not significantly different from baseline values. In separate analyses, only users of antagonists of the renin–angiotensin system and users of diuretics exhibited the same significant treatment-induced reduction in serum IL-6 and TNF-α observed in the whole group.Conclusion: Our data demonstrates that a clinically guided antihypertensive treatment is effective in

  14. An observational study of circulating tumor cells and (18F-FDG PET uptake in patients with treatment-naive non-small cell lung cancer.

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    Viswam S Nair

    Full Text Available We investigated the relationship of circulating tumor cells (CTCs in non-small cell lung cancer (NSCLC with tumor glucose metabolism as defined by (18F-fluorodeoxyglucose (FDG uptake since both have been associated with patient prognosis.We performed a retrospective screen of patients at four medical centers who underwent FDG PET-CT imaging and phlebotomy prior to a therapeutic intervention for NSCLC. We used an Epithelial Cell Adhesion Molecule (EpCAM independent fluid biopsy based on cell morphology for CTC detection and enumeration (defined here as High Definition CTCs or "HD-CTCs". We then correlated HD-CTCs with quantitative FDG uptake image data calibrated across centers in a cross-sectional analysis.We assessed seventy-one NSCLC patients whose median tumor size was 2.8 cm (interquartile range, IQR, 2.0-3.6 and median maximum standardized uptake value (SUVmax was 7.2 (IQR 3.7-15.5. More than 2 HD-CTCs were detected in 63% of patients, whether across all stages (45 of 71 or in stage I disease (27 of 43. HD-CTCs were weakly correlated with partial volume corrected tumor SUVmax (r = 0.27, p-value = 0.03 and not correlated with tumor diameter (r = 0.07; p-value = 0.60. For a given partial volume corrected SUVmax or tumor diameter there was a wide range of detected HD-CTCs in circulation for both early and late stage disease.CTCs are detected frequently in early-stage NSCLC using a non-EpCAM mediated approach with a wide range noted for a given level of FDG uptake or tumor size. Integrating potentially complementary biomarkers like these with traditional patient data may eventually enhance our understanding of clinical, in vivo tumor biology in the early stages of this deadly disease.

  15. Primary Ewing's sarcoma-primitive neuroectodermal tumor of the uterus: a case report and literature review.

    Science.gov (United States)

    Park, Jeong-Yeol; Lee, Sun; Kang, Hyoung Jin; Kim, Hy-Sook; Park, Sang-Yoon

    2007-08-01

    Primary Ewing's sarcoma-primitive neuroectodermal tumor (ES-PNET) of the uterus is an extremely rare malignancy. A 30-year-old Korean woman presented with abnormal uterine bleeding with uterine enlargement. A computed tomography (CT) scan and magnetic resonance imaging (MRI) of the abdomen and pelvis showed a huge uterine mass measuring 18 x 20 x 21 cm, metastasis to both pelvic and para-aortic lymph nodes, and omental infiltration. The pathology report of the uterine mass described a uniformly hypercellular tumor, which was arranged in diffuse solid sheets of uniform, small, rounded, and sometimes spindle-shaped cells, with scanty cytoplasm. Immunohistochemically, the mass tested positive for vimentin, CD99, and chromogranin. The patient received several courses of combination chemotherapy and radiotherapy but died from tumor progression 16 months after the initial diagnosis. This is a rare case of primary uterine ES-PNET in a woman of reproductive age. A review of the literature indicates that primary uterine ES-PNET requires early diagnosis and multimodality treatment including surgery, chemotherapy, and radiotherapy. The behavior of this tumor is potentially aggressive.

  16. The incidence of second primary tumors in thyroid cancer patients is increased, but not related to treatment of thyroid cancer

    NARCIS (Netherlands)

    Verkooijen, Robbert B. T.; Smit, Jan W. A.; Romijn, Johannes A.; Stokkel, Marcel P. M.

    2006-01-01

    The aim of the present study is to assess the prevalence of second primary tumors in patients treated for thyroid cancer. Furthermore, we wanted to assess the standardized risk rates for all second primary tumors, but especially for breast cancer, as data in the literature indicate an excessive risk

  17. A rare case of primary mesenteric gastrointestinal stromal tumor with metastasis to the cervix uteri

    Science.gov (United States)

    Gupta, Nupur; Mittal, Suneeta; Lal, Neena; Misra, Renu; Kumar, Lalit; Bhalla, Sunita

    2007-01-01

    Background Gastrointestinal stromal tumors are CD117 (C Kit) positive mesenchymal neoplasms, that may arise anywhere in the gastrointestinal tract. Their current therapy is imatinib mesylate before or after surgery. Case presentation We describe a case of 17-year-old female with metastasis to the cervix uteri of a primary mesenteric gastrointestinal tumor. Conclusion Surgery remains the mainstay of known curative treatment. The manifestations of GIST are not restricted to the typical locations within the bowel; may have very unusual metastatic sites or infiltrations per continuitatem. PMID:18045506

  18. Primary hyperparathyroidism associated with a giant cell tumor: One case in the distal radius.

    Science.gov (United States)

    Ouzaa, M R; Bennis, A; Iken, M; Abouzzahir, A; Boussouga, M; Jaafar, A

    2015-10-01

    Hyperparathyroidism can present itself as brown tumors (or osteolytic expansive lesions) that usually disappear after normalization of calcium and phosphate levels. It rarely occurs simultaneously with a giant cell tumor. The authors report one case of a localized form at the distal radius in a patient being followed for primary hyperparathyroidism. The diagnostic challenges related to the clinical and radiological similarities of these two pathological entities are discussed, as they can lead to delays in therapeutic management. Copyright © 2015 Elsevier Masson SAS. All rights reserved.

  19. Immunostimulatory sutures that treat local disease recurrence following primary tumor resection

    Energy Technology Data Exchange (ETDEWEB)

    Intra, Janjira; Zhang Xueqing; Salem, Aliasger K [Division of Pharmaceutics, College of Pharmacy, University of Iowa, Iowa City, IA 52242 (United States); Williams, Robin L; Zhu Xiaoyan [Department of Surgery, Roy J and Lucille Carver College of Medicine, University of Iowa, Iowa City, IA 52242 (United States); Sandler, Anthony D, E-mail: aliasger-salem@uiowa.edu [Department of Surgery and Center for Cancer and Immunology Research, Children' s National Medical Center, Washington DC 20010 (United States)

    2011-02-15

    Neuroblastoma is a common childhood cancer that often results in progressive minimal residual disease after primary tumor resection. Cytosine-phosphorothioate-guanine oligonucleotides (CpG ODN) have been reported to induce potent anti-tumor immune responses. In this communication, we report on the development of a CpG ODN-loaded suture that can close up the wound following tumor excision and provide sustained localized delivery of CpG ODN to treat local disease recurrence. The suture was prepared by melt extruding a mixture of polylactic acid-co-glycolic acid (PLGA 75:25 0.47 dL g{sup -1}) pellets and CpG ODN 1826. Scanning electron microscopy images showed that the sutures were free of defects and cracks. UV spectrophotometry measurements at 260 nm showed that sutures provide sustained release of CpG ODN over 35 days. Syngeneic female A/J mice were inoculated subcutaneously with 1 x 10{sup 6} Neuro-2a murine neuroblastoma wild-type cells and tumors were grown between 5 to 10 mm before the tumors were excised. Wounds from the tumor resection were closed using CpG ODN-loaded sutures and/or polyglycolic acid Vicryl suture. Suppression of neuroblastoma recurrence and mouse survival were significantly higher in mice where wounds were closed using the CpG ODN-loaded sutures relative to all other groups. (communication)

  20. CHARACTERISTICS OF CLINICAL COURSE OF METASTATIC AND PRIMARY OVARIAN TUMORS IN COLON CANCER

    Directory of Open Access Journals (Sweden)

    I. A. Dzhanyan

    2015-01-01

    Full Text Available The aim of this study was to investigate clinical pecuiliarities of ovarian tumors in colon cancer patients and determination of complex diagnostic methods.Subject and methods. Russian N.N.  Blokhin Cancer Research Center archives were used for retrospective study, patients, who underwent treatment during 1989–2013  were included. Colon cancer patients with ovarian metastases and with synchronous or metachronous tumors were included.Results. 141 patients were included: 91 patients had colon cancer with ovarian metastases (group 1 and 50 patients had synchronous or metachronous ovarian tumours (group 2. Ovarian tumors were diagnosed during the 1 year in 74 (81.3 % patients in group 1 and in 23 (46 % in group 2. Patients in group 2 less frequently had children (9 (18.0 % vs 5 (5.5 + 2.3 %, р < 0.05, family history of cancer (3 (6 % vs 16 (17.6 %, р < 0.05 and concomitant diseases. Median CA 125 level in group 1 was 64.96 ng/ml and 180 ng/ml in group 2. Ovarian tumors had solid and cystic structure during US examination in 66 (73 % patients in group 1 and 31 (62 % patients in group 2 had solid ovarian tumors on US examination.Conclusions. The differential diagnostics of primary and metastatic ovarian tumors must include CEA, CA 19–9 and CA 125 serum levels and pelvic US.

  1. Ultrastructural characterization of primary cilia in pathologically characterized human glioblastoma multiforme (GBM) tumors.

    Science.gov (United States)

    Moser, Joanna J; Fritzler, Marvin J; Rattner, Jerome B

    2014-01-01

    Primary cilia are non-motile sensory cytoplasmic organelles that are involved in cell cycle progression. Ultrastructurally, the primary cilium region is complex, with normal ciliogenesis progressing through five distinct morphological stages in human astrocytes. Defects in early stages of ciliogenesis are key features of astrocytoma/glioblastoma cell lines and provided the impetus for the current study which describes the morphology of primary cilia in molecularly characterized human glioblastoma multiforme (GBM) tumors. Seven surgically resected human GBM tissue samples were molecularly characterized according to IDH1/2 mutation status, EGFR amplification status and MGMT promoter methylation status and were examined for primary cilia expression and structure using indirect immunofluorescence and electron microscopy. We report for the first time that primary cilia are disrupted in the early stages of ciliogenesis in human GBM tumors. We confirm that immature primary cilia and basal bodies/centrioles have aberrant ciliogenesis characteristics including absent paired vesicles, misshaped/swollen vesicular hats, abnormal configuration of distal appendages, and discontinuity of centriole microtubular blades. Additionally, the transition zone plate is able to form in the absence of paired vesicles on the distal end of the basal body and when a cilium progresses beyond the early stages of ciliogenesis, it has electron dense material clumped along the transition zone and a darkening of the microtubules at the proximal end of the cilium. Primary cilia play a role in a variety of human cancers. Previously primary cilia structure was perturbed in cultured cell lines derived from astrocytomas/glioblastomas; however there was always some question as to whether these findings were a cell culture phenomena. In this study we confirm that disruptions in ciliogenesis at early stages do occur in GBM tumors and that these ultrastructural findings bear resemblance to those previously

  2. A prospective examination of circulating tumor cell profiles in non-small-cell lung cancer molecular subgroups.

    Science.gov (United States)

    Lindsay, C R; Faugeroux, V; Michiels, S; Pailler, E; Facchinetti, F; Ou, D; Bluthgen, M V; Pannet, C; Ngo-Camus, M; Bescher, G; Caramella, C; Billiot, F; Remon, J; Planchard, D; Soria, J-C; Besse, B; Farace, F

    2017-07-01

    We report the first study examining the clinical, numerical and biological properties of circulating tumor cells according to molecular subtypes of non-small-cell lung cancer. 125 patients with treatment-naïve stage IIIb-IV NSCLC were prospectively recruited for CellSearch analysis. Anti-vimentin antibody was included for examination of CTCs to assess their mesenchymal character. Associations of total CTCs and vimentin-positive (vim +) CTCs with clinical characteristics, tumor genotype, and survival were assessed. 51/125 patients (40.8%) were total CTC+ and 26/125 (20.8%) were vim CTC+ at baseline. Multivariate analysis showed patients with ≥5 total CTCs had significantly reduced OS (HR 0.55, 95% CI 0.33-0.92, P = 0.022) but not PFS (HR 0.68, 95% CI 0.42-1.1, P = 0.118) compared to patients with <5 total CTCs. No OS difference was evident between vim+ CTC and vim-negative CTC patients overall (HR 1.24, 95% CI 0.67-2.28, P = 0.494), but after subdivision according to NSCLC driver mutation, we found an increase of vim+ CTCs in the EGFR-mutated subgroup (N = 21/94 patients; mean 1.24 vs 1.22 vim+ CTCs, P = 0.013), a reduction of total CTCs in the ALK-rearranged subgroup (N = 13/90 patients; mean 1.69 vs 5.82 total CTCs, P = 0.029), and a total absence of vim+ CTCs in KRAS-mutated adenocarcinomas (N = 19/78 patients; mean 0 vs 1.4 vim+ CTCs, P = 0.006). We validate that the baseline presence of ≥5 total CTCs in advanced NSCLC confers a poor prognosis. CTCs from EGFR-mutant NSCLC express epithelial-mesenchymal transition characteristics, not seen in CTCs from patients with KRAS-mutant adenocarcinoma. © The Author 2017. Published by Oxford University Press on behalf of the European Society for Medical Oncology. All rights reserved. For Permissions, please email: journals.permissions@oup.com.

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

    Directory of Open Access Journals (Sweden)

    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

  4. The effect of clomethiazole on plasma concentrations of interleukin-6, -8, -1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation.

    LENUS (Irish Health Repository)

    Harmon, D

    2012-02-03

    Clomethiazole (CMZ), a neuroprotective drug, has antiinflammatory actions. We investigated the effects of CMZ administration on plasma concentrations of interleukin (IL)-6, IL-8, IL-1beta, tumor necrosis factor-alpha, and neutrophil adhesion molecule expression during experimental extracorporeal circulation. Five healthy volunteers each donated 500 mL of blood, which was subsequently divided into equal portions. Identical extracorporeal circuits were simultaneously primed with donated blood (250 mL) and circulated for 2 h at 37 degrees C. CMZ was added to 1 of the circuits of each pair to achieve a total plasma concentration of 40 micro mol\\/L. Blood samples were withdrawn at (i) donation, (ii) immediately after addition of CMZ, and at (iii) 30, 60, 90, and 120 min after commencing circulation. Plasma concentrations of IL-6, IL-8, and tumor necrosis factor-alpha were less in the CMZ group compared with control after 60 min of circulation (2.2 [0.3] versus 3.2 [0.4], 14.9 [4.8] versus 21.9 [18.4], 63.3 [43.5] versus 132.2 [118.9] pg\\/mL, respectively, P < 0.05). After 120 min of circulation, neutrophils from CMZ-treated circuits showed significantly less CD18 expression compared with control (237.5 [97.4] versus 280.5 [111.5], P = 0.03). The addition of CMZ to experimental extracorporeal circuits decreases the inflammatory response. This effect may be of clinical benefit by decreasing inflammatory-mediated neurological injury during cardiopulmonary bypass. IMPLICATIONS: Enhancement of gamma-aminobutyric acid(A)-mediated effects by clomethiazole (CMZ) and associated neuroprotection has been established in animal models of cerebral ischemia. In an ex vivo study, we demonstrated antiinflammatory activity of CMZ in experimental extracorporeal circulation. This represents a potential neuroprotective mechanism of CMZ in patients undergoing coronary artery bypass surgery.

