WorldWideScience

Sample records for bone cancer proteomics

  1. Bone Cancer

    Science.gov (United States)

    Cancer that starts in a bone is uncommon. Cancer that has spread to the bone from another ... more common. There are three types of bone cancer: Osteosarcoma - occurs most often between ages 10 and ...

  2. Alteration of cancer pain-related signals by radiation: Proteomic analysis in an animal model with cancer bone invasion

    International Nuclear Information System (INIS)

    Park, Hee Chul; Seong, Jinsil; An, Jung Hee; Kim, Jiyoung; Kim, Un Jung; Lee, Bae Whan

    2005-01-01

    Purpose: Although radiotherapy is highly effective in relieving bone pain due to cancer invasion, its mechanism remains unclear. The aim of this study was to explore this mechanism in an animal model system. Methods and Materials: A hind paw model of cancer pain was developed by transplanting a murine hepatocarcinoma, HCa-1, into the periosteal membrane of the foot dorsum of C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed from sequential tumor sampling. For three experimental groups, a control (N), tumor without radiation (T), and tumor with radiation (TR), the development and level of pain were objectively examined in mice with a growing tumor by assessing pain-associated behavior. The differential expression of pain-related signals in the spinal cord was analyzed by proteomic analysis using high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry, and those of proteins by Western blotting. The pain-mediating neurotransmitters in the spinal cord were also examined by immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P. Results: In the histopathologic examinations, bone invasion from HCa-1 was seen from Day 7 and was evident at Day 14 after transplantation, and measurable pain-associated behaviors were developed from Day 7. After 25 Gy of radiation to the tumors, the objective level of pain in the TR group decreased, with higher thresholds to mechanical and thermal stimulation than in the T group. From the 2-DE of spinal cord, 107 spots were identified; 12 proteins were changed more than fivefold because of tumor formation but then reversed after radiation in the tumor-bearing mice. The proteins involved included secretagogin, syntenin, P2X purinoreceptor 6 (P2X6), and Ca 2+ /Calmodulin-dependent protein kinase 1 (CaM kinase 1), the functions of which have been known to be involved in the Ca 2+ -signaling cascade, ATP-mediated fast synaptic transmission, or control of vesicular

  3. Alteration of cancer pain-related signals by radiation: Proteomic analysis in an animal model with cancer bone invasion

    Energy Technology Data Exchange (ETDEWEB)

    Park, Hee Chul [Department of Radiation Oncology, Hallym University, Chuncheon (Korea, Republic of); Seong, Jinsil [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); An, Jung Hee [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Kim, Jiyoung [Department of Radiation Oncology, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Kim, Un Jung [Yonsei Medical Research Center, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of); Lee, Bae Whan [Yonsei Medical Research Center, Brain Korea 21 Project for Medicine, Yonsei University, Seoul (Korea, Republic of)

    2005-04-01

    Purpose: Although radiotherapy is highly effective in relieving bone pain due to cancer invasion, its mechanism remains unclear. The aim of this study was to explore this mechanism in an animal model system. Methods and Materials: A hind paw model of cancer pain was developed by transplanting a murine hepatocarcinoma, HCa-1, into the periosteal membrane of the foot dorsum of C3H/HeJ mice. Bone invasion from HCa-1 was histopathologically confirmed from sequential tumor sampling. For three experimental groups, a control (N), tumor without radiation (T), and tumor with radiation (TR), the development and level of pain were objectively examined in mice with a growing tumor by assessing pain-associated behavior. The differential expression of pain-related signals in the spinal cord was analyzed by proteomic analysis using high-resolution two-dimensional gel electrophoresis (2-DE) and mass spectrometry, and those of proteins by Western blotting. The pain-mediating neurotransmitters in the spinal cord were also examined by immunohistochemical staining for calcitonin gene-related peptide (CGRP) and substance P. Results: In the histopathologic examinations, bone invasion from HCa-1 was seen from Day 7 and was evident at Day 14 after transplantation, and measurable pain-associated behaviors were developed from Day 7. After 25 Gy of radiation to the tumors, the objective level of pain in the TR group decreased, with higher thresholds to mechanical and thermal stimulation than in the T group. From the 2-DE of spinal cord, 107 spots were identified; 12 proteins were changed more than fivefold because of tumor formation but then reversed after radiation in the tumor-bearing mice. The proteins involved included secretagogin, syntenin, P2X purinoreceptor 6 (P2X6), and Ca{sup 2+}/Calmodulin-dependent protein kinase 1 (CaM kinase 1), the functions of which have been known to be involved in the Ca{sup 2+}-signaling cascade, ATP-mediated fast synaptic transmission, or control of

  4. Proteomic classification of breast cancer.

    LENUS (Irish Health Repository)

    Kamel, Dalia

    2012-11-01

    Being a significant health problem that affects patients in various age groups, breast cancer has been extensively studied to date. Recently, molecular breast cancer classification has advanced significantly with the availability of genomic profiling technologies. Proteomic technologies have also advanced from traditional protein assays including enzyme-linked immunosorbent assay, immunoblotting and immunohistochemistry to more comprehensive approaches including mass spectrometry and reverse phase protein lysate arrays (RPPA). The purpose of this manuscript is to review the current protein markers that influence breast cancer prediction and prognosis and to focus on novel advances in proteomic classification of breast cancer.

  5. Subnuclear proteomics in colorectal cancer

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Knol, Jaco C; Piersma, Sander R

    2010-01-01

    for early cancer detection. Here we evaluate a proteomics work flow for profiling protein constituents in subnuclear domains in colorectal cancer tissues and apply this work flow to a comparative analysis of the nuclear matrix fraction in colorectal adenoma and carcinoma tissue samples. First, we......Abnormalities in nuclear phenotype and chromosome structure are key features of cancer cells. Investigation of the protein determinants of nuclear subfractions in cancer may yield molecular insights into aberrant chromosome function and chromatin organization and in addition may yield biomarkers...... with statistics, we identified proteins that are significantly enriched in the nuclear matrix fraction relative to two earlier fractions (the chromatin-binding and intermediate filament fractions) isolated from six colorectal tissue samples. The total data set contained 2,059 non-redundant proteins. Gene ontology...

  6. Breast Cancer and Bone Loss

    Science.gov (United States)

    ... Menopause Map Featured Resource Find an Endocrinologist Search Breast Cancer and Bone Loss July 2010 Download PDFs English ... G. Komen Foundation What is the link between breast cancer and bone loss? Certain treatments for breast cancer ...

  7. Proteomics in studying cancer stem cell biology.

    Science.gov (United States)

    Kranenburg, Onno; Emmink, Benjamin L; Knol, Jaco; van Houdt, Winan J; Rinkes, Inne H M Borel; Jimenez, Connie R

    2012-06-01

    Normal multipotent tissue stem cells (SCs) are the driving force behind tissue turnover and repair. The cancer stem cell theory holds that tumors also contain stem-like cells that drive tumor growth and metastasis formation. However, very little is known about the regulation of SC maintenance pathways in cancer and how these are affected by cancer-specific genetic alterations and by treatment. Proteomics is emerging as a powerful tool to identify the signaling complexes and pathways that control multi- and pluri-potency and SC differentiation. Here, the authors review the novel insights that these studies have provided and present a comprehensive strategy for the use of proteomics in studying cancer SC biology.

  8. Evolution of Clinical Proteomics and its Role in Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    NCI's Office of Cancer Clinical Proteomics Research authored a review of the current state of clinical proteomics in the peer-reviewed Journal of Proteome Research. The review highlights outcomes from the CPTC program and also provides a thorough overview of the different technologies that have pushed the field forward. Additionally, the review provides a vision for moving the field forward through linking advances in genomic and proteomic analysis to develop new, molecularly targeted interventions.

  9. Proteomic maps of breast cancer subtypes

    DEFF Research Database (Denmark)

    Tyanova, Stefka; Albrechtsen, Reidar; Kronqvist, Pauliina

    2016-01-01

    Systems-wide profiling of breast cancer has almost always entailed RNA and DNA analysis by microarray and sequencing techniques. Marked developments in proteomic technologies now enable very deep profiling of clinical samples, with high identification and quantification accuracy. We analysed 40...... oestrogen receptor positive (luminal), Her2 positive and triple negative breast tumours and reached a quantitative depth of >10,000 proteins. These proteomic profiles identified functional differences between breast cancer subtypes, related to energy metabolism, cell growth, mRNA translation and cell......-cell communication. Furthermore, we derived a signature of 19 proteins, which differ between the breast cancer subtypes, through support vector machine (SVM)-based classification and feature selection. Remarkably, only three proteins of the signature were associated with gene copy number variations and eleven were...

  10. Drugs Approved for Bone Cancer

    Science.gov (United States)

    This page lists cancer drugs approved by the Food and Drug Administration (FDA) for bone cancer. The list includes generic names and brand names. The drug names link to NCI's Cancer Drug Information summaries.

  11. Proteomic Analysis of Gingival Tissue and Alveolar Bone during Alveolar Bone Healing*

    OpenAIRE

    Yang, Hee-Young; Kwon, Joseph; Kook, Min-Suk; Kang, Seong Soo; Kim, Se Eun; Sohn, Sungoh; Jung, Seunggon; Kwon, Sang-Oh; Kim, Hyung-Seok; Lee, Jae Hyuk; Lee, Tae-Hoon

    2013-01-01

    Bone tissue regeneration is orchestrated by the surrounding supporting tissues and involves the build-up of osteogenic cells, which orchestrate remodeling/healing through the expression of numerous mediators and signaling molecules. Periodontal regeneration models have proven useful for studying the interaction and communication between alveolar bone and supporting soft tissue. We applied a quantitative proteomic approach to analyze and compare proteins with altered expression in gingival sof...

  12. Bone metastases from gastric cancer

    International Nuclear Information System (INIS)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi

    1983-01-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N 0 or N 1 regional lymph node metastases, highly deferenciated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone stastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer. (author)

  13. Proteomic alterations in early stage cervical cancer

    OpenAIRE

    Güzel, Coşkun; Govorukhina, Natalia; Wisman, G.B.A.; Stingl, Christoph; Dekker, Lennard; Hollema, Harry; Guryev, Victor; Horvatovich, Peter; van der Zee, Ate; Bischoff, Rainer; Luider, Theo

    2018-01-01

    Laser capture microdissection (LCM) allows the capture of cell types or well-defined structures in tissue. We compared in a semi-quantitative way the proteomes from an equivalent of 8,000 tumor cells from patients with squamous cell cervical cancer (SCC, n = 22) with healthy epithelial and stromal cells obtained from normal cervical tissue (n = 13). Proteins were enzymatically digested into peptides which were measured by high-resolution mass spectrometry and analyzed by “all-or-nothing” anal...

  14. Proteomics of anti-cancer drugs

    Czech Academy of Sciences Publication Activity Database

    Kovářová, Hana; Martinková, Jiřina; Hrabáková, Rita; Skalníková, Helena; Novák, Petr; Hajdůch, M.; Gadher, S. J.

    2009-01-01

    Roč. 276, Supplement 1 (2009), s. 84-84 E-ISSN 1742-4658. [34th FEBS Congress. 04.07.2009-09.07.2009, Praha] R&D Projects: GA MŠk LC07017 Institutional research plan: CEZ:AV0Z50450515; CEZ:AV0Z50200510 Keywords : proteomics * anti-cancer drugs * biomarkers Subject RIV: FD - Oncology ; Hematology

  15. The Proteome of Primary Prostate Cancer

    DEFF Research Database (Denmark)

    Iglesias-Gato, Diego; Wikström, Pernilla; Tyanova, Stefka

    2016-01-01

    for disease aggressiveness. DESIGN, SETTING, AND PARTICIPANTS: Mass spectrometry was used for genome-scale quantitative proteomic profiling of 28 prostate tumors (Gleason score 6-9) and neighboring nonmalignant tissue in eight cases, obtained from formalin-fixed paraffin-embedded prostatectomy samples. Two...... changes occurring during prostate cancer (PCa) initiation and progression can result in clinically relevant discoveries. OBJECTIVES: To study cellular processes altered in PCa using system-wide quantitative analysis of changes in protein expression in clinical samples and to identify prognostic biomarkers......BACKGROUND: Clinical management of the prostate needs improved prognostic tests and treatment strategies. Because proteins are the ultimate effectors of most cellular reactions, are targets for drug actions and constitute potential biomarkers; a quantitative systemic overview of the proteome...

  16. The Clinical Proteomic Technologies for Cancer | Antibody Portal

    Science.gov (United States)

    An objective of the Reagents and Resources component of NCI's Clinical Proteomic Technologies for Cancer Initiative is to generate highly characterized monoclonal antibodies to human proteins associated with cancer.

  17. Bone health in cancer patients

    DEFF Research Database (Denmark)

    Coleman, R; Body, J J; Aapro, M

    2014-01-01

    There are three distinct areas of cancer management that make bone health in cancer patients of increasing clinical importance. First, bone metastases are common in many solid tumours, notably those arising from the breast, prostate and lung, as well as multiple myeloma, and may cause major...... morbidity including fractures, severe pain, nerve compression and hypercalcaemia. Through optimum multidisciplinary management of patients with bone metastases, including the use of bone-targeted treatments such as potent bisphosphonates or denosumab, it has been possible to transform the course of advanced...... cancer for many patients resulting in a major reduction in skeletal complications, reduced bone pain and improved quality of life. Secondly, many of the treatments we use to treat cancer patients have effects on reproductive hormones, which are critical for the maintenance of normal bone remodelling...

  18. Implementation of proteomics for cancer research: past, present, and future.

    Science.gov (United States)

    Karimi, Parisa; Shahrokni, Armin; Ranjbar, Mohammad R Nezami

    2014-01-01

    Cancer is the leading cause of the death, accounts for about 13% of all annual deaths worldwide. Many different fields of science are collaborating together studying cancer to improve our knowledge of this lethal disease, and find better solutions for diagnosis and treatment. Proteomics is one of the most recent and rapidly growing areas in molecular biology that helps understanding cancer from an omics data analysis point of view. The human proteome project was officially initiated in 2008. Proteomics enables the scientists to interrogate a variety of biospecimens for their protein contents and measure the concentrations of these proteins. Current necessary equipment and technologies for cancer proteomics are mass spectrometry, protein microarrays, nanotechnology and bioinformatics. In this paper, we provide a brief review on proteomics and its application in cancer research. After a brief introduction including its definition, we summarize the history of major previous work conducted by researchers, followed by an overview on the role of proteomics in cancer studies. We also provide a list of different utilities in cancer proteomics and investigate their advantages and shortcomings from theoretical and practical angles. Finally, we explore some of the main challenges and conclude the paper with future directions in this field.

  19. Elucidation of cross-species proteomic effects in human and hominin bone proteome identification through a bioinformatics experiment

    DEFF Research Database (Denmark)

    Welker, F.

    2018-01-01

    Background: The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein identificati......Background: The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein...... not been demonstrated. If error-tolerant searches do not overcome the cross-species proteomic issue then there might be inherent biases in the identified proteomes. Here, a bioinformatics experiment is performed to test this using a set of modern human bone proteomes and three independent searches against......), but roughly half of the mutable PSMs were not recovered. As a result, peptide and protein identification rates are higher in error-tolerant mode compared to non-error-tolerant searches but did not recover protein identifications completely. Data indicates that peptide length and the number of mutations...

  20. Elucidation of cross-species proteomic effects in human and hominin bone proteome identification through a bioinformatics experiment.

    Science.gov (United States)

    Welker, F

    2018-02-20

    The study of ancient protein sequences is increasingly focused on the analysis of older samples, including those of ancient hominins. The analysis of such ancient proteomes thereby potentially suffers from "cross-species proteomic effects": the loss of peptide and protein identifications at increased evolutionary distances due to a larger number of protein sequence differences between the database sequence and the analyzed organism. Error-tolerant proteomic search algorithms should theoretically overcome this problem at both the peptide and protein level; however, this has not been demonstrated. If error-tolerant searches do not overcome the cross-species proteomic issue then there might be inherent biases in the identified proteomes. Here, a bioinformatics experiment is performed to test this using a set of modern human bone proteomes and three independent searches against sequence databases at increasing evolutionary distances: the human (0 Ma), chimpanzee (6-8 Ma) and orangutan (16-17 Ma) reference proteomes, respectively. Incorrectly suggested amino acid substitutions are absent when employing adequate filtering criteria for mutable Peptide Spectrum Matches (PSMs), but roughly half of the mutable PSMs were not recovered. As a result, peptide and protein identification rates are higher in error-tolerant mode compared to non-error-tolerant searches but did not recover protein identifications completely. Data indicates that peptide length and the number of mutations between the target and database sequences are the main factors influencing mutable PSM identification. The error-tolerant results suggest that the cross-species proteomics problem is not overcome at increasing evolutionary distances, even at the protein level. Peptide and protein loss has the potential to significantly impact divergence dating and proteome comparisons when using ancient samples as there is a bias towards the identification of conserved sequences and proteins. Effects are minimized

  1. Computational Omics Funding Opportunity | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) and the NVIDIA Foundation are pleased to announce funding opportunities in the fight against cancer. Each organization has launched a request for proposals (RFP) that will collectively fund up to $2 million to help to develop a new generation of data-intensive scientific tools to find new ways to treat cancer.

  2. Opportunities and Challenges for Nutritional Proteomics in Cancer Prevention12

    Science.gov (United States)

    Romagnolo, Donato F.; Milner, John A.

    2012-01-01

    Knowledge gaps persist about the efficacy of cancer prevention strategies based on dietary food components. Adaptations to nutrient supply are executed through tuning of multiple protein networks that include transcription factors, histones, modifying enzymes, translation factors, membrane and nuclear receptors, and secreted proteins. However, the simultaneous quantitative and qualitative measurement of all proteins that regulate cancer processes is not practical using traditional protein methodologies. Proteomics offers an attractive opportunity to fill this knowledge gap and unravel the effects of dietary components on protein networks that impinge on cancer. The articles presented in this supplement are from talks proffered in the “Nutrition Proteomics and Cancer Prevention” session at the American Institute for Cancer Research Annual Research Conference on Food, Nutrition, Physical Activity and Cancer held in Washington, DC on October 21 and 22, 2010. Recent advances in MS technologies suggest that studies in nutrition and cancer prevention may benefit from the adoption of proteomic tools to elucidate the impact on biological processes that govern the transition from normal to malignant phenotype; to identify protein changes that determine both positive and negative responses to food components; to assess how protein networks mediate dose-, time-, and tissue-dependent responses to food components; and, finally, for predicting responders and nonresponders. However, both the limited accessibility to proteomic technologies and research funding appear to be hampering the routine adoption of proteomic tools in nutrition and cancer prevention research. PMID:22649262

  3. Bone metastases from gastric cancer. Clinical evaluation on bone scintigram

    Energy Technology Data Exchange (ETDEWEB)

    Seto, Mikito; Tonami, Norihisa; Koizumi, Kiyoshi; Sui, Osamu; Hisada, Kinichi [Kanazawa Univ. (Japan). School of Medicine

    1983-07-01

    We have studied bone scintigrams in 60 patients with gastric cancer. Of these 60 patients, bone metastases were found in 15 patients (25 %). There were no evidence of bone metastases in polypoid lesions, cancers of the antrum, carcinomas in situ, advanced cancers without invasion to serosa, cancer with N/sub 0/ or N/sub 1/ regional lymph node metastases, highly differentiated adenocarcinomas and papillary adenocarcinomas. On the contrary, high rates of bone metastases were seen in cancers of the corpus, advanced cancers with invasion to neighbouring structures and tubular adenocarcinomas. Of these 15 patients with bone metastasis, 3 patients showed very similar clinical features and the findings of ''diffuse bone metastases on bone scintigrams.'' Cancer of the antrum showed high rates of liver metastases, while cancers of the corpus showed high rates of bone metastases. Sixty percent of the patients with bone metastases did not have liver metastases and there seemed to be no significant relationship between liver metastases and bone metastases. From these results we suppose that non-portal tract through the vertebral venous plexus instead of portal tract may be the other route of bone metastases from gastric cancer.

  4. Proteomic approaches in cancer risk and response assessment.

    Science.gov (United States)

    Petricoin, Emanuel F; Liotta, Lance A

    2004-02-01

    Proteomics is more than just a list-generating exercise where increases or decreases in protein expression are identified. Proteomic technologies will ultimately characterize information-flow through the protein circuitry that interconnects the extracellular microenvironment to the serum or plasma macroenvironment through intracellular signaling systems and their control of gene transcription. The nature of this information can be a cause or a consequence of disease processes and how patients respond to therapy. Analysis of human cancer as a model for how proteomics can have an impact at the bedside can take advantage of several promising new proteomic technologies. These technologies are being developed for early detection and risk assessment, therapeutic targeting and patient-tailored therapy.

  5. Single-cell proteomics: potential implications for cancer diagnostics.

    Science.gov (United States)

    Gavasso, Sonia; Gullaksen, Stein-Erik; Skavland, Jørn; Gjertsen, Bjørn T

    2016-01-01

    Single-cell proteomics in cancer is evolving and promises to provide more accurate diagnoses based on detailed molecular features of cells within tumors. This review focuses on technologies that allow for collection of complex data from single cells, but also highlights methods that are adaptable to routine cancer diagnostics. Current diagnostics rely on histopathological analysis, complemented by mutational detection and clinical imaging. Though crucial, the information gained is often not directly transferable to defined therapeutic strategies, and predicting therapy response in a patient is difficult. In cancer, cellular states revealed through perturbed intracellular signaling pathways can identify functional mutations recurrent in cancer subsets. Single-cell proteomics remains to be validated in clinical trials where serial samples before and during treatment can reveal excessive clonal evolution and therapy failure; its use in clinical trials is anticipated to ignite a diagnostic revolution that will better align diagnostics with the current biological understanding of cancer.

  6. CPTAC Collaborates with Molecular & Cellular Proteomics to Address Reproducibility in Targeted Assay Development | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The journal Molecular & Cellular Proteomics (MCP), in collaboration with the Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announce new guidelines and requirements for papers describing the development and application of targeted mass spectrometry measurements of peptides, modified peptides and proteins (Mol Cell Proteomics 2017; PMID: 28183812).  NCI’s participation is part of NIH’s overall effort to address the r

  7. The Spectra Count Label-free Quantitation in Cancer Proteomics

    OpenAIRE

    Zhou, Weidong; Liotta, Lance A.; Petricoin, Emanuel F.

    2012-01-01

    Mass spectrometry is used routinely for large-scale protein identification from complex biological mixtures. Recently, relative quantitation approach on the basis of spectra count has been applied in several cancer proteomic studies. In this review, we examine the mechanism of this technique and highlight several important parameters associated with its application.

  8. Mass Spectrometry–based Proteomic Profiling of Lung Cancer

    Science.gov (United States)

    Ocak, Sebahat; Chaurand, Pierre; Massion, Pierre P.

    2009-01-01

    In an effort to further our understanding of lung cancer biology and to identify new candidate biomarkers to be used in the management of lung cancer, we need to probe these tissues and biological fluids with tools that address the biology of lung cancer directly at the protein level. Proteins are responsible of the function and phenotype of cells. Cancer cells express proteins that distinguish them from normal cells. Proteomics is defined as the study of the proteome, the complete set of proteins produced by a species, using the technologies of large-scale protein separation and identification. As a result, new technologies are being developed to allow the rapid and systematic analysis of thousands of proteins. The analytical advantages of mass spectrometry (MS), including sensitivity and high-throughput, promise to make it a mainstay of novel biomarker discovery to differentiate cancer from normal cells and to predict individuals likely to develop or recur with lung cancer. In this review, we summarize the progress made in clinical proteomics as it applies to the management of lung cancer. We will focus our discussion on how MS approaches may advance the areas of early detection, response to therapy, and prognostic evaluation. PMID:19349484

  9. Proteomic analysis of tissue samples in translational breast cancer research

    DEFF Research Database (Denmark)

    Gromov, Pavel; Moreira, José; Gromova, Irina

    2014-01-01

    In the last decade, many proteomic technologies have been applied, with varying success, to the study of tissue samples of breast carcinoma for protein expression profiling in order to discover protein biomarkers/signatures suitable for: characterization and subtyping of tumors; early diagnosis...... the translation of basic discoveries into the daily breast cancer clinical practice. In particular, we address major issues in experimental design by reviewing the strengths and weaknesses of current proteomic strategies in the context of the analysis of human breast tissue specimens....

  10. Osthole inhibits bone metastasis of breast cancer

    OpenAIRE

    Wu, Chunyu; Sun, Zhenping; Guo, Baofeng; Ye, Yiyi; Han, Xianghui; Qin, Yuenong; Liu, Sheng

    2017-01-01

    Bone is one of the most common sites for breast cancer metastasis, which greatly contributes to patient morbidity and mortality. Osthole, a major extract from Cnidium monnieri (L.), exhibits many biological and pharmacological activities, however, its potential as a therapeutic agent in the treatment of breast cancer bone metastases remain poorly understood. In this study, we set out to investigate whether osthole could inhibit breast cancer metastasis to bone in mice and clarified the potent...

  11. STATE OF THE ART IN PROTEOMICS FOR CANCER DETECTION

    Directory of Open Access Journals (Sweden)

    Syafrizayanti Syafrizayanti

    2014-12-01

    Full Text Available The earliest stages of cancer detection determine the successful of cancer treatment andtherapy. The existing cancer test or detection methods have been routinely used, but they arelack of sensitivity and specificity that are needed to avoid false positive or negative results. Thegenomic basedtechniques have been applied, although molecular understandings of cancerfar from complete, but few genomic platforms are becoming routine. Application of proteomicsbasedtechniques provide intriguing outcome, which is cancer detection at their earliest stages.Proteomics have exposed a new perspective into the phases of tumorigenesis and depictedmore detailed molecular network scheme, which made important contributions in the discoveryof biomarker of early diagnosis, prognosis and prediction outcome of cancer therapies.The noticeable proteomic platforms to achieve these goals are protein microarray, tissuemicroarray, mass spectrometry-based proteomic, and two-dimensionalgel electrophoresis (2-DE. The application of these techniques will be overviewed, providing a general review ofcurrent proteomic methods in cancer detection and subsequently improvement in prognosisand prediction of cancer therapies.Keywords: proteomics, protein microarrays, mass spectrometry, cancer biomarkerAbstrakDeteksi dini kanker sangat menentukan keberhasilan penanganan dan terapi kanker. Hinggasaat ini, telah banyak jenis metoda deteksi dan uji kanker yang sudah rutin digunakan, akantetapi metoda-metoda tersebut memiliki tingkat sensitifitas dan spesifikasi yang rendah,sehingga sering menyebabkan terjadi kesalahan hasil uji baik secara positif ataupun negatif.Bidang genomik telah banyak digunakan untuk lebih memahami kanker pada level molekuler,meskipun hasil yang diperoleh belum mendalam, akan tetapi beberapa metoda berbasiskangenomik telah mulai rutin digunakan. Bidang pioteomik mulai banyak diaplikasikan untukkeperluan deteksi kankersedini mungkin. Proteomik memberikan perspektif

  12. Proteomic Approaches in Biomarker Discovery: New Perspectives in Cancer Diagnostics

    Science.gov (United States)

    Kocevar, Nina; Komel, Radovan

    2014-01-01

    Despite remarkable progress in proteomic methods, including improved detection limits and sensitivity, these methods have not yet been established in routine clinical practice. The main limitations, which prevent their integration into clinics, are high cost of equipment, the need for highly trained personnel, and last, but not least, the establishment of reliable and accurate protein biomarkers or panels of protein biomarkers for detection of neoplasms. Furthermore, the complexity and heterogeneity of most solid tumours present obstacles in the discovery of specific protein signatures, which could be used for early detection of cancers, for prediction of disease outcome, and for determining the response to specific therapies. However, cancer proteome, as the end-point of pathological processes that underlie cancer development and progression, could represent an important source for the discovery of new biomarkers and molecular targets for tailored therapies. PMID:24550697

  13. Application of Proteomics to Cancer Molecular Diagnostics

    Institute of Scientific and Technical Information of China (English)

    Sam HANASH

    2009-01-01

    @@ Strategies to achieve personalized medicine and improve public health encompass assessment of an individual's risk for disease, early detection and molecular classification of disease resulting in an informed choice of the most appropriate treatment instituted at an early stage of disease develop- ment. A major contribution of proteomics in this field is the development of blood based tests to achieve the goals of personalized medicine.

  14. The proteomic dataset for bone marrow derived human mesenchymal stromal cells: Effect of in vitro passaging

    Directory of Open Access Journals (Sweden)

    Samuel T. Mindaye

    2015-12-01

    Full Text Available Bone-marrow derived mesenchymal stromal cells (BMSCs have been in clinical trials for therapy. One major bottleneck in the advancement of BMSC-based products is the challenge associated with cell isolation, characterization, and ensuring cell fitness over the course of in vitro cell propagation steps. The data in this report is part of publications that explored the proteomic changes following in vitro passaging of BMSCs [4] and the molecular heterogeneity in cultures obtained from different human donors [5,6].The methodological details involving cell manufacturing, proteome harvesting, protein identification and quantification as well as the bioinformatic analyses were described to ensure reproducibility of the results.

  15. P-MartCancer-Interactive Online Software to Enable Analysis of Shotgun Cancer Proteomic Datasets.

    Science.gov (United States)

    Webb-Robertson, Bobbie-Jo M; Bramer, Lisa M; Jensen, Jeffrey L; Kobold, Markus A; Stratton, Kelly G; White, Amanda M; Rodland, Karin D

    2017-11-01

    P-MartCancer is an interactive web-based software environment that enables statistical analyses of peptide or protein data, quantitated from mass spectrometry-based global proteomics experiments, without requiring in-depth knowledge of statistical programming. P-MartCancer offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification, and exploratory data analyses driven by the user via customized workflows and interactive visualization. Currently, P-MartCancer offers access and the capability to analyze multiple cancer proteomic datasets generated through the Clinical Proteomics Tumor Analysis Consortium at the peptide, gene, and protein levels. P-MartCancer is deployed as a web service (https://pmart.labworks.org/cptac.html), alternatively available via Docker Hub (https://hub.docker.com/r/pnnl/pmart-web/). Cancer Res; 77(21); e47-50. ©2017 AACR . ©2017 American Association for Cancer Research.

  16. VIDEO: Dr. Henry Rodriguez - Proteogenomics in Cancer Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Dr. Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research (OCCPR) at NCI, speaks with ecancer television at WIN 2017 about the translation of the proteins expressed in a patient's tumor into a map for druggable targets. By combining genomic and proteomic information (proteogenomics), leading scientists are gaining new insights into ways to detect and treat cancer due to a more complete and unified understanding of complex biological processes.

  17. Paget's disease of bone resembling bone metastasis from gastric cancer.

    Science.gov (United States)

    Shimoyama, Yasuyuki; Kusano, Motoyasu; Shimoda, Yoko; Ishihara, Shingo; Toyomasu, Yoshitaka; Ohno, Tetsuro; Mochiki, Erito; Sano, Takaaki; Hirato, Junko; Mori, Masatomo

    2011-08-01

    A 74-year-old man had an endoscopic type 0'-IIc tumor in the upper gastric body on the greater curvature and biopsy showed the tumor to be a well-differentiated adenocarcinoma (Group 5). He was referred to us for endoscopic submucosal dissection (ESD). Endoscopy revealed fold convergency, fold swelling, and fusion of the fold, indicating tumor invasion into the submucosa, which was outside the indications for ESD. In addition, there was an increase of serum bone-type alkaline phosphatase (ALP-III and ALP-IV) and urinary cross-linked N-terminal telopeptide of type I collagen (a bone metabolism marker), while (18)F-fluorodeoxyglucose positron emission tomography showed increased uptake in the left pelvis and Th10, suggesting bone metastases. We first diagnosed gastric cancer with bone metastases; however, the symptoms suggested pathological bone fracture and no bone pain. Therefore, a computed tomography-guided aspiration bone biopsy was performed to exclude the possibility of Paget's disease of bone. Biopsy specimens revealed no tumor and a mosaic pattern. No increased uptake of (18)F-FAMT (L-[3-(18)F] α-methyltyrosine) supported a diagnosis of no bone metastases from gastric cancer. We finally diagnosed gastric cancer accompanied by Paget's disease of bone and performed a laparoscopy-assisted proximal gastrectomy. The pathological diagnosis was U less 0-IIb, and U post 0-IIc ypT1a (M) N0H0P0M0 yp stage IA. In gastric cancer patients with suspected bone metastasis, we also need to consider Paget's disease of bone.

  18. The amino acid's backup bone - storage solutions for proteomics facilities.

    Science.gov (United States)

    Meckel, Hagen; Stephan, Christian; Bunse, Christian; Krafzik, Michael; Reher, Christopher; Kohl, Michael; Meyer, Helmut Erich; Eisenacher, Martin

    2014-01-01

    Proteomics methods, especially high-throughput mass spectrometry analysis have been continually developed and improved over the years. The analysis of complex biological samples produces large volumes of raw data. Data storage and recovery management pose substantial challenges to biomedical or proteomic facilities regarding backup and archiving concepts as well as hardware requirements. In this article we describe differences between the terms backup and archive with regard to manual and automatic approaches. We also introduce different storage concepts and technologies from transportable media to professional solutions such as redundant array of independent disks (RAID) systems, network attached storages (NAS) and storage area network (SAN). Moreover, we present a software solution, which we developed for the purpose of long-term preservation of large mass spectrometry raw data files on an object storage device (OSD) archiving system. Finally, advantages, disadvantages, and experiences from routine operations of the presented concepts and technologies are evaluated and discussed. This article is part of a Special Issue entitled: Computational Proteomics in the Post-Identification Era. Guest Editors: Martin Eisenacher and Christian Stephan. Copyright © 2013. Published by Elsevier B.V.

  19. Redefining the Breast Cancer Exosome Proteome by Tandem Mass Tag Quantitative Proteomics and Multivariate Cluster Analysis.

    Science.gov (United States)

    Clark, David J; Fondrie, William E; Liao, Zhongping; Hanson, Phyllis I; Fulton, Amy; Mao, Li; Yang, Austin J

    2015-10-20

    Exosomes are microvesicles of endocytic origin constitutively released by multiple cell types into the extracellular environment. With evidence that exosomes can be detected in the blood of patients with various malignancies, the development of a platform that uses exosomes as a diagnostic tool has been proposed. However, it has been difficult to truly define the exosome proteome due to the challenge of discerning contaminant proteins that may be identified via mass spectrometry using various exosome enrichment strategies. To better define the exosome proteome in breast cancer, we incorporated a combination of Tandem-Mass-Tag (TMT) quantitative proteomics approach and Support Vector Machine (SVM) cluster analysis of three conditioned media derived fractions corresponding to a 10 000g cellular debris pellet, a 100 000g crude exosome pellet, and an Optiprep enriched exosome pellet. The quantitative analysis identified 2 179 proteins in all three fractions, with known exosomal cargo proteins displaying at least a 2-fold enrichment in the exosome fraction based on the TMT protein ratios. Employing SVM cluster analysis allowed for the classification 251 proteins as "true" exosomal cargo proteins. This study provides a robust and vigorous framework for the future development of using exosomes as a potential multiprotein marker phenotyping tool that could be useful in breast cancer diagnosis and monitoring disease progression.

  20. Proteomics for discovery of candidate colorectal cancer biomarkers

    Science.gov (United States)

    Álvarez-Chaver, Paula; Otero-Estévez, Olalla; Páez de la Cadena, María; Rodríguez-Berrocal, Francisco J; Martínez-Zorzano, Vicenta S

    2014-01-01

    Colorectal cancer (CRC) is the second most common cause of cancer-related deaths in Europe and other Western countries, mainly due to the lack of well-validated clinically useful biomarkers with enough sensitivity and specificity to detect this disease at early stages. Although it is well known that the pathogenesis of CRC is a progressive accumulation of mutations in multiple genes, much less is known at the proteome level. Therefore, in the last years many proteomic studies have been conducted to find new candidate protein biomarkers for diagnosis, prognosis and as therapeutic targets for this malignancy, as well as to elucidate the molecular mechanisms of colorectal carcinogenesis. An important advantage of the proteomic approaches is the capacity to look for multiple differentially expressed proteins in a single study. This review provides an overview of the recent reports describing the different proteomic tools used for the discovery of new protein markers for CRC such as two-dimensional electrophoresis methods, quantitative mass spectrometry-based techniques or protein microarrays. Additionally, we will also focus on the diverse biological samples used for CRC biomarker discovery such as tissue, serum and faeces, besides cell lines and murine models, discussing their advantages and disadvantages, and summarize the most frequently identified candidate CRC markers. PMID:24744574

  1. Proteomic profiling of urine for the detection of colon cancer

    Directory of Open Access Journals (Sweden)

    Wakelam Michael JO

    2008-06-01

    Full Text Available Abstract Background Colorectal cancer is the second most common cause of cancer related death in the developed world. To date, no blood or stool biomarkers with both high sensitivity and specificity for potentially curable early stage disease have been validated for clinical use. SELDI and MALDI profiling are being used increasingly to search for biomarkers in both blood and urine. Both techniques provide information predominantly on the low molecular weight proteome ( Results We collected urine from 67 patients with colorectal cancer and 72 non-cancer control subjects, diluted to a constant protein concentration and generated MALDI and SELDI spectra. The intensities of 19 peaks differed significantly between cancer and non-cancer patients by both t-tests and after adjusting for confounders using multiple linear regressions. Logistic regression classifiers based on peak intensities identified colorectal cancer with up to 78% sensitivity at 87% specificity. We identified and independently quantified 3 of the discriminatory peaks using synthetic stable isotope peptides (an 1885 Da fragment of fibrinogen and hepcidin-20 or ELISA (β2-microglobulin. Conclusion Changes in the urine proteome may aid in the early detection of colorectal cancer.

  2. Comparative proteome analysis of human epithelial ovarian cancer

    Directory of Open Access Journals (Sweden)

    Gagné Jean-Philippe

    2007-09-01

    Full Text Available Abstract Background Epithelial ovarian cancer is a devastating disease associated with low survival prognosis mainly because of the lack of early detection markers and the asymptomatic nature of the cancer until late stage. Using two complementary proteomics approaches, a differential protein expression profile was carried out between low and highly transformed epithelial ovarian cancer cell lines which realistically mimic the phenotypic changes observed during evolution of a tumour metastasis. This investigation was aimed at a better understanding of the molecular mechanisms underlying differentiation, proliferation and neoplastic progression of ovarian cancer. Results The quantitative profiling of epithelial ovarian cancer model cell lines TOV-81D and TOV-112D generated using iTRAQ analysis and two-dimensional electrophoresis coupled to liquid chromatography tandem mass spectrometry revealed some proteins with altered expression levels. Several of these proteins have been the object of interest in cancer research but others were unrecognized as differentially expressed in a context of ovarian cancer. Among these, series of proteins involved in transcriptional activity, cellular metabolism, cell adhesion or motility and cytoskeleton organization were identified, suggesting their possible role in the emergence of oncogenic pathways leading to aggressive cellular behavior. Conclusion The differential protein expression profile generated by the two proteomics approaches combined to complementary characterizations studies will open the way to more exhaustive and systematic representation of the disease and will provide valuable information that may be helpful to uncover the molecular mechanisms related to epithelial ovarian cancer.

  3. Proteomic indicators of oxidation and hydration state in colorectal cancer

    Directory of Open Access Journals (Sweden)

    Jeffrey M. Dick

    2016-07-01

    Full Text Available New integrative approaches are needed to harness the potential of rapidly growing datasets of protein expression and microbial community composition in colorectal cancer. Chemical and thermodynamic models offer theoretical tools to describe populations of biomacromolecules and their relative potential for formation in different microenvironmental conditions. The average oxidation state of carbon (ZC can be calculated as an elemental ratio from the chemical formulas of proteins, and water demand per residue ( ${\\overline{n}}_{{\\mathrm{H}}_{2}\\mathrm{O}}$ n ¯ H 2 O is computed by writing the overall formation reactions of proteins from basis species. Using results reported in proteomic studies of clinical samples, many datasets exhibit higher mean ZC or ${\\overline{n}}_{{\\mathrm{H}}_{2}\\mathrm{O}}$ n ¯ H 2 O of proteins in carcinoma or adenoma compared to normal tissue. In contrast, average protein compositions in bacterial genomes often have lower ZC for bacteria enriched in fecal samples from cancer patients compared to healthy donors. In thermodynamic calculations, the potential for formation of the cancer-related proteins is energetically favored by changes in the chemical activity of H2O and fugacity of O2 that reflect the compositional differences. The compositional analysis suggests that a systematic change in chemical composition is an essential feature of cancer proteomes, and the thermodynamic descriptions show that the observed proteomic transformations in host tissue could be promoted by relatively high microenvironmental oxidation and hydration states.

  4. Advancement of mass spectrometry-based proteomics technologies to explore triple negative breast cancer.

    Science.gov (United States)

    Miah, Sayem; Banks, Charles A S; Adams, Mark K; Florens, Laurence; Lukong, Kiven E; Washburn, Michael P

    2016-12-20

    Understanding the complexity of cancer biology requires extensive information about the cancer proteome over the course of the disease. The recent advances in mass spectrometry-based proteomics technologies have led to the accumulation of an incredible amount of such proteomic information. This information allows us to identify protein signatures or protein biomarkers, which can be used to improve cancer diagnosis, prognosis and treatment. For example, mass spectrometry-based proteomics has been used in breast cancer research for over two decades to elucidate protein function. Breast cancer is a heterogeneous group of diseases with distinct molecular features that are reflected in tumour characteristics and clinical outcomes. Compared with all other subtypes of breast cancer, triple-negative breast cancer is perhaps the most distinct in nature and heterogeneity. In this review, we provide an introductory overview of the application of advanced proteomic technologies to triple-negative breast cancer research.

  5. Clinical proteomics: Applications for prostate cancer biomarker discovery and detection.

    Science.gov (United States)

    Petricoin, Emanuel F; Ornstein, David K; Liotta, Lance A

    2004-01-01

    The science of proteomics comprises much more than simply generating lists of proteins that change in expression as a cause of or consequence of pathophysiology. The goal of proteomics should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. Serum proteomic pattern diagnostics is a new type of proteomic concept in which patterns of ion signatures generated from high dimensional mass spectrometry data are used as diagnostic classifiers. This recent approach has exciting potential for clinical utility of diagnostic patterns because low molecular weight metabolites, peptides, and protein fragments may have higher accuracy than traditional biomarkers of cancer detection. Intriguingly, we now have discovered that this diagnostic information exists in a bound state, complexed with circulating highly abundant carrier proteins. These diagnostic fragments may one day be harvested by circulating nanoparticles, designed to absorb, enrich, and amplify the repertoire of diagnostic biomarkers generated-even at the critical, initial stages of carcinogenesis. Copyright 2004 Elsevier Inc.

  6. Proteomic approaches for quantitative cancer cell signaling

    DEFF Research Database (Denmark)

    Voellmy, Franziska

    studies in an effort to contribute to the study of signaling dynamics in cancer systems. This thesis is divided into two parts. Part I begins with a brief introduction in the use of omics in systems cancer research with a focus on mass spectrometry as a means to quantitatively measure protein...

  7. Announcing the Launch of CPTAC’s Proteogenomics DREAM Challenge | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    This week, we are excited to announce the launch of the National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) Proteogenomics Computational DREAM Challenge.  The aim of this Challenge is to encourage the generation of computational methods for extracting information from the cancer proteome and for linking those data to genomic and transcriptomic information.  The specific goals are to predict proteomic and phosphoproteomic data from other multiple data types including transcriptomics and genetics.

  8. Bone morphogenetic protein signalling in colorectal cancer

    NARCIS (Netherlands)

    Hardwick, James C.; Kodach, Liudmila L.; Offerhaus, G. Johan; van den Brink, Gijs R.

    2008-01-01

    Much of the current understanding of colorectal cancer stems from the study of rare, inherited colorectal cancer syndromes. Mutations in the bone morphogenetic protein (BMP) pathway have been found in juvenile polyposis, an inherited polyposis syndrome that predisposes to colorectal cancer. The

  9. Comparative proteomics analysis of oral cancer cell lines: identification of cancer associated proteins

    Science.gov (United States)

    2014-01-01

    Background A limiting factor in performing proteomics analysis on cancerous cells is the difficulty in obtaining sufficient amounts of starting material. Cell lines can be used as a simplified model system for studying changes that accompany tumorigenesis. This study used two-dimensional gel electrophoresis (2DE) to compare the whole cell proteome of oral cancer cell lines vs normal cells in an attempt to identify cancer associated proteins. Results Three primary cell cultures of normal cells with a limited lifespan without hTERT immortalization have been successfully established. 2DE was used to compare the whole cell proteome of these cells with that of three oral cancer cell lines. Twenty four protein spots were found to have changed in abundance. MALDI TOF/TOF was then used to determine the identity of these proteins. Identified proteins were classified into seven functional categories – structural proteins, enzymes, regulatory proteins, chaperones and others. IPA core analysis predicted that 18 proteins were related to cancer with involvements in hyperplasia, metastasis, invasion, growth and tumorigenesis. The mRNA expressions of two proteins – 14-3-3 protein sigma and Stress-induced-phosphoprotein 1 – were found to correlate with the corresponding proteins’ abundance. Conclusions The outcome of this analysis demonstrated that a comparative study of whole cell proteome of cancer versus normal cell lines can be used to identify cancer associated proteins. PMID:24422745

  10. Colorectal cancer presenting as bone metastasis

    Directory of Open Access Journals (Sweden)

    M C Suresh Babu

    2017-01-01

    Conclusions: In this study, the patients of colorectal cancer presenting with bone metastasis were of male sex and younger age. The factors that were associated with reduced survival were extraosseous and liver involvement.

  11. Impact of proteomics on bladder cancer research

    DEFF Research Database (Denmark)

    Celis, Julio E; Gromova, Irina; Moreira, José Manuel Alfonso

    2004-01-01

    Detecting bladder cancer at an early stage and predicting how a tumor will behave and act in response to therapy, as well as the identification of new targets for therapeutic intervention, are among the main areas of research that will benefit from the current explosion in the number of powerful ...

  12. Bone Morphogenetic Proteins, Antagonists and Receptors in Prostate Cancer

    National Research Council Canada - National Science Library

    Reddi, A

    2003-01-01

    ...? The predominant site of prostate cancer is bone. However, unlike the osteolytic lesions of breast cancer, prostate cancer causes osteoblastic osteosclerosis which leads ultimately to morbidity and mortality...

  13. Proteomics Analysis for Finding Serum Markers of Ovarian Cancer

    Directory of Open Access Journals (Sweden)

    Yushan Cheng

    2014-01-01

    Full Text Available A combination of peptide ligand library beads (PLLB and 1D gel liquid chromatography-mass spectrometry/mass spectrometry (1DGel-LC-MS/MS was employed to analyze serum samples from patients with ovarian cancer and from healthy controls. Proteomic analysis identified 1200 serum proteins, among which 57 proteins were upregulated and 10 were downregulated in the sera from cancer patients. Retinol binding protein 4 (RBP4 is highly upregulated in the ovarian cancer serum samples. ELISA was employed to measure plasma concentrations of RBP4 in 80 samples from ovarian cancer patients, healthy individuals, myoma patients, and patients with benign ovarian tumor, respectively. The plasma concentrations of RBP4 ranging from 76.91 to 120.08 ng/mL with the mean value 89.13±1.67 ng/mL in ovarian cancer patients are significantly higher than those in healthy individuals (10.85±2.38 ng/mL. Results were further confirmed with immunohistochemistry, demonstrating that RBP4 expression levels in normal ovarian tissue were lower than those in ovarian cancer tissues. Our results suggested that RBP4 is a potential biomarker for diagnostic of screening ovarian cancer.

  14. Bone scintiscanning significance in breast cancer propaedeutics

    International Nuclear Information System (INIS)

    Almeida, J.S. de; Fahel, V.G.; Almeida, M.R.M. de; Hassan, A.T.; Hassan, E.M.M.T.

    1977-01-01

    An evaluation was performed of 139 bone scannings which were accomplished in patients with breast cancer. Bone scintigraphy was concluded to be more important than the radiological examination in this propedeutic. The increase of alkaline phosphatase was very significative too, since there was only one case in which it was increased and the bone scanning was negative and even so the liver scanning was positive. On the other hand there were cases which showed positive both bone scanning and radiological study although the alkaline phosphatase was not increase. The necessity of realizing this examination was emphazised even in initial cases, making possible to modify therapeutic shedules in time, to help patient [pt

  15. Bone scintiscanning significance in breast cancer propaedeutics

    Energy Technology Data Exchange (ETDEWEB)

    de Almeida, J S; Fahel, V G; de Almeida, M R.M.; Hassan, A T; Hassan, E M.M.T. [Hospital Aristides Maltez, Salvador (Brazil). Servico de Medicina Nuclear

    1977-01-01

    An evaluation was performed of 139 bone scannings which were accomplished in patients with breast cancer. Bone scintigraphy was concluded to be more important than the radiological examination in this propedeutic. The increase of alkaline phosphatase was very significative too, since there was only one case in which it was increased and the bone scanning was negative and even so the liver scanning was positive. On the other hand there were cases which showed positive both bone scanning and radiological study although the alkaline phosphatase was not increase. The necessity of realizing this examination was emphazised even in initial cases, making possible to modify therapeutic shedules in time, to help patient.

  16. Clinical proteomics-driven precision medicine for targeted cancer therapy: current overview and future perspectives.

    Science.gov (United States)

    Zhou, Li; Wang, Kui; Li, Qifu; Nice, Edouard C; Zhang, Haiyuan; Huang, Canhua

    2016-01-01

    Cancer is a common disease that is a leading cause of death worldwide. Currently, early detection and novel therapeutic strategies are urgently needed for more effective management of cancer. Importantly, protein profiling using clinical proteomic strategies, with spectacular sensitivity and precision, offer excellent promise for the identification of potential biomarkers that would direct the development of targeted therapeutic anticancer drugs for precision medicine. In particular, clinical sample sources, including tumor tissues and body fluids (blood, feces, urine and saliva), have been widely investigated using modern high-throughput mass spectrometry-based proteomic approaches combined with bioinformatic analysis, to pursue the possibilities of precision medicine for targeted cancer therapy. Discussed in this review are the current advantages and limitations of clinical proteomics, the available strategies of clinical proteomics for the management of precision medicine, as well as the challenges and future perspectives of clinical proteomics-driven precision medicine for targeted cancer therapy.