  5. Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

    Directory of Open Access Journals (Sweden)

    Laura Blumenthal

    2015-10-01

    Full Text Available Merkel cell carcinoma (MCC is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC.

  6. Multiple Primary Merkel Cell Carcinomas Presenting as Pruritic, Painful Lower Leg Tumors

    Science.gov (United States)

    Blumenthal, Laura; VandenBoom, Timothy; Melian, Edward; Peterson, Anthony; Hutchens, Kelli A.

    2015-01-01

    Merkel cell carcinoma (MCC) is a rare and highly aggressive neuroendocrine tumor of the skin which almost exclusively presents as a solitary tumor. It is most often seen on sun-exposed regions, historically almost exclusively on the head and neck, with only rare case reports on the extremities. Although recent studies have shown increased incidence with up to 20% on the extremities, here we present one of these rare emerging presentations, with the addition of a unique treatment option. Our patient is an 80-year-old male with a 3-month history of multiple raised, rapidly enlarging tumors on the right ankle. Two separate biopsies were performed and demonstrated sheets and clusters of small blue cells filling the dermis with scant cytoplasm, dusty chromatin, and nuclear molding. Subsequent immunohistochemical stains confirmed the diagnosis of multiple primary MCC. Despite the characteristic immunohistochemical profile of primary MCC, the possibility of a metastatic neuroendocrine carcinoma from an alternate primary site was entertained, given his unusual clinical presentation. A complete clinical workup including CT scans of the chest, abdomen, and pelvis showed no evidence of disease elsewhere. Instead of amputation, the patient opted for nonsurgical treatment with radiation therapy alone, resulting in a rapid and complete response. This case represents an unusual presentation of primary MCC and demonstrates further evidence that radiation as monotherapy is an effective local treatment option for inoperable MCC. PMID:26594171

  7. Comparative genomic and proteomic analysis of high grade glioma primary cultures and matched tumor in situ.

    LENUS (Irish Health Repository)

    Howley, R

    2012-10-15

    Developing targeted therapies for high grade gliomas (HGG), the most common primary brain tumor in adults, relies largely on glioma cultures. However, it is unclear if HGG tumorigenic signaling pathways are retained under in-vitro conditions. Using array comparative genomic hybridization and immunohistochemical profiling, we contrasted the epidermal and platelet-derived growth factor receptor (EGFR\\/PDGFR) in-vitro pathway status of twenty-six primary HGG cultures with the pathway status of their original HGG biopsies. Genomic gains or amplifications were lost during culturing while genomic losses were more likely to be retained. Loss of EGFR amplification was further verified immunohistochemically when EGFR over expression was decreased in the majority of cultures. Conversely, PDGFRα and PDGFRβ were more abundantly expressed in primary cultures than in the original tumor (p<0.05). Despite these genomic and proteomic differences, primary HGG cultures retained key aspects of dysregulated tumorigenic signaling. Both in-vivo and in-vitro the presence of EGFR resulted in downstream activation of P70s6K while reduced downstream activation was associated with the presence of PDGFR and the tumor suppressor, PTEN. The preserved pathway dysregulation make this glioma model suitable for further studies of glioma tumorigenesis, however individual culture related differences must be taken into consideration when testing responsiveness to chemotherapeutic agents.

  8. Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues.

    Science.gov (United States)

    Cifola, Ingrid; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A

    2011-06-13

    Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

  9. Renal cell carcinoma primary cultures maintain genomic and phenotypic profile of parental tumor tissues

    International Nuclear Information System (INIS)

    Cifola, Ingrid; Magni, Fulvio; Signorini, Stefano; Battaglia, Cristina; Perego, Roberto A; Bianchi, Cristina; Mangano, Eleonora; Bombelli, Silvia; Frascati, Fabio; Fasoli, Ester; Ferrero, Stefano; Di Stefano, Vitalba; Zipeto, Maria A

    2011-01-01

    Clear cell renal cell carcinoma (ccRCC) is characterized by recurrent copy number alterations (CNAs) and loss of heterozygosity (LOH), which may have potential diagnostic and prognostic applications. Here, we explored whether ccRCC primary cultures, established from surgical tumor specimens, maintain the DNA profile of parental tumor tissues allowing a more confident CNAs and LOH discrimination with respect to the original tissues. We established a collection of 9 phenotypically well-characterized ccRCC primary cell cultures. Using the Affymetrix SNP array technology, we performed the genome-wide copy number (CN) profiling of both cultures and corresponding tumor tissues. Global concordance for each culture/tissue pair was assayed evaluating the correlations between whole-genome CN profiles and SNP allelic calls. CN analysis was performed using the two CNAG v3.0 and Partek software, and comparing results returned by two different algorithms (Hidden Markov Model and Genomic Segmentation). A very good overlap between the CNAs of each culture and corresponding tissue was observed. The finding, reinforced by high whole-genome CN correlations and SNP call concordances, provided evidence that each culture was derived from its corresponding tissue and maintained the genomic alterations of parental tumor. In addition, primary culture DNA profile remained stable for at least 3 weeks, till to third passage. These cultures showed a greater cell homogeneity and enrichment in tumor component than original tissues, thus enabling a better discrimination of CNAs and LOH. Especially for hemizygous deletions, primary cultures presented more evident CN losses, typically accompanied by LOH; differently, in original tissues the intensity of these deletions was weaken by normal cell contamination and LOH calls were missed. ccRCC primary cultures are a reliable in vitro model, well-reproducing original tumor genetics and phenotype, potentially useful for future functional approaches

  10. Comparison of three different methods for the detection of circulating tumor cells in mice with lung metastasis.

    Science.gov (United States)

    Xu, Weifeng; Wu, Bing; Fu, Lengxi; Chen, Junying; Wang, Zeng; Huang, Fei; Chen, Jinrong; Zhang, Mei; Zhang, Zhenhuan; Lin, Jingan; Lan, Ruilong; Chen, Ruiqing; Chen, Wei; Chen, Long; Hong, Jinsheng; Zhang, Weijian; Ding, Yuxiong; Okunieff, Paul; Lin, Jianhua; Zhang, Lurong

    2017-06-01

    Circulating tumor cells (CTCs) represent the key step of cancer cell dissemination. The alteration of CTCs correlates with the treatment outcome and prognosis. To enrich and identify CTCs from billions of blood cells renders a very challenging task, which triggers development of several methods, including lysis of RBC plus negative or positive enrichment using antibodies, and filter membrane or spiral microfluidics to capture CTCs. To compare the advantages of different enrichment methods for CTCs, we utilized the 4T1 breast cancer cells transfected with both green fluorescent protein (GFP) and luciferase to trace CTCs in the experimental lung metastasis model. Three methods were used to detect CTCs at the same time: bioluminescence assay, smearing method, and membrane filter method. The in vivo alive mouse imaging was used to dynamically monitor the growth of lung metastases. The sensitivity and accuracy of three detection methods were compared side-by-side. Our results showed that 1) the sensitivity of bioluminescence assay was the highest, but there was no information of CTC morphology; 2) the smearing method and membrane filter method could observe the detail of CTC morphology, such as in single or in cluster, while their sensitivity was lower than bioluminescence assay; 3) A dynamic observation at a 7-day intervals, the lung metastatic cancer grew at a log speed, while CTCs were increased at a low speed. This might be due to the activated immune cells eliminating the CTCs at a speed much faster than CTCs were generated. This comparison of three CTC detection methods in mouse model suggests that bioluminescence assay could be used in quantitative study of the effect of certain agent on the suppression of CTCs, while GFP-based morphological assays could be used to study the dissemination mechanism of CTCs. The combination of both bioluminescence assay and GFP-based assay would generate more information for quantity and quality of CTCs.

  11. Optical Quantification of Cellular Mass, Volume, and Density of Circulating Tumor Cells Identified in an Ovarian Cancer Patient

    International Nuclear Information System (INIS)

    Phillips, Kevin G.; Velasco, Carmen Ruiz; Li, Julia; Kolatkar, Anand; Luttgen, Madelyn; Bethel, Kelly; Duggan, Bridgette; Kuhn, Peter; McCarty, Owen J. T.

    2012-01-01

    Clinical studies have demonstrated that circulating tumor cells (CTCs) are present in the blood of cancer patients with known metastatic disease across the major types of epithelial malignancies. Recent studies have shown that the concentration of CTCs in the blood is prognostic of overall survival in breast, prostate, colorectal, and non-small cell lung cancer. This study characterizes CTCs identified using the high-definition (HD)-CTC assay in an ovarian cancer patient with stage IIIC disease. We characterized the physical properties of 31 HD-CTCs and 50 normal leukocytes from a single blood draw taken just prior to the initial debulking surgery. We utilized a non-interferometric quantitative phase microscopy technique using brightfield imagery to measure cellular dry mass. Next we used a quantitative differential interference contrast microscopy technique to measure cellular volume. These techniques were combined to determine cellular dry mass density. We found that HD-CTCs were more massive than leukocytes: 33.6 ± 3.2 pg (HD-CTC) compared to 18.7 ± 0.6 pg (leukocytes), p < 0.001; had greater volumes: 518.3 ± 24.5 fL (HD-CTC) compared to 230.9 ± 78.5 fL (leukocyte), p < 0.001; and possessed a decreased dry mass density with respect to leukocytes: 0.065 ± 0.006 pg/fL (HD-CTC) compared to 0.085 ± 0.004 pg/fL (leukocyte), p < 0.006. Quantification of HD-CTC dry mass content and volume provide key insights into the fluid dynamics of cancer, and may provide the rationale for strategies to isolate, monitor or target CTCs based on their physical properties. The parameters reported here can also be incorporated into blood cell flow models to better understand metastasis.

  12. An RNA-Based Digital Circulating Tumor Cell Signature Is Predictive of Drug Response and Early Dissemination in Prostate Cancer.

    Science.gov (United States)

    Miyamoto, David T; Lee, Richard J; Kalinich, Mark; LiCausi, Joseph A; Zheng, Yu; Chen, Tianqi; Milner, John D; Emmons, Erin; Ho, Uyen; Broderick, Katherine; Silva, Erin; Javaid, Sarah; Kwan, Tanya Todorova; Hong, Xin; Dahl, Douglas M; McGovern, Francis J; Efstathiou, Jason A; Smith, Matthew R; Sequist, Lecia V; Kapur, Ravi; Wu, Chin-Lee; Stott, Shannon L; Ting, David T; Giobbie-Hurder, Anita; Toner, Mehmet; Maheswaran, Shyamala; Haber, Daniel A

    2018-03-01

    Blood-based biomarkers are critical in metastatic prostate cancer, where characteristic bone metastases are not readily sampled, and they may enable risk stratification in localized disease. We established a sensitive and high-throughput strategy for analyzing prostate circulating tumor cells (CTC) using microfluidic cell enrichment followed by digital quantitation of prostate-derived transcripts. In a prospective study of 27 patients with metastatic castration-resistant prostate cancer treated with first-line abiraterone, pretreatment elevation of the digital CTC M score identifies a high-risk population with poor overall survival (HR = 6.0; P = 0.01) and short radiographic progression-free survival (HR = 3.2; P = 0.046). Expression of HOXB13 in CTCs identifies 6 of 6 patients with ≤12-month survival, with a subset also expressing the ARV7 splice variant. In a second cohort of 34 men with localized prostate cancer, an elevated preoperative CTC L score predicts microscopic dissemination to seminal vesicles and/or lymph nodes ( P digital quantitation of CTC-specific transcripts enables noninvasive monitoring that may guide treatment selection in both metastatic and localized prostate cancer. Significance: There is an unmet need for biomarkers to guide prostate cancer therapies, for curative treatment of localized cancer and for application of molecularly targeted agents in metastatic disease. Digital quantitation of prostate CTC-derived transcripts in blood specimens is predictive of abiraterone response in metastatic cancer and of early dissemination in localized cancer. Cancer Discov; 8(3); 288-303. ©2018 AACR. See related commentary by Heitzer and Speicher, p. 269 This article is highlighted in the In This Issue feature, p. 253 . ©2018 American Association for Cancer Research.

  13. Statistical performance of image cytometry for DNA, lipids, cytokeratin, & CD45 in a model system for circulation tumor cell detection.

    Science.gov (United States)

    Futia, Gregory L; Schlaepfer, Isabel R; Qamar, Lubna; Behbakht, Kian; Gibson, Emily A

    2017-07-01

    Detection of circulating tumor cells (CTCs) in a blood sample is limited by the sensitivity and specificity of the biomarker panel used to identify CTCs over other blood cells. In this work, we present Bayesian theory that shows how test sensitivity and specificity set the rarity of cell that a test can detect. We perform our calculation of sensitivity and specificity on our image cytometry biomarker panel by testing on pure disease positive (D + ) populations (MCF7 cells) and pure disease negative populations (D - ) (leukocytes). In this system, we performed multi-channel confocal fluorescence microscopy to image biomarkers of DNA, lipids, CD45, and Cytokeratin. Using custom software, we segmented our confocal images into regions of interest consisting of individual cells and computed the image metrics of total signal, second spatial moment, spatial frequency second moment, and the product of the spatial-spatial frequency moments. We present our analysis of these 16 features. The best performing of the 16 features produced an average separation of three standard deviations between D + and D - and an average detectable rarity of ∼1 in 200. We performed multivariable regression and feature selection to combine multiple features for increased performance and showed an average separation of seven standard deviations between the D + and D - populations making our average detectable rarity of ∼1 in 480. Histograms and receiver operating characteristics (ROC) curves for these features and regressions are presented. We conclude that simple regression analysis holds promise to further improve the separation of rare cells in cytometry applications. © 2017 International Society for Advancement of Cytometry. © 2017 International Society for Advancement of Cytometry.

  14. Development of on-chip multi-imaging flow cytometry for identification of imaging biomarkers of clustered circulating tumor cells.