  17. CGPD: Cancer Genetics and Proteomics Database - A Dataset for Computational Analysis and Online Cancer Diagnostic Centre

    Directory of Open Access Journals (Sweden)

    Muhammad Rizwan Riaz

    2014-06-01

    Full Text Available Cancer Genetics and Proteomics Database (CGPD is a repository for genetics and proteomics data of those Homo sapiens genes which are involved in Cancer. These genes are categorized in the database on the basis of cancer type. 72 genes of 13 types of cancers are considered in this database yet. Primers, promoters and peptides of these genes are also made available. Primers provided for each gene, with their features and conditions given to facilitate the researchers, are useful in PCR amplification, especially in cloning experiments. CGPD also contains Online Cancer Diagnostic Center (OCDC. It also contains transcription and translation tools to assist research work in progressive manner. The database is publicly available at http://www.cgpd.comyr.com.

  18. Advances in mass spectrometry-based cancer research and analysis: from cancer proteomics to clinical diagnostics.

    Science.gov (United States)

    Timms, John F; Hale, Oliver J; Cramer, Rainer

    2016-06-01

    The last 20 years have seen significant improvements in the analytical capabilities of biological mass spectrometry (MS). Studies using advanced MS have resulted in new insights into cell biology and the etiology of diseases as well as its use in clinical applications. This review discusses recent developments in MS-based technologies and their cancer-related applications with a focus on proteomics. It also discusses the issues around translating the research findings to the clinic and provides an outline of where the field is moving. Expert commentary: Proteomics has been problematic to adapt for the clinical setting. However, MS-based techniques continue to demonstrate potential in novel clinical uses beyond classical cancer proteomics.

  19. Sex Differences and Bone Metastases of Breast, Lung, and Prostate Cancers: Do Bone Homing Cancers Favor Feminized Bone Marrow?

    Directory of Open Access Journals (Sweden)

    Mary C. Farach-Carson

    2017-08-01

    Full Text Available Sex-associated differences in bone metastasis formation from breast, lung, and prostate cancer exist in clinical studies, but have not been systematically reviewed. Differences in the bone marrow niche can be attributed to sexual dimorphism, to genetic variations that affect sex hormone levels, or to the direct effects of sex hormones, natural or exogenously delivered. This review describes the present understanding of sex-associated and sex hormone level differences in the marrow niche and in formation of bone metastasis during the transition of these three cancers from treatable disease to an often untreatable, lethal metastatic one. Our purpose is to provide insight into some underlying molecular mechanisms for hormonal influence in bone metastasis formation, and to the potential influence of sexual dimorphism, genetic differences affecting sex assignment, and sex hormone level differences on the bone niche and its favorability for metastasis formation. We reviewed publications in PubMed and EMBASE, including full length manuscripts, case reports, and clinical studies of relevance to our topic. We focused on bone metastasis formation in breast, lung, and prostate cancer because all three commonly present with bone metastases. Several clear observations emerged. For breast cancer bone metastasis formation, estrogen receptor (ER signaling pathways indicate a role for ER beta (ERβ. Estrogen influences the bone microenvironment, creating and conditioning a favorable niche for colonization and breast cancer progression. For lung cancer, studies support the hypothesis that females have a more favorable bone microenvironment for metastasis formation. For prostate cancer, a decrease in the relative androgen to estrogen balance or a “feminization” of bone marrow favors bone metastasis formation, with a potentially important role for ERβ that may be similar to that in breast cancer. Long-term estrogen administration or androgen blockade in males

  20. Evaluation of the prognosis of cancer patients with metastatic bone tumors based on serial bone scintigrams

    International Nuclear Information System (INIS)

    Ohmori, Kazuo; Matsui, Hisao; Yasuda, Taketoshi; Kanamori, Masahiko; Yudoh, Kazuo; Seto, Hikaru; Tsuji, Haruo

    1997-01-01

    We counted the lesions at the time of detection of bone metastases and calculated the rate of increase in the number of bone metastases from changes in serial bone scintigrams, and investigated the usefulness of serial scintigrams as a prognostic indicator in patients with metastatic bone tumors. Subjects were 112 patients with bone metastases from four types of primary lesion: 21 with prostate cancer, 27 breast cancer, 39 lung cancer and 25 stomach cancer. Of these, 18 (prostate), 19 (breast), nine (lung) and eight (stomach) underwent serial bone scintigrams in which bone metastases were first detected and identified as progressing. The numbers of lesions at the time of detection of bone metastases for prostate and stomach cancers were significantly greater than those for lung cancer. The rate of increase in the number of bone metastases for stomach cancer was significantly higher than that for prostate or breast cancers. There was no correlation between the survival time after the detection of bone metastases and the number of lesions at the time of detection in the four types of cancer. However, in prostate cancer, a negative correlation existed between the survival time after the detection of bone metastases and the rate of increase in the number of bone metastases. Thus, in patients with bone metastases from prostate cancer, it appears that the rate of increase in the number of bone metastases, estimated from serial bone scintigrams, was indicative of prognosis. (author)

  1. Limb Salvage After Bone Cancer

    Science.gov (United States)

    ... Childhood Cancer Statistics Webinars Video Library Types of Children’s Cancer Leukemia Lymphoma Solid Tumors (Sarcomas) More… During Treatment Tests and Procedures Treatment Options Treatment Side Effects ...

  2. Proteomic profiling of bone marrow mesenchymal stem cells upon TGF-beta stimulation

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Daojing; Park, Jennifer S.; Chu, Julia S.F.; Ari, Krakowski; Luo, Kunxin; Chen, David J.; Li, Song

    2004-08-08

    Bone marrow mesenchymal stem cells (MSCs) can differentiate into different types of cells, and have tremendous potential for cell therapy and tissue engineering. Transforming growth factor {beta}1 (TGF-{beta}) plays an important role in cell differentiation and vascular remodeling. We showed that TGF-{beta} induced cell morphology change and an increase in actin fibers in MSCs. To determine the global effects of TGF-{beta} on MSCs, we employed a proteomic strategy to analyze the effect of TGF-{beta} on the human MSC proteome. By using two-dimensional gel electrophoresis and electrospray ionization coupled to Quadrupole/time-of-flight tandem mass spectrometers, we have generated a proteome reference map of MSCs, and identified {approx}30 proteins with an increase or decrease in expression or phosphorylation in response to TGF-{beta}. The proteins regulated by TGF-{beta} included cytoskeletal proteins, matrix synthesis proteins, membrane proteins, metabolic enzymes, etc. TGF-{beta} increased the expression of smooth muscle (SM) {alpha}-actin and decreased the expression of gelsolin. Over-expression of gelsolin inhibited TGF-{beta}-induced assembly of SM {alpha}-actin; on the other hand, knocking down gelsolin expression enhanced the assembly of {alpha}-actin and actin filaments without significantly affecting {alpha}-actin expression. These results suggest that TGF-{beta} coordinates the increase of {alpha}-actin and the decrease of gelsolin to promote MSC differentiation. This study demonstrates that proteomic tools are valuable in studying stem cell differentiation and elucidating the underlying molecular mechanisms.

  3. Radiotherapy for bone metastases from cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Monzen, Yoshio; Nakanishi, Kazue; Ajimu, Akira; Morikawa, Minoru; Hayashi, Kuniaki

    1989-03-01

    The authors have investigated 6 cases of bone metastases from cervical cancer out of a total of 90 cases of metastatic bone tumors that were irradiated for relief of associated pain at the Department of Radiology, Nagasaki University Hospital from April 1977 to March 1987. In 2 of the 6 cases, a rare, delayed recurrence with paraaortic lymph node metastases was seen. An invasion to the proasmajor muscle, iliomajor muscle was demonstrated by Computed Tomography after the initiation of therapy, so that the size of the field was modified. Computed Tomography was found useful to determine the exact field size for radiotherapy of metastatic bone tumor.

  4. NIH Common Fund - Disruptive Proteomics Technologies - Challenges and Opportunities | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    This Request for Information (RFI) is directed toward determining how best to accelerate research in disruptive proteomics technologies. The Disruptive Proteomics Technologies (DPT) Working Group of the NIH Common Fund wishes to identify gaps and opportunities in current technologies and methodologies related to proteome-wide measurements.  For the purposes of this RFI, “disruptive” is defined as very rapid, very significant gains, similar to the "disruptive" technology development that occurred in DNA sequencing technology.

  5. NCI Blog Post: CPTAC, the Complementary Sibling of TCGA (An Interview with Dr. Henry Rodriguez about NCI’s Proteomics Program) | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    What is proteomics? Proteomics is a highly automated and rapid method for measuring all the proteins in a biological sample. Proteins are the molecules that actually do most of the work inside a cell. When researchers develop cancer drugs, those drugs typically target proteins, so scientists and clinicians really have to understand what the proteins are doing. Proteomics researchers are now able to measure up to 10,000 proteins per tumor sample.

  6. Pathway analysis of kidney cancer using proteomics and metabolic profiling

    Directory of Open Access Journals (Sweden)

    Fiehn Oliver

    2006-11-01

    Full Text Available Abstract Background Renal cell carcinoma (RCC is the sixth leading cause of cancer death and is responsible for 11,000 deaths per year in the US. Approximately one-third of patients present with disease which is already metastatic and for which there is currently no adequate treatment, and no biofluid screening tests exist for RCC. In this study, we have undertaken a comprehensive proteomic analysis and subsequently a pathway and network approach to identify biological processes involved in clear cell RCC (ccRCC. We have used these data to investigate urinary markers of RCC which could be applied to high-risk patients, or to those being followed for recurrence, for early diagnosis and treatment, thereby substantially reducing mortality of this disease. Results Using 2-dimensional electrophoresis and mass spectrometric analysis, we identified 31 proteins which were differentially expressed with a high degree of significance in ccRCC as compared to adjacent non-malignant tissue, and we confirmed some of these by immunoblotting, immunohistochemistry, and comparison to published transcriptomic data. When evaluated by several pathway and biological process analysis programs, these proteins are demonstrated to be involved with a high degree of confidence (p values Conclusion Extensive pathway and network analysis allowed for the discovery of highly significant pathways from a set of clear cell RCC samples. Knowledge of activation of these processes will lead to novel assays identifying their proteomic and/or metabolomic signatures in biofluids of patient at high risk for this disease; we provide pilot data for such a urinary bioassay. Furthermore, we demonstrate how the knowledge of networks, processes, and pathways altered in kidney cancer may be used to influence the choice of optimal therapy.

  7. Vitamin D, Breast Cancer, and Bone Health

    Science.gov (United States)

    2011-05-01

    vitamin D and bone from David Feldman, MD and from David Karpf, MD. I am thankful for Department of Defense, Breast Cancer Research Program for...Clin Nutr. Jul 2008;88(1):133-139. 3. Crew KD, Shane E, Cremers S, McMahon DJ, Irani D, Hershman DL. High prevalence of vitamin D deficiency despite

  8. Bone Cancer: Questions and Answers

    Science.gov (United States)

    ... upper arm ( 1 ). Chondrosarcoma , which begins in cartilaginous tissue. Cartilage pads the ends of bones and lines the joints. Chondrosarcoma occurs most often in the pelvis (located between the hip ... in soft tissue (muscle, fat, fibrous tissue, blood vessels , or other ...

  9. Bone scanning in the evaluation of lung cancer

    International Nuclear Information System (INIS)

    Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk

    1994-01-01

    We studied the diagnostic significance of bone scan in evaluation of bone metastasis by lung cancer, prevalence rate, and the causes of false positive bone scan and soft tissue accumulation of bone seeking agent. This subject include 73 lung cancer patients with bone scan, We analyzed the frequency of the metastasis, its distribution and configuration, and any relationship between bone pain and corresponding region on bone scan. The positive findings of bone scans were compared with simple X-ray film, CT, MRI and other diagnostic modalities. The false positive bone scan and the soft tissue accumulation of bone seeking agent were analyzed. The positive findings on bone scan were noted in 26 cases(36%) and they were coexistent with bone pain in 30%. The correspondence between bone scan and bone X-ray was 38%. False positive bone scans were seen in 12 cases(16%), which include fracture due to thoracotomy and trauma, degenerative bone disease, and bifid rib. Accumulation of bone seeking agent in soft tissue were seen in 13 cases(18%), which included primary tumor, enlarged cervical lymph node, pleural effusion, ascites and pleural thickening. Bone scans should be carefully interpreted in detecting bone metastasis in primary malignancy, because of the 16% false positivity and 18% soft tissue accumulation rate. It is very important to note that the correlation between bone pain and positive findings of bone scans was only 38%

  10. Bone scanning in the evaluation of lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Jung, Kun Sik; Zeon, Seok Kil; Lee, Hee Jung; Song, Hong Suk [School of Medicine, Keimyung University, Daegu (Korea, Republic of)

    1994-05-15

    We studied the diagnostic significance of bone scan in evaluation of bone metastasis by lung cancer, prevalence rate, and the causes of false positive bone scan and soft tissue accumulation of bone seeking agent. This subject include 73 lung cancer patients with bone scan, We analyzed the frequency of the metastasis, its distribution and configuration, and any relationship between bone pain and corresponding region on bone scan. The positive findings of bone scans were compared with simple X-ray film, CT, MRI and other diagnostic modalities. The false positive bone scan and the soft tissue accumulation of bone seeking agent were analyzed. The positive findings on bone scan were noted in 26 cases(36%) and they were coexistent with bone pain in 30%. The correspondence between bone scan and bone X-ray was 38%. False positive bone scans were seen in 12 cases(16%), which include fracture due to thoracotomy and trauma, degenerative bone disease, and bifid rib. Accumulation of bone seeking agent in soft tissue were seen in 13 cases(18%), which included primary tumor, enlarged cervical lymph node, pleural effusion, ascites and pleural thickening. Bone scans should be carefully interpreted in detecting bone metastasis in primary malignancy, because of the 16% false positivity and 18% soft tissue accumulation rate. It is very important to note that the correlation between bone pain and positive findings of bone scans was only 38%.

  11. Multifunctional materials for bone cancer treatment

    Directory of Open Access Journals (Sweden)

    Marques C

    2014-05-01

    Full Text Available Catarina Marques,1 José MF Ferreira,1 Ecaterina Andronescu,2 Denisa Ficai,2 Maria Sonmez,3 Anton Ficai21Department of Materials and Ceramics Engineering, Centre for Research in Ceramics and Composite Materials, University of Aveiro, Aveiro, Portugal; 2Faculty of Applied Chemistry and Material Science, University Politehnica of Bucharest, Bucharest, Romania; 3National Research and Development Institute for Textiles and Leather, Bucharest, RomaniaAbstract: The purpose of this review is to present the most recent findings in bone tissue engineering. Special attention is given to multifunctional materials based on collagen and collagen–hydroxyapatite composites used for skin and bone cancer treatments. The multifunctionality of these materials was obtained by adding to the base regenerative grafts proper components, such as ferrites (magnetite being the most important representative, cytostatics (cisplatin, carboplatin, vincristine, methotrexate, paclitaxel, doxorubicin, silver nanoparticles, antibiotics (anthracyclines, geldanamycin, and/or analgesics (ibuprofen, fentanyl. The suitability of complex systems for the intended applications was systematically analyzed. The developmental possibilities of multifunctional materials with regenerative and curative roles (antitumoral as well as pain management in the field of skin and bone cancer treatment are discussed. It is worth mentioning that better materials are likely to be developed by combining conventional and unconventional experimental strategies.Keywords: bone graft, cancer, collagen, magnetite, cytostatics, silver

  12. P-MartCancer–Interactive Online Software to Enable Analysis of Shotgun Cancer Proteomic Datasets

    Energy Technology Data Exchange (ETDEWEB)

    Webb-Robertson, Bobbie-Jo M.; Bramer, Lisa M.; Jensen, Jeffrey L.; Kobold, Markus A.; Stratton, Kelly G.; White, Amanda M.; Rodland, Karin D.

    2017-10-31

    P-MartCancer is a new interactive web-based software environment that enables biomedical and biological scientists to perform in-depth analyses of global proteomics data without requiring direct interaction with the data or with statistical software. P-MartCancer offers a series of statistical modules associated with quality assessment, peptide and protein statistics, protein quantification and exploratory data analyses driven by the user via customized workflows and interactive visualization. Currently, P-MartCancer offers access to multiple cancer proteomic datasets generated through the Clinical Proteomics Tumor Analysis Consortium (CPTAC) at the peptide, gene and protein levels. P-MartCancer is deployed using Azure technologies (http://pmart.labworks.org/cptac.html), the web-service is alternatively available via Docker Hub (https://hub.docker.com/r/pnnl/pmart-web/) and many statistical functions can be utilized directly from an R package available on GitHub (https://github.com/pmartR).

  13. Proteomic profile of acute myeloid leukaemia: A review update

    African Journals Online (AJOL)

    attention to the progress and advancements in cancer proteomics technology with the aim of simplifying ... hematopoietic cells leading to distinct differences ... procedures like bone marrow and tissue biopsies. [7,8]. .... patients who were subjected to transplantation ..... Boyd RS, Dyer MJ, Cain K. Proteomic analysis of b-cell.

  14. Where is the place of bone scan in breast cancer?

    International Nuclear Information System (INIS)

    Nowferesti, G. H.; Ghavam Nasiri, M. R.; Anvari, K.

    2002-01-01

    Breast cancer is the most common female cancer in west and in Iran. The incidence in all over the world in year 2000 was 1050000 cases out of which 370000 were dead. General y bone is the most common site of distant. Metastases in beast cancer. Bone scan has an important place in the bone metastases and extent of bone disease and even in the staging and treatment protocol. In study done during 1 year, breast cancer patients and place of bone scan were studied. Every year more than 2000 new patients with cancer are diagnosed and treated in Khorasan state. And more than half of them are treated in Omid Hospital. In the year 2000 a study was done. 1336 new cases were admitted for treatment out of which 164 persons (13%) were breast cancer patients. 100 patients were selected randomly and different factors were studied. How many patients had bone scan and its place in breast cancer? Where is the most common metastatic place and relation with bone scan? The differential diagnosis in positive bone scans and comparing with radiography and patient's clinic were studied. Bone scan is positive in 35% of patients in stage III. Bone is the most common place for distant metastases in breast cancer in patients admitted in Omid hospital in year 2000. Clinical and para clinical study such as radiography and tumour markers were adjusted with bone scan, more in stages III and IV. 39 patients out of 100 studied patients had bone scan. 28 bone scan were adjusted radiologically. In 20 positive bone scan out of 28 patients with metastases 12 patients had bone metastases. Despite 5% positive bone scan in early stages can suggest that bone scan be taken for all patients with breast cancer as a basic step?

  15. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    Energy Technology Data Exchange (ETDEWEB)

    Thobe, Megan N. [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States); Clark, Robert J. [Department of Molecular Pathogenesis and Molecular Medicine, The University of Chicago, Chicago, IL 60637 (United States); Bainer, Russell O. [Department of Human Genetics, The University of Chicago, Chicago, IL 60637 (United States); Prasad, Sandip M.; Rinker-Schaeffer, Carrie W., E-mail: crinkers@uchicago.edu [Section of Urology, Department of Surgery, The University of Chicago, Chicago, IL 60637 (United States)

    2011-01-27

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies.

  16. From Prostate to Bone: Key Players in Prostate Cancer Bone Metastasis

    International Nuclear Information System (INIS)

    Thobe, Megan N.; Clark, Robert J.; Bainer, Russell O.; Prasad, Sandip M.; Rinker-Schaeffer, Carrie W.

    2011-01-01

    Bone is the most common site for metastasis in human prostate cancer patients. Skeletal metastases are a significant cause of morbidity and mortality and overall greatly affect the quality of life of prostate cancer patients. Despite advances in our understanding of the biology of primary prostate tumors, our knowledge of how and why secondary tumors derived from prostate cancer cells preferentially localize bone remains limited. The physiochemical properties of bone, and signaling molecules including specific chemokines and their receptors, are distinct in nature and function, yet play intricate and significant roles in prostate cancer bone metastasis. Examining the impact of these facets of bone metastasis in vivo remains a significant challenge, as animal models that mimic the natural history and malignant progression clinical prostate cancer are rare. The goals of this article are to discuss (1) characteristics of bone that most likely render it a favorable environment for prostate tumor cell growth, (2) chemokine signaling that is critical in the recruitment and migration of prostate cancer cells to the bone, and (3) current animal models utilized in studying prostate cancer bone metastasis. Further research is necessary to elucidate the mechanisms underlying the extravasation of disseminated prostate cancer cells into the bone and to provide a better understanding of the basis of cancer cell survival within the bone microenvironment. The development of animal models that recapitulate more closely the human clinical scenario of prostate cancer will greatly benefit the generation of better therapies

  17. Proteome-wide dataset supporting functional study of tyrosine kinases in breast cancer

    Directory of Open Access Journals (Sweden)

    Nicos Angelopoulos

    2016-06-01

    Full Text Available Tyrosine kinases (TKs play an essential role in regulating various cellular activities and dysregulation of TK signaling contributes to oncogenesis. However, less than half of the TKs have been thoroughly studied. Through a combined use of RNAi and stable isotope labeling with amino acids in cell culture (SILAC-based quantitative proteomics, a global functional proteomic landscape of TKs in breast cancer was recently revealed highlighting a comprehensive and highly integrated signaling network regulated by TKs (Stebbing et al., 2015 [1]. We collate the enormous amount of the proteomic data in an open access platform, providing a valuable resource for studying the function of TKs in cancer and benefiting the science community. Here we present a detailed description related to this study (Stebbing et al., 2015 [1] and the raw data have been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the identifier http://www.ebi.ac.uk/pride/archive/projects/PXD002065.

  18. Bone metastases in breast cancer and its risk factor

    International Nuclear Information System (INIS)

    Tanaka, Shigeko; Matsumura, Yasumasa; Tanaka, Masahiro

    1991-01-01

    Breast cancer is considered to often involve bone metastasis. Early detection and treatment of bone metastasis are essential in improving the prognosis of this disease. In 47 patients with bone metastasis confirmed with bone scintigraphy, we examined the appearance time of bone metastasis; bone metastasis was frequently observed with the progress of stage, but no association with the appearance time was found. Age was not associated with the incidence of bone metastasis but was found to be closely related to its appearance time. That is to say, patients with breast cancer below 40 years of age showed relatively early bone metastasis. Bone scintigraphy is required every 6 months at least for 3 years after the operation. In patients over 40 years of age, on the other hand, bone scintigraphy is required only once a year but has to be continued for 5 years or more, because they often show relatively late bone metastasis. (author)

  19. A novel proteomic biomarker panel as a diagnostic tool for patients with ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Claus; Fung, Eric T; Christensen, Ib J

    2011-01-01

    Previous reports have shown that the proteomic markers apolipoprotein A1, hepcidin, transferrin, inter-alpha trypsin IV internal fragment, transthyretin, connective-tissue activating protein 3 and beta-2 microglobulin may discriminate between a benign pelvic mass and ovarian cancer (OC). The aim...... was to determine if these serum proteomic biomarkers alone as well as in combination with age and serum CA125, could be helpful in triage of women with a pelvic mass....

  20. Cancer Metastases to Bone: Concepts, Mechanisms, and Interactions with Bone Osteoblasts

    Directory of Open Access Journals (Sweden)

    Alison B. Shupp

    2018-06-01

    Full Text Available The skeleton is a unique structure capable of providing support for the body. Bone resorption and deposition are controlled in a tightly regulated balance between osteoblasts and osteoclasts with no net bone gain or loss. However, under conditions of disease, the balance between bone resorption and deposition is upset. Osteoblasts play an important role in bone homeostasis by depositing new bone osteoid into resorption pits. It is becoming increasingly evident that osteoblasts additionally play key roles in cancer cell dissemination to bone and subsequent metastasis. Our laboratory has evidence that when osteoblasts come into contact with disseminated breast cancer cells, the osteoblasts produce factors that initially reduce breast cancer cell proliferation, yet promote cancer cell survival in bone. Other laboratories have demonstrated that osteoblasts both directly and indirectly contribute to dormant cancer cell reactivation in bone. Moreover, we have demonstrated that osteoblasts undergo an inflammatory stress response in late stages of breast cancer, and produce inflammatory cytokines that are maintenance and survival factors for breast cancer cells and osteoclasts. Advances in understanding interactions between osteoblasts, osteoclasts, and bone metastatic cancer cells will aid in controlling and ultimately preventing cancer cell metastasis to bone.

  1. Stage 1 Breast Cancer and Bone Mass in Older Women

    National Research Council Canada - National Science Library

    Schneider, Diane

    2002-01-01

    The specific aims of the study are 1) to assess the bone mineral density of women 65 years of age and older with breast cancer in comparison with the bone mineral density of same aged women with normal mammograms; 2...

  2. Advances in the proteomic discovery of novel therapeutic targets in cancer

    Directory of Open Access Journals (Sweden)

    Guo S

    2013-10-01

    Full Text Available Shanchun Guo,1 Jin Zou,2 Guangdi Wang3 1Department of Microbiology, Biochemistry, and Immunology, Morehouse School of Medicine, 2Center for Cancer Research and Therapeutic Development, Clark Atlanta University, Atlanta, GA, USA; 3Research Centers in Minority Institutions Cancer Research Program, Xavier University of Louisiana, New Orleans, LA, USA Abstract: Proteomic approaches are continuing to make headways in cancer research by helping to elucidate complex signaling networks that underlie tumorigenesis and disease progression. This review describes recent advances made in the proteomic discovery of drug targets for therapeutic development. A variety of technical and methodological advances are overviewed with a critical assessment of challenges and potentials. A number of potential drug targets, such as baculoviral inhibitor of apoptosis protein repeat-containing protein 6, macrophage inhibitory cytokine 1, phosphoglycerate mutase 1, prohibitin 1, fascin, and pyruvate kinase isozyme 2 were identified in the proteomic analysis of drug-resistant cancer cells, drug action, and differential disease state tissues. Future directions for proteomics-based target identification and validation to be more translation efficient are also discussed. Keywords: proteomics, cancer, therapeutic target, signaling network, tumorigenesis

  3. Immunoscreening of the extracellular proteome of colorectal cancer cells

    International Nuclear Information System (INIS)

    Klein-Scory, Susanne; Schwarte-Waldhoff, Irmgard; Kübler, Salwa; Diehl, Hanna; Eilert-Micus, Christina; Reinacher-Schick, Anke; Stühler, Kai; Warscheid, Bettina; Meyer, Helmut E; Schmiegel, Wolff

    2010-01-01

    The release of proteins from tumors can trigger an immune response in cancer patients involving T lymphocytes and B lymphocytes, which results in the generation of antibodies to tumor-derived proteins. Many studies aim to use humoral immune responses, namely autoantibody profiles, directly, as clinical biomarkers. Alternatively, the antibody immune response as an amplification system for tumor associated alterations may be used to indicate putative protein biomarkers with high sensitivity. Aiming at the latter approach we here have implemented an autoantibody profiling strategy which particularly focuses on proteins released by tumor cells in vitro: the so-called secretome. For immunoscreening, the extracellular proteome of five colorectal cancer cell lines was resolved on 2D gels, immobilized on PVDF membranes and used for serological screening with individual sera from 21 colorectal cancer patients and 24 healthy controls. All of the signals from each blot were assigned to a master map, and autoantigen candidates were defined based of the pattern of immunoreactivities. The corresponding proteins were isolated from preparative gels, identified by MALDI-MS and/or by nano-HPLC/ESI-MS/MS and exemplarily confirmed by duplex Western blotting combining the human serum samples with antibodies directed against the protein(s) of interest. From 281 secretome proteins stained with autoantibodies in total we first defined the 'background patterns' of frequently immunoreactive extracellular proteins in healthy and diseased people. An assignment of these proteins, among them many nominally intracellular proteins, to the subset of exosomal proteins within the secretomes revealed a large overlap. On this basis we defined and consequently confirmed novel biomarker candidates such as the extreme C-terminus of the extracellular matrix protein agrin within the set of cancer-enriched immunorectivities. Our findings suggest, first, that autoantibody responses may be due, in

  4. Targeted Therapies for Myeloma and Metastatic Bone Cancers

    Science.gov (United States)

    2010-09-01

    Cancer J Clin 2003; 53:5. Kasugai S, Fujisawa R, Waki Y, Miyamoto K, Ohya K 2000 Selective drug delivery system to bone: small peptide (Asp)6...page. Bone targeted nanoparticles , bone cancer myeloma, mice studies, PLGA , Biodegradable materials. Targeted Therapies for Myeloma and Metastatic Bone...present results from this program at talk at the Particles 2006 –Medical/Biochemical Diagnostic , Pharmaceutical, and Drug Delivery . 3

  5. Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis

    Science.gov (United States)

    2015-11-01

    1 AD_________________ Award Number: W81XWH-11-1-0593 TITLE: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis PRINCIPAL...3. DATES COVERED (From - To) 09/15/2011 - 08/14/2015 4. TITLE AND SUBTITLE Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis 5a...4 Title of the Grant: Regenerative Stem Cell Therapy for Breast Cancer Bone Metastasis Award number: W81XWH-11-1-0593 Principal Investigator

  6. Mass spectrometry-based serum proteome pattern analysis in molecular diagnostics of early stage breast cancer

    Directory of Open Access Journals (Sweden)

    Stobiecki Maciej

    2009-07-01

    Full Text Available Abstract Background Mass spectrometric analysis of the blood proteome is an emerging method of clinical proteomics. The approach exploiting multi-protein/peptide sets (fingerprints detected by mass spectrometry that reflect overall features of a specimen's proteome, termed proteome pattern analysis, have been already shown in several studies to have applicability in cancer diagnostics. We aimed to identify serum proteome patterns specific for early stage breast cancer patients using MALDI-ToF mass spectrometry. Methods Blood samples were collected before the start of therapy in a group of 92 patients diagnosed at stages I and II of the disease, and in a group of age-matched healthy controls (104 women. Serum specimens were purified and the low-molecular-weight proteome fraction was examined using MALDI-ToF mass spectrometry after removal of albumin and other high-molecular-weight serum proteins. Protein ions registered in a mass range between 2,000 and 10,000 Da were analyzed using a new bioinformatic tool created in our group, which included modeling spectra as a sum of Gaussian bell-shaped curves. Results We have identified features of serum proteome patterns that were significantly different between blood samples of healthy individuals and early stage breast cancer patients. The classifier built of three spectral components that differentiated controls and cancer patients had 83% sensitivity and 85% specificity. Spectral components (i.e., protein ions that were the most frequent in such classifiers had approximate m/z values of 2303, 2866 and 3579 Da (a biomarker built from these three components showed 88% sensitivity and 78% specificity. Of note, we did not find a significant correlation between features of serum proteome patterns and established prognostic or predictive factors like tumor size, nodal involvement, histopathological grade, estrogen and progesterone receptor expression. In addition, we observed a significantly (p = 0

  7. Radioimmune imaging of bone marrow in patients with suspected bone metastases from primary breast cancer

    International Nuclear Information System (INIS)

    Duncker, C.M.; Carrio, I.; Berna, L.; Estorch, M.; Alonso, C.; Ojeda, B.; Blanco, R.; Germa, J.R.; Ortega, V.

    1990-01-01

    Radioimmune imaging of bone marrow was performed by technetium-99m- (99mTc) labeled antigranulocyte monoclonal antibody BW 250/183 (AGMoAb) scans in 32 patients with suspected bone metastases from primary breast cancer. AGMoAb scans showed bone marrow defects in 25/32 (78%) patients; bone invasion was subsequently confirmed in 23 (72%) patients. Conventional bone scans performed within the same week detected bone metastases in 17/32 (53%) patients (p less than 0.001). AGMoAb scans detected more sites indicating metastatic disease than bone scans in 12 of these 17 patients (71%). All patients with bone metastases in the axial skeleton had bone marrow defects at least at the sites of bone metastases. Of 15 patients with normal, or indicative of, benign disease bone scans, 8 patients (53%) presented with bone marrow defects in the AGMoAb scans. Bone invasion was confirmed in six of them. AGMoAb bone marrow scans provide a method for the early detection of bone metastatic invasion in patients with breast cancer and suspected bone metastases

  8. Integrated proteomic and genomic analysis of colorectal cancer

    Science.gov (United States)

    Investigators who analyzed 95 human colorectal tumor samples have determined how gene alterations identified in previous analyses of the same samples are expressed at the protein level. The integration of proteomic and genomic data, or proteogenomics, pro

  9. SELDI-TOF-based serum proteomic pattern diagnostics for early detection of cancer.

    Science.gov (United States)

    Petricoin, Emanuel F; Liotta, Lance A

    2004-02-01

    Proteomics is more than just generating lists of proteins that increase or decrease in expression as a cause or consequence of pathology. The goal should be to characterize the information flow through the intercellular protein circuitry that communicates with the extracellular microenvironment and then ultimately to the serum/plasma macroenvironment. The nature of this information can be a cause, or a consequence, of disease and toxicity-based processes. Serum proteomic pattern diagnostics is a new type of proteomic platform in which patterns of proteomic signatures from high dimensional mass spectrometry data are used as a diagnostic classifier. This approach has recently shown tremendous promise in the detection of early-stage cancers. The biomarkers found by SELDI-TOF-based pattern recognition analysis are mostly low molecular weight fragments produced at the specific tumor microenvironment.

  10. The usefulness of bone marrow scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Morita, Rikushi

    1985-01-01

    A combination study of bone and bone marrow scintigraphy was performed on 25 pts with prostatic cancer, and, in order to study the usefulness in the diagnosis of bone metastasis, the findings of 2 scintigraphies were compared with those of skeletal roentgenography. Out of the 18 cases with the hot spots of sup(99m)Tc-MDP in the lower lumbar spine or/and the pelvic bone, 8 showed normal bone marrow scintigrams which were eventually proved to have degenerative changes of the spine accompanied by aging. On the other hand, nine cases of the ten, who had accumulation defects on the bone marrow scintigrams were finally proved having bone metastasis. All six cases with extensive bone metastases shown by bone scintigraphy with sup(99m)Tc-MDP, demonstrated multiple accumulation defects on bone marrow scintigraphy with sup(99m)Tc-sulfur colloid. In conclusion, bone marrow scintigraphy was thought to be helpful in distinguishing the metastatic lesions from the benign spinal degenerative changes in the cases with suspicions bone involvement and in evaluating equivocal lesions in the pelvis. Therefore, it was shown that, in the detection and diagnosis of bone metastasis from prostatic cancer, bone scintigraphy alone was insufficient, and that combination with bone marrow scintigraphy was found to be useful. (author)

  11. AR Expression in Breast Cancer CTCs Associates with Bone Metastases.

    Science.gov (United States)

    Aceto, Nicola; Bardia, Aditya; Wittner, Ben S; Donaldson, Maria C; O'Keefe, Ryan; Engstrom, Amanda; Bersani, Francesca; Zheng, Yu; Comaills, Valentine; Niederhoffer, Kira; Zhu, Huili; Mackenzie, Olivia; Shioda, Toshi; Sgroi, Dennis; Kapur, Ravi; Ting, David T; Moy, Beverly; Ramaswamy, Sridhar; Toner, Mehmet; Haber, Daniel A; Maheswaran, Shyamala

    2018-04-01

    Molecular drivers underlying bone metastases in human cancer are not well understood, in part due to constraints in bone tissue sampling. Here, RNA sequencing was performed of circulating tumor cells (CTC) isolated from blood samples of women with metastatic estrogen receptor (ER) + breast cancer, comparing cases with progression in bone versus visceral organs. Among the activated cellular pathways in CTCs from bone-predominant breast cancer is androgen receptor (AR) signaling. AR gene expression is evident, as is its constitutively active splice variant AR-v7. AR expression within CTCs is correlated with the duration of treatment with aromatase inhibitors, suggesting that it contributes to acquired resistance to endocrine therapy. In an established breast cancer xenograft model, a bone-tropic derivative displays increased AR expression, whose genetic or pharmacologic suppression reduces metastases to bone but not to lungs. Together, these observations identify AR signaling in CTCs from women with bone-predominant ER + breast cancer, and provide a rationale for testing androgen inhibitors in this subset of patients. Implications: This study highlights a role for the AR in breast cancer bone metastasis, and suggests that therapeutic targeting of the AR may benefit patients with metastatic breast cancer. Mol Cancer Res; 16(4); 720-7. ©2018 AACR . ©2018 American Association for Cancer Research.

  12. Protocadherin-7 induces bone metastasis of breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Li, Ai-Min [Department of Orthopedics, The 5th Central Hospital of Tianjin, Tianjin (China); Tian, Ai-Xian [Department of Biochemistry and Molecular Biology, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Zhang, Rui-Xue [Department of Clinical Laboratory Diagnosis, Tianjin Medical University, Tianjin (China); Ge, Jie [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Sun, Xuan [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Cao, Xu-Chen, E-mail: caoxuch@126.com [Department of Breast Surgery, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China); Key Laboratory of Breast Cancer Prevention and Treatment of the Ministry of Education, Tianjin Medical University Cancer Institute and Hospital, Tianjin (China)

    2013-07-05

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer.

  13. Protocadherin-7 induces bone metastasis of breast cancer

    International Nuclear Information System (INIS)

    Li, Ai-Min; Tian, Ai-Xian; Zhang, Rui-Xue; Ge, Jie; Sun, Xuan; Cao, Xu-Chen

    2013-01-01

    Highlights: •PCDH7 is overexpression in high bone metastatic MDA-MB-231 cells. •PCDH7 is up-regulation in bone metastatic breast cancer tissues. •Suppression of PCDH7 inhibits cell proliferation, migration, and invasion in vitro. •PCDH7 induces breast cancer bone metastasis in vivo. -- Abstract: Breast cancer had a propensity to metastasize to bone, resulting in serious skeletal complications associated with poor outcome. Previous study showed that Protocadherin-7 (PCDH7) play an important role in brain metastatic breast cancer, however, the role of PCDH7 in bone metastatic breast cancer has never been explored. In the present study, we found that PCDH7 expression was up-regulation in bone metastatic breast cancer tissues by real-time PCR and immunohistochemistry assays. Furthermore, suppression of PCDH7 inhibits breast cancer cell proliferation, migration, and invasion in vitro by MTT, scratch, and transwell assays. Most importantly, overexpression of PCDH7 promotes breast cancer cell proliferation and invasion in vitro, and formation of bone metastasis in vivo. These data provide an important insight into the role of PCDH7 in bone metastasis of breast cancer

  14. The distinctive gastric fluid proteome in gastric cancer reveals a multi-biomarker diagnostic profile

    Directory of Open Access Journals (Sweden)

    Eng Alvin KH

    2008-10-01

    Full Text Available Abstract Background Overall gastric cancer survival remains poor mainly because there are no reliable methods for identifying highly curable early stage disease. Multi-protein profiling of gastric fluids, obtained from the anatomic site of pathology, could reveal diagnostic proteomic fingerprints. Methods Protein profiles were generated from gastric fluid samples of 19 gastric cancer and 36 benign gastritides patients undergoing elective, clinically-indicated gastroscopy using surface-enhanced laser desorption/ionization time-of-flight mass spectrometry on multiple ProteinChip arrays. Proteomic features were compared by significance analysis of microarray algorithm and two-way hierarchical clustering. A second blinded sample set (24 gastric cancers and 29 clinically benign gastritides was used for validation. Results By significance analysyis of microarray, 60 proteomic features were up-regulated and 46 were down-regulated in gastric cancer samples (p Conclusion This simple and reproducible multimarker proteomic assay could supplement clinical gastroscopic evaluation of symptomatic patients to enhance diagnostic accuracy for gastric cancer and pre-malignant lesions.

  15. Survival after bone metastasis by primary cancer type

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Christiansen, Christian F; Ulrichsen, Sinna P

    2017-01-01

    %, 11% to 14%). The risk of mortality was increased for the majority of cancer types among patients with bone and synchronous metastases compared with bone only (adjusted relative risk 1.29-1.57), except for cervix, ovarian and bladder cancer. CONCLUSIONS: While patients with bone metastases after most......OBJECTIVE: In the 10 most common primary types with bone metastases, we aimed to examine survival, further stratifying on bone metastases only or with additional synchronous metastases. METHODS: We included all patients aged 18 years and older with incident hospital diagnosis of solid cancer...... between 1994 and 2010, subsequently diagnosed with BM until 2012. We followed patients from date of bone metastasis diagnosis until death, emigration or 31 December 2012, whichever came first. We computed 1-year, 3-year and 5-year survival (%) and the corresponding 95% CIs stratified on primary cancer...

  16. Sample preparation and fractionation for proteome analysis and cancer biomarker discovery by mass spectrometry.

    Science.gov (United States)

    Ahmed, Farid E

    2009-03-01

    Sample preparation and fractionation technologies are one of the most crucial processes in proteomic analysis and biomarker discovery in solubilized samples. Chromatographic or electrophoretic proteomic technologies are also available for separation of cellular protein components. There are, however, considerable limitations in currently available proteomic technologies as none of them allows for the analysis of the entire proteome in a simple step because of the large number of peptides, and because of the wide concentration dynamic range of the proteome in clinical blood samples. The results of any undertaken experiment depend on the condition of the starting material. Therefore, proper experimental design and pertinent sample preparation is essential to obtain meaningful results, particularly in comparative clinical proteomics in which one is looking for minor differences between experimental (diseased) and control (nondiseased) samples. This review discusses problems associated with general and specialized strategies of sample preparation and fractionation, dealing with samples that are solution or suspension, in a frozen tissue state, or formalin-preserved tissue archival samples, and illustrates how sample processing might influence detection with mass spectrometric techniques. Strategies that dramatically improve the potential for cancer biomarker discovery in minimally invasive, blood-collected human samples are also presented.

  17. Incidence of bone metastases and survival after a diagnosis of bone metastases in breast cancer patients.

    Science.gov (United States)

    Harries, M; Taylor, A; Holmberg, L; Agbaje, O; Garmo, H; Kabilan, S; Purushotham, A

    2014-08-01

    Bone is the most common metastatic site associated with breast cancer. Using a database of women with breast cancer treated at Guy's Hospital, London 1976-2006 and followed until end 2010, we determined incidence of and survival after bone metastases. We calculated cumulative incidence of bone metastases considering death without prior bone metastases as a competing risk. Risk of bone metastases was modelled through Cox-regression. Survival after bone metastases diagnosis was calculated using Kaplan-Meier methodology. Of the 7064 women, 589 (22%) developed bone metastases during 8.4 years (mean). Incidence of bone metastases was significantly higher in younger women, tumour size >5 cm, higher tumour grade, lobular carcinoma and ≥ four positive nodes, but was not affected by hormone receptor status. Median survival after bone metastases diagnosis was 2.3 years in women with bone-only metastases compared with early, and proportionately fewer patients in this group. Incidence of bone metastases has decreased but bone metastases remain a highly relevant clinical problem due to the large number of patients being diagnosed with breast cancer. Copyright © 2014 Elsevier Ltd. All rights reserved.

  18. Effects of retinoic acid isomers on proteomic pattern in human breast cancer MCF-7 cell line

    Czech Academy of Sciences Publication Activity Database

    Flodrová, Dana; Benkovská, Dagmar; Macejová, D.; Bialešová, L.; Bobálová, Janette; Brtko, J.

    2013-01-01

    Roč. 47, č. 4 (2013), s. 205-209 ISSN 1210-0668 R&D Projects: GA MŠk(CZ) 7AMB12SK151 Institutional support: RVO:68081715 Keywords : retinoic acid isomers * retinoid * breast cancer * malignant cells * proteomic analysis Subject RIV: CB - Analytical Chemistry, Separation

  19. Recent mass spectrometry-based proteomics for biomarker discovery in lung cancer, COPD, and asthma.

    Science.gov (United States)

    Fujii, Kiyonaga; Nakamura, Haruhiko; Nishimura, Toshihide

    2017-04-01

    Lung cancer and related diseases have been one of the most common causes of deaths worldwide. Genomic-based biomarkers may hardly reflect the underlying dynamic molecular mechanism of functional protein interactions, which is the center of a disease. Recent developments in mass spectrometry (MS) have made it possible to analyze disease-relevant proteins expressed in clinical specimens by proteomic challenges. Areas covered: To understand the molecular mechanisms of lung cancer and its subtypes, chronic obstructive pulmonary disease (COPD), asthma and others, great efforts have been taken to identify numerous relevant proteins by MS-based clinical proteomic approaches. Since lung cancer is a multifactorial disease that is biologically associated with asthma and COPD among various lung diseases, this study focused on proteomic studies on biomarker discovery using various clinical specimens for lung cancer, COPD, and asthma. Expert commentary: MS-based exploratory proteomics utilizing clinical specimens, which can incorporate both experimental and bioinformatic analysis of protein-protein interaction and also can adopt proteogenomic approaches, makes it possible to reveal molecular networks that are relevant to a disease subgroup and that could differentiate between drug responders and non-responders, good and poor prognoses, drug resistance, and so on.

  20. Leaderboard Now Open: CPTAC’s DREAM Proteogenomics Computational Challenge | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute’s Clinical Proteomic Tumor Analysis Consortium (CPTAC) is pleased to announce the opening of the leaderboard to its Proteogenomics Computational DREAM Challenge. The leadership board remains open for submissions during September 25, 2017 through October 8, 2017, with the Challenge expected to run until November 17, 2017.

  1. Proteomics pipeline for biomarker discovery of laser capture microdissected breast cancer tissue

    NARCIS (Netherlands)

    N.Q. Liu (Ning Qing); R.B.H. Braakman (René); C. Stingl (Christoph); T.M. Luider (Theo); J.W.M. Martens (John); J.A. Foekens (John); A. Umar (Arzu)

    2012-01-01

    textabstractMass spectrometry (MS)-based label-free proteomics offers an unbiased approach to screen biomarkers related to disease progression and therapy-resistance of breast cancer on the global scale. However, multi-step sample preparation can introduce large variation in generated data, while

  2. Proteomics of cancer cell lines resistant to microtubule-stabilizing agents

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Angeletti, Ruth H; Horwitz, Susan Band

    2014-01-01

    Despite the clinical success of microtubule-interacting agents (MIA), a significant challenge for oncologists is the inability to predict the response of individual patients with cancer to these drugs. In the present study, six cell lines were compared by 2D DIGE proteomics to investigate cellula...

  3. A novel proteomic biomarker panel as a diagnostic tool for patients with ovarian cancer

    DEFF Research Database (Denmark)

    Høgdall, Claus; Fung, Eric T; Christensen, Ib J

    2011-01-01

    Previous reports have shown that the proteomic markers apolipoprotein A1, hepcidin, transferrin, inter-alpha trypsin IV internal fragment, transthyretin, connective-tissue activating protein 3 and beta-2 microglobulin may discriminate between a benign pelvic mass and ovarian cancer (OC). The aim...

  4. Integrating proteomic and functional genomic technologies in discovery-driven translational breast cancer research

    DEFF Research Database (Denmark)

    Celis, Julio E; Gromov, Pavel; Gromova, Irina

    2003-01-01

    The application of state-of-the-art proteomics and functional genomics technologies to the study of cancer is rapidly shifting toward the analysis of clinically relevant samples derived from patients, as the ultimate aim of translational research is to bring basic discoveries closer to the bedside...

  5. Comparative proteomic analysis of fluoride treated rat bone provides new insights into the molecular mechanisms of fluoride toxicity.

    Science.gov (United States)

    Wei, Yan; Zeng, Beibei; Zhang, Hua; Chen, Cheng; Wu, Yanli; Wang, Nanlan; Wu, Yanqiu; Zhao, Danqing; Zhao, Yuxi; Iqbal, Javed; Shen, Liming

    2018-07-01

    Long-term excessive intake of fluoride (F) could lead to chronic fluorosis. To explore the underlying molecular mechanisms, present study is designed to elucidate the effect of fluoride on proteome expression of bone in sodium fluoride (NaF)-treated SD rats. Hematoxylin and eosin (H&E) staining was used to determine the severity of osteofluorosis, and bone samples were submitted for iTRAQ analysis. The results showed that the cortical thickness and trabecular area of femur bone in medium- and high-dose groups were higher than in control group. Contrary to this, trabecular area was reduced in the low-dose group, indicating that the bone mass was increased in medium- and high-dose groups, and decreased in the low-dose group. Thirteen (13), 35, and 34 differentially expressed proteins were identified in low-, medium-, and high-dose group, respectively. The medium- and high-dose groups shared a more similar protein expression pattern. These proteins were mainly associated with collagen metabolism, proteoglycans (PGs), matrix metalloproteinases (MMPs), etc. The results suggested that the effect of NaF on SD rats is in a dose-dependent manner. Some key proteins found here may be involved in affecting the bone tissues and bone marrow or muscle, and account for the complex pathology and clinical symptoms of fluorosis. Copyright © 2018 Elsevier B.V. All rights reserved.

  6. Gel-based proteomics of liver cancer progression in rat

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Miller, Leah M; Novikoff, Phyllis M

    2011-01-01

    A significant challenge in proteomics biomarker research is to identify the changes that are of highest diagnostic interest, among the many unspecific aberrations associated with disease burden and inflammation. In the present study liver tissue specimens (n=18) from six experimental stages were ...

  7. Esophageal Cancer with Bone Marrow Hyperplasia Mimicking Bone Metastasis: Report of a Case

    Directory of Open Access Journals (Sweden)

    Hiromi Yasuda

    2016-11-01

    Full Text Available A 63-year-old man visited the clinic with numbness in the right hand. Magnetic resonance imaging demonstrated multiple low-intensity lesions in the cervical vertebrae and sacrum, which was suspicious of cervical bone metastasis. Fluorodeoxyglucose positron emission tomography/computed tomography revealed areas of increased fluorodeoxyglucose uptake in the thoracic esophagus, sternum and sacrum. A flat, elevated esophageal cancer was identified by upper gastrointestinal endoscopy, and the macroscopic appearance indicated early-stage disease. From the cervical, thoracic and abdominal computed tomography images, there were no metastatic lesions except for the bone lesions. To confirm whether the bone lesions were metastatic, we performed bone biopsy. The histopathological diagnosis was bone marrow hyperplasia. It was crucial for treatment planning to establish whether the lesions were distant metastases. Here, we report a case of esophageal cancer with bone marrow hyperplasia mimicking bone metastasis.