    Directory of Open Access Journals (Sweden)

    Hyonchol Kim

    Full Text Available An on-chip multi-imaging flow cytometry system has been developed to obtain morphometric parameters of cell clusters such as cell number, perimeter, total cross-sectional area, number of nuclei and size of clusters as "imaging biomarkers", with simultaneous acquisition and analysis of both bright-field (BF and fluorescent (FL images at 200 frames per second (fps; by using this system, we examined the effectiveness of using imaging biomarkers for the identification of clustered circulating tumor cells (CTCs. Sample blood of rats in which a prostate cancer cell line (MAT-LyLu had been pre-implanted was applied to a microchannel on a disposable microchip after staining the nuclei using fluorescent dye for their visualization, and the acquired images were measured and compared with those of healthy rats. In terms of the results, clustered cells having (1 cell area larger than 200 µm2 and (2 nucleus area larger than 90 µm2 were specifically observed in cancer cell-implanted blood, but were not observed in healthy rats. In addition, (3 clusters having more than 3 nuclei were specific for cancer-implanted blood and (4 a ratio between the actual perimeter and the perimeter calculated from the obtained area, which reflects a shape distorted from ideal roundness, of less than 0.90 was specific for all clusters having more than 3 nuclei and was also specific for cancer-implanted blood. The collected clusters larger than 300 µm2 were examined by quantitative gene copy number assay, and were identified as being CTCs. These results indicate the usefulness of the imaging biomarkers for characterizing clusters, and all of the four examined imaging biomarkers-cluster area, nuclei area, nuclei number, and ratio of perimeter-can identify clustered CTCs in blood with the same level of preciseness using multi-imaging cytometry.

  15. Negative enrichment by immunomagnetic nanobeads for unbiased characterization of circulating tumor cells from peripheral blood of cancer patients

    Directory of Open Access Journals (Sweden)

    Tinhofer Ingeborg

    2011-05-01

    Full Text Available Abstract Background A limitation of positive selection strategies to enrich for circulating tumor cells (CTCs is that there might be CTCs with insufficient expression of the surface target marker which may be missed by the procedure. We optimized a method for enrichment, subsequent detection and characterization of CTCs based on depletion of the leukocyte fraction. Methods The 2-step protocol was developed for processing 20 mL blood and based on red blood cell lysis followed by leukocyte depletion. The remaining material was stained with the epithelial markers EpCAM and cytokeratin (CK 7/8 or for the melanoma marker HMW-MAA/MCSP. CTCs were detected by flow cytometry. CTCs enriched from blood of patients with carcinoma were defined as EpCAM+CK+CD45-. CTCs enriched from blood of patients with melanoma were defined as MCSP+CD45-. One-hundred-sixteen consecutive blood samples from 70 patients with metastatic carcinomas (n = 48 or metastatic melanoma (n = 22 were analyzed. Results CTCs were detected in 47 of 84 blood samples (56% drawn from carcinoma patients, and in 17 of 32 samples (53% from melanoma patients. CD45-EpCAM-CK+ was detected in pleural effusion specimens, as well as in peripheral blood samples of patients with NSCLC. EpCAM-CK+ cells have been successfully cultured and passaged longer than six months suggesting their neoplastic origin. This was confirmed by CGH. By defining CTCs in carcinoma patients as CD45-CK+ and/or EpCAM+, the detection rate increased to 73% (61/84. Conclusion Enriching CTCs using CD45 depletion allowed for detection of epithelial cancer cells not displaying the classical phenotype. This potentially leads to a more accurate estimation of the number of CTCs. If detection of CTCs without a classical epithelial phenotype has clinical relevance need to be determined.

  16. The relationship between MDM2 expression and tumor thickness and invasion in primary cutaneous malignant melanoma

    Directory of Open Access Journals (Sweden)

    Parvin Rajabi

    2012-01-01

    Full Text Available Background: Malignant melanoma is the most invasive cutaneous tumor which is associated with an incredibly high mortality rate. The most reliable histological factors associated with melanoma prognosis are tumor thickness- measured by the Breslow index- and invasion depth- measured by Clark level. Murine double minute 2 (MDM2 gene inhibits p53-dependent apoptosis. An increase in MDM2 expression has been found in many tumors. This study aimed to investigate MDM2 expression and its correlation with tumor thickness and invasion level in malignant melanoma. Materials and Methods: This study evaluated paraffin blocks from 43 randomly selected patients with primary cutaneous melanoma who referred to the main university pathology center in Isfahan, Iran. MDM2 expression rate was assessed via immunohistochemical techniques and hematoxylin and eosin staining to determine tumor thickness and invasion level. Correlations between MDM2 expression and tumor thickness and invasion were analyzed using Spearman′s correlation coefficient in SPSS 17 . Results: The mean age of patients was 61.2 ± 15 years. Men and women constituted 55.8% and 44.2% of the participants, respectively. The rate of MDM2 positivity was 28.9%. MDM2 expression was directly associated with tumor thickness (r = 0.425; p = 0.002 and weakly with invasion level (r = 0.343; p = 0.01. Conclusions: Despite the low MDM2 expression rate observed in this study, direct relationships between MDM2 positivity and tumor thickness and invasion level were identified. MDM2 expression can thus be suggested as a potential new predictive prognostic factor.

  17. Assessment of the long-term effects of primary radiation therapy for brain tumors in children

    International Nuclear Information System (INIS)

    Danoff, B.F.; Cowchock, F.S.; Marquette, C.; Mulgrew, L.; Kramer, S.

    1982-01-01

    One-hundred-twelve children with primary brain tumors received definitive radiotherapy between the years 1958-1979. Sixty-nine patients were alive at intervals of 1-21 years. Thirty-eight patients underwent neurologic and endocrine evaluation, psychologic and intelligence testing, and assessment for second malignancy post-treatment. A second intracranial malgnancy developed in one child, for an incidence of 1.6%. Performance status was good to excellent in 89% of the patients studied. Seventeen percent of the group were mentally retarded. Behavioral disorders were identified in 39% of the patients, 59% of the mothers, and 43% of the fathers. Of the 23 patients with nonparasellar tumors, six were found to have growth hormone deficiency, including two patients with panhypopituitarism. Disability was related to age under 3 years at the time of treatment and tumor extension to the hypothalamus

  18. Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

    Energy Technology Data Exchange (ETDEWEB)

    Santhanam, Prasanna; Chandramahanti, Sangeeta [Marshall University, Section of Endocrinology, Department of Internal Medicine, Joan C Edwards School of Medicine, Huntington, WV (United States); Kroiss, Alexander [Medical University Innsbruck, Department of Nuclear Medicine, Innsbruck (Austria); Yu, Run [Cedars-Sinai Medical Center, Division of Endocrinology and Carcinoid and Neuroendocrine Tumor Center, Los Angeles, CA (United States); Ruszniewski, Philippe [Beaujon Hospital and Paris-Diderot University, Department of Gastroenterology-Pancreatology, Paris (France); Kumar, Rakesh [All India Institute of Medical Sciences, Diagnostic Nuclear Medicine Division, Department of Nuclear Medicine, New Delhi (India); Taieb, David [Aix-Marseille University, Department of Nuclear Medicine, La Timone University Hospital, Marseille (France); Institut Paoli-Calmettes, Inserm UMR1068 Marseille Cancerology Research Center, Marseille (France); Aix-Marseille University, European Center for Research in Medical Imaging, Marseille (France)

    2015-03-13

    Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22 %), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as {sup 68}Ga-labeled somatostatin analogs ({sup 68}Ga-DOTA-SSTa) and {sup 18}F-DOPA have shown promise. In direct comparisons between {sup 68}Ga-DOTA-SSTa PET/CT and {sup 99m}Tc-HYNIC-octreotide/{sup 111}In-pentetreotide SPECT(/CT), {sup 68}Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. {sup 18}F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of {sup 18}F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with {sup 68}Ga-DOTA-SSTa, alternatively {sup 18}F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and {sup 18}F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly

  19. Nuclear imaging of neuroendocrine tumors with unknown primary: why, when and how?

    International Nuclear Information System (INIS)

    Santhanam, Prasanna; Chandramahanti, Sangeeta; Kroiss, Alexander; Yu, Run; Ruszniewski, Philippe; Kumar, Rakesh; Taieb, David

    2015-01-01

    Neuroendocrine tumors (NETs) with unknown primary (CUP-NET) are associated with a poor prognosis (10-year survival 22 %), grade 1 and 2 NETs having a more favorable outcome than grade 3 (also called carcinoma). There is evidence that an effort should be made to localize the primary tumor even in the presence of metastasis because resection of the primary tumor(s) may improve disease-free and overall survival, and because the choice of chemotherapeutic agent depends on the location of the primary tumor. Localization of the tumors remains challenging and often relies on a combination of radiological, endoscopic and functional imaging. The functional imaging protocol for evaluation of these patients has historically relied on somatostatin receptor scintigraphy (SRS). However, the sensitivity and specificity of SRS may be unsatisfactory, especially for NETs of midgut origin. Newer PET radiotracers such as 68 Ga-labeled somatostatin analogs ( 68 Ga-DOTA-SSTa) and 18 F-DOPA have shown promise. In direct comparisons between 68 Ga-DOTA-SSTa PET/CT and 99m Tc-HYNIC-octreotide/ 111 In-pentetreotide SPECT(/CT), 68 Ga-DOTA-SSTa performed better than other techniques, giving a compelling reason for switching from SPECT/CT to PET/CT imaging. 18 F-DOPA performs better than SRS and CT in well-differentiated NETs of the small intestine. For detecting pancreatic NETs, the high background uptake of 18 F-DOPA by the normal exocrine pancreas can be somewhat overcome by pretreatment with carbidopa. We have suggested a protocol in which SRS is replaced by one of the two agents (preferably with 68 Ga-DOTA-SSTa, alternatively 18 F-DOPA) as first-line nuclear tracer for detection of CUP-NET in patients with well-differentiated NETs and 18 F-FDG PET/CT may be an additional diagnostic test for poorly differentiated tumors and for prognostication. In the near future, it is expected that patients with CUP-NET will benefit from newly developed PET approaches (radiopharmaceuticals) and

  20. Second primary tumor and radiation induced neoplasma in the uterine cancer

    International Nuclear Information System (INIS)

    Sakurai, Tomoyasu; Nishio, Masamichi; Kagami, Yoshikazu; Murakami, Yoshitaka; Narimatsu, Naoto; Kanemoto, Toshitaka

    1984-01-01

    This report is concerned with multiple primary cancers developing in invasive uterine cancer. Second primary tumors were recorded 27 women with a total of 30 non-uterine cancer (exception of radiation-induced cancer). 17 patients of radiation-induced neoplasm were observed (Rectal cancer 4, soft part sarcoma 4, cancer of urinary bladder 3, bone tumor 3, uterin cancer 2 and cancer of Vulva 1). One case is 4 legions (corpus, sigma, thymoma and stomach), 2 cases are 3 lesions (uterine cervix, stomach and maxillay siuis: uterine cervix, thyroidal gland and radiation-induced soft part sarcoma). Only 5 of these 17 patients were known irradiated dose (50 Gy--55 Gy), however others unknown. The mean latent periods of 17 cases of radiation induced neoplasms are 19.4 years. 16 patients of late second cancers of the cervix appearing from 11 to 36 years (average 19.5 years) after initial radiotherapy were recorded. (author)

  1. Bone tumor

    Science.gov (United States)

    Tumor - bone; Bone cancer; Primary bone tumor; Secondary bone tumor; Bone tumor - benign ... The cause of bone tumors is unknown. They often occur in areas of the bone that grow rapidly. Possible causes include: Genetic defects ...

  2. Primary Cyst adenocarcinoma: exceptional etiology of a retroperitoneal cystic tumor.First National Communication

    International Nuclear Information System (INIS)

    Gonzalez, D.; Ruso, L.; Ettlin, A.

    2010-01-01

    This work is about the clinical case of a 29 year old patient who consulted for right lank pain, where a tumor was identified. Ultrasound confirmed the existence of a cystic process, and complete surgical abscission/exeresis was performed next to an area in the in the abdominal wall. Anatomopathological report confirmed a primary retroperitoneal cistoadenocarcinoma. No adjuvant treatment was applied, evolution was good 11 months after surgery, no evidence of the disease

  3. Primary Lung Signet Ring Cell Carcinoma Presenting as a Cavitary Pancoast Tumor in a 32-Year-Old Man.

    Science.gov (United States)

    Corvini, Michael; Koorji, Alysha; Sgroe, Erica; Nguyen, Uyen

    2018-06-01

    Signet ring cell carcinoma, a subtype of adenocarcinoma, is a rare cause of primary lung cancer. The authors report a case of primary lung signet ring cell carcinoma presenting as a cavitary Pancoast tumor in a 32-year-old male smoker. Beyond the rarity of primary lung signet ring cell carcinoma itself, the youth of the patient, his smoking status, the presence of cavitation, and the location of the tumor in the superior sulcus make it especially atypical.

  4. Expression and activity of the urokinase plasminogen activator system in canine primary brain tumors

    Directory of Open Access Journals (Sweden)

    Rossmeisl JH

    2017-04-01

    Full Text Available John H Rossmeisl,1–3 Kelli Hall-Manning,4 John L Robertson,1,3,5 Jamie N King,1,2 Rafael V Davalos,3,5 Waldemar Debinski,3 Subbiah Elankumaran6,† 1Veterinary and Comparative Neuro-Oncology Laboratory, 2Department of Small Animal Clinical Sciences, 3The Brain Tumor Center of Excellence, Wake Forest Baptist Medical Center Comprehensive Cancer Center, Winston-Salem, NC, 4Virginia Tech Animal Laboratory Services, Virginia-Maryland College of Veterinary Medicine, 5Department of Biomedical Engineering and Mechanics, Virginia Tech-Wake Forest University School of Biomedical Engineering and Sciences, Virginia Tech, 6Department of Biomedical Sciences and Pathobiology, Virginia-Maryland College of Veterinary Medicine, Blacksburg, VA, USA†The authors regret to advise of the passing of Dr Subbiah Elankumaran prior to publicationBackground: The expression of the urokinase plasminogen activator receptor (uPAR, a glycosylphosphatidylinositol-anchored protein family member, and the activity of its ligand, urokinase-type plasminogen activator (uPA, have been associated with the invasive and metastatic potentials of a variety of human brain tumors through their regulation of extracellular matrix degradation. Domesticated dogs develop naturally occurring brain tumors that share many clinical, phenotypic, molecular, and genetic features with their human counterparts, which has prompted the use of the dogs with spontaneous brain tumors as models to expedite the translation of novel brain tumor therapeutics to humans. There is currently little known regarding the role of the uPA system in canine brain tumorigenesis. The objective of this study was to characterize the expression of uPAR and the activity of uPA in canine brain tumors as justification for the development of uPAR-targeted brain tumor therapeutics in dogs.Methods: We investigated the expression of uPAR in 37 primary canine brain tumors using immunohistochemistry, Western blotting, real

  5. Bone and Gallium scintigraphy in primary malignant and benign bone tumors of the extremities

    International Nuclear Information System (INIS)

    Sepahdari, S.; Martin, W.B.; Ryan, J.; Simon, M.; Kirchner, P.

    1985-01-01

    A six yer prospective evaluation of 129 patients suspected of having a primary bone tumor included Tc-99m MDP bone scintigraphy followed by Ga-67 imaging at 48-72 hours. Blood pool images were part of bone scintigraphy in nearly half of the patients. Extent and intensity of tracer uptake in tumor and adjacent bone and joints were recorded for each tracer by two observers blind to the diagnosis. Tissue samples obtained in every patient by biopsy or tumor excision after scintigraphy, revealed 72 malignant and 57 benign bone tumors. The bone scan was positive in 95% (69/72) of malignancies. The scintigraphic intensity of benign and malignant lesions was comparable with both Tc-99m MDP and Ga-67. On the other hand, bone scintigraphy showed 72% (52/72) of bone malignancies to have abnormal proximal and distal bone/joint uptake whereas the Ga-67 images revealed this in only 6% (4/65) of malignancies. Benign lesions manifested this enhanced contiguous bone/joint uptake on only 8% (5/55) of bone and 0% of Ga-67 scans. This study concludes positive bone, blood pool, or Ga-67 images have less specificity for malignancy than the presence of increased Tc-99m MDP deposition in a contiguous bone/joint, but negative scintigraphic results strongly favor a benign lesion. Ga-67 was more accurate than Tc-99m MDP in portraying intraosseous extent of malignant tumors; however, this is now preferably done with C.T

  6. Brain scintigraphy (SPECT) using 201thallium in patients with primary tumors of the brain

    International Nuclear Information System (INIS)

    Barzen, G.; Schubert, C.; Richter, W.; Calder, D.; Eichstaedt, H.; Felix, R.; Baerwald, M.

    1992-01-01

    We evaluated the role of thallium 201 Single-Photon-Emission-Computed-Tomography (SPECT) in diagnosis, differential diagnosis and follow-up of 33 patients with primary brain tumors. 27 of 33 lesions were detectable by Tl-201-SPECT because only two of eight low-grade (grade 1 and 2) astrocytomas showed Tl-201 accumulation up to a tumor to nontumor ratio of 2.6. High grade (grade 3 and 4) astrocytomas showed Tl-201 accumulation in the range of 2.2 up to 13.0 and were different from low-grade astrocytomas. Noninvasive grading of astrocytomas is therefore possible, whereas differential diagnosis of oligodendrogliomas and astrocytomas or meningeomas was not possible with Tl-201. In the follow-up of six patients, we could demonstrate, that tumor progression is correlated with increasing and tumor regression with decreasing Tl-201 accumulations. This functional changings proceed morphological findings in CT. But vanishing of Tl-201 accumulation during therapy does not mean vanishing of tumor as could be demonstrated by follow-up. (orig.) [de

  7. Staging of primary head and neck tumors and detection of recurrences

    International Nuclear Information System (INIS)

    Adams, S.; Baum, R.P.; Knecht, R.; Hoer, G.

    2001-01-01

    Squamous cell carcinomas represent the vast majority of all malignant tumors of the head and neck region. Lymph node involvement is the most important prognostic factor affecting survival of patients with head and neck cancer. The effectiveness of surgical treatment depends on the complete excision of all tumor tissue and an accurate preoperative diagnosis. Tumor-node-metastasis (TNM) staging is therefore mandatory. In comparison to positron emission tomography with fluorine-18 fluorodeoxyglucose (FDG PET), morphological imaging modalities (CT, MRI) have been applied for the localization of primary head and neck tumors because of their better anatomical resolution. Metabolic tumor imaging using FDG PET is superior to morphological imaging by CT and MRI in the detection of small cervical lymph node metastases (Class 1a indication). Increased FDG uptake has also been observed in benign inflammatory lesions after radiation therapy, therefore detection of local recurrence with FDG PET can be problematic. To ensure a high diagnostic accuracy it is been suggested to perform FDG PET not earlier than 3 months after radiation therapy (Class 1a indication for the diagnosis of local recurrence). (orig.) [de

  8. Preliminary clinical results of locoregional hyperthermia for primary and secondary bone tumors

    Energy Technology Data Exchange (ETDEWEB)

    Zhu, J.L.; Nagata, Yasushi; Kanamori, Shuichi; Mitsumori, Michihide; Okuno, Yoshishige; Horii, Naotoshi; Nishimura, Yasumasa; Masunaga, Shinitiro; Hiraoka, Masahiro [Kyoto Univ. (Japan). Graduate School of Medicine

    2000-03-01

    Nineteen primary and secondary bone tumors in 16 patients were treated with hyperthermia plus radiotherapy and/or chemotherapy between 1982 and 1997 at Kyoto University Hospital. The thermometric and clinical results were analyzed retrospectively. In 55 of 86 hyperthermia sessions, the intratumor temperature was measured using a thermometer. Of the 19 tumors, 16 (84%) received heat treatment 4-7 times, and 3 (16%) received 1 or 2 treatments of hyperthermia. The mean maximum, mean minimum and average intratumor temperatures were 42.9, 40.4 and 41.6 deg C, respectively, and 12 (67%) reached a tumor maximum temperature above 42.5 deg C. The durations that intratumor points exceeded 42, 41 and 40 deg C were 27, 34 and 38 min, respectively. The local tumor response to treatment was assessed using X-ray computed tomography. The local response rate was 16% and the local pain relief rate was 63%. The 1-year cumulative survival rate was 60%. Our preliminary results indicated that thermoradiotherapy and thermochemotherapy are clinicaly feasible and potentially beneficial in the management of locally advanced bone tumors. (author)

  9. Computed tomographic aspects of primary brain tumors in dogs and cats

    International Nuclear Information System (INIS)

    Babicsak, Viviam Rocco; Zardo, Karen Maciel; Santos, Debora Rodrigues dos; Silva, Luciana Carandina da; Machado, Vania Maria de Vasconcelos; Vulcano, Luiz Carlos

    2011-01-01

    Over the years, the Veterinary Medicine has made great advances, enabling thus the diagnosis of many diseases. As a result of this new situation, there was an increased expectation of life of animals resulting in an increase in the number of clinical care of older animals. Thus, diseases considered unusual in the past, begin to be diagnosed more frequently, as is the case of brain damage. Recently, computed tomography has been widely used in Brazil as a tool to aid in the diagnosis of several diseases. This noninvasive imaging technique allows the identification and evaluation of lesions of central nervous tissue such as brain tumors. This provides information about the size, shape and location of the lesion, in addition to the magnitude of compression and invasion of adjacent structures by the tumor and its side effects (such as the peritumoral edema and hydrocephalus). The image obtained from computed tomography may suggest the presence of a certain type brain tumor, data of great importance for the prognosis and treatment of the animal. This review covers the computed tomography aspects of primary brain tumors such as meningiomas, astrocytomas, oligodendrogliomas, choroid plexus tumors and ependymomas. However, despite the computed tomography provide much information about the changes inside the skull; no way replace histopathological examination in determining the definitive diagnosis. (author)

  10. Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines

    OpenAIRE

    Fichna, Marta; Fichna, Piotr; Gryczy?ska, Maria; Czarnywojtek, Agata; ?urawek, Magdalena; Rucha?a, Marek

    2014-01-01

    Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7???14.1?years) and 63 healthy c...

  11. Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

    Directory of Open Access Journals (Sweden)

    Sarkar Chitra

    2007-10-01

    Full Text Available Abstract Background A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations. In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells. Methods Random Amplified Polymorphic DNA (RAPD analysis was performed using a set of fifteen 10-mer primers of arbitrary but definite sequences in 17 WHO grade II astrocytomas (low grade diffuse astrocytoma or DA and 16 WHO grade IV astrocytomas (Glioblastoma Multiforme or GBM. The RAPD profile of the tumor tissue was compared with that of the leucocyte DNA of the same patient and alteration(s scored. A quantitative estimate of the overall genomic changes in these tumors was obtained by 2 different modes of calculation. Results The overall change in the tumors was estimated to be 4.24% in DA and 2.29% in GBM by one method and 11.96% and 6.03% in DA and GBM respectively by the other. The difference between high and lower grade tumors was statistically significant by both methods. Conclusion This study demonstrates the presence of extensive clonal mutations in gliomas, more in lower grade. This is consistent with our earlier work demonstrating that technique like RAPD analysis, unbiased for locus, is able to demonstrate more intra-tumor genetic heterogeneity in lower grade gliomas compared to higher grade. The results support the mutator hypothesis proposed by Loeb.

  12. Clonal mutations in primary human glial tumors: evidence in support of the mutator hypothesis

    International Nuclear Information System (INIS)

    Misra, Anjan; Chattopadhyay, Parthaprasad; Chosdol, Kunzang; Sarkar, Chitra; Mahapatra, Ashok K; Sinha, Subrata

    2007-01-01

    A verifiable consequence of the mutator hypothesis is that even low grade neoplasms would accumulate a large number of mutations that do not influence the tumor phenotype (clonal mutations). In this study, we have attempted to quantify the number of clonal mutations in primary human gliomas of astrocytic cell origin. These alterations were identified in tumor tissue, microscopically confirmed to have over 70% neoplastic cells. Random Amplified Polymorphic DNA (RAPD) analysis was performed using a set of fifteen 10-mer primers of arbitrary but definite sequences in 17 WHO grade II astrocytomas (low grade diffuse astrocytoma or DA) and 16 WHO grade IV astrocytomas (Glioblastoma Multiforme or GBM). The RAPD profile of the tumor tissue was compared with that of the leucocyte DNA of the same patient and alteration(s) scored. A quantitative estimate of the overall genomic changes in these tumors was obtained by 2 different modes of calculation. The overall change in the tumors was estimated to be 4.24% in DA and 2.29% in GBM by one method and 11.96% and 6.03% in DA and GBM respectively by the other. The difference between high and lower grade tumors was statistically significant by both methods. This study demonstrates the presence of extensive clonal mutations in gliomas, more in lower grade. This is consistent with our earlier work demonstrating that technique like RAPD analysis, unbiased for locus, is able to demonstrate more intra-tumor genetic heterogeneity in lower grade gliomas compared to higher grade. The results support the mutator hypothesis proposed by Loeb

  13. Primary peripheral primitive neuroectodermal tumor/Ewing's tumor of the testis in a 46-year-old man-differential diagnosis and review of the literature.

    Science.gov (United States)

    Heikaus, Sebastian; Schaefer, Karl-Ludwig; Eucker, Jan; Hogrebe, Esther; Danebrock, Raihanatou; Wai, Daniel H; Krenn, Veit; Gabbert, Helmut E; Poremba, Christopher

    2009-06-01

    Peripheral primitive neuroectodermal tumor/Ewing's tumors are rare bone and soft tissue malignancies with a highly aggressive clinical course and early metastases occurring at multiple peripheral sites. Here, we present for the first time a case of a 46-year-old man with a primary peripheral primitive neuroectodermal tumor/Ewing's tumor of the testis. The diagnosis of peripheral primitive neuroectodermal tumor/Ewing's tumor was established by histology, immunohistochemistry, and molecular pathology. The tumor revealed a rapid progress in 2 months' time. Therefore, the patient was included in the EURO-E.W.I.N.G.99 study and was placed on chemotherapy. However, the tumor progressed during ongoing therapy, and the patient died in March 2008. In conclusion, though being reported here for the first time, peripheral primitive neuroectodermal tumor/Ewing's tumors should be considered in the differential diagnosis of blue round cell tumors of the testis. A rapid and correct diagnosis of this entity is crucial for fast and accurate therapy, which is stressed by the fatal case presented here.

  14. In vitro culture and characterization of human lung cancer circulating tumor cells isolated by size exclusion from an orthotopic nude-mouse model expressing fluorescent protein.

    Science.gov (United States)

    Kolostova, Katarina; Zhang, Yong; Hoffman, Robert M; Bobek, Vladimir

    2014-09-01

    In the present study, we demonstrate an animal model and recently introduced size-based exclusion method for circulating tumor cells (CTCs) isolation. The methodology enables subsequent in vitro CTC-culture and characterization. Human lung cancer cell line H460, expressing red fluorescent protein (H460-RFP), was orthotopically implanted in nude mice. CTCs were isolated by a size-based filtration method and successfully cultured in vitro on the separating membrane (MetaCell®), analyzed by means of time-lapse imaging. The cultured CTCs were heterogeneous in size and morphology even though they originated from a single tumor. The outer CTC-membranes were blebbing in general. Abnormal mitosis resulting in three daughter cells was frequently observed. The expression of RFP ensured that the CTCs originated from lung tumor. These readily isolatable, identifiable and cultivable CTCs can be used to characterize individual patient cancers and for screening of more effective treatment.

  15. Homogeneous pancreatic cancer spheroids mimic growth pattern of circulating tumor cell clusters and macrometastases: displaying heterogeneity and crater-like structure on inner layer.

    Science.gov (United States)

    Feng, Hao; Ou, Bao-Chi; Zhao, Jing-Kun; Yin, Shuai; Lu, Ai-Guo; Oechsle, Eva; Thasler, Wolfgang E

    2017-09-01

    Pancreatic cancer 3D in vitro models including multicellular tumor spheroid (MCTS), single cell-derived tumor spheroid (SCTS), tissue-derived tumor spheroid, and organotypic models provided powerful platforms to mimic in vivo tumor. Recent work supports that circulating tumor cell (CTC) clusters are more efficient in metastasis seeding than single CTCs. The purpose of this study is to establish 3D culture models which can mimic single CTC, monoclonal CTC clusters, and the expansion of macrometastases. Seven pancreatic ductal adenocarcinoma cell lines were used to establish MCTS and SCTS using hanging drop and ultra-low attachment plates. Spheroid immunofluorescence staining, spheroid formation assay, immunoblotting, and literature review were performed to investigate molecular biomarkers and the morphological characteristics of pancreatic tumor spheroids. Single cells experienced different growth patterns to form SCTS, like signet ring-like cells, blastula-like structures, and solid core spheroids. However, golf ball-like hollow spheroids could also be detected, especially when DanG and Capan-1 cells were cultivated with fibroblast-conditioned medium (p cell lines could also establish tumor spheroid with hanging drop plates by adding methylated cellulose. Tumor spheroids derived from pancreatic cancer cell line DanG possessed asymmetrically distributed proliferation center, immune-checkpoint properties. ß-catenin, Ki-67, and F-actin were active surrounding the crater-like structure distributing on the inner layer of viable rim cover of the spheroids, which was relevant to well-differentiated tumor cells. It is possible to establish 3D CTC cluster models from homogenous PDA cell lines using hanging drop and ultra-low attachment plates. PDA cell line displays its own intrinsic properties or heterogeneity. The mechanism of formation of the crater-like structure as well as golf ball-like structure needs further exploration.