  8. Dissecting Tumor-Stromal Interactions in Breast Cancer Bone Metastasis

    Directory of Open Access Journals (Sweden)

    Yibin Kang

    2016-06-01

    Full Text Available Bone metastasis is a frequent occurrence in breast cancer, affecting more than 70% of late stage cancer patients with severe complications such as fracture, bone pain, and hypercalcemia. The pathogenesis of osteolytic bone metastasis depends on cross-communications between tumor cells and various stromal cells residing in the bone microenvironment. Several growth factor signaling pathways, secreted micro RNAs (miRNAs and exosomes are functional mediators of tumor-stromal interactions in bone metastasis. We developed a functional genomic approach to systemically identified molecular pathways utilized by breast cancer cells to engage the bone stroma in order to generate osteolytic bone metastasis. We showed that elevated expression of vascular cell adhesion molecule 1 (VCAM1 in disseminated breast tumor cells mediates the recruitment of pre-osteoclasts and promotes their differentiation to mature osteoclasts during the bone metastasis formation. Transforming growth factor β (TGF-β is released from bone matrix upon bone destruction, and signals to breast cancer to further enhance their malignancy in developing bone metastasis. We furthered identified Jagged1 as a TGF-β target genes in tumor cells that engaged bone stromal cells through the activation of Notch signaling to provide a positive feedback to promote tumor growth and to activate osteoclast differentiation. Substantially change in miRNA expression was observed in osteoclasts during their differentiation and maturation, which can be exploited as circulating biomarkers of emerging bone metastasis and therapeutic targets for the treatment of bone metastasis. Further research in this direction may lead to improved diagnosis and treatment strategies for bone metastasis.

  9. Proteomic-Based Approaches for the Study of Cytokines in Lung Cancer

    Directory of Open Access Journals (Sweden)

    Ángela Marrugal

    2016-01-01

    Full Text Available Proteomic techniques are currently used to understand the biology of different human diseases, including studies of the cell signaling pathways implicated in cancer progression, which is important in knowing the roles of different proteins in tumor development. Due to its poor prognosis, proteomic approaches are focused on the identification of new biomarkers for the early diagnosis, prognosis, and targeted treatment of lung cancer. Cytokines are proteins involved in inflammatory processes and have been proposed as lung cancer biomarkers and therapeutic targets because it has been reported that some cytokines play important roles in tumor development, invasion, and metastasis. In this review, we aim to summarize the different proteomic techniques used to discover new lung cancer biomarkers and therapeutic targets. Several cytokines have been identified as important players in lung cancer using these techniques. We underline the most important cytokines that are useful as biomarkers and therapeutic targets. We also summarize some of the therapeutic strategies targeted for these cytokines in lung cancer.

  10. SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Semkov

    2010-01-01

    Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

  11. SURGICAL TREATMENT FOR BONE METASTASES OF KIDNEY CANCER

    Directory of Open Access Journals (Sweden)

    A. S. Semkov

    2014-08-01

    Full Text Available The data of 67 kidney cancer (KC patients with bone metastases, who had been treated at Moscow City Cancer Hospital Sixty-Two in 2002 to 2009 and had undergone skeletal bone surgery, were retrospectively analyzed. The role of surgical treatment for bone metastases from KC was assessed and the factors influencing the patients survival were determined. Surgical treatment for bone metastases from KC was ascertained to yield satisfactory results in improving the quality of life and increasing survival rates in the patients.

  12. Plasma membrane proteomics and its application in clinical cancer biomarker discovery

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Lund, Rikke; Ditzel, Henrik J

    2010-01-01

    Plasma membrane proteins that are exposed on the cell surface have important biological functions, such as signaling into and out of the cells, ion transport, and cell-cell and cell-matrix interactions. The expression level of many of the plasma membrane proteins involved in these key functions...... targeted by protein drugs, such as human antibodies, that have enhanced survival of several groups of cancer patients. The combination of novel analytical approaches and subcellular fractionation procedures has made it possible to study the plasma membrane proteome in more detail, which will elucidate...... cancer biology, particularly metastasis, and guide future development of novel drug targets. The technical advances in plasma membrane proteomics and the consequent biological revelations will be discussed herein. Many of the advances have been made using cancer cell lines, but because the main goal...

  13. Survival after bone metastasis by primary cancer type

    DEFF Research Database (Denmark)

    Svensson, Elisabeth; Christiansen, Christian F; Ulrichsen, Sinna P

    2017-01-01

    OBJECTIVE: In the 10 most common primary types with bone metastases, we aimed to examine survival, further stratifying on bone metastases only or with additional synchronous metastases. METHODS: We included all patients aged 18 years and older with incident hospital diagnosis of solid cancer...... between 1994 and 2010, subsequently diagnosed with BM until 2012. We followed patients from date of bone metastasis diagnosis until death, emigration or 31 December 2012, whichever came first. We computed 1-year, 3-year and 5-year survival (%) and the corresponding 95% CIs stratified on primary cancer...... prostate (34%), breast (22%) and lung (20%). One-year survival after bone metastasis diagnosis was lowest in patients with lung cancer (10%, 95% CI 9% to 11%) and highest in patients with breast cancer (51%, 50% to 53%). At 5 years of follow-up, only patients with breast cancer had over 10% survival (13...

  14. Quantitative proteomic analysis of microdissected oral epithelium for cancer biomarker discovery.

    Science.gov (United States)

    Xiao, Hua; Langerman, Alexander; Zhang, Yan; Khalid, Omar; Hu, Shen; Cao, Cheng-Xi; Lingen, Mark W; Wong, David T W

    2015-11-01

    Specific biomarkers are urgently needed for the detection and progression of oral cancer. The objective of this study was to discover cancer biomarkers from oral epithelium through utilizing high throughput quantitative proteomics approaches. Morphologically malignant, epithelial dysplasia, and adjacent normal epithelial tissues were laser capture microdissected (LCM) from 19 patients and used for proteomics analysis. Total proteins from each group were extracted, digested and then labelled with corresponding isobaric tags for relative and absolute quantitation (iTRAQ). Labelled peptides from each sample were combined and analyzed by liquid chromatography-mass spectrometry (LC-MS/MS) for protein identification and quantification. In total, 500 proteins were identified and 425 of them were quantified. When compared with adjacent normal oral epithelium, 17 and 15 proteins were consistently up-regulated or down-regulated in malignant and epithelial dysplasia, respectively. Half of these candidate biomarkers were discovered for oral cancer for the first time. Cornulin was initially confirmed in tissue protein extracts and was further validated in tissue microarray. Its presence in the saliva of oral cancer patients was also explored. Myoglobin and S100A8 were pre-validated by tissue microarray. These data demonstrated that the proteomic biomarkers discovered through this strategy are potential targets for oral cancer detection and salivary diagnostics. Copyright © 2015 Elsevier Ltd. All rights reserved.

  15. Maintaining bone health in prostate cancer throughout the disease continuum.

    Science.gov (United States)

    Saad, Fred; Eastham, James

    2010-06-01

    Prostate cancer (PC) is the most prevalent malignancy in men, with 604,506 new cases diagnosed yearly worldwide. Maintaining bone health is important during all stages of PC, including patients who experience bone loss from androgen-deprivation therapy and patients who develop bone metastases. Patients with bone metastases often experience severe bone pain and are at increased risk for potentially debilitating skeletal-related events. Bisphosphonates are a well-established treatment option for patients with bone metastases from solid tumors and bone lesions from multiple myeloma. Zoledronic acid (ZOL) is the only bisphosphonate (BP) that has been extensively studied in patients with castration-recurrent PC and is indicated for treating patients with bone metastases from PC in conjunction with standard antineoplastic therapy. This review will examine the breadth of evidence supporting a role for ZOL and emerging therapies in managing patients with PC throughout the disease continuum. 2010 Elsevier Inc. All rights reserved.

  16. Proteomic Prediction of Breast Cancer Risk: A Cohort Study

    Science.gov (United States)

    2009-03-01

    the SCX equilibrate-system program under Method, to bring all solutions to running- condition. ( Important ! Manually purge both pumps in each delivery...affinity tags. Nat Biotechnol. 1999;17:994- 999.[PMID: 10504701] 10. Washburn MP, Wolters D, Yates JR 3rd. Large-scale analysis of the yeast proteome by...X, Wang R, Wasinger V, Wu CY, Zhao X, Zeng R, Archakov A, Tsugita A, Beer I, Pandey A, Pisano M, Andrews P, Tammen H, Speicher DW, Hanash SM

  17. Comparative proteomic analysis of human malignant ascitic fluids for the development of gastric cancer biomarkers.

    Science.gov (United States)

    Jin, Jonghwa; Son, Minsoo; Kim, Hyeyoon; Kim, Hyeyeon; Kong, Seong-Ho; Kim, Hark Kyun; Kim, Youngsoo; Han, Dohyun

    2018-04-11

    Malignant ascites is a sign of peritoneal seeding, which is one of the most frequent forms of incurable distant metastasis. Because the development of malignant ascites is associated with an extremely poor prognosis, determining whether it resulted from peritoneal seeding has critical clinical implications in diagnosis, choice of treatment, and active surveillance. At present, the molecular characterizations of malignant ascites are especially limited in case of gastric cancer. We aimed to identify malignant ascites-specific proteins that may contribute to the development of alternative methods for diagnosis and therapeutic monitoring and also increase our understanding of the pathophysiology of peritoneal seeding. First, comprehensive proteomic strategies were employed to construct an in-depth proteome of ascitic fluids. Label-free quantitative proteomic analysis was subsequently performed to identify candidates that can differentiate between malignant ascitic fluilds of gastric cancer patients from benign ascitic fluids. Finally, two candidate proteins were verified by ELISA in 84 samples with gastric cancer or liver cirrhosis. Comprehensive proteome profiling resulted in the identification of 5347 ascites proteins. Using label-free quantification, we identified 299 proteins that were differentially expressed in ascitic fluids between liver cirrhosis and stage IV gastric cancer patients. In addition, we identified 645 proteins that were significantly expressed in ascitic fluids between liver cirrhosis and gastric cancer patients with peritoneal seeding. Finally, Gastriscin and Periostin that can distinguish malignant ascites from benign ascites were verified by ELISA. This study identified and verified protein markers that can distinguish malignant ascites with or without peritoneal seeding from benign ascites. Consequently, our results could be a significant resource for gastric cancer research and biomarker discovery in the diagnosis of malignant ascites

  18. Bone metastasis target redox-responsive micell for the treatment of lung cancer bone metastasis and anti-bone resorption.

    Science.gov (United States)

    Ye, Wei-Liang; Zhao, Yi-Pu; Cheng, Ying; Liu, Dao-Zhou; Cui, Han; Liu, Miao; Zhang, Bang-Le; Mei, Qi-Bing; Zhou, Si-Yuan

    2018-01-16

    In order to inhibit the growth of lung cancer bone metastasis and reduce the bone resorption at bone metastasis sites, a bone metastasis target micelle DOX@DBMs-ALN was prepared. The size and the zeta potential of DOX@DBNs-ALN were about 60 nm and -15 mV, respectively. DOX@DBMs-ALN exhibited high binding affinity with hydroxyapatite and released DOX in redox-responsive manner. DOX@DBMs-ALN was effectively up taken by A549 cells and delivered DOX to the nucleus of A549 cells, which resulted in strong cytotoxicity on A549 cells. The in vivo experimental results indicated that DOX@DBMs-ALN specifically delivered DOX to bone metastasis site and obviously prolonged the retention time of DOX in bone metastasis site. Moreover, DOX@DBMs-ALN not only significantly inhibited the growth of bone metastasis tumour but also obviously reduced the bone resorption at bone metastasis sites without causing marked systemic toxicity. Thus, DOX@DBMs-ALN has great potential in the treatment of lung cancer bone metastasis.

  19. Up-regulation of bone marrow stromal protein 2 (BST2) in breast cancer with bone metastasis

    International Nuclear Information System (INIS)

    Cai, Dongqing; Cao, Jie; Li, Zhen; Zheng, Xin; Yao, Yao; Li, Wanglin; Yuan, Ziqiang

    2009-01-01

    Bone metastases are frequent complications of breast cancer. Recent literature implicates multiple chemokines in the formation of bone metastases in breast cancer. However, the molecular mechanism of metastatic bone disease in breast cancer remains unknown. We have recently made the novel observation of the BST2 protein expression in human breast cancer cell lines. The purpose of our present study is to investigate the expression and the role of BST2 in bone metastatic breast cancer. cDNA microarray analysis was used to compare the BST2 gene expression between a metastatic to bone human breast cancer cell line (MDA-231BO) and a primary human breast cancer cell line (MDA-231). The BST2 expression in one bone metastatic breast cancer and seven non-bone metastatic breast cancer cell lines were also determined using real-time RT-PCR and Western blot assays. We then employed tissue array to further study the BST2 expression in human breast cancer using array slides containing 20 independent breast cancer tumors that formed metastatic bone lesions, 30 non-metastasis-forming breast cancer tumors, and 8 normal breast tissues. In order to test the feasibility of utilizing BST2 as a serum marker for the presence of bone metastasis in breast cancer, we had measured the BST2 expression levels in human serums by using ELISA on 43 breast cancer patients with bone metastasis, 43 breast cancer patients without bone metastasis, and 14 normal healthy controls. The relationship between cell migration and proliferation and BST2 expression was also studied in a human breast recombinant model system using migration and FACS analysis. The microarray demonstrated over expression of the BST2 gene in the bone metastatic breast cancer cell line (MDA-231BO) compared to the primary human breast cancer cell line (MDA-231). The expression of the BST2 gene was significantly increased in the bone metastatic breast cancer cell lines and tumor tissues compared to non-bone metastatic breast cancer

  20. Proteomic Technologies for the Study of Osteosarcoma

    Directory of Open Access Journals (Sweden)

    Stephanie D. Byrum

    2012-01-01

    Full Text Available Osteosarcoma is the most common primary bone cancer of children and is established during stages of rapid bone growth. The disease is a consequence of immature osteoblast differentiation, which gives way to a rapidly synthesized incompletely mineralized and disorganized bone matrix. The mechanism of osteosarcoma tumorogenesis is poorly understood, and few proteomic studies have been used to interrogate the disease thus far. Accordingly, these studies have identified proteins that have been known to be associated with other malignancies, rather than being osteosarcoma specific. In this paper, we focus on the growing list of available state-of-the-art proteomic technologies and their specific application to the discovery of novel osteosarcoma diagnostic and therapeutic targets. The current signaling markers/pathways associated with primary and metastatic osteosarcoma that have been identified by early-stage proteomic technologies thus far are also described.

  1. Proteomic validation of multifunctional molecules in mesenchymal stem cells derived from human bone marrow, umbilical cord blood and peripheral blood.

    Directory of Open Access Journals (Sweden)

    Jumi Kim

    Full Text Available Mesenchymal stem cells (MSCs are one of the most attractive therapeutic resources in clinical application owing to their multipotent capability, which means that cells can differentiate into various mesenchymal tissues such as bone, cartilage, fat, tendon, muscle and marrow stroma. Depending on the cellular source, MSCs exhibit different application potentials according to their different in vivo functions, despite similar phenotypic and cytological characteristics. To understand the different molecular conditions that govern the different application or differentiation potential of each MSC according to cellular source, we generated a proteome reference map of MSCs obtained from bone marrow (BM, umbilical cord blood (CB and peripheral blood (PB. We identified approximately 30 differentially regulated (or expressed proteins. Most up-regulated proteins show a cytoskeletal and antioxidant or detoxification role according to their functional involvement. Additionally, these proteins are involved in the increase of cell viability, engraftment and migration in pathological conditions in vivo. In summary, we examined differentially expressed key regulatory factors of MSCs obtained from several cellular sources, demonstrated their differentially expressed proteome profiles and discussed their functional role in specific pathological conditions. With respect to the field of cell therapy, it may be particularly crucial to determine the most suitable cell sources according to target disease.

  2. Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

    Science.gov (United States)

    Paul, Debasish; Kumar, Avinash; Gajbhiye, Akshada; Santra, Manas K.; Srikanth, Rapole

    2013-01-01

    Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA) were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches. PMID:23586059

  3. Mass Spectrometry-Based Proteomics in Molecular Diagnostics: Discovery of Cancer Biomarkers Using Tissue Culture

    Directory of Open Access Journals (Sweden)

    Debasish Paul

    2013-01-01

    Full Text Available Accurate diagnosis and proper monitoring of cancer patients remain a key obstacle for successful cancer treatment and prevention. Therein comes the need for biomarker discovery, which is crucial to the current oncological and other clinical practices having the potential to impact the diagnosis and prognosis. In fact, most of the biomarkers have been discovered utilizing the proteomics-based approaches. Although high-throughput mass spectrometry-based proteomic approaches like SILAC, 2D-DIGE, and iTRAQ are filling up the pitfalls of the conventional techniques, still serum proteomics importunately poses hurdle in overcoming a wide range of protein concentrations, and also the availability of patient tissue samples is a limitation for the biomarker discovery. Thus, researchers have looked for alternatives, and profiling of candidate biomarkers through tissue culture of tumor cell lines comes up as a promising option. It is a rich source of tumor cell-derived proteins, thereby, representing a wide array of potential biomarkers. Interestingly, most of the clinical biomarkers in use today (CA 125, CA 15.3, CA 19.9, and PSA were discovered through tissue culture-based system and tissue extracts. This paper tries to emphasize the tissue culture-based discovery of candidate biomarkers through various mass spectrometry-based proteomic approaches.

  4. Module for applications of bone scan in cancer patients

    International Nuclear Information System (INIS)

    Morales, Rosanna; Cano, Roque; Velasquez, Maria; Vasquez, Edinson; Diaz, Pepe; Vasquez, Mario; Rojas, Peter

    2013-01-01

    This paper reports the application of a software which enables the complete register of patient data, for delivering appropriate information in bone scan reports. Bone scan is a frequent study in Nuclear Medicine, which enables physicians to diagnose a primary bone cancer or metastases. The software was designed in order to complete data given by oncologists and constitutes an aid for the health team attending patients. (authors).

  5. Chronological study for solitary bone metastasis in the sternum from breast cancer with bone scintigraphy

    International Nuclear Information System (INIS)

    Miyoshi, Hidenao; Otsuka, Nobuaki; Sone, Teruki; Nagai, Kiyohisa; Tamada, Tsutomu; Mimura, Hiroaki; Yanagimoto, Shinichi; Tomomitsu, Tatsushi; Fukunaga, Masao

    1999-01-01

    Since breast cancer is frequently associated with bone metastasis, bone scintigraphies have been performed to determine pre-operative staging and to survey postoperative bone metastasis. The sternum, in particular, is a site at which is difficult to differentiate between benign bone disease and bone metastasis, because of varied uptake and wide individual variations. In this study, chronological bone images were scintigraphied in six cases with solitary sternal metastasis and three cases with benign bone disease including two fracture cases and one arthritis case. On bone scintigrams in which solitary sternal metastasis appeared, increased uptake was found in five cases, and photon deficiency was observed in one case. During follow-up scintigraphies, abnormal accumulations, such as hot spots and cold lesions, increased in the bone metastasis while abnormal uptake disappeared or was unchanged in the benign bone disease cases. On CT, four cases showed osteolytic change, and one exhibited osteosclerotic change. These findings indicate that sternal metastasis usually shows osteolytic change, even if a hot lesion is recognized on bone scintigraphy. In solitary sternal metastasis, for which early diagnosis is difficult, both an integrated diagnosis using other imaging techniques and chronological bone scintigraphy are important. (author)

  6. Bone Morphogenetic Proteins, Antagonists and Receptors in Prostate Cancer

    National Research Council Canada - National Science Library

    Reddi, A. H

    2005-01-01

    .... Unfortunately over 40,000 patients succumbed to this horrendous cancer. Death is preceded by a characteristic triad of diffuse osteoblastic-osteosclerotic skeletal metastases, bone pain and pathologic fractures...

  7. Prevention and Treatment of Bone Metastases in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ripamonti Carla

    2013-09-01

    Full Text Available In breast cancer patients, bone is the most common site of metastases. Medical therapies are the basic therapy to prevent distant metastases and recurrence and to cure them. Radiotherapy has a primary role in pain relief, recalcification and stabilization of the bone, as well as the reduction of the risk of complications (e.g., bone fractures, spinal cord compression. Bisphosphonates, as potent inhibitors of osteoclastic-mediated bone resorption are a well-established, standard-of-care treatment option to reduce the frequency, severity and time of onset of the skeletal related events in breast cancer patients with bone metastases. Moreover bisphosphonates prevent cancer treatment-induced bone loss. Recent data shows the anti-tumor activity of bisphosphonates, in particular, in postmenopausal women and in older premenopausal women with hormone-sensitive disease treated with ovarian suppression. Pain is the most frequent symptom reported in patients with bone metastases, and its prevention and treatment must be considered at any stage of the disease. The prevention and treatment of bone metastases in breast cancer must consider an integrated multidisciplinary approach.

  8. Antibody Characterization Lab | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The Antibody Characterization Lab (ACL), an intramural reference laboratory located at the Frederick National Laboratory for Cancer Research in Frederick, Maryland, thoroughly characterizes monoclonal antibodies or other renewable affinity binding reagents for use in cancer related research.

  9. Unlocking biomarker discovery: large scale application of aptamer proteomic technology for early detection of lung cancer.

    Directory of Open Access Journals (Sweden)

    Rachel M Ostroff

    Full Text Available BACKGROUND: Lung cancer is the leading cause of cancer deaths worldwide. New diagnostics are needed to detect early stage lung cancer because it may be cured with surgery. However, most cases are diagnosed too late for curative surgery. Here we present a comprehensive clinical biomarker study of lung cancer and the first large-scale clinical application of a new aptamer-based proteomic technology to discover blood protein biomarkers in disease. METHODOLOGY/PRINCIPAL FINDINGS: We conducted a multi-center case-control study in archived serum samples from 1,326 subjects from four independent studies of non-small cell lung cancer (NSCLC in long-term tobacco-exposed populations. Sera were collected and processed under uniform protocols. Case sera were collected from 291 patients within 8 weeks of the first biopsy-proven lung cancer and prior to tumor removal by surgery. Control sera were collected from 1,035 asymptomatic study participants with ≥ 10 pack-years of cigarette smoking. We measured 813 proteins in each sample with a new aptamer-based proteomic technology, identified 44 candidate biomarkers, and developed a 12-protein panel (cadherin-1, CD30 ligand, endostatin, HSP90α, LRIG3, MIP-4, pleiotrophin, PRKCI, RGM-C, SCF-sR, sL-selectin, and YES that discriminates NSCLC from controls with 91% sensitivity and 84% specificity in cross-validated training and 89% sensitivity and 83% specificity in a separate verification set, with similar performance for early and late stage NSCLC. CONCLUSIONS/SIGNIFICANCE: This study is a significant advance in clinical proteomics in an area of high unmet clinical need. Our analysis exceeds the breadth and dynamic range of proteome interrogated of previously published clinical studies of broad serum proteome profiling platforms including mass spectrometry, antibody arrays, and autoantibody arrays. The sensitivity and specificity of our 12-biomarker panel improves upon published protein and gene expression panels

  10. Risk factors and characteristics of prostate cancer bone metastases

    Directory of Open Access Journals (Sweden)

    Jun-ming LIN

    2017-10-01

    Full Text Available Objective To analyze the risk factors and characteristics of bone metastases in patients with prostate cancer. Methods Patients who were diagnosed as prostate cancer by biopsy and histopathologic analysis between June 2006 and June 2016 were included in this study. The clinical data of the patients were reviewed, and the demographic data, laboratory examination results and Gleason score were recorded. The correlations between clinical factors and bone metastasis were analyzed, and the risk factors of bone metastasis were identified. Results A total of 585 patients were recruited in this study, including 228 with bone metastasis and 357 without bone metastasis. Of the patients with bone metastasis, the incidence of pelvic metastasis was the highest, accounting for 81.58%, followed by spin (63.16% and rib (58.33%, and the incidence of clavicle metastasis was the lowest (14.47%. Logistic regression analysis showed that age 85.5U/L, prostate-specific antigen >79.88μg/L and Gleason score >7.5 were the risk factors of bone metastasis in prostate cancer. ROC curve analysis showed that the sensitivity of diagnosing bone metastasis was 56.1%, 66.7%, 68.4% and 56.1%, and the specificity was 56.6%, 81.8%, 70.0% and 65.3%, respectively for above 4 factors. Conclusions The most common site of bone metastasis in patients with prostate cancer is pelvis. Patients' age, concentrations of plasma ALP and PSA, and Gleason score are the risk factors for bone metastasis in patients with prostate cancer. DOI: 10.11855/j.issn.0577-7402.2017.08.09

  11. Quantitative evaluation of bone scintigraphy in prostate cancer

    International Nuclear Information System (INIS)

    Yamamoto, Yasushi

    2017-01-01

    This paper described the quantitative evaluation of bone scintigraphy that is used in the inspection of the bone-metastasis of prostate cancer. In advanced prostate cancer, bone scintigraphic examination with technetium 99m methylenediphosphonate (complex compound) is indispensable. Since bone metastasis hardly involves soft tissue, the morphological evaluation of soft tissue cancer cannot be used as a reference. Therefore, quantitative evaluation peculiar to bone scintigraphy has been developed. Following the visual evaluation that began in the 1980's, a technique considering highly integrated parts and areas of images was proposed in the 1990's. The computer-aided diagnosis (CAD) software that automated the manual analysis of the above technique was developed in the 2010's. In order to evaluate the usefulness of quantitative evaluation based on bone CAD, the authors performed bone scintigraphy for 42 patients, who were diagnosed as castration-resistant prostate cancer (CRPC) in 2004 to 2011 and received DEC therapy for 4 months. When bone CAD analysis was performed, it was found that the therapeutic effect could not be determined earlier than the judgement using the increase of PSA antigen. Recently quantitative analysis shifted from bone scintigraphy to bone SPECT (single photon emission computed tomography), and papers have also been published since the 2010s. In bone SPECT, the quantitative function of SUV (standardized uptake value) was equipped, and in the clinical use case of SUV, SUV increase was seen earlier than the increase of PSA antigen. The evidences are expected to be accumulated in the future. (A.O.)

  12. Computational Omics Pre-Awardees | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute's Clinical Proteomic Tumor Analysis Consortium (CPTAC) is pleased to announce the pre-awardees of the Computational Omics solicitation. Working with NVIDIA Foundation's Compute the Cure initiative and Leidos Biomedical Research Inc., the NCI, through this solicitation, seeks to leverage computational efforts to provide tools for the mining and interpretation of large-scale publicly available ‘omics’ datasets.

  13. The usefulness of bone-marrow scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Sone, Teruki; Yoneda, Masaya; Tomomitsu, Tatsushi; Yanagimoto, Shinichi; Muranaka, Akira; Morita, Rikushi; Saito, Noriaki; Tanaka, Hiroyoshi

    1985-01-01

    We used a combination of bone and bone-marrow scintigraphy to study 25 patients with prostatic cancer. Of the 18 cases whose sup(99m)Tc-methylene diphosphonate (MDP) bone scans showed hot spots in the lower lumbar region of the spine and/or the pelvic bone, 8 had normal bone-marrow scintigrams. These 8 patients, were subsequently shown to have senile, degenerative changes of the spine. On the other hand, in 9 of the 10 patients whose bone-marrow scintigrams showed accumulation defects, follow-up study and characteristic X-ray findings confirmed the presence of metastases. In all 6 cases with extensive bone metastases shown by sup(99m)Tc-MDP bone scintigraphy, sup(99m)Tc-sulphur-colloid bone-marrow scintigraphy showed multiple accumulation defects. In conclusion, bone-marrow scintigraphy was found to be useful in distinguishing metastatic lesions from benign degenerative changes in the cases with suspected bone involvement, as well as in evaluating equivocal lesions in the pelvis. (orig.)

  14. Synergistic effects of retinoic acid and tamoxifen on human breast cancer cells: Proteomic characterization

    International Nuclear Information System (INIS)

    Wang Ying; He Qingyu; Chen Hongming; Chiu Jenfu

    2007-01-01

    The anti-estrogen tamoxifen and vitamin A-related compound, all-trans retinoic acid (RA), in combination act synergistically to inhibit the growth of MCF-7 human breast cancer cells. In the present study, we applied two-dimensional gel electrophoresis based proteomic approach to globally analyze this synergistic effect of RA and tamoxifen. Proteomic study revealed that multiple clusters of proteins were involved in RA and tamoxifen-induced apoptosis in MCF-7 breast cancer cells, including post-transcriptional and splicing factors, proteins related to cellular proliferation or differentiation, and proteins related to energy production and internal degradation systems. The negative growth factor-transforming growth factor β (TGFβ) was secreted by RA and/or tamoxifen treatment and was studies as a potential mediator of the synergistic effects of RA and tamoxifen in apoptosis. By comparing protein alterations in treatments of RA and tamoxifen alone or in combination to those of TGFβ treatment, or co-treatment with TGFβ inhibitor SB 431542, proteomic results showed that a number of proteins were involved in TGFβ signaling pathway. These results provide valuable insights into the mechanisms of RA and tamoxifen-induced TGFβ signaling pathway in breast cancer cells

  15. Osteoblast-Prostate Cancer Cell Interaction in Prostate Cancer Bone Metastases

    National Research Council Canada - National Science Library

    Navone, Nora

    2001-01-01

    .... This suggests that prostate cancer cells interact with cells from the osteoblastic lineage. To understand the molecular bases of prostatic bone metastases, we established two prostate cancer cell lines, MDA PCa 2a and MDA PCa 2b (1...

  16. Dataset for the proteomic inventory and quantitative analysis of the breast cancer hypoxic secretome associated with osteotropism

    Directory of Open Access Journals (Sweden)

    Thomas R. Cox

    2015-12-01

    Full Text Available The cancer secretome includes all of the macromolecules secreted by cells into their microenvironment. Cancer cell secretomes are significantly different to that of normal cells reflecting the changes that normal cells have undergone during their transition to malignancy. More importantly, cancer secretomes are known to be active mediators of both local and distant host cells and play an important role in the progression and dissemination of cancer. Here we have quantitatively profiled both the composition of breast cancer secretomes associated with osteotropism, and their modulation under normoxic and hypoxic conditions. We detect and quantify 162 secretome proteins across all conditions which show differential hypoxic induction and association with osteotropism. Mass Spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000397 and the complete proteomic, bioinformatic and biological analyses are reported in Cox et al. (2015 [1].

  17. Quantitative and temporal proteome analysis of butyrate-treated colorectal cancer cells.

    Science.gov (United States)

    Tan, Hwee Tong; Tan, Sandra; Lin, Qingsong; Lim, Teck Kwang; Hew, Choy Leong; Chung, Maxey C M

    2008-06-01

    Colorectal cancer is one of the most common cancers in developed countries, and its incidence is negatively associated with high dietary fiber intake. Butyrate, a short-chain fatty acid fermentation by-product of fiber induces cell maturation with the promotion of growth arrest, differentiation, and/or apoptosis of cancer cells. The stimulation of cell maturation by butyrate in colonic cancer cells follows a temporal progression from the early phase of growth arrest to the activation of apoptotic cascades. Previously we performed two-dimensional DIGE to identify differentially expressed proteins induced by 24-h butyrate treatment of HCT-116 colorectal cancer cells. Herein we used quantitative proteomics approaches using iTRAQ (isobaric tags for relative and absolute quantitation), a stable isotope labeling methodology that enables multiplexing of four samples, for a temporal study of HCT-116 cells treated with butyrate. In addition, cleavable ICAT, which selectively tags cysteine-containing proteins, was also used, and the results complemented those obtained from the iTRAQ strategy. Selected protein targets were validated by real time PCR and Western blotting. A model is proposed to illustrate our findings from this temporal analysis of the butyrate-responsive proteome that uncovered several integrated cellular processes and pathways involved in growth arrest, apoptosis, and metastasis. These signature clusters of butyrate-regulated pathways are potential targets for novel chemopreventive and therapeutic drugs for treatment of colorectal cancer.

  18. Differential proteomic analysis of noncardia gastric cancer from individuals of northern Brazil.

    Science.gov (United States)

    Leal, Mariana Ferreira; Chung, Janete; Calcagno, Danielle Queiroz; Assumpção, Paulo Pimentel; Demachki, Samia; da Silva, Ismael Dale Cotrim Guerreiro; Chammas, Roger; Burbano, Rommel Rodríguez; de Arruda Cardoso Smith, Marília

    2012-01-01

    Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in larger clinical study

  19. Differential proteomic analysis of noncardia gastric cancer from individuals of northern Brazil.

    Directory of Open Access Journals (Sweden)

    Mariana Ferreira Leal

    Full Text Available Gastric cancer is the second leading cause of cancer-related death worldwide. The identification of new cancer biomarkers is necessary to reduce the mortality rates through the development of new screening assays and early diagnosis, as well as new target therapies. In this study, we performed a proteomic analysis of noncardia gastric neoplasias of individuals from Northern Brazil. The proteins were analyzed by two-dimensional electrophoresis and mass spectrometry. For the identification of differentially expressed proteins, we used statistical tests with bootstrapping resampling to control the type I error in the multiple comparison analyses. We identified 111 proteins involved in gastric carcinogenesis. The computational analysis revealed several proteins involved in the energy production processes and reinforced the Warburg effect in gastric cancer. ENO1 and HSPB1 expression were further evaluated. ENO1 was selected due to its role in aerobic glycolysis that may contribute to the Warburg effect. Although we observed two up-regulated spots of ENO1 in the proteomic analysis, the mean expression of ENO1 was reduced in gastric tumors by western blot. However, mean ENO1 expression seems to increase in more invasive tumors. This lack of correlation between proteomic and western blot analyses may be due to the presence of other ENO1 spots that present a slightly reduced expression, but with a high impact in the mean protein expression. In neoplasias, HSPB1 is induced by cellular stress to protect cells against apoptosis. In the present study, HSPB1 presented an elevated protein and mRNA expression in a subset of gastric cancer samples. However, no association was observed between HSPB1 expression and clinicopathological characteristics. Here, we identified several possible biomarkers of gastric cancer in individuals from Northern Brazil. These biomarkers may be useful for the assessment of prognosis and stratification for therapy if validated in

  20. Proteome-metabolome profiling of ovarian cancer ascites reveals novel components involved in intercellular communication.

    Science.gov (United States)

    Shender, Victoria O; Pavlyukov, Marat S; Ziganshin, Rustam H; Arapidi, Georgij P; Kovalchuk, Sergey I; Anikanov, Nikolay A; Altukhov, Ilya A; Alexeev, Dmitry G; Butenko, Ivan O; Shavarda, Alexey L; Khomyakova, Elena B; Evtushenko, Evgeniy; Ashrafyan, Lev A; Antonova, Irina B; Kuznetcov, Igor N; Gorbachev, Alexey Yu; Shakhparonov, Mikhail I; Govorun, Vadim M

    2014-12-01

    Ovarian cancer ascites is a native medium for cancer cells that allows investigation of their secretome in a natural environment. This medium is of interest as a promising source of potential biomarkers, and also as a medium for cell-cell communication. The aim of this study was to elucidate specific features of the malignant ascites metabolome and proteome. In order to omit components of the systemic response to ascites formation, we compared malignant ascites with cirrhosis ascites. Metabolome analysis revealed 41 components that differed significantly between malignant and cirrhosis ascites. Most of the identified cancer-specific metabolites are known to be important signaling molecules. Proteomic analysis identified 2096 and 1855 proteins in the ovarian cancer and cirrhosis ascites, respectively; 424 proteins were specific for the malignant ascites. Functional analysis of the proteome demonstrated that the major differences between cirrhosis and malignant ascites were observed for the cluster of spliceosomal proteins. Additionally, we demonstrate that several splicing RNAs were exclusively detected in malignant ascites, where they probably existed within protein complexes. This result was confirmed in vitro using an ovarian cancer cell line. Identification of spliceosomal proteins and RNAs in an extracellular medium is of particular interest; the finding suggests that they might play a role in the communication between cancer cells. In addition, malignant ascites contains a high number of exosomes that are known to play an important role in signal transduction. Thus our study reveals the specific features of malignant ascites that are associated with its function as a medium of intercellular communication. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  1. Characterizing the inorganic/organic interface in cancer bone metastasis

    Science.gov (United States)

    Wu, Fei

    Bone metastasis frequently occurs in patients with advanced breast cancer and remains a major source of mortality. At the molecular level, bone is a nanocomposite composed of inorganic bone mineral deposited within an organic extracellular matrix (ECM). Although the exact mechanisms of bone metastasis remain unclear, the nanoscale materials properties of bone mineral have been implicated in this process. Bone apatite is closely related to synthetic hydroxyapatite (HAP, Ca10(PO4)6(OH)2) in terms of structural and mechanical properties. Additionally, although the primary protein content of bone is collagen I, the glycoprotein fibronectin (Fn) is essential in maintaining the overall integrity of the bone matrix. Importantly, in vivo, neither breast cancer cells nor normal bone cells interact directly with the bone mineral but rather with the protein film adsorbed onto the mineral surface. Therefore, we hypothesized that breast cancer cell functions were regulated by differential fibronectin adsorption onto hydroxyapatite, which led to pathological remodeling of the bone matrix and sustained bone metastasis. Three model systems containing HAP and Fn were developed for this thesis. In model system I, a library of synthetic HAP nanoparticles were utilized to investigate the effect of mineral size, shape, and crystallinity on Fn conformation, using Forster resonance energy transfer (FRET) spectroscopy. In model system II, Fn-functionalized large geologic HAP crystals were used instead of HAP nanoparticles to avoid cellular uptake when investigating subsequent cell functions. Overall our FRET analysis (models I and II) revealed that Fn conformation depended on size, surface chemistry, and roughness of underlying HAP. When breast cancer cells were seeded on the Fn-coated HAP crystal facets (model II), our data indicated high secretion levels of proangiogenic and proinflammatory factors associated with the presence of unfolded Fn conformations, likely caused by differential

  2. Identification of cancer protein biomarkers using proteomic techniques

    Energy Technology Data Exchange (ETDEWEB)

    Mor, Gil G.; Ward, David C.; Bray-Ward, Patricia

    2016-10-18

    The claimed invention describes methods to diagnose or aid in the diagnosis of cancer. The claimed methods are based on the identification of biomarkers which are particularly well suited to discriminate between cancer subjects and healthy subjects. These biomarkers were identified using a unique and novel screening method described herein. The biomarkers identified herein can also be used in the prognosis and monitoring of cancer. The invention comprises the use of leptin, prolactin, OPN and IGF-II for diagnosing, prognosis and monitoring of ovarian cancer.

  3. NGF blockade at early times during bone cancer development attenuates bone destruction and increases limb use.

    Science.gov (United States)

    McCaffrey, Gwen; Thompson, Michelle L; Majuta, Lisa; Fealk, Michelle N; Chartier, Stephane; Longo, Geraldine; Mantyh, Patrick W

    2014-12-01

    Studies in animals and humans show that blockade of nerve growth factor (NGF) attenuates both malignant and nonmalignant skeletal pain. While reduction of pain is important, a largely unanswered question is what other benefits NGF blockade might confer in patients with bone cancer. Using a mouse graft model of bone sarcoma, we demonstrate that early treatment with an NGF antibody reduced tumor-induced bone destruction, delayed time to bone fracture, and increased the use of the tumor-bearing limb. Consistent with animal studies in osteoarthritis and head and neck cancer, early blockade of NGF reduced weight loss in mice with bone sarcoma. In terms of the extent and time course of pain relief, NGF blockade also reduced pain 40% to 70%, depending on the metric assessed. Importantly, this analgesic effect was maintained even in animals with late-stage disease. Our results suggest that NGF blockade immediately upon detection of tumor metastasis to bone may help preserve the integrity and use, delay the time to tumor-induced bone fracture, and maintain body weight. ©2014 American Association for Cancer Research.

  4. Antibody Portal | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Central to reproducibility in biomedical research is being able to use well-characterized and defined reagents. The CPTAC Antibody Portal serves as a National Cancer Institute (NCI) community resource that provides access to a large number of standardized renewable affinity reagents (to cancer-associated targets) and accompanying characterization data.

  5. 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 ...

  6. Pharmacologic management of bone-related complications and bone metastases in postmenopausal women with hormone receptor-positive breast cancer

    Directory of Open Access Journals (Sweden)

    Yardley DA

    2016-05-01

    Full Text Available Denise A Yardley1,2 1Sarah Cannon Research Institute, Nashville, TN, USA; 2Tennessee Oncology, Nashville, TN, USA Abstract: There is a high risk for bone loss and skeletal-related events, including bone metastases, in postmenopausal women with hormone receptor-positive breast cancer. Both the disease itself and its therapeutic treatments can negatively impact bone, resulting in decreases in bone mineral density and increases in bone loss. These negative effects on the bone can significantly impact morbidity and mortality. Effective management and minimization of bone-related complications in postmenopausal women with hormone receptor-positive breast cancer remain essential. This review discusses the current understanding of molecular and biological mechanisms involved in bone turnover and metastases, increased risk for bone-related complications from breast cancer and breast cancer therapy, and current and emerging treatment strategies for managing bone metastases and bone turnover in postmenopausal women with hormone receptor-positive breast cancer. Keywords: breast cancer, bone metastases, hormone receptor-positive, bone-related complications, interventions, management and management strategies, estrogen receptor-positive

  7. The Genomic and Proteomic Content of Cancer Cell-Derived Exosomes

    International Nuclear Information System (INIS)

    Henderson, Meredith C.; Azorsa, David O.

    2012-01-01

    Exosomes are secreted membrane vesicles that have been proposed as an effective means to detect a variety of disease states, including cancer. The properties of exosomes, including stability in biological fluids, allow for their efficient isolation and make them an ideal vehicle for studies on early disease detection and evaluation. Much data has been collected over recent years regarding the messenger RNA, microRNA, and protein contents of exosomes. In addition, many studies have described the functional role that exosomes play in disease initiation and progression. Tumor cells have been shown to secrete exosomes, often in increased amounts compared to normal cells, and these exosomes can carry the genomic and proteomic signatures characteristic of the tumor cells from which they were derived. While these unique signatures make exosomes ideal for cancer detection, exosomes derived from cancer cells have also been shown to play a functional role in cancer progression. Here, we review the unique genomic and proteomic contents of exosomes originating from cancer cells as well as their functional effects to promote tumor progression.

  8. Isotope bone scanning in operable mammary cancer

    Energy Technology Data Exchange (ETDEWEB)

    Maylin, C [Centre Hospitalier Universitaire, 94 - Creteil (France); Vilcoq, J R; Schlienger, P; Calle, R [Institut du Radium, 75 - Paris (France)

    1977-01-01

    In the pre-treatment work-up in breast carcinoma cases, the bone scan findings could be of major interest. If the presence of occult metastases is discovered management may be modified accordingly. In a group involving 78 cases of breast carcinoma, classified as primary, operable, in three cases only scintigraphy revealed bone metastases before they produced clinical and radiological signs. In two of them there was agreement, in one disagreement over the findings. Moreover, in 5 cases a bone metastasis was revealed and immediately confirmed on a complete bone assessment.

  9. Data-Independent Acquisition-Based Quantitative Proteomic Analysis Reveals Potential Biomarkers of Kidney Cancer.

    Science.gov (United States)

    Song, Yimeng; Zhong, Lijun; Zhou, Juntuo; Lu, Min; Xing, Tianying; Ma, Lulin; Shen, Jing

    2017-12-01

    Renal cell carcinoma (RCC) is a malignant and metastatic cancer with 95% mortality, and clear cell RCC (ccRCC) is the most observed among the five major subtypes of RCC. Specific biomarkers that can distinguish cancer tissues from adjacent normal tissues should be developed to diagnose this disease in early stages and conduct a reliable prognostic evaluation. Data-independent acquisition (DIA) strategy has been widely employed in proteomic analysis because of various advantages, including enhanced protein coverage and reliable data acquisition. In this study, a DIA workflow is constructed on a quadrupole-Orbitrap LC-MS platform to reveal dysregulated proteins between ccRCC and adjacent normal tissues. More than 4000 proteins are identified, 436 of these proteins are dysregulated in ccRCC tissues. Bioinformatic analysis reveals that multiple pathways and Gene Ontology items are strongly associated with ccRCC. The expression levels of L-lactate dehydrogenase A chain, annexin A4, nicotinamide N-methyltransferase, and perilipin-2 examined through RT-qPCR, Western blot, and immunohistochemistry confirm the validity of the proteomic analysis results. The proposed DIA workflow yields optimum time efficiency and data reliability and provides a good choice for proteomic analysis in biological and clinical studies, and these dysregulated proteins might be potential biomarkers for ccRCC diagnosis. © 2017 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  10. Global phosphotyrosine proteomics identifies PKCδ as a marker of responsiveness to Src inhibition in colorectal cancer.

    Directory of Open Access Journals (Sweden)

    Eliot T McKinley

    Full Text Available Sensitive and specific biomarkers of protein kinase inhibition can be leveraged to accelerate drug development studies in oncology by associating early molecular responses with target inhibition. In this study, we utilized unbiased shotgun phosphotyrosine (pY proteomics to discover novel biomarkers of response to dasatinib, a small molecule Src-selective inhibitor, in preclinical models of colorectal cancer (CRC. We performed unbiased mass spectrometry shotgun pY proteomics to reveal the pY proteome of cultured HCT-116 colonic carcinoma cells, and then extended this analysis to HCT-116 xenograft tumors to identify pY biomarkers of dasatinib-responsiveness in vivo. Major dasatinib-responsive pY sites in xenograft tumors included sites on delta-type protein kinase C (PKCδ, CUB-domain-containing protein 1 (CDCP1, Type-II SH2-domain-containing inositol 5-phosphatase (SHIP2, and receptor protein-tyrosine phosphatase alpha (RPTPα. The pY313 site PKCδ was further supported as a relevant biomarker of dasatinib-mediated Src inhibition in HCT-116 xenografts by immunohistochemistry and immunoblotting with a phosphospecific antibody. Reduction of PKCδ pY313 was further correlated with dasatinib-mediated inhibition of Src and diminished growth as spheroids of a panel of human CRC cell lines. These studies reveal PKCδ pY313 as a promising readout of Src inhibition in CRC and potentially other solid tumors and may reflect responsiveness to dasatinib in a subset of colorectal cancers.

  11. Definition of molecular determinants of prostate cancer cell bone extravasation.

    Science.gov (United States)

    Barthel, Steven R; Hays, Danielle L; Yazawa, Erika M; Opperman, Matthew; Walley, Kempland C; Nimrichter, Leonardo; Burdick, Monica M; Gillard, Bryan M; Moser, Michael T; Pantel, Klaus; Foster, Barbara A; Pienta, Kenneth J; Dimitroff, Charles J

    2013-01-15

    Advanced prostate cancer commonly metastasizes to bone, but transit of malignant cells across the bone marrow endothelium (BMEC) remains a poorly understood step in metastasis. Prostate cancer cells roll on E-selectin(+) BMEC through E-selectin ligand-binding interactions under shear flow, and prostate cancer cells exhibit firm adhesion to BMEC via β1, β4, and αVβ3 integrins in static assays. However, whether these discrete prostate cancer cell-BMEC adhesive contacts culminate in cooperative, step-wise transendothelial migration into bone is not known. Here, we describe how metastatic prostate cancer cells breach BMEC monolayers in a step-wise fashion under physiologic hemodynamic flow. Prostate cancer cells tethered and rolled on BMEC and then firmly adhered to and traversed BMEC via sequential dependence on E-selectin ligands and β1 and αVβ3 integrins. Expression analysis in human metastatic prostate cancer tissue revealed that β1 was markedly upregulated compared with expression of other β subunits. Prostate cancer cell breaching was regulated by Rac1 and Rap1 GTPases and, notably, did not require exogenous chemokines as β1, αVβ3, Rac1, and Rap1 were constitutively active. In homing studies, prostate cancer cell trafficking to murine femurs was dependent on E-selectin ligand, β1 integrin, and Rac1. Moreover, eliminating E-selectin ligand-synthesizing α1,3 fucosyltransferases in transgenic adenoma of mouse prostate mice dramatically reduced prostate cancer incidence. These results unify the requirement for E-selectin ligands, α1,3 fucosyltransferases, β1 and αVβ3 integrins, and Rac/Rap1 GTPases in mediating prostate cancer cell homing and entry into bone and offer new insight into the role of α1,3 fucosylation in prostate cancer development.

  12. Quantitative Proteomics Identifies Activation of Hallmark Pathways of Cancer in Patient Melanoma.

    Science.gov (United States)

    Byrum, Stephanie D; Larson, Signe K; Avaritt, Nathan L; Moreland, Linley E; Mackintosh, Samuel G; Cheung, Wang L; Tackett, Alan J

    2013-03-01

    Molecular pathways regulating melanoma initiation and progression are potential targets of therapeutic development for this aggressive cancer. Identification and molecular analysis of these pathways in patients has been primarily restricted to targeted studies on individual proteins. Here, we report the most comprehensive analysis of formalin-fixed paraffin-embedded human melanoma tissues using quantitative proteomics. From 61 patient samples, we identified 171 proteins varying in abundance among benign nevi, primary melanoma, and metastatic melanoma. Seventy-three percent of these proteins were validated by immunohistochemistry staining of malignant melanoma tissues from the Human Protein Atlas database. Our results reveal that molecular pathways involved with tumor cell proliferation, motility, and apoptosis are mis-regulated in melanoma. These data provide the most comprehensive proteome resource on patient melanoma and reveal insight into the molecular mechanisms driving melanoma progression.

  13. Detection of dysregulated protein-association networks by high-throughput proteomics predicts cancer vulnerabilities.

    Science.gov (United States)

    Lapek, John D; Greninger, Patricia; Morris, Robert; Amzallag, Arnaud; Pruteanu-Malinici, Iulian; Benes, Cyril H; Haas, Wilhelm

    2017-10-01

    The formation of protein complexes and the co-regulation of the cellular concentrations of proteins are essential mechanisms for cellular signaling and for maintaining homeostasis. Here we use isobaric-labeling multiplexed proteomics to analyze protein co-regulation and show that this allows the identification of protein-protein associations with high accuracy. We apply this 'interactome mapping by high-throughput quantitative proteome analysis' (IMAHP) method to a panel of 41 breast cancer cell lines and show that deviations of the observed protein co-regulations in specific cell lines from the consensus network affects cellular fitness. Furthermore, these aberrant interactions serve as biomarkers that predict the drug sensitivity of cell lines in screens across 195 drugs. We expect that IMAHP can be broadly used to gain insight into how changing landscapes of protein-protein associations affect the phenotype of biological systems.