  16. Reovirus FAST Protein Enhances Vesicular Stomatitis Virus Oncolytic Virotherapy in Primary and Metastatic Tumor Models

    Directory of Open Access Journals (Sweden)

    Fabrice Le Boeuf

    2017-09-01

    Full Text Available The reovirus fusion-associated small transmembrane (FAST proteins are the smallest known viral fusogens (∼100–150 amino acids and efficiently induce cell-cell fusion and syncytium formation in multiple cell types. Syncytium formation enhances cell-cell virus transmission and may also induce immunogenic cell death, a form of apoptosis that stimulates immune recognition of tumor cells. These properties suggest that FAST proteins might serve to enhance oncolytic virotherapy. The oncolytic activity of recombinant VSVΔM51 (an interferon-sensitive vesicular stomatitis virus [VSV] mutant encoding the p14 FAST protein (VSV-p14 was compared with a similar construct encoding GFP (VSV-GFP in cell culture and syngeneic BALB/c tumor models. Compared with VSV-GFP, VSV-p14 exhibited increased oncolytic activity against MCF-7 and 4T1 breast cancer spheroids in culture and reduced primary 4T1 breast tumor growth in vivo. VSV-p14 prolonged survival in both primary and metastatic 4T1 breast cancer models, and in a CT26 metastatic colon cancer model. As with VSV-GFP, VSV-p14 preferentially replicated in vivo in tumors and was cleared rapidly from other sites. Furthermore, VSV-p14 increased the numbers of activated splenic CD4, CD8, natural killer (NK, and natural killer T (NKT cells, and increased the number of activated CD4 and CD8 cells in tumors. FAST proteins may therefore provide a multi-pronged approach to improving oncolytic virotherapy via syncytium formation and enhanced immune stimulation.

  17. Detection of primary tumor by 18F-FDG-TEP in patients with cup syndrome

    International Nuclear Information System (INIS)

    Alberini, J.L.; Belhocine, T.; Daenen, F.; Hustinx, R.; Rigo, P.

    2000-01-01

    To study the performance of whole body 18 F-FDG-PET in the detection of the primary tumor in patients with unknown primary carcinoma in comparison with conventional imaging. Patients and methods: Forty-one patients, without previous history of known cancer, (18 women and 23 men; average age 64,1 years) with bone, brain, lymph node, liver, cutaneous, pleural and epidural metastases were included in a retrospective study. Results of PET (UGM Penn PET 240 H) were compared with those of techniques used in the current conventional procedure. There were 26 true positives, 2 false negatives (1 renal carcinoma and 1 myeloma) and one false positive results. Origins were lung [16], gut [6], breast [3] and head and neck [1] but stayed undetermined in 8 patients. Results of PET were superior to conventional diagnostic procedure in 12 patients and led to modify the therapy management in 11 patients. All known metastatic lesions were detected by PET. FDG-PET can be useful to determine the origin of metastasis. It allows detection of the primary tumor (26/33 patients) and allows evaluation of the spread of the disease. These results have to be confirmed and particularly in patients with highly treatable unknown primary carcinoma. (author)

  18. Glutamate-Mediated Primary Somatosensory Cortex Excitability Correlated with Circulating Copper and Ceruloplasmin

    Directory of Open Access Journals (Sweden)

    Franca Tecchio

    2011-01-01

    Full Text Available Objective. To verify whether markers of metal homeostasis are related to a magnetoencephalographic index representative of glutamate-mediated excitability of the primary somatosensory cortex. The index is identified as the source strength of the earliest component (M20 of the somatosensory magnetic fields (SEFs evoked by right median nerve stimulation at wrist. Method. Thirty healthy right-handed subjects (51±22 years were enrolled in the study. A source reconstruction algorithm was applied to assess the amount of synchronously activated neurons subtending the M20 and the following SEF component (M30, which is generated by two independent contributions of gabaergic and glutamatergic transmission. Serum copper, ceruloplasmin, iron, transferrin, transferrin saturation, and zinc levels were measured. Results. Total copper and ceruloplasmin negatively correlated with the M20 source strength. Conclusion. This pilot study suggests that higher level of body copper reserve, as marked by ceruloplasmin variations, parallels lower cortical glutamatergic responsiveness.

  19. Contaminação tumoral em trajeto de biópsia de tumores ósseos malignos primários Tumor contamination in the biopsy path of primary malignant bone tumors

    Directory of Open Access Journals (Sweden)

    Marcelo Parente Oliveira

    2012-10-01

    Full Text Available OBJETIVO: Estudar os fatores possivelmente associados à contaminação tumoral do trajeto de biópsia de tumores ósseos malignos primários. MÉTODO: Foram estudados, retrospectivamente, 35 pacientes submetidos a tratamento cirúrgico com diagnóstico de osteossarcoma, tumor de Ewing e condrossarcoma. A amostra foi analisada para caracterização quanto à técnica de biópsia empregada, tipo histológico do tumor, realização de quimioterapia neoadjuvante, ocorrência de recidiva local e contaminação tumoral no trajeto da biópsia. RESULTADOS: Nos 35 pacientes avaliados ocorreram quatro contaminações (11,43%. Um caso era de osteossarcoma, dois casos de tumor de Ewing e um caso de condrossarcoma, não se observando associação entre o tipo de tumor e a presença de contaminação tumoral no trajeto da biópsia (p = 0,65. Também não se observou associação entre a presença de contaminação tumoral e a técnica de biópsia (p = 0,06. Por outro lado, observou-se associação entre a presença de contaminação tumoral e a ocorrência de recidiva local (p = 0,01 e entre a presença de contaminação e a não realização de quimioterapia neoadjuvante (p = 0,02. CONCLUSÃO: A contaminação tumoral no trajeto de biópsia de tumores ósseos malignos primários esteve associada à ocorrência de recidiva local. Por outro lado, não mostrou ser influenciada pelo tipo de biópsia realizada e pelo tipo histológico de tumor estudado. A quimioterapia neoadjuvante mostrou um efeito protetor contra esta complicação. A despeito desses achados, a contaminação tumoral é uma complicação que deve sempre ser considerada, sendo recomendada a remoção do trajeto da biópsia na cirurgia de ressecção do tumor.OBJECTIVE: To study factors possibly associated with tumor contamination in the biopsy path of primary malignant bone tumors. METHOD: Thirty-five patients who underwent surgical treatment with diagnoses of osteosarcoma, Ewing's tumor and

  20. Analysis of nodal coverage utilizing image guided radiation therapy for primary gynecologic tumor volumes

    Energy Technology Data Exchange (ETDEWEB)

    Ahmed, Faisal [University of Utah School of Medicine, Salt Lake City, UT (United States); Loma Linda University Medical Center, Department of Radiation Oncology, Loma Linda, CA (United States); Sarkar, Vikren; Gaffney, David K.; Salter, Bill [Department of Radiation Oncology, University of Utah, Salt Lake City, UT (United States); Poppe, Matthew M., E-mail: matthew.poppe@hci.utah.edu [Department of Radiation Oncology, University of Utah, Salt Lake City, UT (United States)

    2016-10-01

    Purpose: To evaluate radiation dose delivered to pelvic lymph nodes, if daily Image Guided Radiation Therapy (IGRT) was implemented with treatment shifts based on the primary site (primary clinical target volume [CTV]). Our secondary goal was to compare dosimetric coverage with patient outcomes. Materials and methods: A total of 10 female patients with gynecologic malignancies were evaluated retrospectively after completion of definitive intensity-modulated radiation therapy (IMRT) to their pelvic lymph nodes and primary tumor site. IGRT consisted of daily kilovoltage computed tomography (CT)-on-rails imaging fused with initial planning scans for position verification. The initial plan was created using Varian's Eclipse treatment planning software. Patients were treated with a median radiation dose of 45 Gy (range: 37.5 to 50 Gy) to the primary volume and 45 Gy (range: 45 to 64.8 Gy) to nodal structures. One IGRT scan per week was randomly selected from each patient's treatment course and re-planned on the Eclipse treatment planning station. CTVs were recreated by fusion on the IGRT image series, and the patient's treatment plan was applied to the new image set to calculate delivered dose. We evaluated the minimum, maximum, and 95% dose coverage for primary and nodal structures. Reconstructed primary tumor volumes were recreated within 4.7% of initial planning volume (0.9% to 8.6%), and reconstructed nodal volumes were recreated to within 2.9% of initial planning volume (0.01% to 5.5%). Results: Dosimetric parameters averaged less than 10% (range: 1% to 9%) of the original planned dose (45 Gy) for primary and nodal volumes on all patients (n = 10). For all patients, ≥99.3% of the primary tumor volume received ≥ 95% the prescribed dose (V95%) and the average minimum dose was 96.1% of the prescribed dose. In evaluating nodal CTV coverage, ≥ 99.8% of the volume received ≥ 95% the prescribed dose and the average minimum dose was 93%. In

  1. Impact of Primary Tumor Location on First-line Bevacizumab or Cetuximab in Metastatic Colorectal Cancer.

    Science.gov (United States)

    Snyder, Matthew; Bottiglieri, Sal; Almhanna, Khaldoun

    2018-01-01

    Colorectal cancer is one of the most common malignancies in the United States, with a large proportion of patients presenting with metastatic disease or developing a recurrence. Systemic chemotherapy is the mainstay of therapy in this setting. There is a clear benefit in the addition of bevacizumab or cetuximab (for rat sarcoma [RAS] wild type tumors) to oxaliplatin- and irinotecan-based regimens which can be considered for first-line therapy. However, many significant questions remain as to which agent reflects best practice. Our review aimed to elucidate the benefit of adding bevacizumab and cetuximab to initial therapy for metastatic colorectal cancer based on primary tumor location and a variety of other disease- and patient-related factors, addressing the paucity of evidence that currently exists in this area and contributing to current literature and clinical practices. The primary endpoints of the study were first Progression-Free Survival (PFS) and Overall Survival (OS). Secondary endpoints included best response to first- and second-line therapies, Treatment- Related Adverse Events (TRAEs), second PFS, cost of therapy, and an assessment of other patient- and disease-related factors affecting PFS and OS. While there were trends towards improved OS in patients with left-sided primary tumors (n=57) compared to those with right-sided disease (n=23), there were no significant differences between the two groups in either primary endpoint. While no differences were found for patients with left- or right- sided tumors stratified by add-on agent, these analyses were limited by the small number of patients receiving cetuximab with first-line therapy (n=4). However, the bevacizumab cohort (n=76) was sizable enough to provide ample data and produce clinically relevant results. Add-on therapy with bevacizumab in our study achieved impressive survival outcomes in both left-sided (median first PFS = 13 months, 95% CI 11-15 months; median OS = 37 months, 95% CI 21

  2. A Study of Patients with Primary Mediastinal Germ Cell Tumors Treated Using Multimodal Therapy

    Directory of Open Access Journals (Sweden)

    Yutaro Tanaka

    2017-01-01

    Full Text Available Objectives. Primary mediastinal germ cell tumors (PMGCTs are rare, which often makes them difficult to treat. Herein, we examined patients with PMGCTs who underwent multimodal treatment. Methods. We examined 6 patients (median age: 25 years, range: 19–27 years with PMGCTs who underwent multimodal treatment between April 2001 and March 2015. Three patients had seminomas, 2 patients had yolk sac tumors, and 1 patient had choriocarcinoma. The median observation period was 32.5 months (range: 8–84 months. Results. Three of the 6 patients received initial operation followed by 3-4 courses of chemotherapy (bleomycin, etoposide, and cisplatin (BEP or etoposide and cisplatin (EP. One patient developed multiple lung metastases 17 months after surgery; received salvage chemotherapy with vinblastine, ifosfamide, and cisplatin; and achieved complete remission. The remaining 3 patients received initial BEP and EP chemotherapy. Multiple lung metastases and supraclavicular lymph node metastases were detected in 2 of these patients at the initial diagnosis. The patients underwent resections to remove residual tumor after treatment, and no viable tumor cells were found. Conclusions. Reliable diagnosis and immediate multimodal treatments are necessary for patients with PMGCTs. The 6 patients treated in our hospital have never experienced recurrence after the multimodal treatment.

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

    Directory of Open Access Journals (Sweden)

    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.

  4. Clinical experience with RF thermotherapy for nonresectable primary and secondary liver tumors

    International Nuclear Information System (INIS)

    Yonemura, Yutaka; Fujimura, Takashi; Takegawa, Shigeru; Miyata, Ryuwa; Kamata, Toru; Miyazaki, Itsuo; Nakajima, Kazuyoshi; Hisazumi, Haruo; Saito, Yasuo

    1987-01-01

    Twenty two patients with primary or secondary liver tumors were treated by radiofrequency hyperthermia (8 MHz) combined with radiation or chemotherapy. Hyperthermia was administered twice a week for 40 - 60 minutes per session up to a total of 5 - 48 sessions. Five fractions per week of irradiation (10 MV X ray) at 180 - 200 cGy or intraarterial chemotherapy using mitomycin C, cis-diamminedichroloplatinum or adriamycine were carried out. Intratumor temperature over 42.5 deg C were obtained in 9 of 17 patients. Of the 22 patients treated, 2 (9 %) showed complete response, 8 (36 %) partial response, 3 (14 %) minor response, 7 (32 %) no change and 2 (9 %) progressive disease. 7 out of 14 tumors, heated over 42.5 deg C showed complete or partial response but only 1 out of 5 tumors, heated under 42.5 deg C was responder. Complication observed were thrombocytopenia and leukopenia in 30 % of cases. These results showed that combined treatment of hyperthermia radiation and chemotherapy appear to be useful from of therapy for the patients with liver tumor. (author)

  5. Brief descriptive epidemiology of primary malignant brain tumors from North-East India.

    Science.gov (United States)

    Krishnatreya, Manigreeva; Kataki, Amal Chandra; Sharma, Jagannath Dev; Bhattacharyya, Mouchumee; Nandy, Pintu; Hazarika, Munlima

    2014-01-01

    Brain tumors are a mixed group of neoplasms that originate from the intracranial tissues and the meninges with degrees of malignancy varying greatly from benign to aggressive. Not much is known about the epidemiology of primary malignant brain tumors (PMBTs) in our population in North-East India. In this analysis, an attempt was made to identify the age groups, gender distribution, topography and different histological types of PMBT with data from a hospital cancer registry. A total of 231 cases of PMBT were identified and included for the present analysis. Our analysis has shown that most of PMBT occur at 20-60 years of age, with a male to female ratio of 2.3:1. Some 70.5% of cases occurred in cerebral lobes except for the occipital lobe, and astrocytic tumors were the most common broad histological type. In our population the prevalence of PMBT is 1% of all cancers, mostly affecting young and middle aged patients. As brain tumors are rare, so case-control analytic epidemiological studies will be required to establish the risk factors prevalent in our population.

  6. Steroid replacement in primary adrenal failure does not appear to affect circulating adipokines.

    Science.gov (United States)

    Fichna, Marta; Fichna, Piotr; Gryczyńska, Maria; Czarnywojtek, Agata; Żurawek, Magdalena; Ruchała, Marek

    2015-03-01

    Despite continuous efforts for an optimal steroid replacement, recent observations suggest increased cardiometabolic risk and related mortality in primary adrenal insufficiency (PAI). Adipokines are peptides from the adipose tissue, markers of cardiometabolic dysfunction. This study was aimed to evaluate serum levels of adipokines: leptin, adiponectin, and resistin in PAI during conventional steroid substitution. The analysis comprised 63 patients (mean age 42.7 ± 14.1 years) and 63 healthy controls. Serum adipokines, lipid profile, and plasma glucose were assessed in both cohorts. ACTH, serum insulin, HOMA-IR, DHEA-S, cortisol and 24 h urinary free cortisol were determined in PAI. Body mass composition was analyzed by Dual-Energy X-ray Absorptiometry. Mean BMI in the control group was 24.1 ± 3.9 kg/m(2) and 23.7 ± 3.9 kg/m(2) in the PAI cohort. Serum leptin and adiponectin levels were similar in both groups, whereas resistin appeared significantly lower among affected subjects (p = 0.0002). Its levels were weakly correlated with HOMA-IR (p = 0.048). Leptin was independently correlated with fasting insulin, HOMA-IR, BMI, and body fat (p regression analysis only weight (p = 0.017), total and HDL cholesterol (p replacement. Serum adipokines in treated PAI follow similar correlations to those reported in healthy subjects. Further prospective studies are warranted to verify and explain plausible excess of cardiovascular mortality in PAI.

  7. When Prostate Cancer Circulates in the Bloodstream

    Directory of Open Access Journals (Sweden)

    Virginie Vlaeminck-Guillem

    2015-10-01

    Full Text Available Management of patients with prostate cancer is currently based on imperfect clinical, biological, radiological and pathological evaluation. Prostate cancer aggressiveness, including metastatic potential, remains difficult to accurately estimate. In an attempt to better adapt therapeutics to an individual (personalized medicine, reliable evaluation of the intrinsic molecular biology of the tumor is warranted, and particularly for all tumor sites (primary tumors and secondary sites at any time of the disease progression. As a consequence of their natural tendency to grow (passive invasion or as a consequence of an active blood vessel invasion by metastase-initiating cells, tumors shed various materials into the bloodstream. Major efforts have been recently made to develop powerful and accurate methods able to detect, quantify and/or analyze all these circulating tumor materials: circulating tumors cells, disseminating tumor cells, extracellular vesicles (including exosomes, nucleic acids, etc. The aim of this review is to summarize current knowledge about these circulating tumor materials and their applications in translational research.

  8. Differential Motion Between Mediastinal Lymph Nodes and Primary Tumor in Radically Irradiated Lung Cancer Patients

    International Nuclear Information System (INIS)

    Schaake, Eva E.; Rossi, Maddalena M.G.; Buikhuisen, Wieneke A.; Burgers, Jacobus A.; Smit, Adrianus A.J.; Belderbos, José S.A.; Sonke, Jan-Jakob

    2014-01-01

    Purpose/Objective: In patients with locally advanced lung cancer, planning target volume margins for mediastinal lymph nodes and tumor after a correction protocol based on bony anatomy registration typically range from 1 to 1.5 cm. Detailed information about lymph node motion variability and differential motion with the primary tumor, however, is lacking from large series. In this study, lymph node and tumor position variability were analyzed in detail and correlated to the main carina to evaluate possible margin reduction. Methods and Materials: Small gold fiducial markers (0.35 × 5 mm) were placed in the mediastinal lymph nodes of 51 patients with non-small cell lung cancer during routine diagnostic esophageal or bronchial endoscopic ultrasonography. Four-dimensional (4D) planning computed tomographic (CT) and daily 4D cone beam (CB) CT scans were acquired before and during radical radiation therapy (66 Gy in 24 fractions). Each CBCT was registered in 3-dimensions (bony anatomy) and 4D (tumor, marker, and carina) to the planning CT scan. Subsequently, systematic and random residual misalignments of the time-averaged lymph node and tumor position relative to the bony anatomy and carina were determined. Additionally, tumor and lymph node respiratory amplitude variability was quantified. Finally, required margins were quantified by use of a recipe for dual targets. Results: Relative to the bony anatomy, systematic and random errors ranged from 0.16 to 0.32 cm for the markers and from 0.15 to 0.33 cm for the tumor, but despite similar ranges there was limited correlation (0.17-0.71) owing to differential motion. A large variability in lymph node amplitude between patients was observed, with an average motion of 0.56 cm in the cranial-caudal direction. Margins could be reduced by 10% (left-right), 27% (cranial-caudal), and 10% (anteroposterior) for the lymph nodes and −2%, 15%, and 7% for the tumor if an online carina registration protocol replaced a

  9. Primary oral and nasal transmissible venereal tumor in a mix-breed dog

    Directory of Open Access Journals (Sweden)

    Mahdieh Rezaei

    2016-05-01

    Full Text Available Transmissible venereal tumor (TVT is a coitally transmitted tumor of dogs with widespread distribution. The present study describes the occurrence of the primary oral and nasal TVT in a 10-year-old, female, mix-breed dog. The case was presented with a history of anorexia, inability to swallow and dyspnea. Clinical examinations revealed the emaciation, muzzle deformity due to the presence of a friable, fleshy, cauliflower-like mass in the oral cavity and submandibular lymphadenopathy. TVT was diagnosed based on histopathological findings. The dog was discharged with therapeutic intervention with vincristine. Unfortunately, the case died before readmission because of the progressive worsening of the general condition. Our findings highlight the need for considering TVT for the differential diagnosis of the extragenital masses in dogs.

  10. Immunological considerations of modern animal models of malignant primary brain tumors

    Directory of Open Access Journals (Sweden)

    James C David

    2009-10-01

    Full Text Available Abstract Recent advances in animal models of glioma have facilitated a better understanding of biological mechanisms underlying gliomagenesis and glioma progression. The limitations of existing therapy, including surgery, chemotherapy, and radiotherapy, have prompted numerous investigators to search for new therapeutic approaches to improve quantity and quality of survival from these aggressive lesions. One of these approaches involves triggering a tumor specific immune response. However, a difficulty in this approach is the the scarcity of animal models of primary CNS neoplasms which faithfully recapitulate these tumors and their interaction with the host's immune system. In this article, we review the existing methods utilized to date for modeling gliomas in rodents, with a focus on the known as well as potential immunological aspects of these models. As this review demonstrates, many of these models have inherent immune system limitations, and the impact of these limitations on studies on the influence of pre-clinical therapeutics testing warrants further attention.

  11. ER, HER2, and TOP2A expression in primary tumor, synchronous axillary nodes, and asynchronous metastases in breast cancer

    DEFF Research Database (Denmark)

    Jensen, Jeanette Dupont; Knoop, Ann; Ewertz, Marianne

    2011-01-01

    with the primary tumors with respect to ER, HER2, and TOP2A. In the prospective tissue-collection study, 81 patients had biopsy from a suspected relapse. Additional archived paired material was included, leaving a total of 119 patients with paired primary tumor, synchronous axillary nodes (available in 52 patients......At recurrence of breast cancer, the therapeutic target is the metastases. However, it is current practice to base the choice of systemic treatment on the biomarker profile of the primary tumor. In the present study, confirmatory biopsies were obtained from suspected metastatic lesions and compared......) and asyncronous metastases available for analysis. ER, HER2, and TOP2A expression of primary tumors, axillary nodes and metastases were re-analysed and determined centrally by immunohistochemistry, chromogenic in situ hybridization, and fluorescence in situ hybridization. Of the 81 patients with a biopsy from...

  12. Feasibility of the evidence-based cognitive telerehabilitation program ReMind for patients with primary brain tumors

    NARCIS (Netherlands)

    van der Linden, S.D.; Sitskoorn, M.M.; Rutten, G.J.M.; Gehring, K.

    2018-01-01

    Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation

  13. Expression and lymphatic microvessel density in primary tumors of node-neagtive colorectal cancer patients predict disease recurrence

    NARCIS (Netherlands)

    Doekhie, F.S.; Morreau, H.; de Bock, G.H.; Speetjens, F.M.; Dekker-Ensink, N.G.; Putter, H.; vand e Velde, C.J.H.; Tollenaar, R.A.E.M.; Kuppen, P.J.K.; Sialyl lewis, X.

    2008-01-01

    Up to 30% of curatively resected colorectal cancer patients with tumor-negative lymph nodes, show disease recurrence. We assessed whether these high-risk patients can be identified by examining primary tumors for the following blood and lymphatic vasculature markers: A) sialyl Lewis X (sLeX),

  14. Multicenter results of stereotactic body radiotherapy (SBRT) for non-resectable primary liver tumors

    Energy Technology Data Exchange (ETDEWEB)

    Ibarra, Rafael A.; Rojas, Daniel; Sanabria, Juan R. [Dept. of Surgery, Univ. Hospitals-Case Medical Center, Cleveland, OH (United States)], email: juan.sanabria@uhhospitals.org [and others

    2012-05-15

    Background. An excess of 100 000 individuals are diagnosed with primary liver tumors every year in USA but less than 20% of those patients are amenable to definitive surgical management due to advanced local disease or comorbidities. Local therapies to arrest tumor growth have limited response and have shown no improvement on patient survival. Stereotactic body radiotherapy (SBRT) has emerged as an alternative local ablative therapy. The purpose of this study was to evaluate the tumor response to SBRT in a combined multicenter database. Study design. Patients with advanced hepatocellular carcinoma (HCC, n = 21) or intrahepatic cholangiocarcinoma (ICC, n = 11) treated with SBRT from four Academic Medical Centers were entered into a common database. Statistical analyses were performed for freedom from local progression (FFLP) and patient survival. Results. The overall FFLP for advanced HCC was 63% at a median follow-up of 12.9 months. Median tumor volume decreased from 334.2 to 135 cm{sup 3} (p < 0.004). The median time to local progression was 6.3 months. The 1- and 2-years overall survival rates were 87% and 55%, respectively. Patients with ICC had an overall FFLP of 55.5% at a median follow-up of 7.8 months. The median time to local progression was 4.2 months and the six-month and one-year overall survival rates were 75% and 45%, respectively. The incidence of grade 1-2 toxicities, mostly nausea and fatigue, was 39.5%. Grade 3 and 4 toxicities were present in two and one patients, respectively. Conclusion. Higher rates of FFLP were achieved by SBRT in the treatment of primary liver malignancies with low toxicity.

  15. Feasibility of the evidence-based cognitive telerehabilitation program Remind for patients with primary brain tumors.

    Science.gov (United States)

    van der Linden, Sophie D; Sitskoorn, Margriet M; Rutten, Geert-Jan M; Gehring, Karin

    2018-05-01

    Many patients with primary brain tumors experience cognitive deficits. Cognitive rehabilitation programs focus on alleviating these deficits, but availability of such programs is limited. Our large randomized controlled trial (RCT) demonstrated positive effects of the cognitive rehabilitation program developed by our group. We converted the program into the iPad-based cognitive rehabilitation program ReMind, to increase its accessibility. The app incorporates psychoeducation, strategy training and retraining. This pilot study in patients with primary brain tumors evaluates the feasibility of the use of the ReMind-app in a clinical (research) setting in terms of accrual, attrition, adherence and patient satisfaction. The intervention commenced 3 months after resective surgery and patients were advised to spend 3 h per week on the program for 10 weeks. Of 28 eligible patients, 15 patients with presumed low-grade glioma or meningioma provided informed consent. Most important reason for decline was that patients (7) experienced no cognitive complaints. Participants completed on average 71% of the strategy training and 76% of the retraining. Some patients evaluated the retraining as too easy. Overall, 85% of the patients evaluated the intervention as "good" or "excellent". All patients indicated that they would recommend the program to other patients with brain tumors. The ReMind-app is the first evidence-based cognitive telerehabilitation program for adult patients with brain tumors and this pilot study suggests that postoperative cognitive rehabilitation via this app is feasible. Based on patients' feedback, we have expanded the retraining with more difficult exercises. We will evaluate the efficacy of ReMind in an RCT.

  16. Microfluidic bead-based multienzyme-nanoparticle amplification for detection of circulating tumor cells in the blood using quantum dots labels

    Energy Technology Data Exchange (ETDEWEB)

    Zhang, He, E-mail: mzhang_he@126.com; Fu, Xin; Hu, Jiayi; Zhu, Zhenjun

    2013-05-24

    Graphical abstract: A microfluidic beads-based nucleic acid sensor for sensitive detection of circulating tumor cells (CTCs) in the blood using multienzyme-nanoparticle amplification and quantum dots labels was developed. The chip-based CTCs analysis could detect reverse transcription-polymerase chain reaction (RT-PCR) products of tumor cell as low as 1 tumor cell (e.g. CEA expressing cell) in 1 mL blood sample. This microfluidic beads-based nucleic acid sensor is a promising platform for disease-related nucleic acid molecules at the lowest level at their earliest incidence. -- Highlights: •Combination of microfluidic bead-based platform and enzyme–probe–AuNPs is proposed. •The developed nucleic acid sensor could respond to 5 fM of tumor associated DNA. •Microfluidic platform and multienzyme-labeled AuNPs greatly enhanced sensitivity. •The developed nucleic acid sensor could respond to RT-PCR products of tumor cell as low as 1 tumor cell in 1 mL blood sample. •We report a sensitive nucleic acid sensor for detection of circulating tumor cells. -- Abstract: This study reports the development of a microfluidic bead-based nucleic acid sensor for sensitive detection of circulating tumor cells in blood samples using multienzyme-nanoparticle amplification and quantum dot labels. In this method, the microbeads functionalized with the capture probes and modified electron rich proteins were arrayed within a microfluidic channel as sensing elements, and the gold nanoparticles (AuNPs) functionalized with the horseradish peroxidases (HRP) and DNA probes were used as labels. Hence, two signal amplification approaches are integrated for enhancing the detection sensitivity of circulating tumor cells. First, the large surface area of Au nanoparticle carrier allows several binding events of HRP on each nanosphere. Second, enhanced mass transport capability inherent from microfluidics leads to higher capture efficiency of targets because continuous flow within micro

  17. Vessel co-option in primary human tumors and metastases: an obstacle to effective anti-angiogenic treatment?

    Science.gov (United States)

    Donnem, Tom; Hu, Jiangting; Ferguson, Mary; Adighibe, Omanma; Snell, Cameron; Harris, Adrian L; Gatter, Kevin C; Pezzella, Francesco

    2013-08-01

    Angiogenesis has been regarded as essential for tumor growth and progression. Studies of many human tumors, however, suggest that their microcirculation may be provided by nonsprouting vessels and that a variety of tumors can grow and metastasize without angiogenesis. Vessel co-option, where tumor cells migrate along the preexisting vessels of the host organ, is regarded as an alternative tumor blood supply. Vessel co-option may occur in many malignancies, but so far mostly reported in highly vascularized tissues such as brain, lung, and liver. In primary and metastatic lung cancer and liver metastasis from different primary origins, as much as 10-30% of the tumors are reported to use this alternative blood supply. In addition, vessel co-option is introduced as a potential explanation of antiangiogenic drug resistance, although the impact of vessel co-option in this clinical setting is still to be further explored. In this review we discuss tumor vessel co-option with specific examples of vessel co-option in primary and secondary tumors and a consideration of the clinical implications of this alternative tumor blood supply.