  14. Proteomic analysis of cervical cancer cells treated with ...

    Indian Academy of Sciences (India)

    PRAKASH KUMAR

    The State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan .... peptide and fragment mass tolerance were set at 1 and 0.2 ... values of the MOWSE score and the number of unique.

  15. Clodronate Therapy in Patients with Breast Cancer and Bone Metastases

    International Nuclear Information System (INIS)

    Saber, M.M.; Shouman, T.

    2003-01-01

    To assess whether clodronate can reduce frequency of skeletal morbidity in women with lytic bone metastases from breast cancer. Methods: Between 1997 and 2001,167 patients with stage IV breast cancer with bone metastases, were randomly assigned to receive clodronate at a dose of 1600 mg per day orally for 12 months, in addition to the standard specific anti cancer therapy (87 patients) or standard anti cancer therapy only (80 patients). Skeletal complications, including pathological fractures, the need for radiation to bone or bone surgery, spinal cord compression and hypercalcaemia (a serum calcium concentration above 12 mg per deci liter (3.0 mmol per liter) or elevated to any degree and requiring treatment) were assessed monthly. Bone pam. use of analgesic drugs, performance status and quality of life were assessed throughout the trial. Results: There was no significant difference between the two groups at study entry regarding clinical characteristics. The median time for first skeletal complication was ,significantly less in the control group (6.1 vs 9.7 months, ρ=0.05). The proportion of patients who had any skeletal complication in the clodronate group than the control group, but the difference was insignificant (ρ 0.09). Clodronate was generally well tolerated and the main side effects were constipation (32%) flatulence/dyspepsia (17%) and anorexia (8%). The overall survival was not affected by clodronate therapy. The median survival was 14 months In the clodronate group and 13.8 months in the control group. Conclusions: Clodronate is an effective supplement to conventional anticancer treatment for breast cancer with bone metastasis. It reduces skeletal complications and relieves symptoms associated with lytic bone lesions. Further clinical trials that recruit a larger number of patients will be needed to clearly define the role of clodronate in metastatic breast cancer

  16. Kinomic and phospho-proteomic analysis of breast cancer stem-like cells

    DEFF Research Database (Denmark)

    Leth-Larsen, Rikke; Christensen, Anne Geske Lindhard; Ehmsen, Sidse

    Kinomic and phospho-proteomic analysis of breast cancer stem-like cells Rikke Leth-Larsen1, Anne G Christensen1, Sidse Ehmsen1, Mark Møller1, Giuseppe Palmisano2, Martin R Larsen2, Henrik J Ditzel1,3 1Institute of Molecular Medicine, University of Southern Denmark, Odense, Denmark 2Institute...... of Biochemistry and Molecular Biology, University of Southern Denmark, Odense, Denmark 3Dept. of Oncology, Odense University Hospital, Odense, Denmark Cancer stem cells are thought to be responsible for tumorigenic potential and to possess resistance mechanisms against chemotherapy- and radiation-induced cancer...... cell death, while the bulk of a tumor lacks these capacities. The resistance mechanisms may cause these cells to survive and become the source of later tumor recurrence, highlighting the need for therapeutic strategies that specifically target pathways central to these cancer stem cells. The CD44hi...

  17. A novel approach to the study of the functional proteome in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hennessy, Bryan; Lu, Yiling; Gonzalez-Angulo, Ana Maria; Carey, Mark; Myhre, Simen; Ju, Zhenlin; Coombes, Kevin; Meric-Bernstam, Funda; Bedrosian, Isabelle; Davies, Michael A.; Siwak, Doris; Agarwal, Roshan; Zhang, Fan; Overgaard, Jens; Alsner, Jan; Neve, Richard M.; Kuo, Wen-Lin; Gray, Joe W.; Borresen-Dale, Anne-Lise; Mills, Gordon B.

    2008-10-10

    Factors including intratumoral heterogeneity and variability in tissue handling potentially hamper the application of reverse phase protein arrays (RPPA) to study of the solid tumor functional proteome. To address this, RPPA was applied to quantify protein expression and activation in 233 human breast tumors and 52 breast cancer cell lines. Eighty-two antibodies that recognize kinase and steroid signaling events and their effectors were validated for RPPA because of the importance of these proteins to breast carcinogenesis. Reproducibility in replicate lysates was excellent. Intratumoral protein expression was less variable than intertumoral expression, and prognostic biomarkers retained the ability to accurately predict patient outcomes when analyzed in different tumor sites. Although 21/82 total and phosphoproteins demonstrated time-dependent instability in breast tumors that were placed at room temperature after surgical excision for 24 hours prior to freezing, the functional proteomic 'fingerprint' was robust in most tumors until at least 24 hours before tissue freezing. Correlations between RPPA and immunohistochemistry were statistically significant for assessed proteins but RPPA demonstrated a superior dynamic range and detected, for example, an 866-fold difference in estrogen receptor alpha level across breast tumors. Protein and mRNA levels were concordant (at p {le} 0.05) for 41.3% and 61.1% of assayed targets in breast tumors and cell lines, respectively. Several phosphorylation and cleavage products did not correlate with the corresponding transcript levels. In conclusion, the reproducibility of RPPA, the faithfulness with which proteins and the functional proteomic 'fingerprint' are preserved in different sections derived from primary breast tumors, and the surprising stability of this 'fingerprint' with increasing time to freezing all facilitate the application of RPPA to the accurate study of protein biomarkers in non

  18. Quantitative Analysis of Differential Proteome Expression in Bladder Cancer vs. Normal Bladder Cells Using SILAC Method.

    Directory of Open Access Journals (Sweden)

    Ganglong Yang

    Full Text Available The best way to increase patient survival rate is to identify patients who are likely to progress to muscle-invasive or metastatic disease upfront and treat them more aggressively. The human cell lines HCV29 (normal bladder epithelia, KK47 (low grade nonmuscle invasive bladder cancer, NMIBC, and YTS1 (metastatic bladder cancer have been widely used in studies of molecular mechanisms and cell signaling during bladder cancer (BC progression. However, little attention has been paid to global quantitative proteome analysis of these three cell lines. We labeled HCV29, KK47, and YTS1 cells by the SILAC method using three stable isotopes each of arginine and lysine. Labeled proteins were analyzed by 2D ultrahigh-resolution liquid chromatography LTQ Orbitrap mass spectrometry. Among 3721 unique identified and annotated proteins in KK47 and YTS1 cells, 36 were significantly upregulated and 74 were significantly downregulated with >95% confidence. Differential expression of these proteins was confirmed by western blotting, quantitative RT-PCR, and cell staining with specific antibodies. Gene ontology (GO term and pathway analysis indicated that the differentially regulated proteins were involved in DNA replication and molecular transport, cell growth and proliferation, cellular movement, immune cell trafficking, and cell death and survival. These proteins and the advanced proteome techniques described here will be useful for further elucidation of molecular mechanisms in BC and other types of cancer.

  19. Antiandrogens act as selective androgen receptor modulators at the proteome level in prostate cancer cells.

    Science.gov (United States)

    Brooke, Greg N; Gamble, Simon C; Hough, Michael A; Begum, Shajna; Dart, D Alwyn; Odontiadis, Michael; Powell, Sue M; Fioretti, Flavia M; Bryan, Rosie A; Waxman, Jonathan; Wait, Robin; Bevan, Charlotte L

    2015-05-01

    Current therapies for prostate cancer include antiandrogens, inhibitory ligands of the androgen receptor, which repress androgen-stimulated growth. These include the selective androgen receptor modulators cyproterone acetate and hydroxyflutamide and the complete antagonist bicalutamide. Their activity is partly dictated by the presence of androgen receptor mutations, which are commonly detected in patients who relapse while receiving antiandrogens, i.e. in castrate-resistant prostate cancer. To characterize the early proteomic response to these antiandrogens we used the LNCaP prostate cancer cell line, which harbors the androgen receptor mutation most commonly detected in castrate-resistant tumors (T877A), analyzing alterations in the proteome, and comparing these to the effect of these therapeutics upon androgen receptor activity and cell proliferation. The majority are regulated post-transcriptionally, possibly via nongenomic androgen receptor signaling. Differences detected between the exposure groups demonstrate subtle changes in the biological response to each specific ligand, suggesting a spectrum of agonistic and antagonistic effects dependent on the ligand used. Analysis of the crystal structures of the AR in the presence of cyproterone acetate, hydroxyflutamide, and DHT identified important differences in the orientation of key residues located in the AF-2 and BF-3 protein interaction surfaces. This further implies that although there is commonality in the growth responses between androgens and those antiandrogens that stimulate growth in the presence of a mutation, there may also be influential differences in the growth pathways stimulated by the different ligands. This therefore has implications for prostate cancer treatment because tumors may respond differently dependent upon which mutation is present and which ligand is activating growth, also for the design of selective androgen receptor modulators, which aim to elicit differential proteomic

  20. Estimation of the proteomic cancer co-expression sub networks by using association estimators.

    Directory of Open Access Journals (Sweden)

    Cihat Erdoğan

    Full Text Available In this study, the association estimators, which have significant influences on the gene network inference methods and used for determining the molecular interactions, were examined within the co-expression network inference concept. By using the proteomic data from five different cancer types, the hub genes/proteins within the disease-associated gene-gene/protein-protein interaction sub networks were identified. Proteomic data from various cancer types is collected from The Cancer Proteome Atlas (TCPA. Correlation and mutual information (MI based nine association estimators that are commonly used in the literature, were compared in this study. As the gold standard to measure the association estimators' performance, a multi-layer data integration platform on gene-disease associations (DisGeNET and the Molecular Signatures Database (MSigDB was used. Fisher's exact test was used to evaluate the performance of the association estimators by comparing the created co-expression networks with the disease-associated pathways. It was observed that the MI based estimators provided more successful results than the Pearson and Spearman correlation approaches, which are used in the estimation of biological networks in the weighted correlation network analysis (WGCNA package. In correlation-based methods, the best average success rate for five cancer types was 60%, while in MI-based methods the average success ratio was 71% for James-Stein Shrinkage (Shrink and 64% for Schurmann-Grassberger (SG association estimator, respectively. Moreover, the hub genes and the inferred sub networks are presented for the consideration of researchers and experimentalists.

  1. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies.

    Science.gov (United States)

    Méplan, Catherine; Johnson, Ian T; Polley, Abigael C J; Cockell, Simon; Bradburn, David M; Commane, Daniel M; Arasaradnam, Ramesh P; Mulholland, Francis; Zupanic, Anze; Mathers, John C; Hesketh, John

    2016-08-01

    Epidemiologic studies highlight the potential role of dietary selenium (Se) in colorectal cancer prevention. Our goal was to elucidate whether expression of factors crucial for colorectal homoeostasis is affected by physiologic differences in Se status. Using transcriptomics and proteomics followed by pathway analysis, we identified pathways affected by Se status in rectal biopsies from 22 healthy adults, including 11 controls with optimal status (mean plasma Se = 1.43 μM) and 11 subjects with suboptimal status (mean plasma Se = 0.86 μM). We observed that 254 genes and 26 proteins implicated in cancer (80%), immune function and inflammatory response (40%), cell growth and proliferation (70%), cellular movement, and cell death (50%) were differentially expressed between the 2 groups. Expression of 69 genes, including selenoproteins W1 and K, which are genes involved in cytoskeleton remodelling and transcription factor NFκB signaling, correlated significantly with Se status. Integrating proteomics and transcriptomics datasets revealed reduced inflammatory and immune responses and cytoskeleton remodelling in the suboptimal Se status group. This is the first study combining omics technologies to describe the impact of differences in Se status on colorectal expression patterns, revealing that suboptimal Se status could alter inflammatory signaling and cytoskeleton in human rectal mucosa and so influence cancer risk.-Méplan, C., Johnson, I. T., Polley, A. C. J., Cockell, S., Bradburn, D. M., Commane, D. M., Arasaradnam, R. P., Mulholland, F., Zupanic, A., Mathers, J. C., Hesketh, J. Transcriptomics and proteomics show that selenium affects inflammation, cytoskeleton, and cancer pathways in human rectal biopsies. © The Author(s).

  2. Identification and characterization of angiogenesis targets through proteomic profiling of endothelial cells in human cancer tissues.

    Directory of Open Access Journals (Sweden)

    Mehdi Mesri

    Full Text Available Genomic and proteomic analysis of normal and cancer tissues has yielded abundant molecular information for potential biomarker and therapeutic targets. Considering potential advantages in accessibility to pharmacological intervention, identification of targets resident on the vascular endothelium within tumors is particularly attractive. By employing mass spectrometry (MS as a tool to identify proteins that are over-expressed in tumor-associated endothelium relative to normal cells, we aimed to discover targets that could be utilized in tumor angiogenesis cancer therapy. We developed proteomic methods that allowed us to focus our studies on the discovery of cell surface/secreted proteins, as they represent key antibody therapeutic and biomarker opportunities. First, we isolated endothelial cells (ECs from human normal and kidney cancer tissues by FACS using CD146 as a marker. Additionally, dispersed human colon and lung cancer tissues and their corresponding normal tissues were cultured ex-vivo and their endothelial content were preferentially expanded, isolated and passaged. Cell surface proteins were then preferentially captured, digested with trypsin and subjected to MS-based proteomic analysis. Peptides were first quantified, and then the sequences of differentially expressed peptides were resolved by MS analysis. A total of 127 unique non-overlapped (157 total tumor endothelial cell over-expressed proteins identified from directly isolated kidney-associated ECs and those identified from ex-vivo cultured lung and colon tissues including known EC markers such as CD146, CD31, and VWF. The expression analyses of a panel of the identified targets were confirmed by immunohistochemistry (IHC including CD146, B7H3, Thy-1 and ATP1B3. To determine if the proteins identified mediate any functional role, we performed siRNA studies which led to previously unidentified functional dependency for B7H3 and ATP1B3.

  3. Proteome profiling analysis of human ovarian cancer serum samples

    International Nuclear Information System (INIS)

    Cognetti, F.; Citro, G.

    2009-01-01

    Mass Spectrometry represents a powerful tool in cancer research to discovery of potential bio markers through peak identification from serum profiling. By using high resolution MALDITOF and bioinformatic analysis almost 400 serum sample homogeneously distributed between biopsy confirmed ovarian cancer and high risk serum samples were analyzed. Each serum sample run in duplicate and whole serum sample preparation procedure has been performed by Hamilton Star Robot in order to reduce bias and the replicates with a low Pearson coefficient are removed. After automated reverse phase magnetic beads separation the samples were tested in MALDI-TOF

  4. Software Tools | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The CPTAC program develops new approaches to elucidate aspects of the molecular complexity of cancer made from large-scale proteogenomic datasets, and advance them toward precision medicine.  Part of the CPTAC mission is to make data and tools available and accessible to the greater research community to accelerate the discovery process.

  5. Bone Sialoproteins and Breast Cancer Detection

    Science.gov (United States)

    2006-07-01

    follow proteolytic activity as previously described (20). This substrate is highly substituted with fluorescein moieties so that the fluorescent signal...and phosphorus , a inverse correlation with parathyroid hormone, and (d) a significant positive correlation with total hip and neck bone mineral...correlate with serum phosphorus , parathyroid hormone and bone mineral density. J. Clin. Endo. Metab.89(8):4158-4161. DAMD17-02-1-0684

  6. Large-scale proteomic identification of S100 proteins in breast cancer tissues

    International Nuclear Information System (INIS)

    Cancemi, Patrizia; Di Cara, Gianluca; Albanese, Nadia Ninfa; Costantini, Francesca; Marabeti, Maria Rita; Musso, Rosa; Lupo, Carmelo; Roz, Elena; Pucci-Minafra, Ida

    2010-01-01

    Attempts to reduce morbidity and mortality in breast cancer is based on efforts to identify novel biomarkers to support prognosis and therapeutic choices. The present study has focussed on S100 proteins as a potentially promising group of markers in cancer development and progression. One reason of interest in this family of proteins is because the majority of the S100 genes are clustered on a region of human chromosome 1q21 that is prone to genomic rearrangements. Moreover, there is increasing evidence that S100 proteins are often up-regulated in many cancers, including breast, and this is frequently associated with tumour progression. Samples of breast cancer tissues were obtained during surgical intervention, according to the bioethical recommendations, and cryo-preserved until used. Tissue extracts were submitted to proteomic preparations for 2D-IPG. Protein identification was performed by N-terminal sequencing and/or peptide mass finger printing. The majority of the detected S100 proteins were absent, or present at very low levels, in the non-tumoral tissues adjacent to the primary tumor. This finding strengthens the role of S100 proteins as putative biomarkers. The proteomic screening of 100 cryo-preserved breast cancer tissues showed that some proteins were ubiquitously expressed in almost all patients while others appeared more sporadic. Most, if not all, of the detected S100 members appeared reciprocally correlated. Finally, from the perspective of biomarkers establishment, a promising finding was the observation that patients which developed distant metastases after a three year follow-up showed a general tendency of higher S100 protein expression, compared to the disease-free group. This article reports for the first time the comparative proteomic screening of several S100 protein members among a large group of breast cancer patients. The results obtained strongly support the hypothesis that a significant deregulation of multiple S100 protein members is

  7. Functional proteomic analysis reveals the involvement of KIAA1199 in breast cancer growth, motility and invasiveness

    International Nuclear Information System (INIS)

    Jami, Mohammad-Saeid; Huang, Xin; Peng, Hong; Fu, Kai; Li, Yan; Singh, Rakesh K; Ding, Shi-Jian; Hou, Jinxuan; Liu, Miao; Varney, Michelle L; Hassan, Hesham; Dong, Jixin; Geng, Liying; Wang, Jing; Yu, Fang

    2014-01-01

    KIAA1199 is a recently identified novel gene that is up-regulated in human cancer with poor survival. Our proteomic study on signaling polarity in chemotactic cells revealed KIAA1199 as a novel protein target that may be involved in cellular chemotaxis and motility. In the present study, we examined the functional significance of KIAA1199 expression in breast cancer growth, motility and invasiveness. We validated the previous microarray observation by tissue microarray immunohistochemistry using a TMA slide containing 12 breast tumor tissue cores and 12 corresponding normal tissues. We performed the shRNA-mediated knockdown of KIAA1199 in MDA-MB-231 and HS578T cells to study the role of this protein in cell proliferation, migration and apoptosis in vitro. We studied the effects of KIAA1199 knockdown in vivo in two groups of mice (n = 5). We carried out the SILAC LC-MS/MS based proteomic studies on the involvement of KIAA1199 in breast cancer. KIAA1199 mRNA and protein was significantly overexpressed in breast tumor specimens and cell lines as compared with non-neoplastic breast tissues from large-scale microarray and studies of breast cancer cell lines and tumors. To gain deeper insights into the novel role of KIAA1199 in breast cancer, we modulated KIAA1199 expression using shRNA-mediated knockdown in two breast cancer cell lines (MDA-MB-231 and HS578T), expressing higher levels of KIAA1199. The KIAA1199 knockdown cells showed reduced motility and cell proliferation in vitro. Moreover, when the knockdown cells were injected into the mammary fat pads of female athymic nude mice, there was a significant decrease in tumor incidence and growth. In addition, quantitative proteomic analysis revealed that knockdown of KIAA1199 in breast cancer (MDA-MB-231) cells affected a broad range of cellular functions including apoptosis, metabolism and cell motility. Our findings indicate that KIAA1199 may play an important role in breast tumor growth and invasiveness, and that it

  8. Irradiated long bone transplants in limb saving surgeries for extremity bone cancers

    International Nuclear Information System (INIS)

    Wang, E.HM.

    1996-01-01

    In the Philippines, the treatment of cancers of the limbs has always been by amputation. In recent decades, better understanding of these cancers and advances in the disciplines of cancer medicine have made the saving of these limbs almost routine in better developed countries. Surgeries entail two steps: (1) excision of the tumor and the bone from which the tumor arose, followed by (2) reconstruction of the defect resulting from the excision. Tumor implants, however, are not available locally, and are too costly for the average Filipino patient. Microvascular surgery is limited by the size of the defect it can bridge; and bone cement, not being biologic, can result in greater long term problems. Recently, the option of long bone transplants (aka large-segment allografts) to reconstruct these defects has become available locally. These bones are harvested from both cadaveric and live amputee donors after appropriate consent and medical work-up. After processing at the UP-PGH Tissue and Bone Bank, the bones are sterilized by irradiation at the PNRI(Philippine Nuclear Research Institute), and store in deep freezers until use. In the Philippines, limb saving surgery for bone cancers of the extremities using these large-segment alloografts was introduced in 1993 at the UP-PGH Musculoskeletal Tumor Unit. This paper will present the author's initial 3-year experience with 19 patients whose limbs were saved using bone transplantation. All surgeries were performed by the author and all patients have been personally followed up by the author (follow-up ranging from 6 months to 3-1/2 years). Cases will be presented to show the pre- and intraoperative processing of the irradiated bone; and the patients before and after the operations with emphasis on their improved quality of life and return to function. These results would seem to show that irradiated long bone transplants coupled with skills for limb saving surgery may make amputations a thing of the past for many of our

  9. Usefulness of serum bone metabolic markers for the diagnosis of differentiated thyroid cancer with bone metastases

    International Nuclear Information System (INIS)

    Wu Xiaohui; Lu Hankui; Gao Yunchao; Yuan Zhibin

    2007-01-01

    Objective: Bone metabolic markers (BMM) are biochemical substances that reflect bone resorption or formation. Some of them have been found to be useful in the diagnosis and management of bone metastases. The aim of this study was to investigate the usefulness of two bone resorption markers: bone-specific alkaline phosphatase (B-ALP) and N-terminal procollagen propeptides of type I collagen (PINP), as well as two bone formation markers: cross linked N and C terminal telepeptides of type I collagen (NTX and CTX) in the detection of bone metastasis in patients with differentiated thyroid cancer (DTC). Methods: There were sixty-three DTC patients in this study, 33 cases with clinically confirmed bone metastases and 30 cases with no bone metastases. The extents of bone metastases (or extents of the disease, EOD) were classified into four grades (0, I, II and III) according to the clinical and imaging findings including 99 Tc m -MDP, 131 I whole body scans and others. Serum BMM levels were measured by chemiluminescence immunoassay for B-ALP, radioimmunoassay for PINP, ELISA for NTX and electrochemiluminescence immunoassay for CTX. Nonparametric Mann-Whitney U test, grade correlation analysis and receiver operator characteristic (ROC) curve were applied to analyze the correlation between BMM and DTC patients with bone metastases. Results: The serum levels of B-ALP, NTX and CTX were significantly higher in DTC patients with bone metastases than those in patients with no bone metastases (all P 0.05). The serum levels of all markers were correlated with EOD grades (r s =0.371-0.558, all P<0.01). B-ALP level was found to have significant difference between EOD 0 to I (P=0.012). The diagnostic sensitivity and specificity of B-ALP for detecting DTC with bone metastases were 71.1% and 76.7% respectively by ROC curve analysis, which were higher than those of the other three markers. Conclusions: Serum BMM levels of B-ALP, NTX and CTX were useful for the evaluation of DTC with

  10. Discrepancy of biologic behavior influenced by bone marrow derived cells in lung cancer.

    Science.gov (United States)

    Zhang, Jie; Niu, Xiao-Min; Liao, Mei-Lin; Liu, Yun; Sha, Hui-Fang; Zhao, Yi; Yu, Yong-Feng; Tan, Qiang; Xiang, Jia-Qing; Fang, Jing; Lv, Dan-Dan; Li, Xue-Bing; Lu, Shun; Chen, Hai-Quan

    2010-11-01

    Disseminated cancer cells may initially require local nutrients and growth factors to thrive and survive in bone marrow. However, data on the influence of bone marrow derived cells (BMDC, also called bone stromal cells in some publications) on lung cancer cells is largely unexplored. This study explored the mechanism of how bone stromal factors contribute to the bone tropism in lung cancer. The difference among lung cancer cell lines in their abilities to metastasize to bone was found using the SCID animal model. Supernatant of bone marrow aspiration (BM) and condition medium from human bone stromal cells (BSC) were used to study the activity of bone stromal factors. We found bone stromal factors significantly increased the proliferation, invasion, adhesion and expression of angiogenosis-related factors, and inhibited the apoptosis for high bone metastasis H460 lung cancer cells. These biologic effects were not seen in SPC-A1 or A549 cells, which are low bone metastasis lung cancer cells. Adhesion of H460 cells to surface coated with bone stromal cells can activate some signal transduction pathways, and alter the expression of adhesion associated factors, including integrin β 3 and ADAMTS-1, two potential targets related with bone metastasis. We concluded that bone marrow derived cells had a profound effect on biological behavior of lung cancers, therefore favoring the growth of lung cancer cells in bone.

  11. Bone pain induced by metastatic cancer: pathophysiology and treatment

    International Nuclear Information System (INIS)

    Salas-Herrera, Isaias; Huertas-Gabert, Luis Carlos

    2004-01-01

    Cancer patients who develop bone metastases are an estimated 60 to 84% . Of these 79% experienced pain syndromes are difficult to manage, of which 50% die without adequate pain relief and with a poor quality of life. Therefore, it is necessary to have accessible and effective medications for the management of this condition. The pathophysiology of pain in bone is reviewed and the drugs used most frequently in the management of this type of cancer pain are described. Furthermore an algorithm of 6 steps is presented and can guide the physician when making a therapeutic decision. (author) [es

  12. Proteomic biomarkers for ovarian cancer risk in women with polycystic ovary syndrome: a systematic review and biomarker database integration.

    Science.gov (United States)

    Galazis, Nicolas; Olaleye, Olalekan; Haoula, Zeina; Layfield, Robert; Atiomo, William

    2012-12-01

    To review and identify possible biomarkers for ovarian cancer (OC) in women with polycystic ovary syndrome (PCOS). Systematic literature searches of MEDLINE, EMBASE, and Cochrane using the search terms "proteomics," "proteomic," and "ovarian cancer" or "ovarian carcinoma." Proteomic biomarkers for OC were then integrated with an updated previously published database of all proteomic biomarkers identified to date in patients with PCOS. Academic department of obstetrics and gynecology in the United Kingdom. A total of 180 women identified in the six studies. Tissue samples from women with OC vs. tissue samples from women without OC. Proteomic biomarkers, proteomic technique used, and methodologic quality score. A panel of six biomarkers was overexpressed both in women with OC and in women with PCOS. These biomarkers include calreticulin, fibrinogen-γ, superoxide dismutase, vimentin, malate dehydrogenase, and lamin B2. These biomarkers could help improve our understanding of the links between PCOS and OC and could potentially be used to identify subgroups of women with PCOS at increased risk of OC. More studies are required to further evaluate the role these biomarkers play in women with PCOS and OC. Copyright © 2012 American Society for Reproductive Medicine. Published by Elsevier Inc. All rights reserved.

  13. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

    Science.gov (United States)

    Campbell, J Preston; Karolak, Matthew R; Ma, Yun; Perrien, Daniel S; Masood-Campbell, S Kathryn; Penner, Niki L; Munoz, Steve A; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A; Elefteriou, Florent

    2012-07-01

    Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress) or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

  14. Biomarker Discovery and Mechanistic Studies of Prostate Cancer Using Targeted Proteomic Approaches

    Science.gov (United States)

    2010-07-01

    EMMPRIN is implicated in metastasis via its ability to confer resistance of breast cancer cells to anoikis by inhibiting BIM [21], and its association with...of Bim . J Biol Chem 2006;281:9719–9727. 22. Gupta N, Wollscheid B, Watts JD, Scheer B, Aebersold R, DeFranco AL. Quantitative proteomic analysis of B...disseminated in electronic form, nor  deployed in part or in whole in any  marketing , promotional or educational  contexts without authorization from

  15. Dataset for the proteomic inventory and quantitative analysis of the breast cancer hypoxic secretome associated with osteotropism

    DEFF Research Database (Denmark)

    Cox, T.R.; Schoof, Erwin; Gartland, A.

    2015-01-01

    secretomes are known to be active mediators of both local and distant host cells and play an important role in the progression and dissemination of cancer. Here we have quantitatively profiled both the composition of breast cancer secretomes associated with osteotropism, and their modulation under normoxic...... and hypoxic conditions. We detect and quantify 162 secretome proteins across all conditions which show differential hypoxic induction and association with osteotropism. Mass Spectrometry proteomics data have been deposited to the ProteomeXchange Consortium with the dataset identifier PXD000397...

  16. Follow-up of breast cancer by bone scintigraphy

    International Nuclear Information System (INIS)

    Garcia N, E.; Castro, F.; Miranda, R.; Leon, L.; Bustamante, G.; Escobar, M.

    2004-01-01

    Full text: Breast cancer is one of the most common cancers in women. It is the second most widespread cancer in Mexican women. Among the several methods for diagnosis and follow up of the disease, tumor markers like CA-53 have high sensitivity and specificity. Bone scan is a useful method in the detection of bone metastases. In comparison to other diagnostic modalities, bone scan is more sensitive and less expensive for detection of early bone abnormalities and hence to select an appropriate treatment for better prognosis. In our country, in about 70% of cases diagnosis of breast cancer is made when the disease is in an advanced state - states III and IV. The aim of this study was to evaluate the follow up of breast cancer by bone scans and to correlate these findings with the stage of the disease and other diagnostic modalities. The work was carried out at Mexican General Hospital. A total of 350 patients with breast tumor were included; bone scans were performed in all patients at the time of clinical diagnosis and at every 6 months for a period of 1 to 5 years using an Elscint APEX SP6 HR gamma camera coupled with ultra high resolution collimator. Scan was performed 2-3 hours after intravenous administration of 555-925 MBq of Tc-99m methyl diphosphonate. Tumor classification was made according to TNM criteria. Serum levels of alkaline phosphates, carcino-embrionic antigen (CEA) and Ca 53 were also measured on the same day. Fifty-one patients confirmed to have a diagnosis of benign breast were excluded from the study group. Of the remaining 299 patients, 89 (39%) were between 41 years to 50 years, 69 between 51 to 60 years. The clinical stage most commonly observed was stage III (n=164, 54%) followed by stage II (25%). In 59.5% of patients, scintigraphy showed bone metastasis. Four patients with bone metastases showed regression and 42 (14%) with negative scans became positive on follow up bone scans. Ninety-three patients were free of bone metastases during all

  17. Comparison of Pancreas Juice Proteins from Cancer Versus Pancreatitis Using Quantitative Proteomic Analysis

    Science.gov (United States)

    Chen, Ru; Pan, Sheng; Cooke, Kelly; Moyes, Kara White; Bronner, Mary P.; Goodlett, David R.; Aebersold, Ruedi; Brentnall, Teresa A.

    2008-01-01

    Objectives Pancreatitis is an inflammatory condition of the pancreas. However, it often shares many molecular features with pancreatic cancer. Biomarkers present in pancreatic cancer frequently occur in the setting of pancreatitis. The efforts to develop diagnostic biomarkers for pancreatic cancer have thus been complicated by the false-positive involvement of pancreatitis. Methods In an attempt to develop protein biomarkers for pancreatic cancer, we previously use quantitative proteomics to identify and quantify the proteins from pancreatic cancer juice. Pancreatic juice is a rich source of proteins that are shed by the pancreatic ductal cells. In this study, we used a similar approach to identify and quantify proteins from pancreatitis juice. Results In total, 72 proteins were identified and quantified in the comparison of pancreatic juice from pancreatitis patients versus pooled normal control juice. Nineteen of the juice proteins were overexpressed, and 8 were underexpressed in pancreatitis juice by at least 2-fold compared with normal pancreatic juice. Of these 27 differentially expressed proteins in pancreatitis, 9 proteins were also differentially expressed in the pancreatic juice from pancreatic cancer patient. Conclusions Identification of these differentially expressed proteins from pancreatitis juice provides useful information for future study of specific pancreatitis-associated proteins and to eliminate potential false-positive biomarkers for pancreatic cancer. PMID:17198186

  18. Proteomic Mass Spectrometry Imaging for Skin Cancer Diagnosis.

    Science.gov (United States)

    Lazova, Rossitza; Seeley, Erin H

    2017-10-01

    Mass spectrometry imaging can be successfully used for skin cancer diagnosis, particularly for the diagnosis of challenging melanocytic lesions. This method analyzes proteins within benign and malignant melanocytic tumor cells and, based on their differences, which constitute a unique molecular signature of 5 to 20 proteins, can render a diagnosis of benign nevus versus malignant melanoma. Mass spectrometry imaging may assist in the differentiation between metastases and nevi as well as between proliferative nodules in nevi and melanoma arising in a nevus. In the difficult area of atypical Spitzoid neoplasms, mass spectrometry diagnosis can predict clinical outcome better than histopathology. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. Does colon cancer ever metastasize to bone first? a temporal analysis of colorectal cancer progression

    International Nuclear Information System (INIS)

    Roth, Eira S; Fetzer, David T; Barron, Bruce J; Joseph, Usha A; Gayed, Isis W; Wan, David Q

    2009-01-01

    It is well recognized that colorectal cancer does not frequently metastasize to bone. The aim of this retrospective study was to establish whether colorectal cancer ever bypasses other organs and metastasizes directly to bone and whether the presence of lung lesions is superior to liver as a better predictor of the likelihood and timing of bone metastasis. We performed a retrospective analysis on patients with a clinical diagnosis of colon cancer referred for staging using whole-body 18 F-FDG PET and CT or PET/CT. We combined PET and CT reports from 252 individuals with information concerning patient history, other imaging modalities, and treatments to analyze disease progression. No patient had isolated osseous metastasis at the time of diagnosis, and none developed isolated bone metastasis without other organ involvement during our survey period. It took significantly longer for colorectal cancer patients to develop metastasis to the lungs (23.3 months) or to bone (21.2 months) than to the liver (9.8 months). Conclusion: Metastasis only to bone without other organ involvement in colorectal cancer patients is extremely rare, perhaps more rare than we previously thought. Our findings suggest that resistant metastasis to the lungs predicts potential disease progression to bone in the colorectal cancer population better than liver metastasis does

  20. Bone scan and serum CA 15-3 in bone metastasis in breast cancer

    International Nuclear Information System (INIS)

    Mendoza, G.; Cano, R.; Morales, R.; Guzman, C.

    1996-01-01

    CA 15-3 is a tumor marker useful in evolution control of breast cancer, being the serum levels trend the most important parameter. The purpose of this study was to report our experience and show the concordance of bone scan and CA 15-3 in patients with breast cancer attending the Breast and Bone Department of INEN from June to December 1993. One hundred patients had serum CA 15-3 quantification between June and December of 1993 in Nuclear Medicine Center (Peruvian Institute of Nuclear Energy and National Institute of Neoplasic Diseases). We selected 52 patients which simultaneously had a bone scan performed. Patients age ranged from 21 to 67 years (media of 44,57 years). 99m Tc methylenediphosphonate produced by IPEN was the radiopharmaceutical employed. A GE AZS-400 gamma camera was utilized to obtain the bone scans. Ca 15-5 quantification was performed with ELSA-CA 15-3 (CIS bio France) IRMA kit. Bone scan and CA 15-3 media of 17,06 U/ml (DS 15,4). Eight patients had a positive bone scan with a CA 15-3 media of 41,6 U/ml (SD 23,0). CA 15-3 levels ranged between 4,6 and 96,0 U/ml in the first group and 10,1 U/ml to 75,0 U/ml in the second group. Using a cut-off point of 30 U/ml the sensitivity of CA 15-3 was 62,5% and the specificity 93,2% respectively. Mean CA 15-3 values of the negative and positive bone scan groups were significantly different (p=0,0361). The high negative predictive value of CA 15-3 may help to establish which patients will benefit from bone scan procedure. (authors) 42 refs., 2 tabs

  1. Imaging Primary Prostate Cancer and Bone Metastasis

    National Research Council Canada - National Science Library

    Chen, Xiaoyuan

    2004-01-01

    ... and androgen independent prostate cancer xenografted mice. Specific Aims: (1) Design, synthesize, and characterize positrori emitting bombesin analogs, labeled with copper-64 or fluorine-I 8; (2...

  2. Comparative Tissue Proteomics of Microdissected Specimens Reveals Novel Candidate Biomarkers of Bladder Cancer*

    Science.gov (United States)

    Chen, Chien-Lun; Chung, Ting; Wu, Chih-Ching; Ng, Kwai-Fong; Yu, Jau-Song; Tsai, Cheng-Han; Chang, Yu-Sun; Liang, Ying; Tsui, Ke-Hung; Chen, Yi-Ting

    2015-01-01

    More than 380,000 new cases of bladder cancer are diagnosed worldwide, accounting for ∼150,200 deaths each year. To discover potential biomarkers of bladder cancer, we employed a strategy combining laser microdissection, isobaric tags for relative and absolute quantitation labeling, and liquid chromatography-tandem MS (LC-MS/MS) analysis to profile proteomic changes in fresh-frozen bladder tumor specimens. Cellular proteins from four pairs of surgically resected primary bladder cancer tumor and adjacent nontumorous tissue were extracted for use in two batches of isobaric tags for relative and absolute quantitation experiments, which identified a total of 3220 proteins. A DAVID (database for annotation, visualization and integrated discovery) analysis of dysregulated proteins revealed that the three top-ranking biological processes were extracellular matrix organization, extracellular structure organization, and oxidation-reduction. Biological processes including response to organic substances, response to metal ions, and response to inorganic substances were highlighted by up-expressed proteins in bladder cancer. Seven differentially expressed proteins were selected as potential bladder cancer biomarkers for further verification. Immunohistochemical analyses showed significantly elevated levels of three proteins—SLC3A2, STMN1, and TAGLN2—in tumor cells compared with noncancerous bladder epithelial cells, and suggested that TAGLN2 could be a useful tumor tissue marker for diagnosis (AUC = 0.999) and evaluating lymph node metastasis in bladder cancer patients. ELISA results revealed significantly increased urinary levels of both STMN1 and TAGLN2 in bladder cancer subgroups compared with control groups. In comparisons with age-matched hernia urine specimens, urinary TAGLN2 in bladder cancer samples showed the largest fold change (7.13-fold), with an area-under-the-curve value of 0.70 (p < 0.001, n = 205). Overall, TAGLN2 showed the most significant

  3. Quantitative Proteomic Analysis of Optimal Cutting Temperature (OCT) Embedded Core-Needle Biopsy of Lung Cancer

    Science.gov (United States)

    Zhao, Xiaozheng; Huffman, Kenneth E.; Fujimoto, Junya; Canales, Jamie Rodriguez; Girard, Luc; Nie, Guangjun; Heymach, John V.; Wistuba, Igacio I.; Minna, John D.; Yu, Yonghao

    2017-10-01

    With recent advances in understanding the genomic underpinnings and oncogenic drivers of pathogenesis in different subtypes, it is increasingly clear that proper pretreatment diagnostics are essential for the choice of appropriate treatment options for non-small cell lung cancer (NSCLC). Tumor tissue preservation in optimal cutting temperature (OCT) compound is commonly used in the surgical suite. However, proteins recovered from OCT-embedded specimens pose a challenge for LC-MS/MS experiments, due to the large amounts of polymers present in OCT. Here we present a simple workflow for whole proteome analysis of OCT-embedded NSCLC tissue samples, which involves a simple trichloroacetic acid precipitation step. Comparisons of protein recovery between frozen versus OCT-embedded tissue showed excellent consistency with more than 9200 proteins identified. Using an isobaric labeling strategy, we quantified more than 5400 proteins in tumor versus normal OCT-embedded core needle biopsy samples. Gene ontology analysis indicated that a number of proliferative as well as squamous cell carcinoma (SqCC) marker proteins were overexpressed in the tumor, consistent with the patient's pathology based diagnosis of "poorly differentiated SqCC". Among the most downregulated proteins in the tumor sample, we noted a number of proteins with potential immunomodulatory functions. Finally, interrogation of the aberrantly expressed proteins using a candidate approach and cross-referencing with publicly available databases led to the identification of potential druggable targets in DNA replication and DNA damage repair pathways. We conclude that our approach allows LC-MS/MS proteomic analyses on OCT-embedded lung cancer specimens, opening the way to bring powerful proteomics into the clinic. [Figure not available: see fulltext.

  4. Detection of bone metastasis of prostate cancer. Comparison of whole-body MRI and bone scintigraphy

    International Nuclear Information System (INIS)

    Ketelsen, D.; Roethke, M.; Aschoff, P.; Lichy, M.P.; Claussen, C.D.; Schlemmer, H.P.; Merseburger, A.S.; Reimold, M.

    2008-01-01

    Purpose: prostate cancer continues to be the third leading cancer-related mortality of western men. Early diagnosis of bone metastasis is important for the therapy regime and for assessing the prognosis. The standard method is bone scintigraphy. Whole-body MRI proved to be more sensitive for early detection of skeletal metastasis. However, studies of homogenous tumor entities are not available. The aim of the study was to compare bone scintigraphy and whole-body MRI regarding the detection of bone metastasis of prostate cancer. Materials and methods: 14 patients with histologically confirmed prostate cancer and a bone scintigraphy as well as whole-body MRI within one month were included. The mean age was 68 years. Scintigraphy was performed using the planar whole-body technique (ventral and dorsal projections). Suspect areas were enlarged. Whole-body MRI was conducted using native T1w and STIR sequences in the coronary plane of the whole body, sagittal imaging of spine and breath-hold STIR and T1w-Flash-2D sequences of ribs and chest. Bone scintigraphy and whole-body MRI were evaluated retrospectively by experienced radiologists in a consensus reading on a lesion-based level. Results: whole-body MRI detected significantly more bone metastasis (p = 0.024). 96.4% of the demonstrated skeletal metastases in bone scintigraphy were founded in whole-body MRI while only 58.6% of the depicted metastases in MRI were able to be located in scintigraphy. There was no significant difference regarding bone metastasis greater than one centimeter (p = 0.082) in contrast to metastasis less than one centimeter (p = 0.035). Small osteoblastic metastases showed a considerably higher contrast in T1w sequences than in STIR imaging. Further advantages of whole-body MRI were additional information about extra-osseous tumor infiltration and their complications, for example stenosis of spinal canal or vertebral body fractures, found in 42.9% of patients. (orig.)

  5. Detection of bone marrow involvement in patients with cancer

    International Nuclear Information System (INIS)

    Federico, M.; Silingardi, V.; Wright, R.M.

    1989-01-01

    Current methods for the study of bone marrow to evaluate possible primary or metastatic cancers are reviewed. Bone marrow biopsy, radionuclide scan, computed tomography and magnetic resonance imaging (MRI) are analyzed with regard to their clinical usefulness at the time of diagnosis and during the course of the disease. Bone marrow biopsy is still the examination of choice not only in hematologic malignancies but also for tumors that metastasize into the marrow. Radionuclide scans are indicated for screening for skeletal metastases, except for those from thyroid carcinoma and multiple myeloma. Computed tomography is useful for cortical bone evaluation. MRI shows a high sensitivity in finding occult sites of disease in the marrow but its use has been restricted by high cost and limited availability. However, the future of MRI in bone marrow evaluation seems assured. MRI is alredy the method of choice for diagnosis of multiple myeloma, when radiography is negative, and for quantitative evaluation of lymphoma when a crucial therapeutic decision (i.e. bone marrow transplantation) must be made. Finally, methods are being developed that will enhance the sensitivity and specificity of MRI studies of bone marrow

  6. The use of bone scintigraphy to establish cancer extension records: application to prostate and breast cancers

    International Nuclear Information System (INIS)

    Methlin, G.; Grob, J.C.; Moyses, B.; Deschler, J.M.; Ott, G.; Berthelen, B.

    1975-01-01

    The recent development of the technique described, especially in the systematic search for metastases was due to the introduction of stannous diphosphate complexed with sup(99m)Tc well suited to bone scintigraphy. The documents are obtained in two stages. First a whole-body scintigraph is taken by means of an omniview device fitted to a Picker dynacamera, and this scanning phase is followed immediately by static views centred mainly on abnormal or doubtful regions. The results are given for 136 breast cancers and 61 prostate cancers, two cancers particularly liable to affect the bone, and show that scintigraphy offers positive advantages over radiological investigations. These advantages are offset to some extent by the non-specific nature of the hyperfixing regions since different diseases involving changes in the bone structure can give similar images, but for breast and prostate cancers bone scintigraphy presents distinct possibilities in the search for metastases of the skeleton [fr

  7. Tumor markers and bone scan in breast cancer patients

    International Nuclear Information System (INIS)

    Ugrinska, A.; Vaskova, O.; Kraleva, S.; Petrova, D.; Smickova, S.

    2004-01-01

    Full text: The objective of this study was to compare the levels of CA15-3 and CEA with the bone scan findings in patients with breast cancer. Retrospective analysis of 76 bone scans from 61 patients diagnosed with breast cancer in the last 5 years was performed by two nuclear medicine specialists. All bone scans were performed after surgical treatment of the disease. Patients with loco-regional residual disease or distant metastases in the liver, lung or the brain were excluded from the study. According to the bone scan the patients were divided in 5 groups: normal bone scan (N), equivocal bone scan (E), single metastasis (1MS), three metastases (3MS) and multiple metastases (MMS). Tumor markers were determined within a month before or after the bone scan was performed. Cut-off value for CA 15-3 was 35 U/ml, and for CEA 3 ng/ml. Statistical analysis was performed using descriptive statistic and Kolmogorov-Smirnov test. Bone metastases were revealed in 38% of the patients referred for bone scintigraphy out of which 26% had MMS, 7.8% had single MS and 4% had 3MS. The results of 6.5% of the patients were determined as equivocal. The values of CA15-3 were higher in all patient groups compared with the group that had normal bone scan, but this difference reached statistical significance only in groups with 3MS and MMS (p < 0.01). The values of CEA were significantly higher only in patients with multiple metastases when compared with group N (p < 0.01). Values higher than cut-off value for CA 15-3 was found in 9 patients out of 42 in the group with normal bone scan. The highest value of CA 15-3 in this group was 47 U/ml. Only one patient in this group showed elevated levels for CEA. Three patients in the group with single metastasis had normal CA 15-3, while CEA was elevated only in one patient. All patients in the group with 3MS had elevated levels of CA 15-3 while CEA was in the normal range. All patients with MMS had elevated CA 15-3 values while CEA was elevated in

  8. Identification of BAG3 target proteins in anaplastic thyroid cancer cells by proteomic analysis.

    Science.gov (United States)

    Galdiero, Francesca; Bello, Anna Maria; Spina, Anna; Capiluongo, Anna; Liuu, Sophie; De Marco, Margot; Rosati, Alessandra; Capunzo, Mario; Napolitano, Maria; Vuttariello, Emilia; Monaco, Mario; Califano, Daniela; Turco, Maria Caterina; Chiappetta, Gennaro; Vinh, Joëlle; Chiappetta, Giovanni

    2018-01-30

    BAG3 protein is an apoptosis inhibitor and is highly expressed in Anaplastic Thyroid Cancer. We investigated the entire set of proteins modulated by BAG3 silencing in the human anaplastic thyroid 8505C cancer cells by using the Stable-Isotope Labeling by Amino acids in Cell culture strategy combined with mass spectrometry analysis. By this approach we identified 37 up-regulated and 54 down-regulated proteins in BAG3-silenced cells. Many of these proteins are reportedly involved in tumor progression, invasiveness and resistance to therapies. We focused our attention on an oncogenic protein, CAV1, and a tumor suppressor protein, SERPINB2, that had not previously been reported to be modulated by BAG3. Their expression levels in BAG3-silenced cells were confirmed by qRT-PCR and western blot analyses, disclosing two novel targets of BAG3 pro-tumor activity. We also examined the dataset of proteins obtained by the quantitative proteomics analysis using two tools, Downstream Effect Analysis and Upstream Regulator Analysis of the Ingenuity Pathways Analysis software. Our analyses confirm the association of the proteome profile observed in BAG3-silenced cells with an increase in cell survival and a decrease in cell proliferation and invasion, and highlight the possible involvement of four tumor suppressor miRNAs and TP53/63 proteins in BAG3 activity.

  9. The Present and Future of Biomarkers in Prostate Cancer: Proteomics, Genomics, and Immunology Advancements

    Directory of Open Access Journals (Sweden)

    Pierre-Olivier Gaudreau

    2016-01-01

    Full Text Available Prostate cancer (PC is the second most common form of cancer in men worldwide. Biomarkers have emerged as essential tools for treatment and assessment since the variability of disease behavior, the cost and diversity of treatments, and the related impairment of quality of life have given rise to a need for a personalized approach. High-throughput technology platforms in proteomics and genomics have accelerated the development of biomarkers. Furthermore, recent successes of several new agents in PC, including immunotherapy, have stimulated the search for predictors of response and resistance and have improved the understanding of the biological mechanisms at work. This review provides an overview of currently established biomarkers in PC, as well as a selection of the most promising biomarkers within these particular fields of development.

  10. Global proteomics profiling improves drug sensitivity prediction: results from a multi-omics, pan-cancer modeling approach.

    Science.gov (United States)

    Ali, Mehreen; Khan, Suleiman A; Wennerberg, Krister; Aittokallio, Tero

    2018-04-15

    Proteomics profiling is increasingly being used for molecular stratification of cancer patients and cell-line panels. However, systematic assessment of the predictive power of large-scale proteomic technologies across various drug classes and cancer types is currently lacking. To that end, we carried out the first pan-cancer, multi-omics comparative analysis of the relative performance of two proteomic technologies, targeted reverse phase protein array (RPPA) and global mass spectrometry (MS), in terms of their accuracy for predicting the sensitivity of cancer cells to both cytotoxic chemotherapeutics and molecularly targeted anticancer compounds. Our results in two cell-line panels demonstrate how MS profiling improves drug response predictions beyond that of the RPPA or the other omics profiles when used alone. However, frequent missing MS data values complicate its use in predictive modeling and required additional filtering, such as focusing on completely measured or known oncoproteins, to obtain maximal predictive performance. Rather strikingly, the two proteomics profiles provided complementary predictive signal both for the cytotoxic and targeted compounds. Further, information about the cellular-abundance of primary target proteins was found critical for predicting the response of targeted compounds, although the non-target features also contributed significantly to the predictive power. The clinical relevance of the selected protein markers was confirmed in cancer patient data. These results provide novel insights into the relative performance and optimal use of the widely applied proteomic technologies, MS and RPPA, which should prove useful in translational applications, such as defining the best combination of omics technologies and marker panels for understanding and predicting drug sensitivities in cancer patients. Processed datasets, R as well as Matlab implementations of the methods are available at https://github.com/mehr-een/bemkl-rbps. mehreen

  11. Rodriguez Recognized as Recipient of the MSSS AACC Chair’s Inspirational Award | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Dr. Henry Rodriguez, director of the Office of Cancer Clinical Proteomics Research, has been recognized as the recipient of the Chair’s Inspirational Award by the Mass Spectrometry and Separation Sciences for Laboratory Medicine Division (MSSS), American Association for Clinical Chemistry (AACC).

  12. Integrative Analysis of Subcellular Quantitative Proteomics Studies Reveals Functional Cytoskeleton Membrane-Lipid Raft Interactions in Cancer.

    Science.gov (United States)

    Shah, Anup D; Inder, Kerry L; Shah, Alok K; Cristino, Alexandre S; McKie, Arthur B; Gabra, Hani; Davis, Melissa J; Hill, Michelle M

    2016-10-07

    Lipid rafts are dynamic membrane microdomains that orchestrate molecular interactions and are implicated in cancer development. To understand the functions of lipid rafts in cancer, we performed an integrated analysis of quantitative lipid raft proteomics data sets modeling progression in breast cancer, melanoma, and renal cell carcinoma. This analysis revealed that cancer development is associated with increased membrane raft-cytoskeleton interactions, with ∼40% of elevated lipid raft proteins being cytoskeletal components. Previous studies suggest a potential functional role for the raft-cytoskeleton in the action of the putative tumor suppressors PTRF/Cavin-1 and Merlin. To extend the observation, we examined lipid raft proteome modulation by an unrelated tumor suppressor opioid binding protein cell-adhesion molecule (OPCML) in ovarian cancer SKOV3 cells. In agreement with the other model systems, quantitative proteomics revealed that 39% of OPCML-depleted lipid raft proteins are cytoskeletal components, with microfilaments and intermediate filaments specifically down-regulated. Furthermore, protein-protein interaction network and simulation analysis showed significantly higher interactions among cancer raft proteins compared with general human raft proteins. Collectively, these results suggest increased cytoskeleton-mediated stabilization of lipid raft domains with greater molecular interactions as a common, functional, and reversible feature of cancer cells.

  13. Proteomic analysis of a pleistocene mammoth femur reveals more than one hundred ancient bone proteins

    DEFF Research Database (Denmark)

    Cappellini, Enrico; Jensen, Lars Juhl; Szklarczyk, Damian Milosz

    2012-01-01

    We used high-sensitivity, high-resolution tandem mass spectrometry to shotgun sequence ancient protein remains extracted from a 43 000 year old woolly mammoth (Mammuthus primigenius) bone preserved in the Siberian permafrost. For the first time, 126 unique protein accessions, mostly low-abundance......We used high-sensitivity, high-resolution tandem mass spectrometry to shotgun sequence ancient protein remains extracted from a 43 000 year old woolly mammoth (Mammuthus primigenius) bone preserved in the Siberian permafrost. For the first time, 126 unique protein accessions, mostly low......-abundance extracellular matrix and plasma proteins, were confidently identified by solid molecular evidence. Among the best characterized was the carrier protein serum albumin, presenting two single amino acid substitutions compared to extant African (Loxodonta africana) and Indian (Elephas maximus) elephants. Strong...

  14. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error.

    Science.gov (United States)

    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M; Berman, D M; Blume-Jensen, P

    2014-09-09

    Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Prostatectomy samples from a large patient cohort with long follow-up were blindly assessed by expert pathologists who identified the tissue regions with the highest and lowest Gleason grade from each patient. To simulate biopsy-sampling error, a core from a high- and a low-Gleason area from each patient sample was used to generate a 'high' and a 'low' tumour microarray, respectively. Using a quantitative proteomics approach, we identified from 160 candidates 12 biomarkers that predicted prostate cancer aggressiveness (surgical Gleason and TNM stage) and lethal outcome robustly in both high- and low-Gleason areas. Conversely, a previously reported lethal outcome-predictive marker signature for prostatectomy tissue was unable to perform under circumstances of maximal sampling error. Our results have important implications for cancer biomarker discovery in general and development of a sampling error-resistant clinical biopsy test for prediction of prostate cancer aggressiveness.

  15. How MMPs Impact Bone Responses to Metastatic Prostate Cancer

    Science.gov (United States)

    2011-04-30

    bone metabolism. J Biol Chem 2006;281:33814–24. 28. Wilson TJ, Nannuru KC, Singh RK. Cathepsin G-mediated activation of pro-matrix metalloproteinase 9...male mice. Nat Genet 2003;35:252–7. [47] Lynch CC, Hikosaka A, Acuff HB, Martin MD, Kawai N, Singh RK, et al. MMP-7 promotes prostate cancer-induced...described (15). A luciferase tagged 4T1 mammary tumor cell line (16) was kindly provided by Dr. Swati Biswas of Vanderbilt Center for Bone Biology. All

  16. Prevalence of bone marrow necrosis in Egyptian cancer patients referring to the National Cancer Institute

    International Nuclear Information System (INIS)

    Elgamal, B.M.; Rashed, R.A.; Raslan, H.N.

    2011-01-01

    Bone marrow necrosis; Egyptian cancer patients Abstract Background: Bone marrow necrosis is a relatively rare entity which has been associated with a poor prognosis. It is most commonly found in patients with neoplastic disorders and severe infections. Methods: study comprised examination of 5043 bone marrow biopsy specimens performed at the National Cancer Institute, Cairo University, over 7 years period (March 2004-March 2011). It included 5 years retrospective (2867 archived samples) and 2 years prospective (2176 samples). Results: Bone marrow necrosis was diagnosed in fifteen out of 5043 examined specimens with a percentage of 0.3% and ranged from mild to massive according to semiquantitative estimation. Prognosis of all patients was poor with survival not exceeding 6 months from the date of marrow necrosis diagnosis. Conclusion: In Egyptian patients, bone marrow necrosis in association with malignancy is a rare disorder which is accompanied by a poor outcome

  17. Proteomic and transcriptomic profiling of in vitro established radiation resistant oral cancer cells for identification of radioresistance related biomarkers

    International Nuclear Information System (INIS)

    Mohd Yasser; Pawar, Sagar; Teni, Tanuja

    2016-01-01

    Radiotherapy is an integral part of oral cancer treatment, either alone or in combination with surgery. But, during radiotherapy, oral tumours of a subset of patients develop radioresistance that creates major obstruction towards its efficacy. The aim of our study was to establish radioresistant cell lines from different oral subsites using clinically admissible low dose radiation and profile them by proteomic and transcriptomic approaches to identify proteins associated with radioresistance in oral cancer

  18. NCI Releases Video: Proteogenomics Research - On the Frontier of Precision Medicine | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The Clinical Proteomic Tumor Analysis Consortium (CPTAC) of the National Cancer Institute (NCI), part of the National Institutes of Health, announces the release of an educational video titled “Proteogenomics Research: On the Frontier of Precision Medicine."  Launched at the HUPO2017 Global Leadership Gala Dinner, catalyzed in part by the Cancer Moonshot initiative and featuring as keynote speaker the 47th Vice President of the United States of America Joseph R.

  19. Proteomics analysis of human breast milk to assess breast cancer risk.

    Science.gov (United States)

    Aslebagh, Roshanak; Channaveerappa, Devika; Arcaro, Kathleen F; Darie, Costel C

    2018-02-01

    Detection of breast cancer (BC) in young women is challenging because mammography, the most common tool for detecting BC, is not effective on the dense breast tissue characteristic of young women. In addition to the limited means for detecting their BC, young women face a transient increased risk of pregnancy-associated BC. As a consequence, reproductively active women could benefit significantly from a tool that provides them with accurate risk assessment and early detection of BC. One potential method for detection of BC is biochemical monitoring of proteins and other molecules in bodily fluids such as serum, nipple aspirate, ductal lavage, tear, urine, saliva and breast milk. Of all these fluids, only breast milk provides access to a large volume of breast tissue, in the form of exfoliated epithelial cells, and to the local breast environment, in the form of molecules in the milk. Thus, analysis of breast milk is a non-invasive method with significant potential for assessing BC risk. Here we analyzed human breast milk by mass spectrometry (MS)-based proteomics to build a biomarker signature for early detection of BC. Ten milk samples from eight women provided five paired-groups (cancer versus control) for analysis of dysregulatedproteins: two within woman comparisons (milk from a diseased breast versus a healthy breast of the same woman) and three across women comparisons (milk from a woman with cancer versus a woman without cancer). Despite a wide range in the time between milk donation and cancer diagnosis (cancer diagnosis occurred from 1 month before to 24 months after milk donation), the levels of some proteins differed significantly between cancer and control in several of the five comparison groups. These pilot data are supportive of the idea that molecular analysis of breast milk will identify proteins informative for early detection and accurate assessment of BC risk, and warrant further research. Data are available via ProteomeXchange with identifier

  20. Application of serum SELDI proteomic patterns in diagnosis of lung cancer

    International Nuclear Information System (INIS)

    Yang, Shuan-ying; Xiao, Xue-yuan; Zhang, Wang-gang; Zhang, Li-juan; Zhang, Wei; Zhou, Bin; Chen, Guoan; He, Da-cheng

    2005-01-01

    Currently, no satisfactory biomarkers are available to screen for lung cancer. Surface-Enhanced Laser Desorption/ionization Time-of- Flight Mass Spectrometry ProteinChip system (SELDI-TOF-MS) is one of the currently used techniques to identify biomarkers for cancers. The aim of this study is to explore the application of serum SELDI proteomic patterns to distinguish lung cancer patients from healthy individuals. A total of 208 serum samples, including 158 lung cancer patients and 50 healthy individuals, were randomly divided into a training set (including 11 sera from patients with stages I/II lung cancer, 63 from patients with stages III/IV lung cancer and 20 from healthy controls) and a blinded test set (including 43 sera from patients with stages I/II lung cancer, 41 from patients with stages III/IV lung cancer and 30 from healthy controls). All samples were analyzed by SELDI technology. The spectra were generated on weak cation exchange (WCX2) chips, and protein peaks clustering and classification analyses were made using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. We additionally determined Cyfra21-1 and NSE in the 208 serum samples included in this study using an electrochemiluminescent immunoassay. Five protein peaks at 11493, 6429, 8245, 5335 and 2538 Da were automatically chosen as a biomarker pattern in the training set. When the SELDI marker pattern was tested with the blinded test set, it yielded a sensitivity of 86.9%, a specificity of 80.0% and a positive predictive value of 92.4%. The sensitivities provided by Cyfra21-1 and NSE used individually or in combination were significantly lower than that of the SELDI marker pattern (P < 0.005 or 0.05, respectively). Based on the results of the test set, we found that the SELDI marker pattern showed a sensitivity of 91.4% in the detection of non-small cell lung cancers (NSCLC), which was significantly higher than that in the detection of small cell lung cancers (P < 0.05); The

  1. Integrative proteomics and tissue microarray profiling indicate the association between overexpressed serum proteins and non-small cell lung cancer.

    Directory of Open Access Journals (Sweden)

    Yansheng Liu

    Full Text Available Lung cancer is the leading cause of cancer deaths worldwide. Clinically, the treatment of non-small cell lung cancer (NSCLC can be improved by the early detection and risk screening among population. To meet this need, here we describe the application of extensive peptide level fractionation coupled with label free quantitative proteomics for the discovery of potential serum biomarkers for lung cancer, and the usage of Tissue microarray analysis (TMA and Multiple reaction monitoring (MRM assays for the following up validations in the verification phase. Using these state-of-art, currently available clinical proteomic approaches, in the discovery phase we confidently identified 647 serum proteins, and 101 proteins showed a statistically significant association with NSCLC in our 18 discovery samples. This serum proteomic dataset allowed us to discern the differential patterns and abnormal biological processes in the lung cancer blood. Of these proteins, Alpha-1B-glycoprotein (A1BG and Leucine-rich alpha-2-glycoprotein (LRG1, two plasma glycoproteins with previously unknown function were selected as examples for which TMA and MRM verification were performed in a large sample set consisting about 100 patients. We revealed that A1BG and LRG1 were overexpressed in both the blood level and tumor sections, which can be referred to separate lung cancer patients from healthy cases.

  2. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    Directory of Open Access Journals (Sweden)

    David Britton

    Full Text Available LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application.Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12, were labelled with tandem mass tags (TMT 8-plex, separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset.Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1, but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites, 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold in different cases highlighting their predictive power.Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  3. Quantification of pancreatic cancer proteome and phosphorylome: indicates molecular events likely contributing to cancer and activity of drug targets.

    Science.gov (United States)

    Britton, David; Zen, Yoh; Quaglia, Alberto; Selzer, Stefan; Mitra, Vikram; Löβner, Christopher; Jung, Stephan; Böhm, Gitte; Schmid, Peter; Prefot, Petra; Hoehle, Claudia; Koncarevic, Sasa; Gee, Julia; Nicholson, Robert; Ward, Malcolm; Castellano, Leandro; Stebbing, Justin; Zucht, Hans Dieter; Sarker, Debashis; Heaton, Nigel; Pike, Ian

    2014-01-01

    LC-MS/MS phospho-proteomics is an essential technology to help unravel the complex molecular events that lead to and propagate cancer. We have developed a global phospho-proteomic workflow to determine activity of signaling pathways and drug targets in pancreatic cancer tissue for clinical application. Peptides resulting from tryptic digestion of proteins extracted from frozen tissue of pancreatic ductal adenocarcinoma and background pancreas (n = 12), were labelled with tandem mass tags (TMT 8-plex), separated by strong cation exchange chromatography, then were analysed by LC-MS/MS directly or first enriched for phosphopeptides using IMAC and TiO2, prior to analysis. In-house, commercial and freeware bioinformatic platforms were used to identify relevant biological events from the complex dataset. Of 2,101 proteins identified, 152 demonstrated significant difference in abundance between tumor and non-tumor tissue. They included proteins that are known to be up-regulated in pancreatic cancer (e.g. Mucin-1), but the majority were new candidate markers such as HIPK1 & MLCK. Of the 6,543 unique phosphopeptides identified (6,284 unique phosphorylation sites), 635 showed significant regulation, particularly those from proteins involved in cell migration (Rho guanine nucleotide exchange factors & MRCKα) and formation of focal adhesions. Activator phosphorylation sites on FYN, AKT1, ERK2, HDAC1 and other drug targets were found to be highly modulated (≥2 fold) in different cases highlighting their predictive power. Here we provided critical information enabling us to identify the common and unique molecular events likely contributing to cancer in each case. Such information may be used to help predict more bespoke therapy suitable for an individual case.

  4. The usefulness of measurement of whole body count in assessing bone marrow metastasis in cancer patients with increased periarticular bone uptake on follow-up bone scan: a comparison with bone marrow scan

    International Nuclear Information System (INIS)

    Jin, Seong Chan; Choi, Yun Young; Cho, Suk Shin

    2003-01-01

    Increased periarticular uptake could be associated with peripheral bone marrow expansion in cancer patients with axial bone marrow metastasis. We compared bone scan and bone marrow scan to investigate whether the increased whole body count in patients with increased periarticular uptake on bone scan is useful in the diagnosis of axial marrow metastasis, and evaluate the role of additional bone marrow scan in these cases. Twelve patients with malignant diseases who showed increased periarticular uptake on bone scan were included. Whole body count was measured on bone scan and it is considered to be increased when the count is more than twice of other patients. Bone marrow scan was taken within 3-7 days. Five hematologic malignancy, 3 stomach cancer, 2 breast cancer, 1 prostate cancer and 1 lung canner were included. All three patients with increased whole body count on bone scan showed axial marrow suppression and peripheral marrow expansion. Eight of 9 patients without increased whole body count showed axial marrow suppression and peripheral marrow expansion. One turned out to be blastic crisis of chronic myelogeneous leukemia, and seven showed normal axial marrow with peripheral marrow expansion in chronic anemia of malignancy. The last one without increased whole body count showed normal bone marrow scan finding. Increased whole body count on bone scan could be a clue to axial bone marrow metastasis in cancer patients with increased periarticular uptake, and bone marrow scan is a valuable method for differential diagnosis in these cases

  5. The Bone Marrow Transplantation Center of the National Cancer Institute - its resources to assist patients with bone marrow failure

    International Nuclear Information System (INIS)

    Tabak, Daniel

    1997-01-01

    This paper describes the bone marrow transplantation center of the brazilian National Cancer Institute, which is responsible for the cancer control in Brazil. The document also describes the resources available in the Institute for assisting patients presenting bone marrow failures. The Center provides for allogeneic and autologous bone marrow transplants, peripheral stem cell transplants, umbilical cord collections and transplants, and a small experience with unrelated bone marrow transplants. The Center receives patient from all over the country and provides very sophisticated medical care at no direct cost to the patients

  6. SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

    Directory of Open Access Journals (Sweden)

    S. V. Kostritsky

    2014-07-01

    Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

  7. SURGICAL TREATMENT FOR KIDNEY CANCER METASTASES TO THE LONG TUBULAR BONES

    Directory of Open Access Journals (Sweden)

    S. V. Kostritsky

    2013-01-01

    Full Text Available The data of 35 kidney cancer patients with metastases in long bones, who had been operated, were retrospectively analyzed. The role of surgery in patients with long bones metastases of kidney cancer was assessed and application of surgical treatment was ascertained to yield satisfactory results in improving the quality of life and duration of life in patients with solitary bone metastases.

  8. Paracrine interactions between LNCaP prostate cancer cells and bioengineered bone in 3D in vitro culture reflect molecular changes during bone metastasis.

    Science.gov (United States)

    Sieh, Shirly; Taubenberger, Anna V; Lehman, Melanie L; Clements, Judith A; Nelson, Colleen C; Hutmacher, Dietmar W

    2014-06-01

    As microenvironmental factors such as three-dimensionality and cell-matrix interactions are increasingly being acknowledged by cancer biologists, more complex 3D in vitro models are being developed to study tumorigenesis and cancer progression. To better understand the pathophysiology of bone metastasis, we have established and validated a 3D indirect co-culture model to investigate the paracrine interactions between prostate cancer (PCa) cells and human osteoblasts. Co-culture of the human PCa, LNCaP cells embedded within polyethylene glycol hydrogels with human osteoblasts in the form of a tissue engineered bone construct (TEB), resulted in reduced proliferation of LNCaP cells. LNCaP cells in both monoculture and co-culture were responsive to the androgen analog, R1881, as indicated by an increase in the expression (mRNA and/or protein induction) of androgen-regulated genes including prostate specific antigen and fatty acid synthase. Microarray gene expression analysis further revealed an up-regulation of bone markers and other genes associated with skeletal and vasculature development and a significant activation of transforming growth factor β1 downstream genes in LNCaP cells after co-culture with TEB. LNCaP cells co-cultured with TEB also unexpectedly showed similar changes in classical androgen-responsive genes under androgen-deprived conditions not seen in LNCaP monocultures. The molecular changes of LNCaP cells after co-culturing with TEBs suggest that osteoblasts exert a paracrine effect that may promote osteomimicry and modulate the expression of androgen-responsive genes in LNCaP cells. Taken together, we have presented a novel 3D in vitro model that allows the study of cellular and molecular changes occurring in PCa cells and osteoblasts that are relevant to metastatic colonization of bone. This unique in vitro model could also facilitate cancer biologists to dissect specific biological hypotheses via extensive genomic or proteomic assessments to

  9. Label free quantitative proteomics analysis on the cisplatin resistance in ovarian cancer cells.

    Science.gov (United States)

    Wang, F; Zhu, Y; Fang, S; Li, S; Liu, S

    2017-05-20

    Quantitative proteomics has been made great progress in recent years. Label free quantitative proteomics analysis based on the mass spectrometry is widely used. Using this technique, we determined the differentially expressed proteins in the cisplatin-sensitive ovarian cancer cells COC1 and cisplatin-resistant cells COC1/DDP before and after the application of cisplatin. Using the GO analysis, we classified those proteins into different subgroups bases on their cellular component, biological process, and molecular function. We also used KEGG pathway analysis to determine the key signal pathways that those proteins were involved in. There are 710 differential proteins between COC1 and COC1/DDP cells, 783 between COC1 and COC1/DDP cells treated with cisplatin, 917 between the COC1/DDP cells and COC1/DDP cells treated with LaCl3, 775 between COC1/DDP cells treated with cisplatin and COC1/DDP cells treated with cisplatin and LaCl3. Among the same 411 differentially expressed proteins in cisplatin-sensitive COC1 cells and cisplain-resistant COC1/DDP cells before and after cisplatin treatment, 14% of them were localized on the cell membrane. According to the KEGG results, differentially expressed proteins were classified into 21 groups. The most abundant proteins were involved in spliceosome. This study lays a foundation for deciphering the mechanism for drug resistance in ovarian tumor.

  10. Comparison of FDG-PET/CT and bone scintigraphy for detection of bone metastases in breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    Hahn, Steffen; Heusner, Till; Forsting, Michael; Antoch, Gerald (Dept. of Diagnostic and Interventional Radiology and Neuroradiology, Univ. Hospital Essen, Univ. Duisburg-Essen, Essen (Germany)), email: steffen.hahn@uk-essen.de; Kuemmel, Sherko; Koeninger, Angelika (Dept. of Gynecology and Obstetrics, Univ. Hospital Essen, Univ. Duisburg-Essen, Essen (Germany)); Nagarajah, James; Mueller, Stefan; Boy, Christian; Bockisch, Andreas; Stahl, Alexander (Dept. of Nuclear Medicine, Univ. Hospital Essen, Univ. Duisburg-Essen, Essen (Germany))

    2011-11-15

    Background Bone scintigraphy is the standard procedure for the detection of bone metastases in breast cancer patients. FDG-PET/CT has been reported to be a sensitive tool for tumor staging in different malignant diseases. However, its accuracy for the detection of bone metastases has not been compared to bone scintigraphy. Purpose To compare whole-body FDG-PET/CT and bone scintigraphy for the detection of bone metastases on a lesion basis in breast cancer patients. Material and Methods Twenty-nine consecutive women (mean age 58 years, range 35-78 years) with histologically proven breast cancer were assessed with bone scintigraphy and whole-body FDG-PET/CT. Twenty-one patients (72%) were suffering from primary breast cancer and eight patients (28%) were in aftercare with a history of advanced breast cancer. Both imaging procedures were assessed for bone metastases by a radiologist and a nuclear medicine physician. Concordant readings between bone scintigraphy and FDG-PET/CT were taken as true. Discordant readings were verified with additional MRI imaging in all patients and follow-up studies in most patients. Results A total of 132 lesions were detected on bone scintigraphy, FDG-PET/CT or both. According to the reference standard, 70/132 lesions (53%) were bone metastases, 59/132 lesions (45%) were benign, and three lesions (2%) remained unclear. The sensitivity of bone scintigraphy was 76% (53/70) compared to 96% (67/70) for FDG-PET/CT. The specificity of bone scintigraphy and FDG-PET/CT was 95% (56/59) and 92% (54/59), respectively. According to the reference standard bone metastases were present in eight out of the 29 patients (28%), whereas 20 patients (69%) were free of bone metastases. One (3%) patient had inconclusive readings on both modalities as well as on MRI and follow-up studies. Bone scintigraphy and FDG-PET/CT correctly identified seven out of eight patients with bone metastases and 20 out of 20 patients free of metastases. Conclusion On a lesion

  11. Prospective study of bone metastasis from prostate cancer: comparison between large field diffusion-weighted imaging and bone scintigraphy

    International Nuclear Information System (INIS)

    Wang Xiaoying; Zhang Chunyan; Jiang Xuexiang

    2009-01-01

    Objective: To evaluate the large field diffusion weighted imaging (DWI) (from head vertex to lower leg) in detection of bone metastases from prostate cancer. Methods: One hundred and sixty- six consecutive patients who were suspected of prostate cancer received pelvic MRI and large field diffusion weighted imaging examination. Forty-nine of them underwent bone scintigraphy within one month of the examination of large field DWI. The images were double-blindly evaluated without the knowledge of the pathology result. Conventional MR T 1 and fat saturation T 2 weighted images were taken as standard for the diagnosis of bone metastasis. The sensitivity, specificity, and area under curve between large field DWI and bone scintigraphy were compared with McNemar test. Five patients with bone metastases exceeding 10 per patient were excluded in the lesion-by-lesion analysis. Results: Ten of the 49 patients were diagnosed as bone metastases. The diagnosis of bone metastasis were made in 15 patients by large field DWI and in 17 patients by bone scintigraphy. With patient number as study units (n=49), the diagnostic sensitivity of bone metastases with large field DWI and bone metastases were both 100% (10/10), and specificity were 87.2% (34/39) vs. 82.1% (32/39), respectively. ROC study showed the area under curve (AUC) of large field DWI and bone scintigraphy were 0.936 vs. 0.910, respectively. Totally 68 abnormal foci were identified from large field DWI and/or bone scintigraphy in 44 patients (while 5 patients with bone metastases exceeding 10 foci per patient were excluded), 20 of them were diagnosed as foci of bone metastasis. The diagnosis of bone metastases was made in 23 foci by large field DWI and in 34 by bone scintigraphy. With lesion numbers as study units (n=68), the diagnostic sensitivity of large field DWI and bone scintigraphy were both 90.0% (18/20), and specificity were 89.6% (43/48) vs. 66.7% (32/48), respectively. ROC study showed the area under curve of

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

    International Nuclear Information System (INIS)

    Aizawa, Taku

    1996-01-01

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

  13. Plasma membrane proteomic analysis of human Gastric Cancer tissues: revealing flotillin 1 as a marker for Gastric Cancer

    International Nuclear Information System (INIS)

    Gao, Wen; Xu, Jing; Wang, Fuqiang; Zhang, Long; Peng, Rui; Shu, Yongqian; Wu, Jindao; Tang, Qiyun; Zhu, Yunxia

    2015-01-01

    Gastric cancer remains the second leading cause of cancer-related deaths in the world. Successful early gastric cancer detection is hampered by lack of highly sensitive and specific biomarkers. Plasma membrane proteins participate and/or have a central role in the metastatic process of cancer cells and are potentially useful for cancer therapy due to easy accessibility of the targets. In the present research, TMT method followed by mass spectrometry analysis was used to compare the relative expression levels of plasma membrane proteins between noncancer and gastric cancer tissues. Of a total data set that included 501 identified proteins, about 35% of the identified proteins were found to be plasma membrane and associated proteins. Among them, 82 proteins were at least 1.5-fold up- or down-regulated in gastric cancer compared with the adherent normal tissues. A number of markers (e.g. annexin A6, caveolin 1, epidermal growth factor receptor, integrin beta 4) were previously reported as biomarkers of GC. Additionally, several potential biomarkers participated in endocytosis pathway and integrin signaling pathways were firstly identified as differentially expressed proteins in GC samples. Our findings also supported the notion that flotillin 1 is a potential biomarker that could be exploited for molecular imaging-based detection of gastric cancer. Together, the results show that subcellular proteomics of tumor tissue is a feasible and promising avenue for exploring oncogenesis. The online version of this article (doi:10.1186/s12885-015-1343-5) contains supplementary material, which is available to authorized users

  14. The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

    International Nuclear Information System (INIS)

    Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi

    1994-01-01

    Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of 99m Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, γ-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author)

  15. The usefulness of early whole body bone scintigraphy in the detection of bone metastasis from prostatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Nobuaki; Fukunaga, Masao; Furukawa, Yohji; Tanaka, Hiroyoshi [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1994-06-01

    Early whole body bone scintigraphy was performed on 25 patients with prostatic cancer (15 cases with bone metastases and 10 cases without bone metastasis) to obtain anterior and posterior whole body images five minutes after administration of [sup 99m]Tc-hydroxymethylene diphosphonate(HMDP). The results were compared with the findings of routine bone scintigraphy after three hours, and the usefulness of the above method for the diagnosis of bone metastasis from prostatic cancer was evaluated. In cases in which increased activity was found in the upper and lower lumbar vertebrae by routine bone scintigraphy but no abnormality was seen by early whole body bone scintigraphy, senile degenerative bone changes such as spondylosis deformance were observed by bone radiography. In cases with multiple bone metastases, abnormal multiple accumulations were found by both early whole body bone scintigraphy and routine bone scintigraphy. In addition, in cases showing super bone scan, high accumulation in the skeletal system had already been detected by early whole body bone scintigraphy. When the courses before and after treatment in nine cases of multiple bone metastases were passaged from the results of early whole body bone scintigraphy and from changes in tumor markers (prostatic specific antigen, [gamma]-semino protein and prostatic acid phosphatase), increased activity and the appearance of new hot spots as well as an increase in tumor markers were detected by early whole body scintigraphy in three of the four advanced cases, whereas decreased accumulations and a decrease in and normalization of tumor markers were observed in five improved cases. (author).

  16. Stimulation of host bone marrow stromal cells by sympathetic nerves promotes breast cancer bone metastasis in mice.

    Directory of Open Access Journals (Sweden)

    J Preston Campbell

    2012-07-01

    Full Text Available Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depression, promotes MDA-231 breast cancer cell colonization of bone via a neurohormonal effect on the host bone marrow stroma. We demonstrate that induction of RANKL expression in bone marrow osteoblasts, following β2AR stimulation, increases the migration of metastatic MDA-231 cells in vitro, independently of SDF1-CXCR4 signaling. We also show that the stimulatory effect of endogenous (chronic stress or pharmacologic sympathetic activation on breast cancer bone metastasis in vivo can be blocked with the β-blocker propranolol, and by knockdown of RANK expression in MDA-231 cells. These findings indicate that RANKL promotes breast cancer cell metastasis to bone via its pro-migratory effect on breast cancer cells, independently of its effect on bone turnover. The emerging clinical implication, supported by recent epidemiological studies, is that βAR-blockers and drugs interfering with RANKL signaling, such as Denosumab, could increase patient survival if used as adjuvant therapy to inhibit both the early colonization of bone by metastatic breast cancer cells and the initiation of the "vicious cycle" of bone destruction induced by these cells.

  17. Constructing Support Vector Machine Ensembles for Cancer Classification Based on Proteomic Profiling

    Institute of Scientific and Technical Information of China (English)

    Yong Mao; Xiao-Bo Zhou; Dao-Ying Pi; You-Xian Sun

    2005-01-01

    In this study, we present a constructive algorithm for training cooperative support vector machine ensembles (CSVMEs). CSVME combines ensemble architecture design with cooperative training for individual SVMs in ensembles. Unlike most previous studies on training ensembles, CSVME puts emphasis on both accuracy and collaboration among individual SVMs in an ensemble. A group of SVMs selected on the basis of recursive classifier elimination is used in CSVME, and the number of the individual SVMs selected to construct CSVME is determined by 10-fold cross-validation. This kind of SVME has been tested on two ovarian cancer datasets previously obtained by proteomic mass spectrometry. By combining several individual SVMs, the proposed method achieves better performance than the SVME of all base SVMs.

  18. Proteomic investigation into betulinic acid-induced apoptosis of human cervical cancer HeLa cells.

    Science.gov (United States)

    Xu, Tao; Pang, Qiuying; Zhou, Dong; Zhang, Aiqin; Luo, Shaman; Wang, Yang; Yan, Xiufeng

    2014-01-01

    Betulinic acid is a pentacyclic triterpenoid that exhibits anticancer functions in human cancer cells. This study provides evidence that betulinic acid is highly effective against the human cervical cancer cell line HeLa by inducing dose- and time-dependent apoptosis. The apoptotic process was further investigated using a proteomics approach to reveal protein expression changes in HeLa cells following betulinic acid treatment. Proteomic analysis revealed that there were six up- and thirty down-regulated proteins in betulinic acid-induced HeLa cells, and these proteins were then subjected to functional pathway analysis using multiple analysis software. UDP-glucose 6-dehydrogenase, 6-phosphogluconate dehydrogenase decarboxylating, chain A Horf6-a novel human peroxidase enzyme that involved in redox process, was found to be down-regulated during the apoptosis process of the oxidative stress response pathway. Consistent with our results at the protein level, an increase in intracellular reactive oxygen species was observed in betulinic acid-treated cells. The proteins glucose-regulated protein and cargo-selection protein TIP47, which are involved in the endoplasmic reticulum pathway, were up-regulated by betulinic acid treatment. Meanwhile, 14-3-3 family proteins, including 14-3-3β and 14-3-3ε, were down-regulated in response to betulinic acid treatment, which is consistent with the decrease in expression of the target genes 14-3-3β and 14-3-3ε. Furthermore, it was found that the antiapoptotic bcl-2 gene was down-regulated while the proapoptotic bax gene was up-regulated after betulinic acid treatment in HeLa cells. These results suggest that betulinic acid induces apoptosis of HeLa cells by triggering both the endoplasmic reticulum pathway and the ROS-mediated mitochondrial pathway.

  19. A 3D printed nano bone matrix for characterization of breast cancer cell and osteoblast interactions

    Science.gov (United States)

    Zhu, Wei; Castro, Nathan J.; Cui, Haitao; Zhou, Xuan; Boualam, Benchaa; McGrane, Robert; Glazer, Robert I.; Zhang, Lijie Grace

    2016-08-01

    Bone metastasis is one of the most prevalent complications of late-stage breast cancer, in which the native bone matrix components, including osteoblasts, are intimately involved in tumor progression. The development of a successful in vitro model would greatly facilitate understanding the underlying mechanism of breast cancer bone invasion as well as provide a tool for effective discovery of novel therapeutic strategies. In the current study, we fabricated a series of in vitro bone matrices composed of a polyethylene glycol hydrogel and nanocrystalline hydroxyapatite of varying concentrations to mimic the native bone microenvironment for the investigation of breast cancer bone metastasis. A stereolithography-based three-dimensional (3D) printer was used to fabricate the bone matrices with precisely controlled architecture. The interaction between breast cancer cells and osteoblasts was investigated in the optimized bone matrix. Using a Transwell® system to separate the two cell lines, breast cancer cells inhibited osteoblast proliferation, while osteoblasts stimulated breast cancer cell growth, whereas, both cell lines increased IL-8 secretion. Breast cancer cells co-cultured with osteoblasts within the 3D bone matrix formed multi-cellular spheroids in comparison to two-dimensional monolayers. These findings validate the use of our 3D printed bone matrices as an in vitro metastasis model, and highlights their potential for investigating breast cancer bone metastasis.

  20. Assessment on zoledronic acid use in patients with bone metastatic breast cancer

    International Nuclear Information System (INIS)

    Soriano Garcia, Jorge L; Batista Albuerne, Noyde; Lima Perez, Mayte

    2010-01-01

    The biphosphonates are the cornerstone in the bone metastases treatment. In present paper the effectiveness and safety of the zoledronic acid (ZA) use in patients with bone metastatic breast cancer (MBC)

  1. Biological Differences Between Prostate Cancer Cells that Metastasize to Bone Versus Soft Tissue Sites

    National Research Council Canada - National Science Library

    Pienta, Kenneth J

    2004-01-01

    .... Comparisons were made between patients as well as within the same patient. No consistent differences were found between bone and soft tissue sites that could explain the predilection of prostate cancer cells to metastasize to bone...

  2. SPECT-CT bone scintigraphy in cancer patients

    International Nuclear Information System (INIS)

    Sergieva, S; Alexandrova, A.; Nikolova, N.; Dimcheva, M.; Baichev, G.

    2012-01-01

    Full text: Introduction: SPECT-CT study allows the precise correlation between functional and morphological data on the same image. Methods: Whole body bone scan (WBBS) is a diagnostic modality still firmly established as a valuable tool to assess skeleton abnormalities. CT is an imaging method for characterizing destruction of the bone spongy lesions, their consolidation or calcium accumulation. This fact allows differentiation of the osteolytic metastases from the osteosclerotic and mixed lesions and also from degenerative ones. Whole body bone scan followed by SPECT-CT scanning increases the accuracy of the study and potentially accelerates the diagnosis of the patient based on a single imaging session. This is especially important in cancer patients. Results and discussion: After retrospectively review of WBBS and SPECT-CT fused images 141 bone lesions in 89 pts were analyzed The skeletal findings with previously uncertain character were classified as definitely benign, indeterminate or definitely malignant. 1. 47 (33%) of all lesions in 36 pts could be correlated with benign degenerative findings on SPECT-CT images. 5 (3%) lesions in 3 of these pts were indeterminate on the SPECT-CT images. They were localized in the area of articulation parts and corpus of the thoracic vertebra and ribs. After additional MRT examination and 6 months follow-up these changes were considered degenerative: osteopathy changes and presence of spondyloarthrosis and osteochondrosis; compression fractures due to advanced osteoporosis. These pts were with prolonged chormono/chemotherapy; chronic inflammatory disease of the coxofemoral articulation, coxarthrosis, aseptic necrosis of the femoral head and postoperative sacroiliitis; post-traumatic fractures or surgical intervention; hyperplastic degenerative lesions in the skeleton and asymmetrical pelvic bone structures due to M. Paget. 2. 41 (28,1%) single osseous metastatic spots (up to 3 foci) were scanned in 31 pts. 3. 13 (10

  3. Macrophage Efferocytosis and Prostate Cancer Bone Metastasis

    Science.gov (United States)

    2018-03-01

    E) ELISA for total CXCL1 and CXCL5 levels in supernatants of MΦs alone or cocultured with RM1(HA) or PC3(HA). (F) Transcriptional activ- ity cell...marrow macrophages (Fig- ure 1D). ELISA evaluation for CXCL1 and CXCL5 proteins in the coculture media for apoptotic cancer cells (Figure 1E) confirmed... ELISA analysis of total pro- tein lysates from VEH- (n = 10) and AP-treated (n = 11) tumor vossicles. (G) Graphs depicting the correlation between

  4. Application of serum SELDI proteomic patterns in diagnosis of lung cancer

    Directory of Open Access Journals (Sweden)

    Zhou Bin

    2005-07-01

    Full Text Available Abstract Background Currently, no satisfactory biomarkers are available to screen for lung cancer. Surface-Enhanced Laser Desorption/ionization Time-of- Flight Mass Spectrometry ProteinChip system (SELDI-TOF-MS is one of the currently used techniques to identify biomarkers for cancers. The aim of this study is to explore the application of serum SELDI proteomic patterns to distinguish lung cancer patients from healthy individuals. Methods A total of 208 serum samples, including 158 lung cancer patients and 50 healthy individuals, were randomly divided into a training set (including 11 sera from patients with stages I/II lung cancer, 63 from patients with stages III/IV lung cancer and 20 from healthy controls and a blinded test set (including 43 sera from patients with stages I/II lung cancer, 41 from patients with stages III/IV lung cancer and 30 from healthy controls. All samples were analyzed by SELDI technology. The spectra were generated on weak cation exchange (WCX2 chips, and protein peaks clustering and classification analyses were made using Ciphergen Biomarker Wizard and Biomarker Pattern software, respectively. We additionally determined Cyfra21-1 and NSE in the 208 serum samples included in this study using an electrochemiluminescent immunoassay. Results Five protein peaks at 11493, 6429, 8245, 5335 and 2538 Da were automatically chosen as a biomarker pattern in the training set. When the SELDI marker pattern was tested with the blinded test set, it yielded a sensitivity of 86.9%, a specificity of 80.0% and a positive predictive value of 92.4%. The sensitivities provided by Cyfra21-1 and NSE used individually or in combination were significantly lower than that of the SELDI marker pattern (P P Conclusion These results suggest that serum SELDI protein profiling can distinguish lung cancer patients, especially NSCLC patients, from normal subjects with relatively high sensitivity and specificity, and the SELDI-TOF-MS is a potential tool

  5. Quantitative Proteomic Analysis of Serum Exosomes from Patients with Locally Advanced Pancreatic Cancer Undergoing Chemoradiotherapy.

    Science.gov (United States)

    An, Mingrui; Lohse, Ines; Tan, Zhijing; Zhu, Jianhui; Wu, Jing; Kurapati, Himabindu; Morgan, Meredith A; Lawrence, Theodore S; Cuneo, Kyle C; Lubman, David M

    2017-04-07

    Pancreatic cancer is the third leading cause of cancer-related death in the USA. Despite extensive research, minimal improvements in patient outcomes have been achieved. Early identification of treatment response and metastasis would be valuable to determine the appropriate therapeutic course for patients. In this work, we isolated exosomes from the serum of 10 patients with locally advanced pancreatic cancer at serial time points over a course of therapy, and quantitative analysis was performed using the iTRAQ method. We detected approximately 700-800 exosomal proteins per sample, several of which have been implicated in metastasis and treatment resistance. We compared the exosomal proteome of patients at different time points during treatment to healthy controls and identified eight proteins that show global treatment-specific changes. We then tested the effect of patient-derived exosomes on the migration of tumor cells and found that patient-derived exosomes, but not healthy controls, induce cell migration, supporting their role in metastasis. Our data show that exosomes can be reliably extracted from patient serum and analyzed for protein content. The differential loading of exosomes during a course of therapy suggests that exosomes may provide novel insights into the development of treatment resistance and metastasis.

  6. Proteomics Core

    Data.gov (United States)

    Federal Laboratory Consortium — Proteomics Core is the central resource for mass spectrometry based proteomics within the NHLBI. The Core staff help collaborators design proteomics experiments in a...

  7. Can bone metabolism markers be adopted as an alternative to scintigraphic imaging in monitoring bone metastases from breast cancer?

    International Nuclear Information System (INIS)

    Bombardieri, E.; Martinetti, A.; Castellani, M.R.; Seregni, E.; Miceli, R.; Mariani, L.

    1997-01-01

    Bone scintigraphy plays a major role in the diagnosis of bone metastases. The clinical utility of new biochemical markers of bone metabolism has recently been investigated in various bone diseases. This study evaluated the role of some bone metabolism markers in comparison with bone scan in the follow-up of breast cancer patients. We studied 149 patients with breast cancer, 33 (22%) of whom had bone metastases. IRMAs were used for the evaluation of blood levels of osteocalcin, bone alkaline phosphatase (BAP), the C-terminal propeptide of type I procollagen and the C-terminal cross-linked telopeptide of type I collagen (ICTP). Multivariate regression analysis showed that menopausal status (P=0.007) and metastatic bone lesions (P=0.001) affected bone marker levels. When considering post-menopausal women, the only subset in which bone metabolism marker behaviour could be reliably investigated, we found a high degree of overlap in marker distribution for scan-positive and scan-negative patients. Discrimination between scan-negative and scan-positive patients based on the above markers, taken singly or jointly, was assessed by means of logistic discriminant analysis. The best discrimination was achieved with BAP, closely followed by ICTP. BAP and ICTP together gave a slight improvement over the use of the two markers separately. However, even in this case the degree of discrimination was poor and its clinical utility was limited. In fact, to achieve a specificity of 95%, the sensitivity of the test was about 20%; conversely, with a sensitivity of 95%, the specificity was below 10%. In conclusion, based on our findings, we believe that blood levels of the investigated markers cannot replace bone scintigraphy in the follow-up of breast cancer patients for the early detection of bone metastases. (orig.)

  8. Non-synonymous variations in cancer and their effects on the human proteome: workflow for NGS data biocuration and proteome-wide analysis of TCGA data.

    Science.gov (United States)

    Cole, Charles; Krampis, Konstantinos; Karagiannis, Konstantinos; Almeida, Jonas S; Faison, William J; Motwani, Mona; Wan, Quan; Golikov, Anton; Pan, Yang; Simonyan, Vahan; Mazumder, Raja

    2014-01-27

    Next-generation sequencing (NGS) technologies have resulted in petabytes of scattered data, decentralized in archives, databases and sometimes in isolated hard-disks which are inaccessible for browsing and analysis. It is expected that curated secondary databases will help organize some of this Big Data thereby allowing users better navigate, search and compute on it. To address the above challenge, we have implemented a NGS biocuration workflow and are analyzing short read sequences and associated metadata from cancer patients to better understand the human variome. Curation of variation and other related information from control (normal tissue) and case (tumor) samples will provide comprehensive background information that can be used in genomic medicine research and application studies. Our approach includes a CloudBioLinux Virtual Machine which is used upstream of an integrated High-performance Integrated Virtual Environment (HIVE) that encapsulates Curated Short Read archive (CSR) and a proteome-wide variation effect analysis tool (SNVDis). As a proof-of-concept, we have curated and analyzed control and case breast cancer datasets from the NCI cancer genomics program - The Cancer Genome Atlas (TCGA). Our efforts include reviewing and recording in CSR available clinical information on patients, mapping of the reads to the reference followed by identification of non-synonymous Single Nucleotide Variations (nsSNVs) and integrating the data with tools that allow analysis of effect nsSNVs on the human proteome. Furthermore, we have also developed a novel phylogenetic analysis algorithm that uses SNV positions and can be used to classify the patient population. The workflow described here lays the foundation for analysis of short read sequence data to identify rare and novel SNVs that are not present in dbSNP and therefore provides a more comprehensive understanding of the human variome. Variation results for single genes as well as the entire study are available

  9. The level of serum tumor makers and bone metastases of lung cancer correlation

    International Nuclear Information System (INIS)

    Li Li; Jin Jianhua

    2014-01-01

    Objective: To study the correlation between the level of serum tumor makers and bone metastases of lung cancer. Method: In 128 diagnosed patients with lung cancer, small cell lung cancer were 26 cases, non-small cell lung cancer were 102 cases which included 44 cases of adenocarcinoma, 50 cases of squamous cell carcinoma, 4 cases of large cell carcinoma, 4 cases of squamous adenocarcinoma. "9"9"mTc-MDP whole-body bone scanning was performed in 128 patients with lung cancer. over the same period, the serum samples were collected in these patients and 30 comparison controls. CEA, CA125, CA199, SCC, NSE, CA15-3, and AFP were measured by ELISA technique. Bone imaging findings analysis used t-test, and serum levels of tumor markers analysis used χ"2 test. Results: The diagnostic of 53 cases of lung cancer with bone metastasis was subject to clinical criteria of lung cancer with bone metastases. The positive ratio of patients with osseous metastasis was confirmed by "9"9"mTc-MDP whole-body bone scanning was 23.44% (30/128), including 16 cases of lung adenocarcinoma, 9 cases of squamous cell carcinoma, 3 cases of small cell lung cancer , 1 case of large cell lung cancer, 1 case of squamous adenocarcinoma and multiple bone metastases accounted for 66.67% (20/30). The levels of serum CEA, CA125, CA199, SCC, NSE and CA15-3 were higher than the control group (P < O.05). 29 cases of CEA positive and 21 cases of CA125 positive were included in 30 cases of lung cancer with bone metastasis. There was a significant difference between the levels of CEA, CA125, CA199, NSE in lung cancer with bone metastases and without bone metastases (P < 0.05). The sensitivity of "9"9"mTc-MDP whole-body bone scanning in diagnosis of lung cancer with bone metastasis was 84.91%. Conclusion: The average value of CEA, CA125, and CA199, SCC, NSE and CA15-3 in lung cancer patients were significantly higher than the control group. In addition, there is a significantly correlation between the occurrence

  10. Quantification of mutant SPOP proteins in prostate cancer using mass spectrometry-based targeted proteomics

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Hui; Barbieri, Christopher E.; He, Jintang; Gao, Yuqian; Shi, Tujin; Wu, Chaochao; Schepmoes, Athena A.; Fillmore, Thomas L.; Chae, Sung-Suk; Huang, Dennis; Mosquera, Juan Miguel; Qian, Wei-Jun; Smith, Richard D.; Srivastava, Sudhir; Kagan, Jacob; Camp, David G.; Rodland, Karin D.; Rubin, Mark A.; Liu, Tao

    2017-08-15

    Speckle-type POZ protein (SPOP) is an E3 ubiquitin ligase adaptor protein that functions as a potential tumor suppressor, and SPOP mutations have been identified in ~10% of human prostate cancers. However, it remains unclear if mutant SPOP proteins can be utilized as biomarkers for early detection, diagnosis, prognosis or targeted therapy of prostate cancer. Moreover, the SPOP mutation sites are distributed in a relatively short region where multiple lysine residues, posing significant challenges for bottom-up proteomics analysis of the SPOP mutations. To address this issue, PRISM (high-pressure, high-resolution separations coupled with intelligent selection and multiplexing)-SRM (selected reaction monitoring) mass spectrometry assays have been developed for quantifying wild-type SPOP protein and 11 prostate cancer-derived SPOP mutations. Despite inherent limitations due to amino acid sequence constraints, all the PRISM-SRM assays developed using Arg-C digestion showed a linear dynamic range of at least two orders of magnitude, with limits of quantification range from 0.1 to 1 fmol/μg of total protein in the cell lysate. Applying these SRM assays to analyze HEK293T cells with and without expression of the three most frequent SPOP mutations in prostate cancer (Y87N, F102C or F133V) led to confident detection of all three SPOP mutations in corresponding positive cell lines but not in the negative cell lines. Expression of the F133V mutation and wild-type SPOP was at much lower levels compared to that of F102C and Y87N mutations; however, at present it is unknown if this also affects the activity of the SPOP protein. In summary, PRISM-SRM enables multiplexed, isoform-specific detection of mutant SPOP proteins in cell lysates, which holds great potential in biomarker development for prostate cancer.

  11. Does increased local bone resorption secondary to breast and prostate cancer result in increased cartilage degradation?

    DEFF Research Database (Denmark)

    Leeming, Diana J; Byrjalsen, Inger; Qvist, Per

    2008-01-01

    BACKGROUND: Breast and prostate cancer patients often develop lesions of locally high bone turnover, when the primary tumor metastasizes to the bone causing an abnormal high bone resorption at this site. The objective of the present study was to determine whether local increased bone turnover in ...... experiments revealed that osteoclasts released CTXI fragments but not CTXII from bone specimens. The same was observed for cathepsin K. CONCLUSION: Data suggest that an uncoupling between bone resorption and cartilage degradation occurs in breast and lung cancer patient....