  18. Surgical management and perioperative morbidity of patients with primary borderline ovarian tumor (BOT).

    Science.gov (United States)

    Trillsch, Fabian; Ruetzel, Jan David; Herwig, Uwe; Doerste, Ulrike; Woelber, Linn; Grimm, Donata; Choschzick, Matthias; Jaenicke, Fritz; Mahner, Sven

    2013-07-09

    Surgery is the cornerstone for clinical management of patients with borderline ovarian tumors (BOT). As these patients have an excellent overall prognosis, perioperative morbidity is the critical point for decision making when the treatment strategy is developed and the primary surgical approach is defined. Clinical and surgical parameters of patients undergoing surgery for primary BOT at our institutions between 1993 and 2008 were analyzed with regard to perioperative morbidity depending on the surgical approach (laparotomy vs. laparoscopy). A total of 105 patients were analyzed (44 with primary laparoscopy [42%], 61 with primary laparotomy [58%]). Complete surgical staging was achieved in 33 patients at primary surgical approach (31.4%) frequently leading to formal indication of re-staging procedures. Tumor rupture was significantly more frequent during laparoscopy compared to laparotomy (29.5% vs. 13.1%, p = 0.038) but no other intraoperative complications were seen in laparoscopic surgery in contrast to 7 of 61 laparotomies (0% vs. 11.5%, p = 0.020). Postoperative complication rates were similar in both groups (19.7% vs. 18.2%, p = 0.848). Irrespective of the surgical approach, surgical management of BOT has acceptable rates of perioperative complications and morbidity. Choice of initial surgical approach can therefore be made independent of complication-concerns. As the recently published large retrospective AGO ROBOT study observed similar oncologic outcome for both approaches, laparoscopy can be considered for staging of patients with BOT if this appears feasible. An algorithm for the surgical management of BOT patients has been developed.

  19. Primary benign tumors in chiropractic practice and the importance of x-ray diagnosis: A report of two cases

    Science.gov (United States)

    Pelletier, Jacques C.

    1987-01-01

    Two cases of primary benign bone tumors were diagnosed radiographically in a chiropractic practice. Although primary osseous tumors are somewhat uncommon, their potential presence emphasizes the importance of x-ray diagnosis as an essential adjunct to chiropractic practice. This procedure may preclude underlying lesions before considering treatment of seemingly uncomplicated injuries. Two such cases are presented: unicameral bone cyst and osteochondroma. ImagesFigure 1Figure 2Figure 3

  20. Temporalis myofascial flap for primary cranial base reconstruction after tumor resection.

    Science.gov (United States)

    Eldaly, Ahmed; Magdy, Emad A; Nour, Yasser A; Gaafar, Alaa H

    2008-07-01

    To evaluate the use of the temporalis myofascial flap in primary cranial base reconstruction following surgical tumor ablation and to explain technical issues, potential complications, and donor site consequences along with their management. Retrospective case series. Tertiary referral center. Forty-one consecutive patients receiving primary temporalis myofascial flap reconstructions following cranial base tumor resections in a 4-year period. Flap survival, postoperative complications, and donor site morbidity. Patients included 37 males and 4 females ranging in age from 10 to 65 years. Two patients received preoperative and 18 postoperative radiation therapy. Patient follow-up ranged from 4 to 39 months. The whole temporalis muscle was used in 26 patients (63.4%) and only part of a coronally split muscle was used in 15 patients (36.6%). Nine patients had primary donor site reconstruction using a Medpor((R)) (Porex Surgical, Inc., Newnan, GA) temporal fossa implant; these had excellent aesthetic results. There were no cases of complete flap loss. Partial flap dehiscence was seen in six patients (14.6%); only two required surgical débridement. None of the patients developed cerebrospinal leaks or meningitis. One patient was left with complete paralysis of the temporal branch of the facial nerve. Three patients (all had received postoperative irradiation) developed permanent trismus. The temporalis myofascial flap was found to be an excellent reconstructive alternative for a wide variety of skull base defects following tumor ablation. It is a very reliable, versatile flap that is usually available in the operative field with relatively low donor site aesthetic and functional morbidity.

  1. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity.

    Science.gov (United States)

    Mete, Ozgur; Duan, Kai

    2018-01-01

    Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype-phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations ( KCNJ5, ATP1A1, ATP2B3 , and CACNA1D ) involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5 -mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3 , and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations ( PRKACA, PRKAR1A, GNAS, PDE11A , and PDE8B ) involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH) have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  2. The Many Faces of Primary Aldosteronism and Cushing Syndrome: A Reflection of Adrenocortical Tumor Heterogeneity

    Directory of Open Access Journals (Sweden)

    Ozgur Mete

    2018-03-01

    Full Text Available Adrenal cortical tumors constitute a heterogeneous group of neoplasms with distinct clinical, morphological, and molecular features. Recent discoveries of specific genotype–phenotype correlations in adrenal cortical adenomas have transformed our understanding of their respective endocrine syndromes. Indeed, a proportion of patients with primary aldosteronism are now known to harbor adrenal cortical adenomas with heterogeneous molecular alterations (KCNJ5, ATP1A1, ATP2B3, and CACNA1D involving the calcium/calmodulin kinase signaling pathway. Several lines of evidence suggest that KCNJ5-mutant aldosterone-producing adenomas have distinct clinicopathological phenotype compared to those harboring ATP1A1, ATP2B3, and CACNA1D mutations. Benign adrenal cortical tumors presenting with Cushing syndrome often have diverse mutations (PRKACA, PRKAR1A, GNAS, PDE11A, and PDE8B involving the cyclic AMP signaling pathway. In addition to cortisol-producing adenomas, bilateral micronodular adrenocortical disease and primary bilateral macronodular adrenal hyperplasia (PBMAH have also expanded the spectrum of benign neoplasms causing adrenal Cushing disease. The recent discovery of inactivating ARMC5 germline mutations in PBMAH has challenged the old belief that this disorder is mainly a sporadic disease. Emerging evidence suggests that PBMAH harbors multiple distinct clonal proliferations, reflecting the heterogeneous genomic landscape of this disease. Although most solitary adrenal cortical tumors are sporadic, there is an increasing recognition that inherited susceptibility syndromes may also play a role in their pathogenesis. This review highlights the molecular and morphological heterogeneity of benign adrenal cortical neoplasms, reflected in the diverse presentations of primary aldosteronism and adrenal Cushing syndrome.

  3. Interstitial brachytherapy with 192-IR in treatment of recurrent malignant primary brain tumors

    International Nuclear Information System (INIS)

    Cardenes, R.; Martinez, R.; Victoria, C.; Nunez, L.; Clavo, B.; Sancedo, G.

    1994-01-01

    Seven patients with recurrent malignant primary brain tumors after surgery and radiation therapy were treated at the Clinica Puerta de Hierro (Madrid) by interstitial brachytherapy with 192-Ir sources. Implantations were performed using computerized tomography and dose prescription were determined following the Paris system rules for interstitial implants. The means dose deliberated was 50 to 65 Gy to the reference isodoses. At the last follow-up all patients except for one are alive and without evidence of progression of the disease. (Author) 35 refs

  4. Combination of neck dissection for cervical metastasis and irradiation of primary tumors for carcinomas of the mesopharynx, hypopharynx, and larynx

    International Nuclear Information System (INIS)

    Sato, Katsuro; Hanazawa, Hideyuki; Takahashi, Sugata; Watanabe, Jun; Tomita, Masahiko

    2006-01-01

    Carcinomas of the mesopharynx, hypopharynx, and larynx with early-stage primary tumor and with cervical lymph node metastasis, were treated by neck dissection for cervical metastasis and definitive irradiation of the primary tumor. In this study, the primary sites of the 16 cases were the mesopharynx (10), the hypopharynx (3), and the larynx (3). Twelve cases of early T stages (T1 or T2) and 15 cases of advanced N stages (N2 or N3) were chosen for this treatment concept. Neck lesions were controlled in all cases and all the primary tumors showed complete response at the end of the initial treatment. One case of mesopharyngeal cancer died due to recurrence of the primary tumor and one case of hypopharyngeal cancer died due to complicated lung cancer. The treatment modality for cases of early primary cancer and advanced cervical lymph node metastasis requires well-balanced strategies for both lesions. In these cases, optimal prognosis was obtained because of careful patient selection. The treatment strategy described in this paper should be considered for cases of early T tumors and advanced N tumors. (author)

  5. Three-Dimensional Scaffold Chip with Thermosensitive Coating for Capture and Reversible Release of Individual and Cluster of Circulating Tumor Cells.

    Science.gov (United States)

    Cheng, Shi-Bo; Xie, Min; Chen, Yan; Xiong, Jun; Liu, Ya; Chen, Zhen; Guo, Shan; Shu, Ying; Wang, Ming; Yuan, Bi-Feng; Dong, Wei-Guo; Huang, Wei-Hua

    2017-08-01

    Tumor metastasis is attributed to circulating tumor cells (CTC) or CTC clusters. Many strategies have hitherto been designed to isolate CTCs, but there are few methods that can capture and gently release CTC clusters as efficient as single CTCs. Herein, we developed a three-dimensional (3D) scaffold chip with thermosensitive coating for high-efficiency capture and release of individual and cluster CTCs. The 3D scaffold chip successfully combines the specific recognition and physically obstructed effect of 3D scaffold structure to significantly improve cell clusters capture efficiency. Thermosensitive gelatin hydrogel uniformly coated on the scaffold dissolves at 37 °C quickly, and the captured cells are gently released from chip with high viability. Notably, this platform was applied to isolate CTCs from cancer patients' blood samples. This allows global DNA and RNA methylation analysis of collected single CTC and CTC clusters, indicating the great potential of this platform in cancer diagnosis and downstream analysis at the molecular level.

  6. Print Capitalism, New School and Circulation of Reading Models. A Brazilian Collection at the Primary Education Museum-Library in Portugal (1931-1950)

    Science.gov (United States)

    Toledo, Maria Rita Almeida; Carvalho, Marta Maria Chagas

    2011-01-01

    The present article is the fruit of research on the circulation of Brazilian books from the "Atualidades Pedagogicas" collection at the "Biblioteca Museu do Ensino Primario" (Primary Education Museum-Library) in Lisbon. This library was headed by Adolfo Lima, one of the exponents of the Portuguese New School, and gave form to…

  7. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    International Nuclear Information System (INIS)

    Bodei, L.; Kidd, M.; Modlin, I.M.; Severi, S.; Nicolini, S.; Paganelli, G.; Drozdov, I.; Kwekkeboom, D.J.; Krenning, E.P.; Baum, R.P.

    2016-01-01

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with 177 Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 18 FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ 2 = 27.4; p = 1.2 x 10 -7 ) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0.004) for predicting

  8. Measurement of circulating transcripts and gene cluster analysis predicts and defines therapeutic efficacy of peptide receptor radionuclide therapy (PRRT) in neuroendocrine tumors

    Energy Technology Data Exchange (ETDEWEB)

    Bodei, L. [European Institute of Oncology, Division of Nuclear Medicine, Milan (Italy); LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Kidd, M. [Wren Laboratories, Branford, CT (United States); Modlin, I.M. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Yale School of Medicine, New Haven, CT (United States); Severi, S.; Nicolini, S.; Paganelli, G. [Istituto Scientifico Romagnolo per lo Studio e la Cura dei Tumori (IRST) IRCCS, Nuclear Medicine and Radiometabolic Units, Meldola (Italy); Drozdov, I. [Bering Limited, London (United Kingdom); Kwekkeboom, D.J.; Krenning, E.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Erasmus Medical Center, Nuclear Medicine Department, Rotterdam (Netherlands); Baum, R.P. [LuGenIum Consortium, Milan, Rotterdam, Bad Berka, London, Italy, Netherlands, Germany (Country Unknown); Zentralklinik Bad Berka, Theranostics Center for Molecular Radiotherapy and Imaging, Bad Berka (Germany)

    2016-05-15

    Peptide receptor radionuclide therapy (PRRT) is an effective method for treating neuroendocrine tumors (NETs). It is limited, however, in the prediction of individual tumor response and the precise and early identification of changes in tumor size. Currently, response prediction is based on somatostatin receptor expression and efficacy by morphological imaging and/or chromogranin A (CgA) measurement. The aim of this study was to assess the accuracy of circulating NET transcripts as a measure of PRRT efficacy, and moreover to identify prognostic gene clusters in pretreatment blood that could be interpolated with relevant clinical features in order to define a biological index for the tumor and a predictive quotient for PRRT efficacy. NET patients (n = 54), M: F 37:17, median age 66, bronchial: n = 13, GEP-NET: n = 35, CUP: n = 6 were treated with {sup 177}Lu-based-PRRT (cumulative activity: 6.5-27.8 GBq, median 18.5). At baseline: 47/54 low-grade (G1/G2; bronchial typical/atypical), 31/49 {sup 18}FDG positive and 39/54 progressive. Disease status was assessed by RECIST1.1. Transcripts were measured by real-time quantitative reverse transcription PCR (qRT-PCR) and multianalyte algorithmic analysis (NETest); CgA by enzyme-linked immunosorbent assay (ELISA). Gene cluster (GC) derivations: regulatory network, protein:protein interactome analyses. Statistical analyses: chi-square, non-parametric measurements, multiple regression, receiver operating characteristic and Kaplan-Meier survival. The disease control rate was 72 %. Median PFS was not achieved (follow-up: 1-33 months, median: 16). Only grading was associated with response (p < 0.01). At baseline, 94 % of patients were NETest-positive, while CgA was elevated in 59 %. NETest accurately (89 %, χ{sup 2} = 27.4; p = 1.2 x 10{sup -7}) correlated with treatment response, while CgA was 24 % accurate. Gene cluster expression (growth-factor signalome and metabolome) had an AUC of 0.74 ± 0.08 (z-statistic = 2.92, p < 0

  9. Tumor Necrosis Factor Inhibitor Primary Failure Predicts Decreased Ustekinumab Efficacy in Psoriasis Patients.

    Science.gov (United States)

    Sorensen, Eric P; Fanucci, Kristina A; Saraiya, Ami; Volf, Eva; Au, Shiu-chung; Argobi, Yahya; Mansfield, Ryan; Gottlieb, Alice B

    2015-08-01

    Additional studies are needed to examine the efficacy of ustekinumab in psoriasis patients who have previously been exposed to tumor necrosis factor inhibitors (TNFi). To examine the predictive effect of TNFi primary failure and the number of TNFi exposures on the efficacy of ustekinumab in psoriasis treatment. This retrospective study examined 44 psoriasis patients treated at the Tufts Medical Center Department of Dermatology between January 2008 and July 2014. Patients were selected if they were treated with ustekinumab and had ≥ 1 previous TNFi exposure. The following subgroups were compared: patients with vs without a previous TNFi primary failure, and patients with one vs multiple previous TNFi exposures. The efficacy measure used was the previously validated Simple Measure for Assessing Psoriasis Activity (S-MAPA), which is calculated by the product of the body surface area and physician global assessment. The primary outcome was the percentage improvement S-MAPA from course baseline at week 12 of ustekinumab treatment. Secondary outcomes were the psoriasis clearance, primary failure, and secondary failure rates with ustekinumab treatment. Patients with a previous TNFi primary failure had a significantly lower percentage improvement in S-MAPA score at week 12 of ustekinumab treatment compared with patients without TNFi primary failure (36.2% vs 61.1%, P=.027). Multivariate analysis demonstrated that this relationship was independent of patient demographics and medical comorbidities. Patients with multiple TNFi exposures had a non-statistically significant lower percentage S-MAPA improvement at week 12 (40.5% vs 52.9%, P=.294) of ustekinumab treatment compared with patients with a single TNFi exposure. Among psoriasis patients previously exposed to TNFi, a history of a previous TNFi primary failure predicts a decreased response to ustekinumab independent of patient demographics and medical comorbidities.