  12. Cost of palliative radiation to the bone for patients with bone metastases secondary to breast or prostate cancer

    Directory of Open Access Journals (Sweden)

    Hess Gregory

    2012-10-01

    Full Text Available Abstract Background To estimate the costs (paid amounts of palliative radiation episodes of care (REOCs to the bone for patients with bone metastases secondary to breast or prostate cancer. Methods Claims-linked medical records from patients at 98 cancer treatment centers in 16 US states were analyzed. Inclusion criteria included a primary neoplasm of breast or prostate cancer with a secondary neoplasm of bone metastases; ≥2 visits to ≥1 radiation center during the study period (1 July 2008 through 31 December 2009 on or after the metastatic cancer diagnosis date; radiation therapy to ≥1 bone site; and ≥1 complete REOC as evidenced by a >30-day gap pre- and post-radiation therapy. Results The total number of REOCs was 220 for 207 breast cancer patients and 233 for 213 prostate cancer patients. In the main analysis (which excluded records with unpopulated costs the median number of fractions per a REOC for treatment of metastases was 10. Mean total radiation costs (i.e., radiation direct cost + cost of radiation-related procedures and visits per REOC were $7457 for patients with breast cancer and $7553 for patients with prostate cancer. Results were consistent in sensitivity analyses excluding patients with unpopulated costs. Conclusions In the US, current use of radiation therapy for bone metastases is relatively costly and the use of multi-fraction schedules remains prevalent.

  13. Stimulation of Host Bone Marrow Stromal Cells by Sympathetic Nerves Promotes Breast Cancer Bone Metastasis in Mice

    OpenAIRE

    Campbell, J. Preston; Karolak, Matthew R.; Ma, Yun; Perrien, Daniel S.; Masood-Campbell, S. Kathryn; Penner, Niki L.; Munoz, Steve A.; Zijlstra, Andries; Yang, Xiangli; Sterling, Julie A.; Elefteriou, Florent

    2012-01-01

    Bone and lung metastases are responsible for the majority of deaths in patients with breast cancer. Following treatment of the primary cancer, emotional and psychosocial factors within this population precipitate time to recurrence and death, however the underlying mechanism(s) remain unclear. Using a mouse model of bone metastasis, we provide experimental evidence that activation of the sympathetic nervous system, which is one of many pathophysiological consequences of severe stress and depr...

  14. Plasma membrane proteomics of human breast cancer cell lines identifies potential targets for breast cancer diagnosis and treatment.

    Directory of Open Access Journals (Sweden)

    Yvonne S Ziegler

    Full Text Available The use of broad spectrum chemotherapeutic agents to treat breast cancer results in substantial and debilitating side effects, necessitating the development of targeted therapies to limit tumor proliferation and prevent metastasis. In recent years, the list of approved targeted therapies has expanded, and it includes both monoclonal antibodies and small molecule inhibitors that interfere with key proteins involved in the uncontrolled growth and migration of cancer cells. The targeting of plasma membrane proteins has been most successful to date, and this is reflected in the large representation of these proteins as targets of newer therapies. In view of these facts, experiments were designed to investigate the plasma membrane proteome of a variety of human breast cancer cell lines representing hormone-responsive, ErbB2 over-expressing and triple negative cell types, as well as a benign control. Plasma membranes were isolated by using an aqueous two-phase system, and the resulting proteins were subjected to mass spectrometry analysis. Overall, each of the cell lines expressed some unique proteins, and a number of proteins were expressed in multiple cell lines, but in patterns that did not always follow traditional clinical definitions of breast cancer type. From our data, it can be deduced that most cancer cells possess multiple strategies to promote uncontrolled growth, reflected in aberrant expression of tyrosine kinases, cellular adhesion molecules, and structural proteins. Our data set provides a very rich and complex picture of plasma membrane proteins present on breast cancer cells, and the sorting and categorizing of this data provides interesting insights into the biology, classification, and potential treatment of this prevalent and debilitating disease.

  15. Topical Treatment with Xiaozheng Zhitong Paste (XZP Alleviates Bone Destruction and Bone Cancer Pain in a Rat Model of Prostate Cancer-Induced Bone Pain by Modulating the RANKL/RANK/OPG Signaling

    Directory of Open Access Journals (Sweden)

    Yanju Bao

    2015-01-01

    Full Text Available To explore the effects and mechanisms of Xiaozheng Zhitong Paste (XZP on bone cancer pain, Wistar rats were inoculated with vehicle or prostate cancer PC-3 into the tibia bone and treated topically with inert paste, XZP at 15.75, 31.5, or 63 g/kg twice per day for 21 days. Their bone structural damage, nociceptive behaviors, bone osteoclast and osteoblast activity, and the levels of OPG, RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were examined. In comparison with that in the placebo group, significantly reduced numbers of invaded cancer cells, decreased levels of bone damage and mechanical threshold and paw withdrawal latency, lower levels of serum TRACP5b, ICTP, PINP, and BAP, and less levels of bone osteoblast and osteoclast activity were detected in the XZP-treated rats (P<0.05. Moreover, significantly increased levels of bone OPG but significantly decreased levels of RANL, RNAK, PTHrP, IGF-1, M-CSF, IL-8, and TNF-α were detected in the XZP-treated rats (P<0.05 for all. Together, XZP treatment significantly mitigated the cancer-induced bone damage and bone osteoclast and osteoblast activity and alleviated prostate cancer-induced bone pain by modulating the RANKL/RANK/OPG pathway and bone cancer-related inflammation in rats.

  16. Radiotherapy Results of Breast Cancer Patients with Metastatic Bone Disease

    Directory of Open Access Journals (Sweden)

    Ahmet Dirier

    2006-01-01

    Full Text Available Breast cancer patients with bone metastasis who had admitted to Dicle University Department of Radiation Oncology for palliative radiation therapy between September 2001 and December 2003 were evaluated. There were 31 patients (26 female, 5 male. Median age was 43 years (range 23-79. Histopathological subtypes were infiltrating ductal carcinoma (88%, tubulolobuler carcinoma (6% and inflammatory carcinoma (6%. Loci of bone metastasis were vertebra only in twelve patients (39%, non-vertebral bones only in 8 patients (26% and both vertebral and nonvertebral bones in 11 patients (35%. Two patients had refused radiotherapy. Radiation doses were 3000 cGy with 10 fractions in 15 patients, 2000 cGy with 5 fractions in 6 patients and 800 cGy single fraction in eight patients. Complete palliation of pain was achieved in 18 patients (62% and partial palliation was achieved in 11 patients (38%. Treatment related toxicity was grade I-II dermatitis. In conclusion; same respons rates in terms of palliation can be achieved in the three radiotherapy schedules.

  17. Construction and analysis of protein-protein interaction networks based on proteomics data of prostate cancer

    Science.gov (United States)

    CHEN, CHEN; SHEN, HONG; ZHANG, LI-GUO; LIU, JIAN; CAO, XIAO-GE; YAO, AN-LIANG; KANG, SHAO-SAN; GAO, WEI-XING; HAN, HUI; CAO, FENG-HONG; LI, ZHI-GUO

    2016-01-01

    Currently, using human prostate cancer (PCa) tissue samples to conduct proteomics research has generated a large amount of data; however, only a very small amount has been thoroughly investigated. In this study, we manually carried out the mining of the full text of proteomics literature that involved comparisons between PCa and normal or benign tissue and identified 41 differentially expressed proteins verified or reported more than 2 times from different research studies. We regarded these proteins as seed proteins to construct a protein-protein interaction (PPI) network. The extended network included one giant network, which consisted of 1,264 nodes connected via 1,744 edges, and 3 small separate components. The backbone network was then constructed, which was derived from key nodes and the subnetwork consisting of the shortest path between seed proteins. Topological analyses of these networks were conducted to identify proteins essential for the genesis of PCa. Solute carrier family 2 (facilitated glucose transporter), member 4 (SLC2A4) had the highest closeness centrality located in the center of each network, and the highest betweenness centrality and largest degree in the backbone network. Tubulin, beta 2C (TUBB2C) had the largest degree in the giant network and subnetwork. In addition, using module analysis of the whole PPI network, we obtained a densely connected region. Functional annotation indicated that the Ras protein signal transduction biological process, mitogen-activated protein kinase (MAPK), neurotrophin and the gonadotropin-releasing hormone (GnRH) signaling pathway may play an important role in the genesis and development of PCa. Further investigation of the SLC2A4, TUBB2C proteins, and these biological processes and pathways may therefore provide a potential target for the diagnosis and treatment of PCa. PMID:27121963

  18. Organized proteomic heterogeneity in colorectal cancer liver metastases and implications for therapies.

    Science.gov (United States)

    Turtoi, Andrei; Blomme, Arnaud; Debois, Delphine; Somja, Joan; Delvaux, David; Patsos, Georgios; Di Valentin, Emmanuel; Peulen, Olivier; Mutijima, Eugène Nzaramba; De Pauw, Edwin; Delvenne, Philippe; Detry, Olivier; Castronovo, Vincent

    2014-03-01

    Tumor heterogeneity is a major obstacle for developing effective anticancer treatments. Recent studies have pointed to large stochastic genetic heterogeneity within cancer lesions, where no pattern seems to exist that would enable a more structured targeted therapy approach. Because to date no similar information is available at the protein (phenotype) level, we employed matrix assisted laser desorption ionization (MALDI) image-guided proteomics and explored the heterogeneity of extracellular and membrane subproteome in a unique collection of eight fresh human colorectal carcinoma (CRC) liver metastases. Monitoring the spatial distribution of over 1,000 proteins, we found unexpectedly that all liver metastasis lesions displayed a reproducible, zonally delineated pattern of functional and therapeutic biomarker heterogeneity. The peritumoral region featured elevated lipid metabolism and protein synthesis, the rim of the metastasis displayed increased cellular growth, movement, and drug metabolism, whereas the center of the lesion was characterized by elevated carbohydrate metabolism and DNA-repair activity. From the aspect of therapeutic targeting, zonal expression of known and novel biomarkers was evident, reinforcing the need to select several targets in order to achieve optimal coverage of the lesion. Finally, we highlight two novel antigens, LTBP2 and TGFBI, whose expression is a consistent feature of CRC liver metastasis. We demonstrate their in vivo antibody-based targeting and highlight their potential usefulness for clinical applications. The proteome heterogeneity of human CRC liver metastases has a distinct, organized pattern. This particular hallmark can now be used as part of the strategy for developing rational therapies based on multiple sets of targetable antigens. © 2014 by the American Association for the Study of Liver Diseases.

  19. Quantitative Proteomics Analysis Identifies Mitochondria as Therapeutic Targets of Multidrug-Resistance in Ovarian Cancer

    Science.gov (United States)

    Chen, Xiulan; Wei, Shasha; Ma, Ying; Lu, Jie; Niu, Gang; Xue, Yanhong; Chen, Xiaoyuan; Yang, Fuquan

    2014-01-01

    Doxorubicin is a widely used chemotherapeutic agent for the treatment of a variety of solid tumors. However, resistance to this anticancer drug is a major obstacle to the effective treatment of tumors. As mitochondria play important roles in cell life and death, we anticipate that mitochondria may be related to drug resistance. Here, stable isotope labeling by amino acids in cell culture (SILAC)-based quantitative proteomic strategy was applied to compare mitochondrial protein expression in doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI_ADR/RES cells. A total of 2085 proteins were quantified, of which 122 proteins displayed significant changes in the NCI_ADR/RES cells. These proteins participated in a variety of cell processes including cell apoptosis, substance metabolism, transport, detoxification and drug metabolism. Then qRT-PCR and western blot were applied to validate the differentially expressed proteins quantified by SILAC. Further functional studies with RNAi demonstrated TOP1MT, a mitochondrial protein participated in DNA repair, was involved in doxorubicin resistance in NCI_ADR/RES cells. Besides the proteomic study, electron microscopy and fluorescence analysis also observed that mitochondrial morphology and localization were greatly altered in NCI_ADR/RES cells. Mitochondrial membrane potential was also decreased in NCI_ADR/RES cells. All these results indicate that mitochondrial function is impaired in doxorubicin-resistant cells and mitochondria play an important role in doxorubicin resistance. This research provides some new information about doxorubicin resistance, indicating that mitochondria could be therapeutic targets of doxorubicin resistance in ovarian cancer cells. PMID:25285166

  20. Bioinformatics analysis of differentially expressed proteins in prostate cancer based on proteomics data

    Directory of Open Access Journals (Sweden)

    Chen C

    2016-03-01

    Full Text Available Chen Chen,1 Li-Guo Zhang,1 Jian Liu,1 Hui Han,1 Ning Chen,1 An-Liang Yao,1 Shao-San Kang,1 Wei-Xing Gao,1 Hong Shen,2 Long-Jun Zhang,1 Ya-Peng Li,1 Feng-Hong Cao,1 Zhi-Guo Li3 1Department of Urology, North China University of Science and Technology Affiliated Hospital, 2Department of Modern Technology and Education Center, 3Department of Medical Research Center, International Science and Technology Cooperation Base of Geriatric Medicine, North China University of Science and Technology, Tangshan, People’s Republic of China Abstract: We mined the literature for proteomics data to examine the occurrence and metastasis of prostate cancer (PCa through a bioinformatics analysis. We divided the differentially expressed proteins (DEPs into two groups: the group consisting of PCa and benign tissues (P&b and the group presenting both high and low PCa metastatic tendencies (H&L. In the P&b group, we found 320 DEPs, 20 of which were reported more than three times, and DES was the most commonly reported. Among these DEPs, the expression levels of FGG, GSN, SERPINC1, TPM1, and TUBB4B have not yet been correlated with PCa. In the H&L group, we identified 353 DEPs, 13 of which were reported more than three times. Among these DEPs, MDH2 and MYH9 have not yet been correlated with PCa metastasis. We further confirmed that DES was differentially expressed between 30 cancer and 30 benign tissues. In addition, DEPs associated with protein transport, regulation of actin cytoskeleton, and the extracellular matrix (ECM–receptor interaction pathway were prevalent in the H&L group and have not yet been studied in detail in this context. Proteins related to homeostasis, the wound-healing response, focal adhesions, and the complement and coagulation pathways were overrepresented in both groups. Our findings suggest that the repeatedly reported DEPs in the two groups may function as potential biomarkers for detecting PCa and predicting its aggressiveness. Furthermore

  1. Best Performers Announced for the NCI-CPTAC DREAM Proteogenomics Computational Challenge | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI) Clinical Proteomic Tumor Analysis Consortium (CPTAC) is pleased to announce that teams led by Jaewoo Kang (Korea University), and Yuanfang Guan with Hongyang Li (University of Michigan) as the best performers of the NCI-CPTAC DREAM Proteogenomics Computational Challenge. Over 500 participants from 20 countries registered for the Challenge, which offered $25,000 in cash awards contributed by the NVIDIA Foundation through its Compute the Cure initiative.

  2. Quantitative comparison of a human cancer cell surface proteome between interphase and mitosis.

    Science.gov (United States)

    Özlü, Nurhan; Qureshi, Mohammad H; Toyoda, Yusuke; Renard, Bernhard Y; Mollaoglu, Gürkan; Özkan, Nazlı E; Bulbul, Selda; Poser, Ina; Timm, Wiebke; Hyman, Anthony A; Mitchison, Timothy J; Steen, Judith A

    2015-01-13

    The cell surface is the cellular compartment responsible for communication with the environment. The interior of mammalian cells undergoes dramatic reorganization when cells enter mitosis. These changes are triggered by activation of the CDK1 kinase and have been studied extensively. In contrast, very little is known of the cell surface changes during cell division. We undertook a quantitative proteomic comparison of cell surface-exposed proteins in human cancer cells that were tightly synchronized in mitosis or interphase. Six hundred and twenty-eight surface and surface-associated proteins in HeLa cells were identified; of these, 27 were significantly enriched at the cell surface in mitosis and 37 in interphase. Using imaging techniques, we confirmed the mitosis-selective cell surface localization of protocadherin PCDH7, a member of a family with anti-adhesive roles in embryos. We show that PCDH7 is required for development of full mitotic rounding pressure at the onset of mitosis. Our analysis provided basic information on how cell cycle progression affects the cell surface. It also provides potential pharmacodynamic biomarkers for anti-mitotic cancer chemotherapy. © 2014 The Authors.

  3. Bioinformatics analysis of breast cancer bone metastasis related gene-CXCR4

    Institute of Scientific and Technical Information of China (English)

    Heng-Wei Zhang; Xian-Fu Sun; Ya-Ning He; Jun-Tao Li; Xu-Hui Guo; Hui Liu

    2013-01-01

    Objective: To analyze breast cancer bone metastasis related gene-CXCR4. Methods: This research screened breast cancer bone metastasis related genes by high-flux gene chip. Results:It was found that the expressions of 396 genes were different including 165 up-regulations and 231 down-regulations. The expression of chemokine receptor CXCR4 was obviously up-regulated in the tissue with breast cancer bone metastasis. Compared with the tissue without bone metastasis, there was significant difference, which indicated that CXCR4 played a vital role in breast cancer bone metastasis. Conclusions: The bioinformatics analysis of CXCR4 can provide a certain basis for the occurrence and diagnosis of breast cancer bone metastasis, target gene therapy and evaluation of prognosis.

  4. Differential effect of TGFβ on the proteome of cancer associated fibroblasts and cancer epithelial cells in a co-culture approach - a short report.

    Science.gov (United States)

    Koczorowska, Maria Magdalena; Friedemann, Charlotte; Geiger, Klaus; Follo, Marie; Biniossek, Martin Lothar; Schilling, Oliver

    2017-12-01

    Solid tumors contain various components that together form the tumor microenvironment. Cancer associated fibroblasts (CAFs) are capable of secreting and responding to signaling molecules and growth factors. Due to their role in tumor development, CAFs are considered as potential therapeutic targets. A prominent tumor-associated signaling molecule is transforming growth factor β (TGFβ), an inducer of epithelial-to-mesenchymal transition (EMT). The differential action of TGFβ on CAFs and ETCs (epithelial tumor cells) has recently gained interest. Here, we aimed to investigate the effects of TGFβ on CAFs and ETCs at the proteomic level. We established a 2D co-culture system of differentially fluorescently labeled CAFs and ETCs and stimulated this co-culture system with TGFβ. The respective cell types were separated using FACS and subjected to quantitative analyses of individual proteomes using mass spectrometry. We found that TGFβ treatment had a strong impact on the proteome composition of CAFs, whereas ETCs responded only marginally to TGFβ. Quantitative proteomic analyses of the different cell types revealed up-regulation of extracellular matrix (ECM) proteins in TGFβ treated CAFs. In addition, we found that the TGFβ treated CAFs exhibited increased N-cadherin levels. From our data we conclude that CAFs respond to TGFβ treatment by changing their proteome composition, while ETCs appear to be rather resilient.

  5. Novel anti-cancer strategy in bone tumors by targeting molecular and cellular modulators of bone resorption.

    Science.gov (United States)

    Brounais, Bénédicte; Ruiz, Carmen; Rousseau, Julie; Lamoureux, François; Blanchard, Frédéric; Heymann, Dominique; Redini, Françoise

    2008-11-01

    Tumor cells alter the balanced process of bone formation and bone resorption mediated respectively by osteoblasts and osteoclasts, leading to the disruption of the normal equilibrium and resulting in a spectrum of osteolytic to osteoblastic lesions. This review will summarize research on molecules that play direct and essential roles in the differentiation and activity of osteoclasts, and the role of these molecules in bone destruction caused by cancer. Results from experimental models suggest that the Receptor Activator of NF-kB Ligand (RANKL), a member of the TNF superfamily is a common effector of bony lesions in osteolysis caused by primary and secondary bone tumors. Therefore, osteoclast represents an attractive target across a broad range of tumors that develop in bone. Elucidation of the mechanisms of RANKL interactions with its activator (RANK) and decoy (osteoprotegerin: OPG) receptors has enable the development of pharmacological inhibitors of RANKL (and of its signalling pathway) which have been recently patented, with potential for the treatment of cancer-induced bone disease. Blocking bone resorption by specific other drugs such as bisphosphonates, inhibitors of cathepsin K (the main enzyme involved in bone resorption mechanisms) or signalling pathways regulating osteoclast differentiation and activation is also a promising target for the treatment of osteolysis associated to bone tumors.

  6. Bone metastases from breast cancer at the time or radical mastectomy as detected by bone scan. Eight-year follow-up.

    Science.gov (United States)

    Sklaroff, R B; Sklaroff, D M

    1976-07-01

    Sixty-four women with Stage II breast cancer who had Sr85 bone scans at the time of radical mastectomy were followed for 8 years in a prospective study. Those women with positive scans had a slight, but statistically significant, increased incidence of metastic disease, particularly for metastases to bone.However, 40% of those women with positive bone scans and negative roentgenograms survived 8 years without evidence of any metastatic disease. Therefore, it has not been shown at this time that bone scans should be obtained in order to exclude bone metastasis before regional therapy for breast cancer is instituted. Also, a significant percentage of women with negative bone scans developed both bone and soft tissue metastases. As many as 30% of asymptomatic women with a history of breast cancer and positive bone scans and negative bone roentgenograms may still harbor disease in bone after 8 years.

  7. Is retention of zoledronic acid onto bone different in multiple myeloma and breast cancer patients with bone metastasis?

    DEFF Research Database (Denmark)

    Søe, Kent; Plesner, Torben; Jakobsen, Erik H

    2013-01-01

    Zoledronic acid (Zol) is used to treat bone disease in both multiple myeloma (MM) and breast cancer patients with bone metastasis (BC). However, bones of MM and BC patients show a difference in retention of the bisphosphonate used for bone scintigraphy. Therefore, we hypothesized that disease...... of Zol correlated with bone-specific alkaline phosphatase (bALP) levels in BC (p = 0.001), and with CTX/bALP in Zol naive MM patients (p = 0.012). Especially in BC patients, WBrt correlated with age (p = 0.014) independently of kidney function. In MM patients WBrt was found to primarily correlate...... with the extent of bone disease (p = 0.028). Multivariate linear regression analyses of the entire cohort pointed out that WBrt of Zol was best predicted by age (p ...

  8. The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Appel, Camilla Kristine; Gallego-Pedersen, Simone; Andersen, Line

    2017-01-01

    -induced bone pain, including cancer growth, osteoclastic bone degradation and nociceptive signalling. Here we investigate the role of dasatinib, an oral Src kinase family and Bcr-Abl tyrosine kinase inhibitor, in an animal model of cancer-induced bone pain. Daily administration of dasatinib (15 mg/kg, p...

  9. A Timely shift from shotgun to targeted proteomics and how it can be groundbreaking for cancer research

    DEFF Research Database (Denmark)

    Faria, Sara S.; Morris, Carlos F.M.; Silva, Adriano R.

    2017-01-01

    shifting potential of modern targeted proteomics applied to cancer research can be demonstrated by the large number of advancements and increasing examples of new and more useful biomarkers found during the course of this review in different aspects of cancer research. Out of the many studies dedicated...... to cancer biomarker discovery, we were able to devise some clear trends, such as the fact that breast cancer is the most common type of tumor studied and that most of the research for any given type of cancer is focused on the discovery diagnostic biomarkers, with the exception of those that rely on samples...... applicable results have called for the implementation of more direct, hypothesis-based studies such as those made available through targeted approaches, that might be able to streamline biomarker discovery and validation as a means to increase survivability of affected patients. In fact, the paradigm...

  10. Opportunities for Cancer-relevant Innovative Technologies with Transformative Potential | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The National Cancer Institute (NCI) is seeking input from the community on identifying priorities with regards to supporting innovative technology development for cancer-relevant research. While the NCI provides support for technology development through a variety of mechanisms, it is important to understand whether or not these are sufficient for catalyzing and supporting the development of tools with significant potential for advancing important fields of cancer research or clinical care.

  11. Serum proteomic patterns of patients with non-small cell lung cancer treated by radiochemotherapy

    International Nuclear Information System (INIS)

    Li Xianglan; You Qingshan; Yang Yanmei; Ma Yuyan; Tang Yali; Cai Huilong

    2007-01-01

    Objective:To detect the serum proteomic patterns of patients with non-small cell lung (NSCLC) treated with radiochemotherapy by surface enhanced laser desorption ionization time of flight mass spectrometry (SELDI-TOF-MS) protein chip array techniques, and to screen differential expression protein and observe the changes between the patterns before and after the treatment. Methods: SELDI-TOF-MS and CM-10 protein chips were used to detect the serum proteomic patterns of 35 healthy persons (normal control) and 35 patients with NSCLC before radiochemotherapy. Twenty-six out of the 35 patients after the treatment were also studied. BioMarker Wizard 3.01 and BioMarker Pattern System 5. 01 were used in combination to analyze the data and to develop diagnostic models. Results: Sixteen differential expression protein peaks from a total of 251 protein peaks were automatically chosen, including 8 high expressions and 8 low expressions in patients with NSCLC. Of the 16 protein peaks, 6 protein peak patterns ( M 2 572.1, M 2 885.8, M 3 870.4, M 4 161.4, M 5 739.7 and M 8 164.3 mass/charge ratio [ m/z] ) were observed in model that could be used to distinguish lung cancer' from non-cancer diseases. The sensitivity and specificity results were 91% (32/35)and 83% (29/35). When the SELDI marker pattern was tested with the blinded test set, the sensitivity and specificity were 80% (28/35) and 71% (25/35). The 16 differential expression protein peaks of patients before and after the treatment were obviously different. But the peaks of patients after the treatment trended to those of the normal control. Of the 16 protein peaks, M 2 572.1, M 2 885.8, M 4 664.78, M 9 228.39 and M 9 396.42 were significantly changed. Conclusions: SELDI-TOF-MS is possibly significant for screening differential expression proteins and assessing the treatment efficacy and prognosis of patients, which needs to be demonstrated by further study. (authors)

  12. Proteomic Profiling of Exosomes Leads to the Identification of Novel Biomarkers for Prostate Cancer

    Energy Technology Data Exchange (ETDEWEB)

    Duijvesz, Diederick; Burnum-Johnson, Kristin E.; Gritsenko, Marina A.; Hoogland, Marije; Vredenbregt-van den Berg, Mirella S.; Willemsen, Rob; Luider, Theo N.; Pasa-Tolic, Ljiljana; Jenster, Guido

    2013-12-31

    Introduction: Current markers for prostate cancer, such as PSA lack specificity. Therefore, novel biomarkers are needed. Unfortunately, biomarker discovery from body fluids is often hampered by the high abundance of many proteins unrelated to disease. An attractive alternative biomarker discovery approach is the isolation of small vesicles (exosomes, ~100 nm). They contain proteins that are specific to the tissue from which they are derived and therefore can be considered as treasure chests for disease-specific marker discovery. Profiling prostate cancer-derived exosomes could reveal new markers for this malignancy. Materials and Methods: Exosomes were isolated from 2 immortalized primary prostate epithelial cells (PNT2C2 and RWPE-1) and 2 PCa cell lines (PC346C and VCaP) by ultracentrifugation. Proteomic analyses utilized a nanoLC coupled with an LTQ-Orbitrap operated in tandem MS (MS/MS) mode, followed by the Accurate Mass and Time (AMT) tag approach. Exosomal proteins were validated by Western blotting. A Tissue Micro Array, containing 481 different PCa samples (radical prostatectomy), was used to correlate candidate markers with several clinical-pathological parameters such as PSA, Gleason score, biochemical recurrence, and (PCa-related) death. Results: Proteomic characterization resulted in the identification of 263 proteins by at least 2 peptides. Specifically analysis of exosomes from PNT2C2, RWPE-1, PC346C, and VCaP identified 248, 233, 169, and 216 proteins, respectively. Statistical analyses revealed 52 proteins differently expressed between PCa and control cells, 9 of which were more abundant in PCa. Validation by Western blotting confirmed a higher abundance of FASN, XPO1 and PDCD6IP (ALIX) in PCa exosomes. The Tissue Micro 4 Array showed strong correlation of higher Gleason scores and local recurrence with increased cytoplasmic XPO1 (P<0.001). Conclusions: Differentially abundant proteins of cell line-derived exosomes make a clear subdivision between

  13. Differential expression of proteomics models of colorectal cancer, colorectal benign disease and healthy controls

    Directory of Open Access Journals (Sweden)

    Zhang Shu-Jun

    2010-03-01

    Full Text Available Abstract Background Colorectal cancer (CRC is often diagnosed at a late stage with concomitant poor prognosis. The hypersensitive analytical technique of proteomics can detect molecular changes before the tumor is palpable. The surface-enhanced laser desorption/ionization-time of flight-mass spectra (SELDI-TOF-MS is a newly-developed technique of evaluating protein separation in recent years. The protein chips have established the expression of tumor protein in the serum specimens and become the newly discovered markers for tumor diagnosis. The objective of this study was to find new markers of the diagnosis among groups of CRC, colorectal benign diseases (CBD and healthy controls. The assay of SELDI-TOF-MS with analytical technique of protein-chip bioinformatics was used to detect the expression of protein mass peaks in the sera of patients or controls. One hundred serum samples, including 52 cases of colorectal cancer, 27 cases of colorectal benign disease, and 21 cases of healthy controls, were examined by SELDI-TOF-MS with WCX2 protein-chips. Results The diagnostic models (I, II and III were setup by analyzed the data and sieved markers using Ciphergen - Protein-Chip-Software 5.1. These models were combined with 3 protein mass peaks to discriminate CRC, CBD, and healthy controls. The accuracy, the sensitivity and the particularity of cross verification of these models are all highly over 80%. Conclusions The SELDI-TOF-MS is a useful tool to help diagnose colorectal cancer, especially during the early stage. However, identification of the significantly differentiated proteins needs further study.

  14. Bone scintigraphy, plasma ALP, TAP and PAP in patients with prostatic cancer

    International Nuclear Information System (INIS)

    Imamura, Akihiko; Hoshi, Hiroaki; Jinnouchi, Seishi; Samejima, Masahiko; Watanabe, Katsushi

    1988-01-01

    This study assessed the ability of bone scintigraphy, alkaline phosphatase (ALP), total acid phosphatase (TAP), and prostatic acid phosphatase (PAP) to diagnose bone metastasis in a series of 62 patients with histologically proven prostatic cancer. Abnormal uptake was seen on the bone scan in 49 patients (79 %). A final diagnosis of bone metastasis was made in 40 patients (65 %). The sensitivity and specificity were 100 % and 59 %, respectively, for bone scintigraphy; 50 % and 96 % for ALP; 65 % and 82 % for TAP; and 73 % and 77 % for PAP. For 40 patients with bone metastasis, all of the ALP, TAP, and PAP were positive in 17 patients (43 %) and negative in 8 patients (20 %). Higher levels of ALP, TAP, and PAP tended to be associated with more extensive bone metastasis. Although serological examination showed lower sensitivity than bone scintigraphy in the diagnosis of bone metastasis, PAP may be most frequently used as a screening procedure of bone metastasis. (Namekawa, K.)

  15. A proteome-based design of bitter peptide digestion regime to attenuate cod-bone soup bitterness: comparison with a rainbow trout extract-mediated bitter taste masking approach

    OpenAIRE

    Jin, Feng; Yan, Zhengyu; Zhang, Zhizhou; Jiang, Jie; Han, Ying; Guo, Changlu

    2018-01-01

    BACKGROUND: The fresh bones (with some meat on them; frequently discarded as a large quantity of industry garbage) of marine fish such as cod and salmon are good materials for manufacture of food additives (taste adjusters). However, such fish-bone originated additives often have apparent bitter taste and need additional debittering regime. RESULTS: In this study, 46 known bitter peptides in the cod proteome were targeted for specific protease digestion to eliminate bitter taste from the cod ...

  16. Research of bone metastases in prostate cancer: scintigraphy and radiological study

    International Nuclear Information System (INIS)

    Seibel, I.; Monteiro, T.S.

    1981-01-01

    This paper analyses the results of bone scan and radiologic study of the bones on the search of metastases of prostate cancer seen in the last two years. In 44 patients with prostatic cancer the diagnostic of metastatic disease was made by the 99m Tc scan in 52%, and by the metastatic radiologic survey in only 25%. (author)

  17. Three-dimensional trabecular bone architecture of the lumbar spine in bone metastasis from prostate cancer: comparison with degenerative sclerosis

    International Nuclear Information System (INIS)

    Tamada, Tsutomu; Sone, Teruki; Imai, Shigeki; Kajihara, Yasumasa; Fukunaga, Masao; Jo, Yoshimasa

    2005-01-01

    Prostate cancer frequently metastasizes to bone, inducing osteosclerotic lesions. The objective of this study was to clarify the three-dimensional (3D) trabecular bone microstructure in bone metastasis from prostate cancer by comparison with normal and degenerative sclerotic bone lesions, using microcomputed tomography (micro-CT). A total of 32 cancellous bone samples were excised from the lumbar spine of six autopsy patients: 15 metastatic samples (one patient), eight degenerative sclerotic samples (four patients) and the rest from normal sites (three patients). The samples were serially scanned cross-sectionally by micro-CT with a pixel size of 23.20 μm, slice thickness of 18.56 μm, and image matrix of 512 x 512. Each image data set consisted of 250 consecutive slices. The volumes of interest (96 x 96 x 120 voxels) were defined in the original image sets and 3D indices of the trabecular microstructure were determined. The trabecular thickness (Tb.Th) in degenerative sclerotic lesions was significantly higher than that in normal sites, whereas no significant difference was observed in trabecular number (Tb.N). By contrast, in metastatic lesions, the Tb.N was significantly higher with increased bone volume fraction (BV/TV) than in normal sites, and no significant difference was found in Tb.Th. The characteristics of the trabecular surface in the metastatic samples showed concave structural elements with an increase in BV/TV, indicating osteolysis of the trabecular bone. In 3D reconstructed images, increased trabecular bone with an irregular surface was observed in samples from metastatic sites, which were uniformly sclerotic on soft X-ray radiographs. These results support, through 3D morphological features, the strong bone resorption effect in bone metastasis from prostate cancer. (orig.)

  18. Bone health history in breast cancer patients on aromatase inhibitors.

    Directory of Open Access Journals (Sweden)

    Marilyn L Kwan

    Full Text Available A cross-sectional study was performed to assess bone health history among aromatase inhibitor (AI users before breast cancer (BC diagnosis, which may impact fracture risk after AI therapy and choice of initial hormonal therapy. A total of 2,157 invasive BC patients initially treated with an AI were identified from a prospective cohort study at Kaiser Permanente Northern California (KPNC. Data on demographic and lifestyle factors were obtained from in-person interviews, and bone health history and clinical data from KPNC clinical databases. The prevalence of osteoporosis and fractures in postmenopausal AI users was assessed, compared with 325 postmenopausal TAM users. The associations of bone health history with demographic and lifestyle factors in AI users were also examined. Among all initial AI users, 11.2% had a prior history of osteoporosis, 16.3% had a prior history of any fracture, and 4.6% had a prior history of major fracture. Postmenopausal women who were taking TAM as their initial hormonal therapy had significantly higher prevalence of prior osteoporosis than postmenopausal AI users (21.5% vs. 11.8%, p<0.0001. Among initial AI users, the associations of history of osteoporosis and fracture in BC patients with demographic and lifestyle factors were, in general, consistent with those known in healthy older women. This study is one of the first to characterize AI users and risk factors for bone morbidity before BC diagnosis. In the future, this study will examine lifestyle, molecular, and genetic risk factors for AI-induced fractures.

  19. NCI-CPTAC DREAM Proteogenomics Challenge (Registration Now Open) | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Proteogenomics, integration of proteomics, genomics, and transcriptomics, is an emerging approach that promises to advance basic, translational and clinical research.  By combining genomic and proteomic information, leading scientists are gaining new insights due to a more complete and unified understanding of complex biological processes.

  20. Clinical characteristics and outcome of bone-only metastasis in inflammatory and noninflammatory breast cancers.

    Science.gov (United States)

    Kai, Megumi; Kogawa, Takahiro; Liu, Diane D; Fouad, Tamer M; Kai, Kazuharu; Niikura, Naoki; Hsu, Limin; Willey, Jie S; Theriault, Richard L; Valero, Vicente; Ueno, Naoto T

    2015-02-01

    Inflammatory breast cancer is a rare and aggressive presentation of breast cancer. Bone is a common metastatic site in breast cancer, and bone-only metastatic disease is clinically considered to have a better prognosis than visceral metastasis. However, bone-only metastasis in IBC (bone-only IBC) has not been compared with bone-only metastasis in non-IBC (bone-only non-IBC) in terms of clinical features and outcome. Because of the intrinsically aggressive nature of IBC, we hypothesized that bone-only IBC has a poorer prognosis than does bone-only non-IBC. We retrospectively identified patients with stage III primary diagnosed breast cancer who, between January 1997 and December 2012, had a first recurrence located only in the bone. Among the 197 patients that we defined as a study cohort, 50 patients had IBC and 147 patients had non-IBC. Progression-free survival (PFS) and overall survival (OS) from the date of recurrence were estimated using the Kaplan-Meier method, and patient characteristic groups were compared using the log-rank test. OS did not differ significantly between the 2 groups (P = .2467), but a shorter PFS was seen in patients with bone-only IBC than in patients with bone-only non-IBC (P = .0357). Among patients with estrogen receptor (ER)-positive disease, a much shorter PFS was seen in bone-only IBC than in bone-only non-IBC (P = .0159). Bone-only IBC has a poorer prognosis than does bone-only non-IBC, particularly in those with ER-positive tumors. We might need to consider more aggressive intervention (e.g., chemotherapy) for IBC patients with ER-positive bone-only metastatic disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  1. Proteomic profiling of the hypothalamus in a mouse model of cancer-induced anorexia-cachexia.

    Science.gov (United States)

    Ihnatko, R; Post, C; Blomqvist, A

    2013-10-01

    Anorexia-cachexia is a common and severe cancer-related complication but the underlying mechanisms are largely unknown. Here, using a mouse model for tumour-induced anorexia-cachexia, we screened for proteins that are differentially expressed in the hypothalamus, the brain's metabolic control centre. The hypothalamus of tumour-bearing mice with implanted methylcholanthrene-induced sarcoma (MCG 101) displaying anorexia and their sham-implanted pair-fed or free-fed littermates was examined using two-dimensional electrophoresis (2-DE)-based comparative proteomics. Differentially expressed proteins were identified by liquid chromatography-tandem mass spectrometry. The 2-DE data showed an increased expression of dynamin 1, hexokinase, pyruvate carboxylase, oxoglutarate dehydrogenase, and N-ethylmaleimide-sensitive factor in tumour-bearing mice, whereas heat-shock 70 kDa cognate protein, selenium-binding protein 1, and guanine nucleotide-binding protein Gα0 were downregulated. The expression of several of the identified proteins was similarly altered also in the caloric-restricted pair-fed mice, suggesting an involvement of these proteins in brain metabolic adaptation to restricted nutrient availability. However, the expression of dynamin 1, which is required for receptor internalisation, and of hexokinase, and pyruvate carboxylase were specifically changed in tumour-bearing mice with anorexia. The identified differentially expressed proteins may be new candidate molecules involved in the pathophysiology of tumour-induced anorexia-cachexia.

  2. Quality Assessments of Long-Term Quantitative Proteomic Analysis of Breast Cancer Xenograft Tissues

    Energy Technology Data Exchange (ETDEWEB)

    Zhou, Jian-Ying; Chen, Lijun; Zhang, Bai; Tian, Yuan; Liu, Tao; Thomas, Stefani N.; Chen, Li; Schnaubelt, Michael; Boja, Emily; Hiltket, Tara; Kinsinger, Christopher; Rodriguez, Henry; Davies, Sherri; Li, Shunqiang; Snider, Jacqueline E.; Erdmann-Gilmore, Petra; Tabb, David L.; Townsend, Reid; Ellis, Matthew; Rodland, Karin D.; Smith, Richard D.; Carr, Steven A.; Zhang, Zhen; Chan, Daniel W.; Zhang, Hui

    2017-09-21

    The identification of protein biomarkers requires large-scale analysis of human specimens to achieve statistical significance. In this study, we evaluated the long-term reproducibility of an iTRAQ (isobaric tags for relative and absolute quantification) based quantitative proteomics strategy using one channel for universal normalization across all samples. A total of 307 liquid chromatography tandem mass spectrometric (LC-MS/MS) analyses were completed, generating 107 one-dimensional (1D) LC-MS/MS datasets and 8 offline two-dimensional (2D) LC-MS/MS datasets (25 fractions for each set) for human-in-mouse breast cancer xenograft tissues representative of basal and luminal subtypes. Such large-scale studies require the implementation of robust metrics to assess the contributions of technical and biological variability in the qualitative and quantitative data. Accordingly, we developed a quantification confidence score based on the quality of each peptide-spectrum match (PSM) to remove quantification outliers from each analysis. After combining confidence score filtering and statistical analysis, reproducible protein identification and quantitative results were achieved from LC-MS/MS datasets collected over a 16 month period.

  3. NCI Requests Cancer Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 11, 2014.

  4. Quantitative proteomics and transcriptomics addressing the estrogen receptor subtype-mediated effects in T47D breast cancer cells exposed to the phytoestrogen genistein

    NARCIS (Netherlands)

    Sotoca Covaleda, A.M.; Sollewijn Gelpke, M.D.; Boeren, S.; Ström, A.; Gustafsson, J.A.; Murk, A.J.; Rietjens, I.M.C.M.; Vervoort, J.J.M.

    2011-01-01

    The present study addresses, by transcriptomics and quantitative SILAC-based proteomics, the estrogen receptor alpha (ER) and beta (ERß)-mediated effects on gene and protein expression in T47D breast cancer cells exposed to the phytoestrogen genistein. Using the T47D human breast cancer cell line

  5. [Search for potential gastric cancer biomarkers using low molecular weight blood plasma proteome profiling by mass spectrometry].

    Science.gov (United States)

    Shevchenko, V E; Arnotskaia, N E; Ogorodnikova, E V; Davydov, M M; Ibraev, M A; Turkin, I N; Davydov, M I

    2014-01-01

    Gastric cancer, one of the most widespread malignant tumors, still lacks reliable serum/plasma biomarkers of its early detection. In this study we have developed, unified, and tested a new methodology for search of gastric cancer biomarkers based on profiling of low molecular weight proteome (LMWP) (1-17 kDa). This approach included three main components: sample pre-fractionation, matrix-assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF-MS), data analysis by a bioinformatics software package. Applicability and perspectives of the developed approach for detection of potential gastric cancer markers during LMWP analysis have been demonstrated using 69 plasma samples from patients with gastric cancer (stages I-IV) and 238 control samples. The study revealed peptides/polypeptides, which may be potentially used for detection of this pathology.

  6. Value of bone scintigraphy for pre-, postoperative assessment and follow-up study of breast cancer

    International Nuclear Information System (INIS)

    Lee, Hae Giu; Park, Jeong Mi; Chung, Soo Kyo; Kim, Choon Yul; Bahk, Yong Whee

    1985-01-01

    Early detection of neoplastic disease and metastatic spread is very important. Carcinoma of the breast is known to readily metastasize to the bone. The use of Tc-99m-phosphate as bone imaging agent has been shown to demonstrate early evidence of bone metastasis well before radiographic evidence is visualized and as thus become a very useful technique for establishing and monitoring the bony metastatic element of breast cancer. In this study, serial bone imaging studies were performed to monitor the management of 84 breast cancer patients before and after mastectomy and biopsy. We attempted to analyse bone scans of breast cancer and to correlate the scan findings with the clinical stage, status of lymph nodes, distant metastasis, bone pain, and laboratory data. The following useful patterns were emerged: 1. Positive bone scan rate was definitely higher in clinical stage III and IV (42, 57%) than in stage I and II (4, 18%) in initial studies. However, no correlation between positive bone scan rate and clinical stage was found in follow up studies. 2. Positive bone scan rate was high in both groups with locally advanced tumor (T3 and T4) and distant metastasis. 3. No correlation between positive bone scan and status of lymph node involvement was noted. 4. Positive bone scan rate was also very high in patients with bone pain and abnormal laboratory data

  7. Use of Proteomics Analysis for Molecular Precision Approaches in Cancer Therapy

    Directory of Open Access Journals (Sweden)

    Yuqiao Shen

    2008-01-01

    Full Text Available The rapidly expanding data sets derived from genomic and transcriptomic analyses have allowed greater understanding of structural and functional network patterns within the genome resulting in a realignment of thinking within a systems biologic framework of cancer. However, insofar as spatially and temporally dynamic differential gene expression at the protein level is the mediate effector of cellular behavior and, in view of extensive post translational modification (PTM, the need for sensitive, quantitative, and high throughput proteomic analytic techniques has emerged. To circumvent the problems of tissue sample heterogeneity, laser capture microdissection (LCM allows for the acquisition of homogeneous cell populations. Using different fl uorescent dyes to label protein samples prior to gel electrophoresis, 2-D DIGE (two- dimensional differential in-gel electrophoresis can, with reasonable sensitivity, process three protein samples on the same gel allowing for intragel relative quantification. MudPIT (multidimensional protein identification technology is a non-gel approach exploiting the unique physical properties of charge and hydrophobicity which allows the separation of peptide mixtures as well as direct MS (mass spectrometry and database searching. The introduction of iTRAQ (isobaric tags for relative and absolute quantification achieves labeling of all peptides by employing an 8-plex set of amine reactive tags to derivatize peptides at the N-terminus and lysine side chains allowing for absolute quantification and assessment of PTM. These and other new laboratory technologies, along with improved bioinformatics tools, have started to make signifi cant contributions in cancer diagnostics and treatments.

  8. Prostate Cancer Metastases to Bone: Role of High Bone Turnover Induced by Androgen Deprivation

    National Research Council Canada - National Science Library

    Padalecki, Susan

    2002-01-01

    .... Treatment with androgen deprivation therapy leads to an increase in bone turnover as indicated by the loss of bone mineral density and the increase in markers of bone turnover in patients on treatment...

  9. The clinical value of "9"9Tc"m-MDP whole body bone imaging in diagnosing bone metastasis of lung cancer

    International Nuclear Information System (INIS)

    Zhao Yigang; Gou Zhengxing

    2016-01-01

    Objective: To discuss the clinical value of whole body bone imaging on lung cancer bone metastases diagnosis, so as to evaluate the staging of lung cancer patients. Methods: A total of 113 cases of patients diagnosed with lung cancer received whole body imaging, alkaline phosphatase and blood calcium examination. Bone metastasis probability of lung cancer was assessed based on different pathological types. Accuracy rates of bone metastases was compared by whole body bone imaging and suspicious bone metastasis factors (Including one or several items in ostalgia, alkaline phosphatase rising and hypercalcemia). Results The occurrence rate of lung cancer bone metastasis is 36.7%, and the bone metastasis occurrence rate of adenocarcinoma of lung is higher than that of squamous cell lung carcinoma (P < 0.01). Whole body Imaging diagnose of lung cancer bone metastases had sensitivity (92.7%), specificity (83.2%) and accuracy (85.7%). Conclusion: "9"9Tc"m-MDP whole body imaging is a highly sensitive tool to review whole body bone. Lung cancer patients are recommended to receive routine whole body bone imaging. (authors)

  10. C-C motif ligand 5 promotes migration of prostate cancer cells in the prostate cancer bone metastasis microenvironment.

    Science.gov (United States)

    Urata, Satoko; Izumi, Kouji; Hiratsuka, Kaoru; Maolake, Aerken; Natsagdorj, Ariunbold; Shigehara, Kazuyoshi; Iwamoto, Hiroaki; Kadomoto, Suguru; Makino, Tomoyuki; Naito, Renato; Kadono, Yoshifumi; Lin, Wen-Jye; Wufuer, Guzailinuer; Narimoto, Kazutaka; Mizokami, Atsushi

    2018-03-01

    Chemokines and their receptors have key roles in cancer progression. The present study investigated chemokine activity in the prostate cancer bone metastasis microenvironment. Growth and migration of human prostate cancer cells were assayed in cocultures with bone stromal cells. The migration of LNCaP cells significantly increased when co-cultured with bone stromal cells isolated from prostate cancer bone metastases. Cytokine array analysis of conditioned medium from bone stromal cell cultures identified CCL5 as a concentration-dependent promoter of LNCaP cell migration. The migration of LNCaP cells was suppressed when C-C motif ligand 5 (CCL5) neutralizing antibody was added to cocultures with bone stromal cells. Knockdown of androgen receptor with small interfering RNA increased the migration of LNCaP cells compared with control cells, and CCL5 did not promote the migration of androgen receptor knockdown LNCaP. Elevated CCL5 secretion in bone stromal cells from metastatic lesions induced prostate cancer cell migration by a mechanism consistent with CCL5 activity upstream of androgen receptor signaling. © 2017 The Authors. Cancer Science published by John Wiley & Sons Australia, Ltd on behalf of Japanese Cancer Association.

  11. Detection of occult bone metastases of lung cancer with Fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Foo, S.S.; Ramdave, S.; Berlangieri, S.U.; Scott, A.M.

    2004-01-01

    Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastasesin patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans. Copyright (2004) Blackwell Science Pty Ltd

  12. Detection of occult bone metastases of lung cancer with fluorine-18 fluorodeoxyglucose positron emission tomography

    International Nuclear Information System (INIS)

    Ramdave, Shankar; Berlangieri, Salvatore U.

    2004-01-01

    Accurate staging of cancer has a critical role in optimal patient management. Fluorine-18 fluorodeoxyglucose positron emission tomography (FDG PET) is superior to CT in the detection of local and distant metastases in patients with non-small cell lung cancer. Although Tc-99 m methylene diphosphonate (MDP) bone scanning is well established in the evaluation of bone metastases, there are conflicting reports on the use of FDG PET in the evaluation of skeletal metastases. We report on a patient with locally advanced lung carcinoma in whom FDG PET accurately identified previously unsuspected widespread asymptomatic bone metastases (bone scan and X-rays negative, confirmed on MRI). Assessment of glucose metabolism with FDG PET might represent a more powerful tool to detect bone metastases in lung cancer compared with conventional bone scans Copyright (2004) Blackwell Publishing Asia Pty Ltd

  13. Bone-targeted cabazitaxel nanoparticles for metastatic prostate cancer skeletal lesions and pain.

    Science.gov (United States)

    Gdowski, Andrew S; Ranjan, Amalendu; Sarker, Marjana R; Vishwanatha, Jamboor K

    2017-09-01

    The aim of this study was to develop a novel cabazitaxel bone targeted nanoparticle (NP) system for improved drug delivery to the bone microenvironment. Nanoparticles were developed using poly(D,L-lactic-co-glycolic acid) and cabazitaxel as the core with amino-bisphosphonate surface conjugation. Optimization of nanoparticle physiochemical properties, in vitro evaluation in prostate cancer cell lines and in vivo testing in an intraosseous model of metastatic prostate cancer was performed. This bone targeted cabazitaxel nanocarrier system showed significant reduction in tumor burden, while at the same time maintaining bone structure integrity and reducing pain in the mouse tumor limb. This bone microenvironment targeted nanoparticle system and clinically relevant approach of evaluation represents a promising advancement for treating bone metastatic cancer.

  14. The value of combined examination of serum CA15-3, CEA level and whole body bone scan in the diagnosis of bone metastasis in breast cancer

    International Nuclear Information System (INIS)

    Lu Baoshi; Gao Yufang

    2011-01-01

    Objective: To explore the value of combined examination of serum tumormarkers carbohydrate antigen 15-3 (CA15-3), carcinoembryonic antigen (CEA) and whole body bone scan in the diagnosis of bone metastasis in breast cancer. Methods: Whole body bone scan and serum CA15-3 and CEA levels with a electrochemical luminescence assay were performed in 97 patients with breast cancer (46 cases with bone metastasis and 51 cases without bone metastasis) and 45 patients with benign breast diseases. As for the negative cases who had significant pains in bones, CT or MRI was performed to make sure. Results: The serum level of CA15-3 and CEA were significantly higher in patients with bone metastasis than those in patients without bone metastasis and the benign lesions. The positive predicting values were 76.09% and 80.43%. Most patients with bone metastasis had positive results in bone scan (95.65%), only 2 cases had negative results (4.35%), which is positive by CT or MRI Seven. Seven patients without bone metastasis and Three patients with the benign lesions had positive results in bone scan, that may be caused by previous operation or injury. The combined determination of CA15-3, CEA and whole body bone scan had a better performance in sensitivity, specificity and accuracy than each single way. Conclusion: The combined determination of CA 15-3, CEA and whole body bone scan were valuable in the diagnosis of bone metastasis in breast cancer. (authors)

  15. The Src family kinase inhibitor dasatinib delays pain-related behaviour and conserves bone in a rat model of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Appel, Camilla Kristine; Gallego-Pedersen, Simone; Andersen, Line

    2017-01-01

    Pain is a severe and debilitating complication of metastatic bone cancer. Current analgesics do not provide sufficient pain relief for all patients, creating a great need for new treatment options. The Src kinase, a non-receptor protein tyrosine kinase, is implicated in processes involved in cancer......-induced bone pain, including cancer growth, osteoclastic bone degradation and nociceptive signalling. Here we investigate the role of dasatinib, an oral Src kinase family and Bcr-Abl tyrosine kinase inhibitor, in an animal model of cancer-induced bone pain. Daily administration of dasatinib (15 mg/kg, p...

  16. Bone scan in breast cancer patients with mastectomy and breast reconstruction with a myocutaneous TRAM flap

    International Nuclear Information System (INIS)

    Morales, Rosanna; Cano, Roque; Delgado, Ricardo; Munive, Carlos

    2014-01-01

    Objectives: To report findings in bone scans for breast cancer patients with mastectomy and breast reconstruction with transverse rectus abdominis myocutaneous flap (TRAM). Material and Methods: Inclusion criteria were: confirmed breast cancer, mastectomy, breast reconstruction with TRAM flap and bone scan performed after TRAM. Exclusion criteria were: Absence of bone scan image, breast reconstruction by other approaches. Results: Absence of uptake in TRAM flap in six patients, diminished uptake in skin near TRAM, with peripheral increased uptake in three and increased uptake in TRAM flap, in a patient with cancer recurrence, confirmed by biopsy. Conclusions: Bone scans in breast cancer patients with mastectomy and TRAM flap can have different imaging presentations, procedure details diminish reporting errors. TRAM flap may present fat necrosis areas, which should be differentiated from recurrence in bone scans. Additional imaging and biopsy will be needed to diagnose this finding. (authors).

  17. The effect of radiation therapy for bone metastasis in urinary organ cancer

    International Nuclear Information System (INIS)

    Chikazawa, Ippei; Inoue, Shinya; Nakazawa, Yusuke

    2016-01-01

    Bone metastasis symptoms are complications that greatly reduce the quality of life (QOL) of cancer patients. We report a retrospective study on the efficacy of radiation therapy for patients with bone metastasis in urinary organ cancer. (Subjects and methods) Subjects are comprised of 17 patients; total irradiated areas consist of 25 sites. There are 5 patients diagnosed with renal cell carcinoma, 1 patient with bladder cancer and 11 patients with prostatic cancer. All of them have undergone radiation therapy for bone metastasis in urinary organ cancer between April 2007 and March 2014 in the Department of Urology, Kanazawa Medical University. The mean age of the patients was 66.7 years old. We looked at irradiated areas, exposure dose and changes of symptom in all patients. Irradiated areas are thoracolumbar vertebrae (14 sites), cranial base (2 sites), pubic bone (1 site), ilium bone (2 sites), sacral bone (1 site), rib bone (1 site) and hip joint (1 site). The mean exposure dose of one area is 37.5 Gy (13.5-60). 19 irradiated sites which were previously reported to have sharp pain have gained improvement at 16 sites. These 16 sites have comparatively lesser pain or no pain. 8 cases in acknowledgment of walk difficulty, it was with 7 cases walking alone possibility again. This study showed that radiation therapy have significant improvement in terms of symptoms and QOL for the patients with bone metastasis in urinary organ cancer. (author)

  18. Awareness, concern, and communication between physicians and patients on bone health in cancer.

    Science.gov (United States)

    Tripathy, Debu; Durie, Brian G M; Mautner, Beatrice; Ferenz, Krag S; Moul, Judd W

    2014-06-01

    This study aims to explore physician-patient communications about bone metastases and cancer treatment-induced bone loss (CTIBL). The study utilizes online survey of patients with breast cancer, prostate cancer, and multiple myeloma, and the physicians who treat them. Even though 69 and 48 % of patients with nonmetastatic breast and prostate cancer aware of treatment-induced bone loss, only 39 and 23 %, respectively, were concerned about bone loss. Yet, 62 and 71 % of oncologists treating breast and prostate cancer felt that their patients were concerned. Among patients with metastatic breast and prostate cancer, two thirds had not discussed treatment for bone metastases with their doctor; when discussed, 88 and 91 % of discussions were initiated by the doctor, usually prior to initiating treatment. Most myeloma patients (77 %) had discussed treatment options with their physicians; 99 % of hematologists reported discussing treatment of bone disease with patients. Physicians are primary sources of information to patients regarding bone health. There is a gap between what physicians assume their patients know about bone health and the patients' perceptions, presenting a need for systematic awareness and education.

  19. Use of Bone Scan During Initial Prostate Cancer Workup, Downstream Procedures, and Associated Medicare Costs

    Energy Technology Data Exchange (ETDEWEB)

    Falchook, Aaron D. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Salloum, Ramzi G. [Department of Health Services Policy and Management, University of South Carolina, Columbia, South Carolina (United States); Hendrix, Laura H. [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Chen, Ronald C., E-mail: ronald_chen@med.unc.edu [Department of Radiation Oncology, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Cecil G. Sheps Center for Health Services Research, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States); Lineberger Comprehensive Cancer Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina (United States)

    2014-06-01

    Purpose: For patients with a high likelihood of having metastatic disease (high-risk prostate cancer), bone scan is the standard, guideline-recommended test to look for bony metastasis. We quantified the use of bone scans and downstream procedures, along with associated costs, in patients with high-risk prostate cancer, and their use in low- and intermediate-risk patients for whom these tests are not recommended. Methods and Materials: Patients in the Surveillance, Epidemiology, and End Results (SEER)-Medicare database diagnosed with prostate cancer from 2004 to 2007 were included. Prostate specific antigen (PSA), Gleason score, and clinical T stage were used to define D'Amico risk categories. We report use of bone scans from the date of diagnosis to the earlier of treatment or 6 months. In patients who underwent bone scans, we report use of bone-specific x-ray, computed tomography (CT), and magnetic resonance imaging (MRI) scans, and bone biopsy within 3 months after bone scan. Costs were estimated using 2012 Medicare reimbursement rates. Results: In all, 31% and 48% of patients with apparent low- and intermediate-risk prostate cancer underwent a bone scan; of these patients, 21% underwent subsequent x-rays, 7% CT, and 3% MRI scans. Bone biopsies were uncommon. Overall, <1% of low- and intermediate-risk patients were found to have metastatic disease. The annual estimated Medicare cost for bone scans and downstream procedures was $11,300,000 for low- and intermediate-risk patients. For patients with apparent high-risk disease, only 62% received a bone scan, of whom 14% were found to have metastasis. Conclusions: There is overuse of bone scans in patients with low- and intermediate-risk prostate cancers, which is unlikely to yield clinically actionable information and results in a potential Medicare waste. However, there is underuse of bone scans in high-risk patients for whom metastasis is likely.

  20. Application of a global proteomic approach to archival precursor lesions: deleted in malignant brain tumors 1 and tissue transglutaminase 2 are upregulated in pancreatic cancer precursors

    DEFF Research Database (Denmark)

    Cheung, Wang; Darfler, Marlene M; Alvarez, Hector

    2008-01-01

    BACKGROUND: Pancreatic cancer is an almost uniformly fatal disease, and early detection is a critical determinant of improved survival. A variety of noninvasive precursor lesions of pancreatic adenocarcinoma have been identified, which provide a unique opportunity for intervention prior to onset ...... their overexpression in IPMNs. CONCLUSION: Global proteomics analysis using the Liquid Tissue workflow is a feasible approach for unbiased biomarker discovery in limited archival material, particularly applicable to precursor lesions of cancer......., and mass spectrometry to conduct a global proteomic analysis of an intraductal papillary mucinous neoplasm (IPMN). Tissue microarrays comprised of 38 IPMNs were used for validation of candidate proteins. RESULTS: The proteomic analysis of the IPMN Liquid Tissue lysate resulted in identification of 1......,534 peptides corresponding to 523 unique proteins. A subset of 25 proteins was identified that had previously been reported as upregulated in pancreatic cancer. Immunohistochemical analysis for two of these, deleted in malignant brain tumors 1 (DMBT1) and tissue transglutaminase 2 (TGM2), confirmed...

  1. Suppression of asparaginyl endopeptidase attenuates breast cancer-induced bone pain through inhibition of neurotrophin receptors.

    Science.gov (United States)

    Yao, Peng; Ding, Yuanyuan; Han, Zhenkai; Mu, Ying; Hong, Tao; Zhu, Yongqiang; Li, Hongxi

    2017-01-01

    Objective Cancer-induced bone pain is a common clinical problem in breast cancer patients with bone metastasis. However, the mechanisms driving cancer-induced bone pain are poorly known. Recent studies show that a novel protease, asparaginyl endopeptidase (AEP) plays crucial roles in breast cancer metastasis and progression. We aim to determine the functions and targeted suppress of AEP in a mouse model of breast cancer-induced bone pain. Methods Breast cancer cells with AEP knocked-down or overexpression were constructed and implanted into the intramedullary space of the femur to induce pain-like behavior in mice. AEP-specific inhibitors or purified AEP proteins were further used in animal model. The histological characters of femur and pain ethological changes were measured. The expressions of AEP and neurotrophin receptors (p75NTR and TrkA) in dorsal root ganglion and spinal cord were examined. Results Femur radiographs and histological analysis revealed that cells with AEP knocked-down reduced bone destruction and pain behaviors. However, cells with AEP overexpression elevated bone damage and pain behaviors. Further, Western blot results found that the expressions of p75NTR and TrkA in dorsal root ganglions and spinal cords were reduced in mice inoculated with AEP knocked-down cells. Targeted suppression of AEP with specific small compounds significantly reduced the bone pain while purified recombinant AEP proteins increased bone pain. Conclusions AEP aggravate the development of breast cancer bone metastasis and bone pain by increasing the expression of neurotrophin receptors. AEP might be an effective target for treatment of breast cancerinduced bone pain.

  2. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Brockton, Nigel T.; Gill, Stephanie J.; Laborge, Stephanie L.; Paterson, Alexander H. G.; Cook, Linda S.; Vogel, Hans J.; Shemanko, Carrie S.; Hanley, David A.; Magliocco, Anthony M.; Friedenreich, Christine M.

    2015-01-01

    Bone is the most common site of breast cancer distant metastasis, affecting 50–70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  3. The Breast Cancer to Bone (B2B) Metastases Research Program: a multi-disciplinary investigation of bone metastases from breast cancer.

    Science.gov (United States)

    Brockton, Nigel T; Gill, Stephanie J; Laborge, Stephanie L; Paterson, Alexander H G; Cook, Linda S; Vogel, Hans J; Shemanko, Carrie S; Hanley, David A; Magliocco, Anthony M; Friedenreich, Christine M

    2015-07-10

    Bone is the most common site of breast cancer distant metastasis, affecting 50-70 % of patients who develop metastatic disease. Despite decades of informative research, the effective prevention, prediction and treatment of these lesions remains elusive. The Breast Cancer to Bone (B2B) Metastases Research Program consists of a prospective cohort of incident breast cancer patients and four sub-projects that are investigating priority areas in breast cancer bone metastases. These include the impact of lifestyle factors and inflammation on risk of bone metastases, the gene expression features of the primary tumour, the potential role for metabolomics in early detection of bone metastatic disease and the signalling pathways that drive the metastatic lesions in the bone. The B2B Research Program is enrolling a prospective cohort of 600 newly diagnosed, incident, stage I-IIIc breast cancer survivors in Alberta, Canada over a five year period. At baseline, pre-treatment/surgery blood samples are collected and detailed epidemiologic data is collected by in-person interview and self-administered questionnaires. Additional self-administered questionnaires and blood samples are completed at specified follow-up intervals (24, 48 and 72 months). Vital status is obtained prior to each follow-up through record linkages with the Alberta Cancer Registry. Recurrences are identified through medical chart abstractions. Each of the four projects applies specific methods and analyses to assess the impact of serum vitamin D and cytokine concentrations, tumour transcript and protein expression, serum metabolomic profiles and in vitro cell signalling on breast cancer bone metastases. The B2B Research Program will address key issues in breast cancer bone metastases including the association between lifestyle factors (particularly a comprehensive assessment of vitamin D status) inflammation and bone metastases, the significance or primary tumour gene expression in tissue tropism, the

  4. A reappraisal of serial isotope bone scans in prostate cancer

    Energy Technology Data Exchange (ETDEWEB)

    O' Donoghue, J M; Rogers, E; Grimes, H; McCarthy, P; Corcoran, M; Bredin, H; Given, H F [University College Hospital, Galway (Ireland)

    1993-08-01

    The authors have evaluated prostate-specific antigen (PSA) and prostatic acid phosphatase (PAP) as alternatives to conventional serial bone scanning in 129 patients with newly diagnosed prostate cancer over a period of 3 years. Although serum PSA did not reflect local tumour burden at presentation, it was significantly elevated in those with stage D disease (p < 0.01). 45 patients presented de novo with metastatic bone deposits and a further 18 patients developed metastases during the study. The sensitivity of PSA in detecting secondary deposits at presentation for levels in excess of 100 [mu]g/l was 93.75%, the positive predictive value 95.7% and the negative predictive value for levels less than 5 [mu]g/l was 90.6%. During the follow-up period sensitivity was 94.4%, the positive predictive value 100%, the negative predictive value 100%, with a median lead time of 3 months in predicting metastases in the 18 patients with progressive disease. (author).

  5. Quantitative proteomic analysis of paired colorectal cancer and non-tumorigenic tissues reveals signature proteins and perturbed pathways involved in CRC progression and metastasis.

    Science.gov (United States)

    Sethi, Manveen K; Thaysen-Andersen, Morten; Kim, Hoguen; Park, Cheol Keun; Baker, Mark S; Packer, Nicolle H; Paik, Young-Ki; Hancock, William S; Fanayan, Susan

    2015-08-03

    Modern proteomics has proven instrumental in our understanding of the molecular deregulations associated with the development and progression of cancer. Herein, we profile membrane-enriched proteome of tumor and adjacent normal tissues from eight CRC patients using label-free nanoLC-MS/MS-based quantitative proteomics and advanced pathway analysis. Of the 948 identified proteins, 184 proteins were differentially expressed (P1.5) between the tumor and non-tumor tissue (69 up-regulated and 115 down-regulated in tumor tissues). The CRC tumor and non-tumor tissues clustered tightly in separate groups using hierarchical cluster analysis of the differentially expressed proteins, indicating a strong CRC-association of this proteome subset. Specifically, cancer associated proteins such as FN1, TNC, DEFA1, ITGB2, MLEC, CDH17, EZR and pathways including actin cytoskeleton and RhoGDI signaling were deregulated. Stage-specific proteome signatures were identified including up-regulated ribosomal proteins and down-regulated annexin proteins in early stage CRC. Finally, EGFR(+) CRC tissues showed an EGFR-dependent down-regulation of cell adhesion molecules, relative to EGFR(-) tissues. Taken together, this study provides a detailed map of the altered proteome and associated protein pathways in CRC, which enhances our mechanistic understanding of CRC biology and opens avenues for a knowledge-driven search for candidate CRC protein markers. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Bone marrow radioimmune scintigraphy in the assessment of breast cancer treatment

    International Nuclear Information System (INIS)

    Klissarova, A.; Georgieva, Zh.; Tsekov, H.; Temelkov, T.

    2004-01-01

    Full text: Breast cancer is the most common cancer, affecting women in all developed countries of the world. 60 to 70% of women who die with breast cancer have bone metastases. These metastases are currently detected by means of bone scintigraphy and X-ray examinations. Serial bone scans provide significant prognostic information but the assessment of the treatment response remains a problem as the 'flare phenomena' seen shortly after treatment causes difficulty in interpretation of the bone scan. Moreover, an unchanged bone scan findings do not always indicate poor / absent response to therapy. The assessment of bone marrow regeneration in patients with breast cancer is important because it is the primary site of metastases. The aim of this study was to assess the efficacy of chemotherapy treatment in patients with breast cancer by means of radioimmuno bone marrow scintigraphy. We studied 15 patients (mean age 63 years) with advanced breast cancer (II - III stage) and bone metastases revealed by whole body bone scintigraphy and X-ray examination. All patients were treated with two courses of chemotherapy with FEC (Farmorubicin, Cyclophosphamide and 5-Fuoracil) at an interval of four weeks. After the treatment, all patients underwent bone marrow radioimmuno scintigraphy with AGMoAb BW 250/183 (Granulozyt). The AGMoAb was injected by slow intravenous injection in a dose 0.5 mg labelled with 740 Mbq of Tc-99m in a volume of 2 ml of. The images were obtained between 5 - 6 hours after the injection. Whole body scan was performed in anterior and posterior views under a gamma camera (DIACAM-Siemens) coupled with low energy collimator. Radioimmuno imaging before surgery and chemotherapy showed absence of granulopoeitic bone marrow in many areas of the skeleton coinciding with the bone metastases detected by bone scintigraphy. Radioimmuno imaging performed after chemotherapy demonstrated presence of bone marrow in 8 patients (53%) in areas where it was previously absent

  7. Proteome screening of pleural effusions identifies IL1A as a diagnostic biomarker for non-small cell lung cancer.

    Science.gov (United States)

    Li, Yuanyuan; Lian, Hengning; Jia, Qingzhu; Wan, Ying

    2015-02-06

    Non-small cell lung cancer (NSCLC) is a common malignant disease, and in ~10-20% of patients, pleural effusion is the first symptom. The pleural effusion proteome contains information on pulmonary disease that directly or indirectly reflects pathophysiological status. However, the proteome of pleural effusion in NSCLC patients is not well understood, nor is the variability in protein composition between malignant and benign pleural effusions. Here, we investigated the different proteins in pleural effusions from NSCLC and tuberculosis (TB) patients by using nano-scale liquid chromatography-tandem mass spectrometry (nLC-MS/MS) analysis. In total, 363 proteins were identified in the NSCLC pleural effusion proteome with a low false discovery rate (pleural effusion were involved in cell adhesion, proteolysis, and cell migration. Furthermore, interleukin 1 alpha (IL1A), a protein that regulates tumor growth, angiogenesis, and metastasis, was significantly more abundant in the NSCLC group compared to the TB group, a finding that was validated with an ELISA assay. Copyright © 2014 Elsevier Inc. All rights reserved.

  8. Diagnostic performance of [18F] FDG PET-CT compared to bone scintigraphy for the detection of bone metastases in lung cancer patients

    International Nuclear Information System (INIS)

    RODRIGUES, Margarida; STARK, Hannes; RENDL, Gundula; RETTENBACHER, Lukas; PIRICH, Christian; DATZ, Lidwina; STUDNICKA, Michael

    2016-01-01

    Accurate staging of lung cancer is essential for effective patient management and selection of appropriate therapeutic strategy. The aim of this paper was to compare the value of bone scintigraphy and FDG PET-CT for detecting bone metastases in lung cancer patients and the impact of these modalities in disease staging. One hundred sixty-four lung cancer patients who had undergone both FDG PET-CT and bone scintigraphy within 14 days were included into this study. The analysis of FDG PET-CT and bone scintigraphy was carried out patient- and lesion-based. One hundred twenty-one patients were negative and 43 patients positive for bone metastases. FDG PET-CT found bone metastases in 42/43 patients and bone scintigraphy in 38/43 patients. Sensitivity, specificity and accuracy of FDG PET-CT and bone scintigraphy for detecting bone metastases were 97.7%, 100% and 99.4%, and 87.8%, 97.5% and 94.2%, respectively. FDG PET-CT identified 430 bone metastases and bone scintigraphy 246 bone metastases. Skull was the only region where bone scintigraphy identified more lesions than FDG PET-CT. Based on both scintigraphic modalities disagreement concerning disease stage was found in 3 patients. In conclusion, FDG PET-CT yielded a higher sensitivity, specificity and accuracy than bone scintigraphy for identifying bone metastases in lung cancer patients. FDG PET-CT thus can be recommended for initial staging of lung cancer patients without applying bone scintigraphy for the detection of bone metastases.

  9. Mining novel biomarkers for prognosis of gastric cancer with serum proteomics

    Directory of Open Access Journals (Sweden)

    Sui Mei-Hua

    2009-09-01

    Full Text Available Abstract Background Although gastric caner (GC remains the second cause of cancer-related death, useful biomarkers for prognosis are still unavailable. We present here the attempt of mining novel biomarkers for GC prognosis by using serum proteomics. Methods Sera from 43 GC patients and 41 controls with gastritis as Group 1 and 11 GC patients as Group 2 was successively detected by Surface Enhanced Laser Desorption/ionization Time of Flight Mass Spectrometry (SELDI-TOF-MS with Q10 chip. Peaks were acquired by Ciphergen ProteinChip Software 3.2.0 and analyzed by Zhejiang University-ProteinChip Data Analysis System (ZJU-PDAS. CEA level were evaluated by chemiluminescence immunoassay. Results After median follow-up periods of 33 months, Group 1 with 4 GC patients lost was divided into 20 good-prognosis GC patients (overall survival more than 24 months and 19 poor-prognosis GC patients (no more than 24 months. The established prognosis pattern consisted of 5 novel prognosis biomarkers with 84.2% sensitivity and 85.0% specificity, which were significantly higher than those of carcinoembryonic antigen (CEA and TNM stage. We also tested prognosis pattern blindly in Group 2 with 66.7% sensitivity and 80.0% specificity. Moreover, we found that 4474-Da peak elevated significantly in GC and was associated with advanced stage (III+IV and short survival (p Conclusion We have identified a number of novel biomarkers for prognosis prediction of GC by using SELDI-TOF-MS combined with sophisticated bioinformatics. Particularly, elevated expression of 4474-Da peak showed very promising to be developed into a novel biomarker associated with biologically aggressive features of GC.

  10. Rodriguez and Pennington Address Proteogenomics and Data Sharing in the Journal Cell | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Precision medicine is an approach that allows doctors to understand how a patient's genetic profile may cause cancer to grow and spread, leading to a more personalized treatment strategy based on molecular characterization of a person's tumor. However, precision medicine as a genomics-based approach does not yet apply to all patients because genetic mutations do not always lead to changes of the corresponding proteins. Therefore, integrating genomics and proteomics data, or proteogenomics, presents as a new approach that may help make precision medicine a more effective treatment option for patients.

  11. Video Release: 47th Vice President of the United States Joseph R. Biden Jr. Speech at HUPO2017 Global Leadership Gala | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    The Human Proteome Organization (HUPO) has released a video of the keynote speech given by the 47th Vice President of the United States of America Joseph R. Biden Jr. at the HUPO2017 Global Leadership Gala. Under the gala theme “International Cooperation in the Fight Against Cancer,” Biden recognized cancer as a collection of related diseases, the importance of data sharing and harmonization, and the need for collaboration across scientific disciplines as inflection points in cancer research.

  12. Breast Cancer Cell Colonization of the Human Bone Marrow Adipose Tissue Niche.

    Science.gov (United States)

    Templeton, Zach S; Lie, Wen-Rong; Wang, Weiqi; Rosenberg-Hasson, Yael; Alluri, Rajiv V; Tamaresis, John S; Bachmann, Michael H; Lee, Kitty; Maloney, William J; Contag, Christopher H; King, Bonnie L

    2015-12-01

    Bone is a preferred site of breast cancer metastasis, suggesting the presence of tissue-specific features that attract and promote the outgrowth of breast cancer cells. We sought to identify parameters of human bone tissue associated with breast cancer cell osteotropism and colonization in the metastatic niche. Migration and colonization patterns of MDA-MB-231-fLuc-EGFP (luciferase-enhanced green fluorescence protein) and MCF-7-fLuc-EGFP breast cancer cells were studied in co-culture with cancellous bone tissue fragments isolated from 14 hip arthroplasties. Breast cancer cell migration into tissues and toward tissue-conditioned medium was measured in Transwell migration chambers using bioluminescence imaging and analyzed as a function of secreted factors measured by multiplex immunoassay. Patterns of breast cancer cell colonization were evaluated with fluorescence microscopy and immunohistochemistry. Enhanced MDA-MB-231-fLuc-EGFP breast cancer cell migration to bone-conditioned versus control medium was observed in 12/14 specimens (P = .0014) and correlated significantly with increasing levels of the adipokines/cytokines leptin (P = .006) and IL-1β (P = .001) in univariate and multivariate regression analyses. Fluorescence microscopy and immunohistochemistry of fragments underscored the extreme adiposity of adult human bone tissues and revealed extensive breast cancer cell colonization within the marrow adipose tissue compartment. Our results show that breast cancer cells migrate to human bone tissue-conditioned medium in association with increasing levels of leptin and IL-1β, and colonize the bone marrow adipose tissue compartment of cultured fragments. Bone marrow adipose tissue and its molecular signals may be important but understudied components of the breast cancer metastatic niche. Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.

  13. Bone remodeling and regulating biomarkers in women at the time of breast cancer diagnosis.

    Science.gov (United States)

    Yao, Song; Zhang, Yali; Tang, Li; Roh, Janise M; Laurent, Cecile A; Hong, Chi-Chen; Hahn, Theresa; Lo, Joan C; Ambrosone, Christine B; Kushi, Lawrence H; Kwan, Marilyn L

    2017-02-01

    The majority of breast cancer patients receive endocrine therapy, including aromatase inhibitors known to cause increased bone resorption. Bone-related biomarkers at the time of breast cancer diagnosis may predict future risk of osteoporosis and fracture after endocrine therapy. In a large population of 2,401 female breast cancer patients who later underwent endocrine therapy, we measured two bone remodeling biomarkers, TRAP5b and BAP, and two bone regulating biomarkers, RANKL and OPG, in serum samples collected at the time of breast cancer diagnosis. We analyzed these biomarkers and their ratios with patients' demographic, lifestyle, clinical tumor characteristics, as well as bone health history. The presence of bone metastases, prior bisphosphonate (BP) treatment, and blood collection after chemotherapy had a significant impact on biomarker levels. After excluding these cases and controlling for blood collection time, several factors, including age, race/ethnicity, body mass index, physical activity, alcohol consumption, smoking, and hormonal replacement therapy, were significantly associated with bone biomarkers, while vitamin D or calcium supplements and tumor characteristics were not. When prior BP users were included in, recent history of osteoporosis and fracture was also associated. Our findings support further investigation of these biomarkers with bone health outcomes after endocrine therapy initiation in women with breast cancer.

  14. The diagnostic and prognostic value of serum bone Gla protein (osteocalcin) in patients with recurrent breast cancer

    DEFF Research Database (Denmark)

    Kamby, C; Egsmose, C; Söletormos, G

    1993-01-01

    Serum bone Gla protein (S-BGP), a marker of bone metabolism, was measured in 60 patients included in a staging programme for recurrent breast cancer. Other diagnostic procedures comprised S-alkaline phosphatase (S-AP), bone scan (B-scan), bilateral iliac crest bone marrow biopsies, and radiological...... bone survey. The sites of recurrence were bone (61%), bone marrow (46%), soft tissue (52%), lung (13%), pleura (11%), liver (4%), and brain (2%). Radiology and bone biopsy served as key diagnoses as to the presence or absence of bone metastases. The diagnostic efficiency of B-scan and S-AP was greater...

  15. Module for applications of bone scan in cancer patients; Modulo para solicitudes de gammagrafia osea en pacientes con cancer

    Energy Technology Data Exchange (ETDEWEB)

    Morales, Rosanna; Cano, Roque; Velasquez, Maria [Centro de Medicina Nuclear, Instituto Peruano de Energia Nuclear, Lima (Peru); Vasquez, Edinson; Diaz, Pepe; Vasquez, Mario; Rojas, Peter [Instituto Nacional de Enfermedades Neoplasicas, Av. Angamos 2520, Surquillo, Lima (Peru)

    2013-07-01

    This paper reports the application of a software which enables the complete register of patient data, for delivering appropriate information in bone scan reports. Bone scan is a frequent study in Nuclear Medicine, which enables physicians to diagnose a primary bone cancer or metastases. The software was designed in order to complete data given by oncologists and constitutes an aid for the health team attending patients. (authors).

  16. Targeting S100P Inhibits Colon Cancer Growth and Metastasis by Lentivirus-Mediated RNA Interference and Proteomic Analysis

    Science.gov (United States)

    Jiang, Lei; Lai, Yiu-Kay; Zhang, Jinfang; Wang, Hua; Lin, Marie CM; He, Ming-liang; Kung, Hsiang-fu

    2011-01-01

    S100P was recently found to be overexpressed in a variety of cancers and is considered a potential target for cancer therapy, but the functional role or mechanism of action of S100P in colon cancer is not fully understood. In the present study, we knocked down the gene expression of S100P in colon cancer cells using lentivirus-mediated RNA interference. This step resulted in significant inhibition of cancer cell growth, migration and invasion in vitro and tumor growth and liver metastasis in vivo. Moreover, S100P downstream target proteins were identified by proteomic analysis in colon cancer DLD-1 cells with deletion of S100P. Knockdown of S100P led to downregulation of thioredoxin 1 and β-tubulin and upregulation of Rho guanosine diphosphate (GDP) dissociation inhibitor α (RhoGDIA), all potential therapeutic targets in cancer. Taken together, these findings suggest that S100P plays an important role in colon tumorigenesis and metastasis, and the comprehensive and comparative analyses of proteins associated with S100P could contribute to understanding the downstream signal cascade of S100P, leading to tumorigenesis and metastasis. PMID:21327297

  17. Bone metastasis pattern in initial metastatic breast cancer: a population-based study

    Directory of Open Access Journals (Sweden)

    Xiong Z

    2018-02-01

    Full Text Available Zhenchong Xiong,1–3,* Guangzheng Deng,1–3,* Xinjian Huang,1–3,* Xing Li,1–3 Xinhua Xie,1–3 Jin Wang,1–3 Zeyu Shuang,1–3 Xi Wang1–3 1Department of Breast Surgery, Sun Yat-sen University Cancer Center, Guangzhou, China; 2State Key Laboratory of Oncology in Southern China, Guangzhou, China; 3Collaborative Innovation Center for Cancer Medicine, Guangzhou, China *These authors contributed equally to this work Purpose: Bone is one of the most common sites of breast cancer metastasis, and population-based studies of patients with bone metastasis in initial metastatic breast cancer (MBC are lacking. Materials and methods: From 2010 to 2013, 245,707 breast cancer patients and 8901 patients diagnosed with initial bone metastasis were identified by Surveillance, Epidemiology, and End Results database of the National Cancer Institute. Multivariate logistic and Cox regression were used to identify predictive factors for the presence of bone metastasis and prognosis factors. Kaplan–Meier method and log-rank test were used for survival analysis. Results: Eight thousand nine hundred one patients with initial MBC had bone involvement, accounting for 3.6% of the entire cohort and 62.5% of the patients with initial MBC. Also, 70.5% of patients with bone metastasis were hormone receptor (HR positive (HR+/human epidermal growth factor receptor 2 [HER2]−: 57.6%; HR+/HER2+: 12.9%. Patients with initial bone metastasis had a better 5-year survival rate compared to those with initial brain, liver, or lung metastasis. HR+/HER2− and HR+/HER2+ breast cancer had a propensity of bone metastasis in the entire cohort and were correlated with better prognosis in patients with initial bone metastasis. Local surgery had significantly improved overall survival in initial MBC patients with bone metastasis. Conclusion: Our study has provided population-based estimates of epidemiologic characteristics and prognosis in patients with bone metastasis at the time of

  18. In-vitro studies with 188Re-HEDP, a clinically used bone pain palliating agent, on bone cancer cells

    International Nuclear Information System (INIS)

    Sharma, Rohit; Kumar, Chandan; Mallia, Madhava B.; Banerjee, Sharmila; Kameswaran, Mythili

    2017-01-01

    Rhenium-188 is an attractive radioisotope for a wide variety of radiotherapy applications. 188 Re-HEDP (HEDPhydroxyethylidene- 1,1-diphosphonic acid) is one such, clinically useful, radiopharmaceutical for palliation of bone pain due to osseous metastasis. Herein, our aim was to study the uptake and retention of 188 Re-HEDP in mineralized bone and to assess its cellular toxicity, along with its underlying mechanism in human osteocarcinoma (MG-63 and Soas-2) cell lines. 188 Re-HEDP uptake was found to be significantly higher in mineralized bone. The 188 Re-HEDP complex also induces G2-M cell cycle arrest and thus contributing to apoptosis and cellular toxicity in bone cancer cells. (author)

  19. Correlative study of SPECT bone scan, serum tPSA and fPSA/tPSA ratio and the pathological grade of prostate cancer with bone metastasis

    International Nuclear Information System (INIS)

    Xu Haiqing; Duan Jun

    2011-01-01

    Objective: To study the rules and characteristics of SPECT bone scan, serum TPSA, fPSA/tPSA ratio and the pathological grade of prostate cancer with bone metastasis. Methods: Nuclear medicine SPECT bone scan as the gold standard, retrospective analysis of the in vitro radioimmunoassay in 107 patients with prostate cancer serum PSA (prostate specific antigen) levels, serum fPSA/tPSA ratio and whole body bone imaging studies and pathological classification. Results: 107 patients with prostate cancer : 49 patients had bone metastases, accounting for 45.8% (49/107), in which groups of different pathological comparison between the incidence of bone metastasis significantly, the lower the degree of differentiation, the more the incidence of bone metastases high; with elevated levels of tPSA, the incidence of bone metastasis increased significantly; serum tPSA 4 - 40 ng/ml, the use of fPSA/tPSA ratio may improve the diagnostic specificity of prostate cancer. Conclusion: Patients with bone metastases of prostate cancer incidence and degree of differentiation of prostate cancer, serum PSA levels and fPSA/tPSA ratio of a certain relationship. The lower degree of differentiation,the higher the incidence of bone metastasis. (authors)

  20. The response to neoadjuvant chemoradiotherapy with 5-fluorouracil in locally advanced rectal cancer patients: a predictive proteomic signature.

    Science.gov (United States)

    Chauvin, Anaïs; Wang, Chang-Shu; Geha, Sameh; Garde-Granger, Perrine; Mathieu, Alex-Ane; Lacasse, Vincent; Boisvert, François-Michel

    2018-01-01

    Colorectal cancer is the third most common and the fourth most lethal cancer in the world. In the majority of cases, patients are diagnosed at an advanced stage or even metastatic, thus explaining the high mortality. The standard treatment for patients with locally advanced non-metastatic rectal cancer is neoadjuvant radio-chemotherapy (NRCT) with 5-fluorouracil (5-FU) followed by surgery, but the resistance rate to this treatment remains high with approximately 30% of non-responders. The lack of evidence available in clinical practice to predict NRCT resistance to 5-FU and to guide clinical practice therefore encourages the search for biomarkers of this resistance. From twenty-three formalin-fixed paraffin-embedded (FFPE) biopsies performed before NRCT with 5-FU of locally advanced non-metastatic rectal cancer patients, we extracted and analysed the tumor proteome of these patients. From clinical data, we were able to classify the twenty-three patients in our cohort into three treatment response groups: non-responders (NR), partial responders (PR) and total responders (TR), and to compare the proteomes of these different groups. We have highlighted 384 differentially abundant proteins between NR and PR, 248 between NR and TR and 417 between PR and TR. Among these proteins, we have identified many differentially abundant proteins identified as having a role in cancer (IFIT1, FASTKD2, PIP4K2B, ARID1B, SLC25A33: overexpressed in TR; CALD1, CPA3, B3GALT5, CD177, RIPK1: overexpressed in NR). We have also identified that DPYD, the main degradation enzyme of 5-FU, was overexpressed in NR, as well as several ribosomal and mitochondrial proteins also overexpressed in NR. Data are available via ProteomeXchange with identifier PXD008440. From these retrospective study, we implemented a protein extraction protocol from FFPE biopsy to highlight protein differences between different response groups to RCTN with 5-FU in patients with locally advanced non-metastatic rectal cancer

  1. Technetium 99m pyrophosphate bone scintigraphy in the exploration of breast cancer bone metastases (analysis of 311 examinations)

    International Nuclear Information System (INIS)

    Bonichon, Francoise.

    1976-01-01

    Sodium pyrophosphate was chosen for its ease of application and the quality of the images it gives. The aim of this study, in the context of breast cancer exploration, is to examine: - its reliability for the detection of bone metastases, - the correlation of its results with other factors. The first part reviews the properties of sup(99m)Tc-labelled sodium pyrophosphate and the current hypotheses on the mechanism of its bone fixation, essential for an understanding of the image formation mechanism and for the interpretation of anomalies. Part two gives an analysis of 311 examinations carried out on 223 patients, obtained by the use of a coded file and modern data processing methods. The following are dealt with in turn: - material and methods, - the results themselves and especially their reliability for the whole skeleton and for one bone at a time, - discussion and comparison with published data. Sup(99m)Tc pyrophosphate bone scintigraphy is a simple examination easy to interpret and allows the whole skeleton to be explored. Abnormal scintigraphic images are: - seldom hypofixing lacunae, - usually 'hyperfixing centres' which point to a perilesional bone reaction and depend on: vascular factors, the affinity of technetium for the immature collagen fibres of the forming bone matrix, the affinity of pyrophosphate for the bone mineral substance [fr

  2. Influence of sex differences on the progression of cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Uldall, Maria; Appel, Camilla

    2013-01-01

    Background: Pain caused by bone metastases has a severe impact on the quality of life for many patients with cancer. Good translational in vivo models are required to understand the molecular mechanism and develop better treatment. In the current study we evaluated the influence of sex differences...... on the progression of cancer-induced bone pain. Materials and Methods: 4T1-luc2 mammary cancer cells were introduced into the femoral cavity of female and male BALB/cJ mice. Bioluminescence tumor signal, pain-related behavior and bone degradation were monitored for 14 days. Results: Female mice demonstrated...... a significantly greater bioluminescence signal on day 2 compared to male mice and, in addition, a significant earlier onset of pain-related behavior was observed in the females. No sex difference was observed for bone degradation. Finally, a strong correlation between pain-related behavior and bone degradation...

  3. The status of nuclear medicine techniques in the diagnosis of bone metastases in breast cancer

    International Nuclear Information System (INIS)

    Makaiova, I.; Kausitz, J.; Hupka, S.; Vivodova, M.

    1989-01-01

    Experience is presented with the diagnosis of bone metastases in patients with breast cancer using bone scintigraphy with 99m TC phosphonate and radioimmunological determination of carcinoembryonic antigen (CEA) and tissue polypeptic antigen (TPA). In a group of 395 patients, there was agreement between tumor markers (CEA, TPA) and the results of bone scintigraphy in 331 cases (84%) - negative in 193 cases (49%) and positive (i.e., in terms of bone scintigraphy results and the presence of at least one tumor marker) in 138 cases (35%). On the basis of this agreement between bone scintigraphy and CEA and TPA levels, the following algorithm is recommended in monitoring patients with breast cancer: a) follow-up of tumor markers at several month intervals and in case of an increase in their levels the patient should be referred to further examination using imaging techniques including bone scintigraphy. (author). 1 fig., 1 tab., 23 refs

  4. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

    Energy Technology Data Exchange (ETDEWEB)

    Skiöld, Sara [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Azimzadeh, Omid [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Merl-Pham, Juliane [Research Unit Protein Science, German Research Center for Environmental Health, Helmholtz Zentrum München, Neuherberg (Germany); Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet [Division of Radiotherapy, Radiumhemmet, Karolinska University Hospital, Stockholm (Sweden); Tapio, Soile [Institute of Radiation Biology, German Research Center for Environmental Health, Helmholtz Zentrum München (Germany); Harms-Ringdahl, Mats [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden); Haghdoost, Siamak, E-mail: Siamak.Haghdoost@su.se [Center for Radiation Protection Research, Department of Molecular Biosciences, The Wernner-Gren Institute, Stockholm University, Stockholm (Sweden)

    2015-06-15

    Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy.

  5. Unique proteomic signature for radiation sensitive patients; a comparative study between normo-sensitive and radiation sensitive breast cancer patients

    International Nuclear Information System (INIS)

    Skiöld, Sara; Azimzadeh, Omid; Merl-Pham, Juliane; Naslund, Ingemar; Wersall, Peter; Lidbrink, Elisabet; Tapio, Soile; Harms-Ringdahl, Mats; Haghdoost, Siamak

    2015-01-01

    Highlights: • The unique protein expression profiles were found that separate radiosensitive from normal sensitive breast cancer patients. • The oxidative stress response, coagulation properties and acute phase response suggested to be the hallmarks of radiation sensitivity. - Abstract: Radiation therapy is a cornerstone of modern cancer treatment. Understanding the mechanisms behind normal tissue sensitivity is essential in order to minimize adverse side effects and yet to prevent local cancer reoccurrence. The aim of this study was to identify biomarkers of radiation sensitivity to enable personalized cancer treatment. To investigate the mechanisms behind radiation sensitivity a pilot study was made where eight radiation-sensitive and nine normo-sensitive patients were selected from a cohort of 2914 breast cancer patients, based on acute tissue reactions after radiation therapy. Whole blood was sampled and irradiated in vitro with 0, 1, or 150 mGy followed by 3 h incubation at 37 °C. The leukocytes of the two groups were isolated, pooled and protein expression profiles were investigated using isotope-coded protein labeling method (ICPL). First, leukocytes from the in vitro irradiated whole blood from normo-sensitive and extremely sensitive patients were compared to the non-irradiated controls. To validate this first study a second ICPL analysis comparing only the non-irradiated samples was conducted. Both approaches showed unique proteomic signatures separating the two groups at the basal level and after doses of 1 and 150 mGy. Pathway analyses of both proteomic approaches suggest that oxidative stress response, coagulation properties and acute phase response are hallmarks of radiation sensitivity supporting our previous study on oxidative stress response. This investigation provides unique characteristics of radiation sensitivity essential for individualized radiation therapy

  6. The value of combined examination of serum CYFRA21-1 levels and bone scan in the diagnosis of bone metastasis in lung cancer

    International Nuclear Information System (INIS)

    Yu Jing; Wang Junhong; Zhengping

    2007-01-01

    Objective: To explore the value of combined examination of serum tumor markers CYFRA21-1 and bone scan in the diagnosis of bone metastasis in lung cancer. Methods: Bone scan and serum CYFRA21-1 levels (with CLIA) determination were performed in 138 patients with lung cancer and 56 patients with benign lung diseases. Results: The serum level of CYFRA21-1 were significantly higher in patients with bone metastasis than those in patients without bone metastasis. The levels were also higher in patients without bone metastasis than those in controls. Most patients with bone metastasis had positive results in bone scan (97.4%), only 2 of the 78 had negative bone scan but positive with CT or MRI. A few patients without bone metastasis and controls had positive bone scan results, caused by previous operation or injury. Conclusion: The combined detection of CYFRA21-1 and bone scan were valuable in the diagnosis of bone metastasis of lung cancer. (authors)

  7. Disseminated carcinomatosis of the bone marrow from pancreatic cancer: a case report

    International Nuclear Information System (INIS)

    Namikawa, Hiroki; Takemoto, Yasuhiko; Makuuchi, Ayako; Kobayashi, Masanori; Kinuhata, Shigeki; Morimura, Mina; Ikebe, Takashi; Tanaka, Hiromu; Shuto, Taichi

    2016-01-01

    Most cases of disseminated carcinomatosis of the bone marrow (DCBM) arise from gastric cancer. DCBM from pancreatic cancer is very rare. We herein present a case of DCBM from pancreatic cancer. A 57-year-old man was referred to our hospital for severe lumbago. Laboratory data indicated that he suffered from disseminated intravascular coagulation (DIC). Non-contrast abdominal computed tomography (CT) revealed multiple bone masses but no other abnormal findings. Left iliac bone marrow biopsy revealed poorly differentiated adenocarcinoma cells. Positron emission tomography (PET)-CT showed diffuse abnormal uptake in the bones and tail of the pancreas. Contrast whole-body CT showed a tumor measuring approximately 28 mm in diameter with poor enhancement in the tail of the pancreas. The patient’s final diagnosis was pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC. His DCBM was thus believed to originate from the pancreatic cancer. He succumbed to the disease approximately 2 months after admission to our hospital. We herein describe a case of pancreatic cancer located in the tail of the pancreas with diffuse bone metastases and DIC, which, in our case, was DCBM. Therefore, in cases of DCBM with an unknown primary tumor, pancreatic cancer should be considered during differential diagnosis

  8. Interaction between tumor cell surface receptor RAGE and proteinase 3 mediates prostate cancer metastasis to bone

    Science.gov (United States)

    Kolonin, Mikhail G.; Sergeeva, Anna; Staquicini, Daniela I.; Smith, Tracey L.; Tarleton, Christy A.; Molldrem, Jeffrey J.; Sidman, Richard L.; Marchiò, Serena; Pasqualini, Renata; Arap, Wadih

    2017-01-01

    Human prostate cancer often metastasizes to bone, but the biological basis for such site-specific tropism remains largely unresolved. Recent work led us to hypothesize that this tropism may reflect pathogenic interactions between RAGE, a cell surface receptor expressed on malignant cells in advanced prostate cancer, and proteinase 3 (PR3), a serine protease present in inflammatory neutrophils and hematopoietic cells within the bone marrow microenvironment. In this study, we establish that RAGE-PR3 interaction mediates homing of prostate cancer cells to the bone marrow. PR3 bound to RAGE on the surface of prostate cancer cells in vitro, inducing tumor cell motility through a non-proteolytic signal transduction cascade involving activation and phosphorylation of ERK1/2 and JNK1. In preclinical models of experimental metastasis, ectopic expression of RAGE on human prostate cancer cells was sufficient to promote bone marrow homing within a short time frame. Our findings demonstrate how RAGE-PR3 interactions between human prostate cancer cells and the bone marrow microenvironment mediate bone metastasis during prostate cancer progression, with potential implications for prognosis and therapeutic intervention. PMID:28428279

  9. Cancer of the prostate presenting with diffuse osteolytic metastatic bone lesions: a case report

    Directory of Open Access Journals (Sweden)

    Segamwenge Innocent Lule

    2012-12-01

    Full Text Available Abstract Introduction Prostate cancer is the second most common cancer in men and the fifth most common cancer worldwide. In the USA it is more common in African-American men than in Caucasian men. Prostate cancer frequently metastasizes to bone and the lesions appear osteoblastic on radiographs. Presentation with diffuse osteolytic bone lesions is rare. We describe an unusual presentation of metastatic prostate cancer with diffuse osteolytic bone lesions. Case presentation A 65-year-old Namibian man presented with anemia, thrombocytopenia and worsening back pains. In addition he had complaints of effort intolerance, palpitations, dysuria and mild symptoms of bladder outlet obstruction. On examination he was found to be anemic, had a swollen tender right shoulder joint and spine tenderness to percussion. On digital rectal examination he had asymmetrical enlargement of the prostate which felt nodular and hard with diffuse firmness in some parts. His prostate-specific antigen was greater than 100ng/mL and he had diffuse osteolytic lesions involving the right humerus, and all vertebral, femur and pelvic bones. His screen for multiple myeloma was negative and the prostate biopsy confirmed prostate cancer. Conclusion Prostate cancer rarely presents with diffuse osteolytic bone lesions and should be considered in the differential diagnosis when evaluating male patients with osteolytic bone lesions.

  10. Study on 41Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    International Nuclear Information System (INIS)

    Shen, Hongtao; Pang, Fangfang; Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang; Pang, Yijun; Yang, Xianlin; Ruan, Xiangdong; Liu, Manjun; Xia, Chunbo

    2015-01-01

    The annual incidence of new cancer patients in China is about 2 million, 30–40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of 41 Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague–Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl 2 solution (containing 1.4 mg Ca and 5nCi 41 Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for 41 Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of 41 Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that 41 Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  11. Mechanisms of Bone Metastasis from Breast Cancer Using a Clinically Relevant Model

    National Research Council Canada - National Science Library

    Anderson, Robin

    2001-01-01

    .... We have developed a murine model of breast cancer that actively mimics the human disease. After implantation of tumor cells into the mammary gland, a primary tumour develops and subsequently metastasises to the lymph nodes, lung and bone...