  10. F-18 FDG PET/CT imaging of primary hepatic neuroendocrine tumor

    Directory of Open Access Journals (Sweden)

    Katsuya Mitamura

    2015-01-01

    Full Text Available Primary hepatic neuroendocrine tumors (PHNETs are extremely rare neoplasms. Herein, we report a case of a 70-year-old man with a hepatic mass. The non-contrast computed tomography (CT image showed a low-density mass, and dynamic CT images indicated the enhancement of the mass in the arterial phase and early washout in the late phase. F18- fluorodeoxyglucose (18F-FDG positron emission tomography (PET and fused PET/CT images showed increased uptake in the hepatic mass. Whole-body 18F-FDG PET images showed no abnormal activity except for the liver lesion. Presence of an extrahepatic tumor was also ruled out by performing upper gastrointestinal endoscopy, total colonoscopy, and chest and abdominal CT. A posterior segmentectomy was performed, and histologic examination confirmed a neuroendocrine tumor (grade 1. The patient was followed up for about 2 years after the resection, and no extrahepatic lesions were radiologically found. Therefore, the patient was diagnosed with PHNET. To the best of our knowledge, no previous case of PHNET have been detected by 18F-FDG PET imaging.

  11. Predicting survival in patients with metastatic kidney cancer by gene-expression profiling in the primary tumor.

    Science.gov (United States)

    Vasselli, James R; Shih, Joanna H; Iyengar, Shuba R; Maranchie, Jodi; Riss, Joseph; Worrell, Robert; Torres-Cabala, Carlos; Tabios, Ray; Mariotti, Andra; Stearman, Robert; Merino, Maria; Walther, McClellan M; Simon, Richard; Klausner, Richard D; Linehan, W Marston

    2003-06-10

    To identify potential molecular determinants of tumor biology and possible clinical outcomes, global gene-expression patterns were analyzed in the primary tumors of patients with metastatic renal cell cancer by using cDNA microarrays. We used grossly dissected tumor masses that included tumor, blood vessels, connective tissue, and infiltrating immune cells to obtain a gene-expression "profile" from each primary tumor. Two patterns of gene expression were found within this uniformly staged patient population, which correlated with a significant difference in overall survival between the two patient groups. Subsets of genes most significantly associated with survival were defined, and vascular cell adhesion molecule-1 (VCAM-1) was the gene most predictive for survival. Therefore, despite the complex biological nature of metastatic cancer, basic clinical behavior as defined by survival may be determined by the gene-expression patterns expressed within the compilation of primary gross tumor cells. We conclude that survival in patients with metastatic renal cell cancer can be correlated with the expression of various genes based solely on the expression profile in the primary kidney tumor.

  12. A Prospective Comparison of 18F-FDG PET/CT and CT as Diagnostic Tools to Identify the Primary Tumor Site in Patients with Extracervical Carcinoma of Unknown Primary Site

    DEFF Research Database (Denmark)

    Moller, Anne Kirstine H; Loft, Annika; Berthelsen, Anne K

    2012-01-01

    that the same set of criteria were used for classification of patients, that is, either as CUP patients or patients with a suggested primary tumor site. The independently obtained suggestions of primary tumor sites using PET/CT and CT were correlated with the SR to reach a consensus regarding true-positive (TP......), true-negative, false-negative, and false-positive results.Results. SR identified a primary tumor site in 66 CUP patients (48.9%). PET/CT identified 38 TP primary tumor sites and CT identified 43 TP primary tumor sites. No statistically significant differences were observed between (18)F-FDG PET...

  13. Primary solitary peritoneal tumor of the abdominal wall—report of a rare case and review of the literature

    Science.gov (United States)

    Efthimiadis, Christoforos; Ioannidis, Aristeidis; Grigoriou, Marios

    2017-01-01

    Abstract Abdominal wall tumors are sometimes diagnosed as metastases of ovarian cancer, however, primary peritoneal tumors should be taken into consideration in the final diagnosis. A 49-year-old female patient was admitted in our Department for the excision of a pulpable abdominal wall lump, with no other abnormalities shown on imaging investigation. On histology examination, the excised specimen revealed characteristics of metastatic high-grade serous ovarian carcinoma. Total hysterectomy, bilateral oophorectomy, omentectomy and appendectomy were performed. No signs of malignancy were proved on histology, leading to the final diagnosis of a primary serous peritoneal tumor. This is the third described case of solitary primary serous peritoneal tumor located in the abdominal wall. This condition should be included in the differential diagnosis of a probable metastatic ovarian carcinoma, as both present similar histologic characteristics. PMID:28616156

  14. Primary solitary peritoneal tumor of the abdominal wall-report of a rare case and review of the literature.

    Science.gov (United States)

    Efthimiadis, Christoforos; Ioannidis, Aristeidis; Kofina, Konstantinia; Grigoriou, Marios

    2017-06-01

    Abdominal wall tumors are sometimes diagnosed as metastases of ovarian cancer, however, primary peritoneal tumors should be taken into consideration in the final diagnosis. A 49-year-old female patient was admitted in our Department for the excision of a pulpable abdominal wall lump, with no other abnormalities shown on imaging investigation. On histology examination, the excised specimen revealed characteristics of metastatic high-grade serous ovarian carcinoma. Total hysterectomy, bilateral oophorectomy, omentectomy and appendectomy were performed. No signs of malignancy were proved on histology, leading to the final diagnosis of a primary serous peritoneal tumor. This is the third described case of solitary primary serous peritoneal tumor located in the abdominal wall. This condition should be included in the differential diagnosis of a probable metastatic ovarian carcinoma, as both present similar histologic characteristics.

  15. Radiation therapy for primary carcinoma of the eyelid. Tumor control and visual function

    Energy Technology Data Exchange (ETDEWEB)

    Hata, M.; Koike, I.; Odagiri, K.; Kasuya, T.; Minagawa, Y.; Kaizu, H.; Mukai, Y.; Inoue, T. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Radiology; Maegawa, J. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Plastic and Reconstructive Surgery; Kaneko, A. [Yokohama City Univ. Graduate School of Medicine, Kanagawa (Japan). Dept. of Ophthalmology

    2012-12-15

    Background and purpose: Surgical excision remains the standard and most reliable curative treatment for eyelid carcinoma, but frequently causes functional and cosmetic impairment of the eyelid. We therefore investigated the efficacy and safety of radiation therapy in eyelid carcinoma. Patients and methods: Twenty-three patients with primary carcinoma of the eyelid underwent radiation therapy. Sebaceous carcinoma was histologically confirmed in 16 patients, squamous cell carcinoma in 6, and basal cell carcinoma in 1. A total dose of 50-66.6 Gy (median, 60 Gy) was delivered to tumor sites in 18-37 fractions (median, 30 fractions). Results: All but 3 of the 23 patients had survived at a median follow-up period of 49 months. The overall survival and local progression-free rates were 87% and 93% at 2 years, and 80% and 93% at 5 years, respectively. Although radiation-induced cataracts developed in 3 patients, visual acuity in the other patients was relatively well preserved. There were no other therapy-related toxicities of grade 3 or greater. Conclusion: Radiation therapy is safe and effective for patients with primary carcinoma of the eyelid. It appears to contribute to prolonged survival as a result of good tumor control, and it also facilitates functional and cosmetic preservation of the eyelid. (orig.)

  16. Utility of SPECT imaging for determination of vertebral metastases in patients with known primary tumors

    International Nuclear Information System (INIS)

    Bushnell, D.L.; Kahn, D.; Huston, B.; Bevering, C.G.

    1995-01-01

    Determining the etiology of a focal lesion seen on bone scan in patients with primary tumors usually requires the use of other imaging procedures or biopsy. Single positron emission computed tomography (SPECT) with high resolution multidetector systems can localize the specific site of a vertebral lesion and in this way potentially differentiate between benign and metastatic disease. SPECT images of the lower thoracic and lumbar spine were reviewed for lesion location and intensity by two experienced interpreters. Follow-up data were adequate to ascertain the cause of 71 lesions seen on SPECT in 29 patients. Twenty-six of these lesions were not seen on planar images. Of the 71 lesions, 44 were benign and 27 metastatic. Of the 15 lesions where the pedicle was involved, 11 were found to metastatic. There were a total of 14 facet lesions, 9 of which were present in vertebra with no lesions at sites other than the facets. All 9 of these isolated facet lesions turned out to be benign. Lesion intensity did not distinguish benign from malignant disease. We conclude that SPECT imaging is useful in determining the etiology of focal lesions seen on bone scan in patients with a known primary tumor referred for evaluation of metastatic disease. (orig.)

  17. Androgen receptor expression in Circulating Tumor Cells from castration-resistant prostate cancer patients with novel endocrine agents

    NARCIS (Netherlands)

    Crespo, M.; van Dalum, Guus; Ferraldeschi, R.; Zafeiriou, Z.; Sideris, S.; Lorente, D.; Bianchini, D.; Rodrigues, D.N.; Rijsnaes, R.; Miranda, S.; Figueiredo, I.; Flohr, P.; Nowakowska, K.; de Bono, J.S.; Terstappen, Leonardus Wendelinus Mathias Marie; Attard, G.

    2015-01-01

    Background: Abiraterone and enzalutamide are novel endocrine treatments that abrogate androgen receptor (AR) signalling in castration-resistant prostate cancer (CRPC). Here, we developed a circulating tumour cells (CTCs)-based assay to evaluate AR expression in real-time in CRPC and investigated

  18. Calculation of primary and secondary dose in proton therapy of brain tumors using Monte Carlo method

    International Nuclear Information System (INIS)

    Moghbel Esfahani, F.; Alamatsaz, M.; Karimian, A.

    2012-01-01

    High-energy beams of protons offer significant advantages for the treatment of deep-seated local tumors. Their physical depth-dose distribution in tissue is characterized by a small entrance dose and a distinct maximum - Bragg peak - near the end of range with a sharp falloff at the distal edge. Therefore, research must be done to investigate the possible negative and positive effects of using proton therapy as a treatment modality. In proton therapy, protons do account for the vast majority of dose. However, when protons travel through matter, secondary particles are created by the interactions of protons and matter en route to and within the patient. It is believed that secondary dose can lead to secondary cancer, especially in pediatric cases. Therefore, the focus of this work is determining both primary and secondary dose. Dose calculations were performed by MCNPX in tumoral and healthy parts of brain. The brain tumor has a 10 mm diameter and is located 16 cm under the skin surface. The brain was simulated by a cylindrical water phantom with the dimensions of 19 x 19cm 2 (length x diameter), with 0.5 cm thickness of plexiglass (C 4 H 6 O 2 ). Then beam characteristics were investigated to ensure the accuracy of the model. Simulations were initially validated with against packages such as SRIM/TRIM. Dose calculations were performed using different configurations to evaluate depth-dose profiles and dose 2D distributions.The results of the simulation show that the best proton energy interval, to cover completely the brain tumor, is from 152 to 154 MeV. (authors)

  19. ZnO-Based Microfluidic pH Sensor: A Versatile Approach for Quick Recognition of Circulating Tumor Cells in Blood.

    Science.gov (United States)

    Mani, Ganesh Kumar; Morohoshi, Madoka; Yasoda, Yutaka; Yokoyama, Sho; Kimura, Hiroshi; Tsuchiya, Kazuyoshi

    2017-02-15

    The present study is concerned about the development of highly sensitive and stable microfluidic pH sensor for possible identification of circulating tumor cells (CTCs) in blood. The precise pH measurements between silver-silver chloride (Ag/AgCl) reference electrode and zinc oxide (ZnO) working electrode have been investigated in the microfluidic device. Since there is a direct link between pH and cancer cells, the developed device is one of the valuable tools to examine circulating tumor cells (CTCs) in blood. The ZnO-based working electrode was deposited by radio frequency (rf) sputtering technique. The potential voltage difference between the working and reference electrodes (Ag/AgCl) is evaluated on the microfluidic device. The ideal Nernstian response of -43.71165 mV/pH was achieved along with high stability and quick response time. Finally, to evaluate the real time capability of the developed microfluidic device, in vitro testing was done with A549, A7r5, and MDCK cells.

  20. Cervical Lymph Node Metastases of Unknown Origin: Primary Tumor Detection with Whole-Body Positron Emission Tomography/Computed Tomography

    International Nuclear Information System (INIS)

    Nassenstein, K.; Veit-Haibach, P.; Stergar, H.; Gutzeit, A.; Freudenberg, L.; Kuehl, H.; Fischer, M.; Barkhausen, J.; Bockisch, A.; Antoch, G.

    2007-01-01

    Background: Identification of primary tumor in patients with cervical lymph node metastasis of unknown primary (MUO) has a great impact on therapy approach and potentially on patient prognosis. Purpose: To assess the diagnostic accuracy of combined positron emission tomography (PET)/computer tomography (CT) for primary tumor detection in cervical metastases of unknown origin compared to PET, CT, and PET+CT side-by-side evaluation. Material and Methods: 39 consecutive patients (eight women, 31 men; mean age 59.9±11.2 years) with MUO were enrolled in this study. PET/CT images were obtained 1 hour after injection of 350 MBq of fluor