  12. Remarkable soft tissue uptake during bone scintigraphy in patients with ovarial cancer: Report of two cases

    International Nuclear Information System (INIS)

    Koenig, S.; Koreuber, K.

    1993-01-01

    Two cases of patients with an ovarial cancer are described. Bone scintigraphy was able to diagnose previously unknown soft tissue metastases with important consequences for the patients' diagnosis and therapy. (orig.) [de

  13. Method for palliation of pain in human bone cancer using therapeutic tin-117m compositions

    International Nuclear Information System (INIS)

    Srivastava, S.C.; Meinken, G.E.; Mausner, L.F.; Atkins, H.L.

    1998-01-01

    The invention provides a method for the palliation of bone pain due to cancer by the administration of a unique dosage of a tin-117m (Sn-117m) stannic chelate complex in a pharmaceutically acceptable composition. In addition, the invention provides a method for simultaneous palliation of bone pain and radiotherapy in cancer patients using compositions containing Sn-117m chelates. The invention also provides a method for palliating bone pain in cancer patients using Sn-117m-containing compositions and monitoring patient status by imaging the distribution of the Sn-117m in the patients. Also provided are pharmaceutically acceptable compositions containing Sn-117m chelate complexes for the palliation of bone pain in cancer patients. 5 figs

  14. The role of purinergic receptors in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; Uldall, Maria; Heegaard, Anne-Marie

    2012-01-01

    Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular...

  15. Combined Mass Spectrometry Imaging and Top-down Microproteomics Reveals Evidence of a Hidden Proteome in Ovarian Cancer.

    Science.gov (United States)

    Delcourt, Vivian; Franck, Julien; Leblanc, Eric; Narducci, Fabrice; Robin, Yves-Marie; Gimeno, Jean-Pascal; Quanico, Jusal; Wisztorski, Maxence; Kobeissy, Firas; Jacques, Jean-François; Roucou, Xavier; Salzet, Michel; Fournier, Isabelle

    2017-07-01

    Recently, it was demonstrated that proteins can be translated from alternative open reading frames (altORFs), increasing the size of the actual proteome. Top-down mass spectrometry-based proteomics allows the identification of intact proteins containing post-translational modifications (PTMs) as well as truncated forms translated from reference ORFs or altORFs. Top-down tissue microproteomics was applied on benign, tumor and necrotic-fibrotic regions of serous ovarian cancer biopsies, identifying proteins exhibiting region-specific cellular localization and PTMs. The regions of interest (ROIs) were determined by MALDI mass spectrometry imaging and spatial segmentation. Analysis with a customized protein sequence database containing reference and alternative proteins (altprots) identified 15 altprots, including alternative G protein nucleolar 1 (AltGNL1) found in the tumor, and translated from an altORF nested within the GNL1 canonical coding sequence. Co-expression of GNL1 and altGNL1 was validated by transfection in HEK293 and HeLa cells with an expression plasmid containing a GNL1-FLAG (V5) construct. Western blot and immunofluorescence experiments confirmed constitutive co-expression of altGNL1-V5 with GNL1-FLAG. Taken together, our approach provides means to evaluate protein changes in the case of serous ovarian cancer, allowing the detection of potential markers that have never been considered. Copyright © 2017 The Author(s). Published by Elsevier B.V. All rights reserved.

  16. cAMP-response-element-binding protein positively regulates breast cancer metastasis and subsequent bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Son, Jieun; Lee, Jong-Ho; Kim, Ha-Neui; Ha, Hyunil, E-mail: hyunil74@hotmail.com; Lee, Zang Hee, E-mail: zang1959@snu.ac.kr

    2010-07-23

    Research highlights: {yields} CREB is highly expressed in advanced breast cancer cells. {yields} Tumor-related factors such as TGF-{beta} further elevate CREB expression. {yields} CREB upregulation stimulates metastatic potential of breast cancer cells. {yields} CREB signaling is required for breast cancer-induced bone destruction. -- Abstract: cAMP-response-element-binding protein (CREB) signaling has been reported to be associated with cancer development and poor clinical outcome in various types of cancer. However, it remains to be elucidated whether CREB is involved in breast cancer development and osteotropism. Here, we found that metastatic MDA-MB-231 breast cancer cells exhibited higher CREB expression than did non-metastatic MCF-7 cells and that CREB expression was further increased by several soluble factors linked to cancer progression, such as IL-1, IGF-1, and TGF-{beta}. Using wild-type CREB and a dominant-negative form (K-CREB), we found that CREB signaling positively regulated the proliferation, migration, and invasion of MDA-MB-231 cells. In addition, K-CREB prevented MDA-MB-231 cell-induced osteolytic lesions in a mouse model of cancer metastasis. Furthermore, CREB signaling in cancer cells regulated the gene expression of PTHrP, MMPs, and OPG, which are closely involved in cancer metastasis and bone destruction. These results indicate that breast cancer cells acquire CREB overexpression during their development and that this CREB upregulation plays an important role in multiple steps of breast cancer bone metastasis.

  17. Triple SILAC quantitative proteomic analysis reveals differential abundance of cell signaling proteins between normal and lung cancer-derived exosomes.

    Science.gov (United States)

    Clark, David J; Fondrie, William E; Yang, Austin; Mao, Li

    2016-02-05

    Exosomes are 30-100 nm sized membrane vesicles released by cells into the extracellular space that mediate intercellular communication via transfer of proteins and other biological molecules. To better understand the role of these microvesicles in lung carcinogenesis, we employed a Triple SILAC quantitative proteomic strategy to examine the differential protein abundance between exosomes derived from an immortalized normal bronchial epithelial cell line and two non-small cell lung cancer (NSCLC) cell lines harboring distinct activating mutations in the cell signaling molecules: Kirsten rat sarcoma viral oncogene homolog (KRAS) or epidermal growth factor receptor (EGFR). In total, we were able to quantify 721 exosomal proteins derived from the three cell lines. Proteins associated with signal transduction, including EGFR, GRB2 and SRC, were enriched in NSCLC exosomes, and could actively regulate cell proliferation in recipient cells. This study's investigation of the NSCLC exosomal proteome has identified enriched protein cargo that can contribute to lung cancer progression, which may have potential clinical implications in biomarker development for patients with NSCLC. The high mortality associated with lung cancer is a result of late-stage diagnosis of the disease. Current screening techniques used for early detection of lung cancer lack the specificity for accurate diagnosis. Exosomes are nano-sized extracellular vesicles, and the increased abundance of select protein cargo in exosomes derived from cancer cells may be used for diagnostic purposes. In this paper, we applied quantitative proteomic analysis to elucidate abundance differences in exosomal protein cargo between two NSCLC cell lines with distinctive oncogene mutations and an immortalized normal bronchial epithelial cell line. This study revealed proteins associated with cell adhesion, the extracellular matrix, and a variety of signaling molecules were enriched in NSCLC exosomes. The present data reveals

  18. Where Do Bone-Targeted Agents RANK in Breast Cancer Treatment?

    Directory of Open Access Journals (Sweden)

    Roger von Moos

    2013-08-01

    Full Text Available Breast cancer cells preferentially metastasise to the skeleton, owing, in part, to the fertile environment provided by bone. Increased bone turnover releases growth factors that promote tumour cell growth. In turn, tumour cells release factors that stimulate further bone turnover, resulting in a vicious cycle of metastasis growth and bone destruction. The RANK-RANK ligand (RANKL pathway plays a key role in this cycle, and inhibition of RANKL using the fully-human monoclonal antibody denosumab, has demonstrated efficacy in delaying skeletal complications associated with bone metastases in three phase 3 trials. Preclinical studies suggest that the RANKL pathway also plays a role in breast cancer tumourigenesis and migration to bone. In a subgroup analysis of the negative Adjuvant Zoledronic Acid to Reduce Recurrence (AZURE trial, the bisphosphonate zoledronic acid showed potential for improving survival in patients who were postmenopausal; however, a prospective study in this patient population is required to validate this observation. Ongoing trials are examining whether adjuvant blockade of the RANKL pathway using denosumab can prevent disease recurrence in patients with high-risk breast cancer. These are building on analogous studies that have shown that denosumab improves bone metastasis-free survival in prostate cancer and suggested that it confers an overall survival benefit in non-small-cell lung cancer.

  19. Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment

    OpenAIRE

    Schwartz, Boris; Benadjaoud, Mohamed Amine; Clero, Enora; Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Teinturier, Cecile; Oberlin, Odile; Veres, Cristina; Pacquement, Helene; Munzer, Martine; Tan Dat N'Guyen; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne

    2014-01-01

    International audience; : Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated be...

  20. An in vitro 3D bone metastasis model by using a human bone tissue culture and human sex-related cancer cells.

    Science.gov (United States)

    Salamanna, Francesca; Borsari, Veronica; Brogini, Silvia; Giavaresi, Gianluca; Parrilli, Annapaola; Cepollaro, Simona; Cadossi, Matteo; Martini, Lucia; Mazzotti, Antonio; Fini, Milena

    2016-11-22

    One of the main limitations, when studying cancer-bone metastasis, is the complex nature of the native bone environment and the lack of reliable, simple, inexpensive models that closely mimic the biological processes occurring in patients and allowing the correct translation of results. To enhance the understanding of the mechanisms underlying human bone metastases and in order to find new therapies, we developed an in vitro three-dimensional (3D) cancer-bone metastasis model by culturing human breast or prostate cancer cells with human bone tissue isolated from female and male patients, respectively. Bone tissue discarded from total hip replacement surgery was cultured in a rolling apparatus system in a normoxic or hypoxic environment. Gene expression profile, protein levels, histological, immunohistochemical and four-dimensional (4D) micro-CT analyses showed a noticeable specificity of breast and prostate cancer cells for bone colonization and ingrowth, thus highlighting the species-specific and sex-specific osteotropism and the need to widen the current knowledge on cancer-bone metastasis spread in human bone tissues. The results of this study support the application of this model in preclinical studies on bone metastases and also follow the 3R principles, the guiding principles, aimed at replacing/reducing/refining (3R) animal use and their suffering for scientific purposes.

  1. Radiation therapy for metastatic lesions from breast cancer. Breast cancer metastasis to bone

    International Nuclear Information System (INIS)

    Hayashi, Shinya; Hoshi, Hiroaki

    2000-01-01

    This paper summarizes radiation therapy in the treatment of bone metastases from breast cancer. Bone metastasis occurs in approximately 70% of breast cancer patients, and the goals of radiation therapy for bone metastasis are: palliation of pain, prevention and treatment of neuropathic symptoms, and prevention of pathologic fractures. The prognosis of bone metastasis from breast cancer is known to be better than that of bone metastasis from other solid tumors. Local-field radiation, hemibody (or wide-field) radiation, and systemic radionuclide treatment are the major methods of radiation therapy for pain palliation. Although many studies have shown that breast cancer is more responsive to radiation therapy for pain palliation than other solid tumors, some studies found no significant difference. Local-field radiation therapy, which includes multi-fraction irradiation and single-fraction irradiation, is currently the most generally used method of radiotherapy for pain palliation. Pain palliation has been reported to be achieved in approximately 80% to 90% of patients treated with local-field external beam irradiation. Three types of multi-fraction irradiation therapy are administered depending on the prognosis: high-dose fraction irradiation (36-50 Gy/12-25 Fr/2.4-5 wk), short-course irradiation (20-30 Gy/10-15 Fr/2-3 wk), and ultra-short-course irradiation (15-25 Gy/2-5 Fr/1 wk). The most common irradiation schedule is 30 Gy/10 Fr/2 wk. Although many reports indicate no significant difference in pain palliation according to the dose, the percentage of patients who show a complete cure is significantly higher in those treated with doses of 30 Gy or more, and thus the total irradiation dose should be at least 30 Gy. High-dose fraction irradiation is indicated for patients with an expected survival time of 6 months or more while short-course or single-fraction irradiation is indicated for those with an expected survival time of 3 months or more. Single

  2. The heat-shock, or HSF1-mediated proteotoxic stress, response in cancer: from proteomic stability to oncogenesis.

    Science.gov (United States)

    Dai, Chengkai

    2018-01-19

    The heat-shock, or HSF1-mediated proteotoxic stress, response (HSR/HPSR) is characterized by induction of heat-shock proteins (HSPs). As molecular chaperones, HSPs facilitate the folding, assembly, transportation and degradation of other proteins. In mammals, heat shock factor 1 (HSF1) is the master regulator of this ancient transcriptional programme. Upon proteotoxic insults, the HSR/HPSR is essential to proteome homeostasis, or proteostasis, thereby resisting stress and antagonizing protein misfolding diseases and ageing. Contrasting with these benefits, an unexpected pro-oncogenic role of the HSR/HPSR is unfolding. Whereas HSF1 remains latent in primary cells without stress, it becomes constitutively activated within malignant cells, rendering them addicted to HSF1 for their growth and survival. Highlighting the HSR/HPSR as an integral component of the oncogenic network, several key pathways governing HSF1 activation by environmental stressors are causally implicated in malignancy. Importantly, HSF1 impacts the cancer proteome systemically. By suppressing tumour-suppressive amyloidogenesis, HSF1 preserves cancer proteostasis to support the malignant state, both providing insight into how HSF1 enables tumorigenesis and suggesting disruption of cancer proteostasis as a therapeutic strategy. This review provides an overview of the role of HSF1 in oncogenesis, mechanisms underlying its constitutive activation within cancer cells and its pro-oncogenic action, as well as potential HSF1-targeting strategies.This article is part of the theme issue 'Heat shock proteins as modulators and therapeutic targets of chronic disease: an integrated perspective'. © 2017 The Author(s).

  3. Bone mineral density deficits in childhood cancer survivors: Pathophysiology, prevalence, screening, and management

    Directory of Open Access Journals (Sweden)

    Min Jae Kang

    2013-02-01

    Full Text Available As chemotherapy and other sophisticated treatment strategies evolve and the number of survivors of long-term childhood cancer grows, the long-term complications of treatment and the cancer itself are becoming ever more important. One of the most important but often neglected complications is osteoporosis and increased risk of fracture during and after cancer treatment. Acquisition of optimal peak bone mass and strength during childhood and adolescence is critical to preventing osteoporosis later in life. However, most childhood cancer patients have multiple risk factors for bone mineral loss. Cancer itself, malnutrition, decreased physical activity during treatment, chemotherapeutic agents such as steroids, and radiotherapy cause bone mineral deficit. Furthermore, complications such as growth hormone deficiency and musculoskeletal deformity have negative effects on bone metabolism. Low bone mineral density is associated with fractures, skeletal deformity, pain, and substantial financial burden not only for childhood cancer survivors but also for public health care systems. Thus, it is important to monitor bone health in these patients and minimize their risk of developing osteoporosis and fragility fractures later in life.

  4. Laser capture microdissection in the genomic and proteomic era: targeting the genetic basis of cancer.

    Science.gov (United States)

    Domazet, Barbara; Maclennan, Gregory T; Lopez-Beltran, Antonio; Montironi, Rodolfo; Cheng, Liang

    2008-03-15

    The advent of new technologies has enabled deeper insight into processes at subcellular levels, which will ultimately improve diagnostic procedures and patient outcome. Thanks to cell enrichment methods, it is now possible to study cells in their native environment. This has greatly contributed to a rapid growth in several areas, such as gene expression analysis, proteomics, and metabolonomics. Laser capture microdissection (LCM) as a method of procuring subpopulations of cells under direct visual inspection is playing an important role in these areas. This review provides an overview of existing LCM technology and its downstream applications in genomics, proteomics, diagnostics and therapy.

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

    International Nuclear Information System (INIS)

    Yildiz, M.; Oral, B.

    2004-01-01

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

  6. Cold metastases detected by bone scintigraphy in aggressive lung cancer

    International Nuclear Information System (INIS)

    Martinez Carsi, C.; Perales Vila, A.; Ruiz Hernandez, G.; Sanchez Marchori, C.; Oro Camps, J.

    1998-01-01

    A case of a 55-year-old man was remitted to Traumatology Department to present back pain of two weeks of evolution. The results of bone scintigraphy and the patient's evolution allowed the diagnosis. This case report and a literature review showed the importance of using a routine bone scan in diagnosis of bone metastases. (orig.) [de

  7. Plasma low-molecular-weight proteome profiling identified neuropeptide-Y as a prostate cancer biomarker polypeptide.

    Science.gov (United States)

    Ueda, Koji; Tatsuguchi, Ayako; Saichi, Naomi; Toyama, Atsuhiko; Tamura, Kenji; Furihata, Mutsuo; Takata, Ryo; Akamatsu, Shusuke; Igarashi, Masahiro; Nakayama, Masato; Sato, Taka-Aki; Ogawa, Osamu; Fujioka, Tomoaki; Shuin, Taro; Nakamura, Yusuke; Nakagawa, Hidewaki

    2013-10-04

    In prostate cancer diagnosis, PSA test has greatly contributed to the early detection of prostate cancer; however, expanding overdiagnosis and unnecessary biopsies have emerged as serious issues. To explore plasma biomarkers complementing the specificity of PSA test, we developed a unique proteomic technology QUEST-MS (Quick Enrichment of Small Targets for Mass Spectrometry). The QUEST-MS method based on 96-well formatted sequential reversed-phase chromatography allowing efficient enrichment of <20 kDa proteins quickly and reproducibly. Plasma from 24 healthy controls, 19 benign prostate hypertrophy patients, and 73 prostate cancer patients were purified with QUEST-MS and analyzed by LC/MS/MS. Among 153 057 nonredundant peptides, 189 peptides showed prostate cancer specific detection pattern, which included a neurotransmitter polypeptide neuropeptide-Y (NPY). We further validated the screening results by targeted multiple reaction monitoring technology using independent sample set (n = 110). The ROC curve analysis revealed that logistic regression-based combination of NPY, and PSA showed 81.5% sensitivity and 82.2% specificity for prostate cancer diagnosis. Thus QUEST-MS technology allowed comprehensive and high-throughput profiling of plasma polypeptides and had potential to effectively uncover very low abundant tumor-derived small molecules, such as neurotransmitters, peptide hormones, or cytokines.

  8. Diagnostic accuracy of bone metastases detection in cancer patients. Comparison between bone scintigraphy and whole-body FDG-PET

    International Nuclear Information System (INIS)

    Fujimoto, Ryota; Higashi, Tatsuya; Nakamoto, Yuji

    2006-01-01

    18 F-fluorodeoxyglucose (FDG) positron emission tomography (PET) has become widely available and an important oncological technique. To evaluate the influence of PET on detection of bone metastasis, we compared the diagnostic accuracy of PET and conventional bone scintigraphy (BS) in a variety of cancer patients. Consecutive ninety-five patients with various cancers, who received both PET and BS within one month, were retrospectively analyzed. A whole-body PET (from face to upper thigh) and a standard whole body BS were performed and these images were interpreted by two experienced nuclear medicine physicians with and without patient information using monitor diagnosis. Each image interpretation was performed according to 8 separate areas (skull, vertebra, upper limbs, sternum and clavicles, scapula, ribs, pelvis, and lower limbs) using a 5-point-scale (0: definitely negative, 1: probably negative, 2: equivocal, 3: probably positive, 4: definitely positive for bone metastasis). Twenty-one of 95 patients (22.1%) with 43 of 760 areas (5.7%) of bone metastases were finally confirmed. In untreated patients, 12 of 14 bone metastasis positive patients were detected by PET, while 9 of 14 were detected by BS. Three cases showed true positive in PET and false negative in BS due to osteolytic type bone metastases. In untreated cases, PET with and without clinical information showed better sensitivity than BS in patient-based diagnosis. For the purpose of treatment effect evaluation, PET showed better results because of its ability in the evaluation of rapid response of tumor cells to chemotherapy. Out of 10 cases of multiple-area metastases, 9 cases included vertebrae. There was only one solitary lesion located outside of field of view (FOV) of PET scan in the femur, but with clinical information that was no problem for PET diagnosis. Diagnostic accuracy of bone metastasis was comparable in PET and BS in the present study. In a usual clinical condition, limited FOV (from

  9. Incidental bone scan findings in oral cavity in patients with cancer

    International Nuclear Information System (INIS)

    Gutierrez G, Patricia; Salvatierra R, Guillermo; Garcia, Arlene; Morales, Rosanna; Cano, Roque; Ortiz L, Jesus; Sotelo R, Silvia; Bustamante, Cesar

    2007-01-01

    The main aim of the present work, done in the Nuclear medicine Center IPEN-INEN, was to identify as incidental findings, increased inflammatory uptake in oral cavity in routine bone scintigraphies for neoplasic diseases control. A descriptive and retrospective study was performed studying bone scans from patients with cancer, that came to the Nuclear Medicine Center in 2003 and revising records of those who had inflammatory uptake in the oral cavity. It is concluded that, in cancer patients these findings are underestimated. Prospective research should be needed in order to determine the frequency of inflammatory oral cavity pathology detected in bone scintigraphies. (author)

  10. Bone marrow scintigraphy: evaluation of damage caused by cancer chemotherapy

    International Nuclear Information System (INIS)

    Ciambellotti, E.; Cartia, G.L.; Coda, C.

    1988-01-01

    For various reasons the well-known myelopoietic damage caused by cancer chemotherapy is not easy to quantify by means of usual diagnostic procedures. The bone marrow scan with 99m Tc-nanocolloid rapidly cleared by the phagocitic action of the RES, which has a topographic extension similar to red marrow, has been used for many years to evaluate the inflammatory and neoplastic diseases, both localized and diffuse. Such examination was thus performed in patients undergoing cytostatic therapy, either to follow-up metastatic lesions or to evaluate a tissue damage due to different drugs. The BMS is easily performed and has no side-effects. It consists of a dinamic and a static part. Moreover, it helped pointing out important diagnostic data, such as the reduction of the sacroiliac uptake index below the normal values (3.7) in 33 out of 57 cases, and an abnormal distribution of nanocolloid in the skeleton (Munz's classification, 1983) in 37 out of 69 cases, higher in more myelotoxic cytostatic, which could be detected even after a few months

  11. Bone Health in Patients with Breast Cancer: Recommendations from an Evidence-Based Canadian Guideline

    Directory of Open Access Journals (Sweden)

    Alexander H. G. Paterson

    2013-12-01

    Full Text Available Bone loss is common in patients with breast cancer. Bone modifying agents (BMAs, such as bisphosphonates and denosumab, have been shown to reverse or stabilize bone loss and may be useful in the primary and metastatic settings. The purpose of this review is to provide clear evidence-based strategies for the management of bone loss and its symptoms in breast cancer. A systematic review of clinical trials and meta-analyses published between 1996 and 2012 was conducted of MEDLINE and EMBASE. Reference lists were hand-searched for additional publications. Recommendations were developed based on the best available evidence. Zoledronate, pamidronate, clodronate, and denosumab are recommended for metastatic breast cancer patients; however, no one agent can be recommended over another. Zoledronate or any oral bisphosphonate and denosumab should be considered in primary breast cancer patients who are postmenopausal on aromatase inhibitor therapy and have a high risk of fracture and/or a low bone mineral density and in premenopausal primary breast cancer patients who become amenorrheic after therapy. No one agent can be recommended over another. BMAs are not currently recommended as adjuvant therapy in primary breast cancer for the purpose of improving survival, although a major Early Breast Cancer Cooperative Trialists’ Group meta-analysis is underway which may impact future practice. Adverse events can be managed with appropriate supportive care.

  12. P2X7 receptor-deficient mice are susceptible to bone cancer pain

    DEFF Research Database (Denmark)

    Hansen, Rikke Rie; Nielsen, Christian K.; Nasser, Arafat

    2011-01-01

    The purinergic P2X7 receptor is implicated in both neuropathic and inflammatory pain, and has been suggested as a possible target in pain treatment. However, the specific role of the P2X7 receptor in bone cancer pain is unknown. We demonstrated that BALB/cJ P2X7 receptor knockout (P2X7R KO) mice...... were susceptible to bone cancer pain and moreover had an earlier onset of pain-related behaviours compared with cancer-bearing, wild-type mice. Furthermore, acute treatment with the selective P2X7 receptor antagonist, A-438079, failed to alleviate pain-related behaviours in models of bone cancer pain...... with and without astrocyte activation (BALB/cJ or C3H mice inoculated with 4T1 mammary cancer cells or NCTC 2472 osteosarcoma cells, respectively), suggesting that astrocytic P2X7 receptors play a negligible role in bone cancer pain. The results support the hypothesis that bone cancer pain is a separate pain state...

  13. Proteomics of a new esophageal cancer cell line established from Persian patient.

    Science.gov (United States)

    Moghanibashi, Mehdi; Jazii, Ferdous Rastgar; Soheili, Zahra-Soheila; Zare, Maryam; Karkhane, Aliasghar; Parivar, Kazem; Mohamadynejad, Parisa

    2012-05-25

    Although the highest incidence of esophageal squamous cell carcinoma (ESCC) has repeatedly been reported from Persia (Iran), nevertheless the so far proteomic published reports were limited to one study on tissue specimens. Here we report the proteome of a newly established cell line from Persian ESCC patients and compare it with the normal primary cell proteome. Among polypeptides, whose expression was different in cell line sixteen polypeptides were identified by MALDI/TOF/TOF spectrometry. S100-A8 protein, annexin A1, annexin A2, regulatory subunit of calpain, subunit alpha type-3 of proteasome and glutamate dehydrogenase 1 were proteins down-regulated in cell line while peroxiredoxin-5, non-muscle myosin light polypeptide 6, keratin 1, annexin A4, keratin 8, tropomyosin 3, stress-induced-phosphoprotein 1 and albumin were found to be subject of up-regulation in cell line compared to the primary normal cells. The proteomic results were further verified by western blotting and RT-PCR on annexin A1 and keratin 8. In addition, among the aforementioned proteins, glutamate dehydrogenase 1, regulatory subunit of calpain, subunit alpha of type-3 proteasome and annexin A4 are proteins whose deregulation in ESCC is reported for the first time by this study. Copyright © 2012 Elsevier B.V. All rights reserved.

  14. Relationship of natural incidence and radiosensitivity for bone cancer in dogs

    International Nuclear Information System (INIS)

    Taylor, G.N.; Lloyd, R.D.; Miller, S.C.; Jee, W.S.S.

    1997-01-01

    A comparison of the risk coefficients for 239 Pu- or 226 Ra-induced bone cancer in two canine breeds, one with a relatively low (beagle) and the other with a very high (St. Bernard) natural incidence, indicated only slightly higher risk in the giant breed. The differences in risk for skeletal malignancy in 239 Pu and 226 Ra dogs were nonsignificant (p > 0.05). Likewise, the values of the 239 Pu: 226 Ra open-quotes toxicity ratiosclose quotes for these respective breeds, using bone cancer as the endpoint, were not significantly different at the 0.05 level. The anatomical distribution of the radiation-induced bone tumors tended to be a function of both the bone mass and the skeletal distribution of the radio nuclide, not the site of predilection for naturally occurring bone neoplasia. Although the etiology of the higher natural incidence of bone cancer in the St. Bernard was not determined, several possible factors, including a higher osteoblastic activity level in the St. Bernards, are presented. These data suggest that making extrapolations of radiation-induced bone cancer risk from animals to humans is valid. 26 refs., 5 tabs

  15. Zoledronic acid use in patients with bone metastases from renal cell carcinoma or bladder cancer.

    Science.gov (United States)

    Saad, Fred; Eastham, James A

    2010-06-01

    Approximately 30% of patients with renal cell carcinoma (RCC) and 40% of patients with bladder cancer develop bone metastases that can disrupt normal bone homeostasis and place patients at risk for potentially life-limiting skeletal-related events (SREs). In the absence of bone-directed therapies, patients with RCC may experience up to four SREs per year. In patients with bone metastases from RCC or bladder cancer, zoledronic acid (ZOL) significantly reduced the risk of SREs compared with placebo. In addition to its bone-protective effects, preclinical and early clinical evidence indicates that ZOL prevents tumor progression. For example, retrospective subset analysis in patients with RCC indicated that ZOL extended time to disease progression and demonstrated a trend toward improved overall survival compared with placebo. Additionally, a study in patients with bone metastases from bladder cancer demonstrated that ZOL improved 1-year overall survival compared with placebo. Bone metastases place a heavy burden on patients with RCC or bladder cancer, and early, continuous treatment with ZOL may provide anticancer benefits in addition to important patient quality of life. 2010. Published by Elsevier Inc.

  16. Current role of bone scan with phosphonates in the follow-up of breast cancer

    International Nuclear Information System (INIS)

    Maffioli, Lorenzo; Florimonte, Luigia; Pagani, Luca; Butti, Ivana; Roca, Isabel

    2004-01-01

    A number of studies have demonstrated that bone scintigraphy has high sensitivity and efficacy in the early detection of bone metastases from several tumours, including breast cancer. Bone scintigraphy is the most definitive tool for diagnosing and monitoring metastatic spread of breast cancer. However, in the past decade there has been a wide debate on its impact on survival time, morbidity and quality of life. Worldwide economic restrictions and these studies have led to the adoption of an almost minimalist policy for breast cancer follow-up using evidence-based guidelines. The recommended breast cancer surveillance testing includes only a few procedures (history, physical and breast self-examination, patient education on symptoms, pelvic examination). The routine use of additional tests, such as blood cell count, tumour markers, liver ultrasonography, bone scan and chest X-rays, is not recommended. Accordingly, scintigraphy should be reserved for a limited number of patients. On the other hand, early diagnosis of bone involvement may reduce the risk of skeletal related events, thus leading to a significant improvement in quality of life. Furthermore, new drugs (e.g. bisphosphonates) can now delay the onset of bone metastasis and reduce the number of patients who experience skeletal complications. In conclusion, the evidence of the clinical usefulness of bone scintigraphy (to allow early planning of new treatments in advanced disease) has to be re-evaluated, possibly by large randomised prospective trials. (orig.)

  17. Methotrexate Toxicity in Growing Long Bones of Young Rats: A Model for Studying Cancer Chemotherapy-Induced Bone Growth Defects in Children

    Directory of Open Access Journals (Sweden)

    Chiaming Fan

    2011-01-01

    Full Text Available The advancement and intensive use of chemotherapy in treating childhood cancers has led to a growing population of young cancer survivors who face increased bone health risks. However, the underlying mechanisms for chemotherapy-induced skeletal defects remain largely unclear. Methotrexate (MTX, the most commonly used antimetabolite in paediatric cancer treatment, is known to cause bone growth defects in children undergoing chemotherapy. Animal studies not only have confirmed the clinical observations but also have increased our understanding of the mechanisms underlying chemotherapy-induced skeletal damage. These models revealed that high-dose MTX can cause growth plate dysfunction, damage osteoprogenitor cells, suppress bone formation, and increase bone resorption and marrow adipogenesis, resulting in overall bone loss. While recent rat studies have shown that antidote folinic acid can reduce MTX damage in the growth plate and bone, future studies should investigate potential adjuvant treatments to reduce chemotherapy-induced skeletal toxicities.

  18. Radiation therapy for metastatic lesions from breast cancer. Breast cancer metastasis to bone

    Energy Technology Data Exchange (ETDEWEB)

    Hayashi, Shinya; Hoshi, Hiroaki [Gifu Univ. (Japan). School of Medicine

    2000-10-01

    This paper summarizes radiation therapy in the treatment of bone metastases from breast cancer. Bone metastasis occurs in approximately 70% of breast cancer patients, and the goals of radiation therapy for bone metastasis are: palliation of pain, prevention and treatment of neuropathic symptoms, and prevention of pathologic fractures. The prognosis of bone metastasis from breast cancer is known to be better than that of bone metastasis from other solid tumors. Local-field radiation, hemibody (or wide-field) radiation, and systemic radionuclide treatment are the major methods of radiation therapy for pain palliation. Although many studies have shown that breast cancer is more responsive to radiation therapy for pain palliation than other solid tumors, some studies found no significant difference. Local-field radiation therapy, which includes multi-fraction irradiation and single-fraction irradiation, is currently the most generally used method of radiotherapy for pain palliation. Pain palliation has been reported to be achieved in approximately 80% to 90% of patients treated with local-field external beam irradiation. Three types of multi-fraction irradiation therapy are administered depending on the prognosis: high-dose fraction irradiation (36-50 Gy/12-25 Fr/2.4-5 wk), short-course irradiation (20-30 Gy/10-15 Fr/2-3 wk), and ultra-short-course irradiation (15-25 Gy/2-5 Fr/1 wk). The most common irradiation schedule is 30 Gy/10 Fr/2 wk. Although many reports indicate no significant difference in pain palliation according to the dose, the percentage of patients who show a complete cure is significantly higher in those treated with doses of 30 Gy or more, and thus the total irradiation dose should be at least 30 Gy. High-dose fraction irradiation is indicated for patients with an expected survival time of 6 months or more while short-course or single-fraction irradiation is indicated for those with an expected survival time of 3 months or more. Single

  19. Utilization of bone densitometry for prediction and administration of bisphosphonates to prevent osteoporosis in patients with prostate cancer without bone metastases receiving antiandrogen therapy

    International Nuclear Information System (INIS)

    Holt, Abby; Khan, Muhammad A; Gujja, Swetha; Govindarajan, Rangaswmy

    2014-01-01

    Prostate cancer subjects with prostate-specific antigen (PSA) relapse who are treated with androgen deprivation therapy (ADT) are recommended to have baseline and serial bone densitometry and receive bisphosphonates. The purpose of this community population study was to assess the utilization of bone densitometry and bisphosphonate therapy in men receiving ADT for non-metastatic prostate cancer. A cohort study of men aged 65 years or older with non-metastatic incident diagnoses of prostate cancer was obtained from the Surveillance Epidemiology End Results (SEER)-linked Medicare claims between 2004 and 2008. Claims were used to assess prescribed treatment of ADT, bone densitometry, and bisphosphonates. A total of 30,846 incident prostate cancer cases receiving ADT and aged 65 years or older had no bone metastases; 87.3% (n=26,935) on ADT did not receive either bone densitometry or bisphosphonate therapy. Three percent (n=931) of the cases on ADT received bisphosphonate therapy without ever receiving bone densitometry, 8.8% (n=2,702) of the cases on ADT received bone densitometry without receiving intravenous bisphosphonates, while nearly 1% (0.90%, n=278) of the cases on ADT received both bone densitometry and bisphosphonates. Analysis showed treatment differed by patient characteristics. Contrary to the recommendations, bone densitometry and bisphosphonate therapy are underutilized in men receiving ADT for non-metastatic prostate cancer

  20. Dystrophic Cutaneous Calcification and Metaplastic Bone Formation due to Long Term Bisphosphonate Use in Breast Cancer

    Directory of Open Access Journals (Sweden)

    Ali Murat Tatlı

    2013-01-01

    Full Text Available Bisphosphonates are widely used in the treatment of breast cancer with bone metastases. We report a case of a female with breast cancer presented with a rash around a previous mastectomy site and a discharge lesion on her right chest wall in August 2010. Biopsy of the lesion showed dystrophic calcification and metaplastic bone formation. The patient’s history revealed a long term use of zoledronic acid for the treatment of breast cancer with bone metastasis. We stopped the treatment since we believed that the cutaneous dystrophic calcification could be associated with her long term bisphosphonate therapy. Adverse cutaneous events with bisphosphonates are very rare, and dystrophic calcification has not been reported previously. The dystrophic calcification and metaplastic bone formation in this patient are thought to be due to long term bisphosphonate usage.

  1. The Role of Purinergic Receptors in Cancer-Induced Bone Pain

    Directory of Open Access Journals (Sweden)

    Sarah Falk

    2012-01-01

    Full Text Available Cancer-induced bone pain severely compromises the quality of life of many patients suffering from bone metastasis, as current therapies leave some patients with inadequate pain relief. The recent development of specific animal models has increased the understanding of the molecular and cellular mechanisms underlying cancer-induced bone pain including the involvement of ATP and the purinergic receptors in the progression of the pain state. In nociception, ATP acts as an extracellular messenger to transmit sensory information both at the peripheral site of tissue damage and in the spinal cord. Several of the purinergic receptors have been shown to be important for the development and maintenance of neuropathic and inflammatory pain, and studies have demonstrated the importance of both peripheral and central mechanisms. We here provide an overview of the current literature on the role of purinergic receptors in cancer-induced bone pain with emphasis on some of the difficulties related to studying this complex pain state.

  2. Clinical observation of 89Sr treatment efficacy of multiple bone metastases in breast and prostate cancer patients

    International Nuclear Information System (INIS)

    Yuan Chao; Li Weipeng; Hu Yongquan; Tao Jian

    2010-01-01

    Objective: To evaluate the efficacy of 89 Sr in treatment of multiple bone metastases of breast and prostate cancer patients. Methods: Seventy multiple bone metastases patients (30 females with breast cancer and 40 males with prostate cancer) were treated with 89 Sr. The clinical effectiveness was assessed by Karnofsky performance score and whole body bone scanning data. Results: The total pain relief rate was 79% in bone metastases of breast cancer and 85% in bone metastases of prostate cancer, respectively. There was no significant differences between the two groups (χ 2 =0.78, P>0.05). The Karnofsky score was significantly improved in both groups (t=2.46, P 89 Sr treatment was good, and the quality of life was improved in patients with multiple bone metastases breast or prostate cancer. (authors)

  3. Proteomics Analysis of Cancer Exosomes Using a Novel Modified Aptamer-based Array (SOMAscanTM) Platform*

    Science.gov (United States)

    Webber, Jason; Stone, Timothy C.; Katilius, Evaldas; Smith, Breanna C.; Gordon, Bridget; Mason, Malcolm D.; Tabi, Zsuzsanna; Brewis, Ian A.; Clayton, Aled

    2014-01-01

    We have used a novel affinity-based proteomics technology to examine the protein signature of small secreted extracellular vesicles called exosomes. The technology uses a new class of protein binding reagents called SOMAmers® (slow off-rate modified aptamers) and allows the simultaneous precise measurement of over 1000 proteins. Exosomes were highly purified from the Du145 prostate cancer cell line, by pooling selected fractions from a continuous sucrose gradient (within the density range of 1.1 to 1.2 g/ml), and examined under standard conditions or with additional detergent treatment by the SOMAscanTM array (version 3.0). Lysates of Du145 cells were also prepared, and the profiles were compared. Housekeeping proteins such as cyclophilin-A, LDH, and Hsp70 were present in exosomes, and we identified almost 100 proteins that were enriched in exosomes relative to cells. These included proteins of known association with cancer exosomes such as MFG-E8, integrins, and MET, and also those less widely reported as exosomally associated, such as ROR1 and ITIH4. Several proteins with no previously known exosomal association were confirmed as exosomally expressed in experiments using individual SOMAmer® reagents or antibodies in micro-plate assays. Western blotting confirmed the SOMAscanTM-identified enrichment of exosomal NOTCH-3, L1CAM, RAC1, and ADAM9. In conclusion, we describe here over 300 proteins of hitherto unknown association with prostate cancer exosomes and suggest that the SOMAmer®-based assay technology is an effective proteomics platform for exosome-associated biomarker discovery in diverse clinical settings. PMID:24505114

  4. A proteomic strategy to identify novel serum biomarkers for liver cirrhosis and hepatocellular cancer in individuals with fatty liver disease

    Directory of Open Access Journals (Sweden)

    Stewart Stephen

    2009-08-01

    Full Text Available Abstract Background Non-alcoholic fatty liver disease (NAFLD has a prevalence of over 20% in Western societies. Affected individuals are at risk of developing both cirrhosis and hepatocellular cancer (HCC. Presently there is no cost effective population based means of identifying cirrhotic individuals and even if there were, our ability to perform HCC surveillance in the at risk group is inadequate. We have performed a pilot proteomic study to assess this as a strategy for serum biomarker detection. Methods 2D Gel electrophoresis was performed on immune depleted sera from 3 groups of patients, namely those with (1 pre-cirrhotic NAFLD (2 cirrhotic NAFLD and (3 cirrhotic NAFLD with co-existing HCC. Five spots differentiating at least one of these three groups were characterised by mass spectroscopy. An ELISA assay was optimised and a cross sectional study assessing one of these serum spots was performed on serum from 45 patients with steatohepatitis related cirrhosis and HCC and compared to 77 patients with histologically staged steatohepatitis. Results Four of the spots identified were apolipoprotein isoforms, the pattern of which was able to differentiate the three groups. The 5th spot, seen in the serum of cirrhotic individuals and more markedly in those with HCC, was identified as CD5 antigen like (CD5L. By ELISA assay, although CD5L was markedly elevated in a number of cirrhotic individuals with HCC, its overall ability to distinguish non-cancer from cancer individuals as determined by AUC ROC analysis was poor. However, serum CD5L was dramatically increased, independently of age, sex, and the presence of necroinflammation, in the serum of individuals with NAFLD cirrhosis relative to those with pre-cirrhotic disease. Conclusion This novel proteomic strategy has identified a number of candidate biomarkers which may have benefit in the surveillance and diagnosis of individuals with chronic liver disease and/or HCC.

  5. 186Re-HEDP for metastatic bone pain in breast cancer patients

    International Nuclear Information System (INIS)

    Lam, Marnix G.E.H.; Rijk, Peter P. van; Klerk, John M.H. de

    2004-01-01

    Two-thirds of patients with metastatic cancer suffer from pain. Pain originating from skeletal metastases is the most common form of cancer-related pain. Bone pain, often exacerbated by pressure or movement, limits the patient's autonomy and social life. Pain palliation with bone-seeking radiopharmaceuticals has proven to be an effective treatment modality in patients with metastatic bone pain. These bone-seeking radiopharmaceuticals are extremely powerful in treating scattered painful bone metastases, for which external beam radiotherapy is impossible because of the large field of irradiation. 186 Re-hydroxyethylidene diphosphonate (HEDP) is a potentially useful radiopharmaceutical for this purpose, having numerous advantageous characteristics. Bone marrow toxicity is limited and reversible, which makes repetitive treatment safe. Studies have shown encouraging clinical results of palliative therapy using 186 Re-HEDP, with an overall response rate of ca. 70% in painful bone metastases. It is effective for fast palliation of painful bone metastases from various tumours and the effect tends to last longer if patients are treated early in the course of their disease. 186 Re-HEDP is at least as effective in breast cancer patients with painful bone metastases as in patients with metastatic prostate cancer. It is to be preferred to radiopharmaceuticals with a long physical half-life in this group of patients, who tend to have more extensive haematological toxicity since they have frequently been pretreated with bone marrow suppressive chemotherapy. This systemic form of radionuclide therapy is simple to administer and complements other treatment options. It has been associated with marked pain reduction, improved mobility in many patients, reduced dependence on analgesics, and improved performance status and quality of life. (orig.)

  6. Cancer treatment-induced bone loss in premenopausal women: a need for therapeutic intervention?

    Science.gov (United States)

    Hadji, P; Gnant, M; Body, J J; Bundred, N J; Brufsky, A; Coleman, R E; Guise, T A; Lipton, A; Aapro, M S

    2012-10-01

    Current clinical treatment guidelines recommend cytotoxic chemotherapy, endocrine therapy, or both (with targeted therapy if indicated) for premenopausal women with early-stage breast cancer, depending on the biologic characteristics of the primary tumor. Some of these therapies can induce premature menopause or are specifically designed to suppress ovarian function and reduce circulating estrogen levels. In addition to bone loss associated with low estrogen levels, cytotoxic chemotherapy may have a direct negative effect on bone metabolism. As a result, cancer treatment-induced bone loss poses a significant threat to bone health in premenopausal women with breast cancer. Clinical trials of antiresorptive therapies, such as bisphosphonates, have demonstrated the ability to slow or prevent bone loss in this setting. Current fracture risk assessment tools are based on data from healthy postmenopausal women and do not adequately address the risks associated with breast cancer therapy, especially in younger premenopausal women. We therefore recommend that all premenopausal women with breast cancer be informed about the potential risk of bone loss prior to beginning anticancer therapy. Women who experience amenorrhea should have bone mineral density assessed by dual-energy X-ray absorptiometry and receive regular follow-up to monitor bone health. Regular exercise and daily calcium and vitamin D supplementation are recommended. Women with a Z-score <-2.0 or Z-score ≤-1.0 and/or a 5-10% annual decrease in bone mineral density should be considered for bisphosphonate therapy in addition to calcium and vitamin D supplements. Copyright © 2012 Elsevier Ltd. All rights reserved.

  7. 32-Phosphorus for bone pain palliation due to bone metastases, its safety and efficacy in patients with advanced cancer

    International Nuclear Information System (INIS)

    Fettich, J.; Nair, G.; Padky, A.K.; Stare, J.; Nair, N.; Moralles, R.; Riccabona, G.; Tanumihardia, M.

    2001-01-01

    Bone pain due to bony metastases can seriously affect a patient's quality of life. External irradiation, narcotic drugs and polyphosphates may cause important side effects or are expensive, therefore in many patients radionuclide treatment using a single dose of beta emitting bone seeking radiopharmaceuticals has become widely accepted. Except 32-Phosphorus (32-P) all of them are expensive and difficult to obtain in certain countries. The aim of the study was to evaluate safety and efficacy of 32-P for palliation of bone pain due to bony metastases by comparing it to 89-Strontium (89-Sr), the most commonly used radiopharmaceutical for bone pain palliation in the framework of a prospective IAEA co-ordinated multicenter study. A very strict protocol for unified patient inclusion and follow up was used. 93 cancer patients with osteoblastic bony metastases were included into the study, 48 were treated by 89-Sr (150 MBq) and 45 by 32-P (450 MBq). Pain score, analgesic consumption, quality of life, and indices of bone marrow depression were monitored 2 weeks pre- and up to 4 months post treatment. Favourable response to treatment was recorded in 75% of the patients treated with 89-Sr and in 60% of those treated with 32-P (p=0,122). There was no significant difference between the duration of favourable effect for both radiopharmaceuticals. Moderate decrease of white blood cell (WBC) and platelet counts, and haemoglobin (Hb) levels was detected more often in the 32-P treated group. Although 32-P appears to be more toxic, no toxic effects requiring specific treatment were seen in either group. Due to its comparable efficacy and safety, general availability and low cost its more widespread use should be encouraged to increase quality of life and reduce cost of medical care of patients with intractable bone pain due to cancer metastases. (author)

  8. P2X7 receptor-mediated analgesia in cancer-induced bone pain

    DEFF Research Database (Denmark)

    Falk, Sarah; D. Schwab, Samantha; Frøsig-Jørgensen, Majbrit

    2015-01-01

    Pain is a common and debilitating complication for cancer patients significantly compromising their quality of life. Cancer-induced bone pain involves a complex interplay of molecular events, including mechanisms observed in inflammatory and neuropathic pain states, but also changes unique for ca...

  9. Protein content and functional characteristics of serum-purified exosomes from patients with colorectal cancer revealed by quantitative proteomics.

    Science.gov (United States)

    Chen, Yanyu; Xie, Yong; Xu, Lai; Zhan, Shaohua; Xiao, Yi; Gao, Yanpan; Wu, Bin; Ge, Wei

    2017-02-15

    Tumor cells of colorectal cancer (CRC) release exosomes into the circulation. These exosomes can mediate communication between cells and affect various tumor-related processes in their target cells. We present a quantitative proteomics analysis of the exosomes purified from serum of patients with CRC and normal volunteers; data are available via ProteomeXchange with identifier PXD003875. We identified 918 proteins with an overlap of 725 Gene IDs in the Exocarta proteins list. Compared with the serum-purified exosomes (SPEs) of normal volunteers, we found 36 proteins upregulated and 22 proteins downregulated in the SPEs of CRC patients. Bioinformatics analysis revealed that upregulated proteins are involved in processes that modulate the pretumorigenic microenvironment for metastasis. In contrast, differentially expressed proteins (DEPs) that play critical roles in tumor growth and cell survival were principally downregulated. Our study demonstrates that SPEs of CRC patients play a pivotal role in promoting the tumor invasiveness, but have minimal influence on putative alterations in tumor survival or proliferation. According to bioinformatics analysis, we speculate that the protein contents of exosomes might be associated with whether they are involved in premetastatic niche establishment or growth and survival of metastatic tumor cells. This information will be helpful in elucidating the pathophysiological functions of tumor-derived exosomes, and aid in the development of CRC diagnostics and therapeutics. © 2016 UICC.

  10. Proteomic analysis of bronchoalveolar lavage fluid (BALF) from lung cancer patients using label-free mass spectrometry.

    Science.gov (United States)

    Hmmier, Abduladim; O'Brien, Michael Emmet; Lynch, Vincent; Clynes, Martin; Morgan, Ross; Dowling, Paul

    2017-06-01

    Lung cancer is the leading cause of cancer-related mortality in both men and women throughout the world. The need to detect lung cancer at an early, potentially curable stage, is essential and may reduce mortality by 20%. The aim of this study was to identify distinct proteomic profiles in bronchoalveolar fluid (BALF) and plasma that are able to discriminate individuals with benign disease from those with non-small cell lung cancer (NSCLC). Using label-free mass spectrometry analysis of BALF during discovery-phase analysis, a significant number of proteins were found to have different abundance levels when comparing control to adenocarcinoma (AD) or squamous cell lung carcinoma (SqCC). Validation of candidate biomarkers identified in BALF was performed in a larger cohort of plasma samples by detection with enzyme-linked immunoassay. Four proteins (Cystatin-C, TIMP-1, Lipocalin-2 and HSP70/HSPA1A) were selected as a representative group from discovery phase mass spectrometry BALF analysis. Plasma levels of TIMP-1, Lipocalin-2 and Cystatin-C were found to be significantly elevated in AD and SqCC compared to control. The results presented in this study indicate that BALF is an important proximal biofluid for the discovery and identification of candidate lung cancer biomarkers. There is good correlation between the trend of protein abundance levels in BALF and that of plasma which validates this approach to develop a blood biomarker to aid lung cancer diagnosis, particularly in the era of lung cancer screening. The protein signatures identified also provide insight into the molecular mechanisms associated with lung malignancy.

  11. Targeted Therapies for Myeloma and Metastatic Bone Cancers

    National Research Council Canada - National Science Library

    Vail, Neal

    2008-01-01

    ... done. Quantified functional groups available for ligand conjugation using S35-labeled ligands. Developed alternative assay to confirm affinity of bone-targeting nanoparticles to hydroxyapatite substrates...

  12. A proteome study of secreted prostatic factors affecting osteoblastic activity: galectin-1 is involved in differentiation of human bone marrow stromal cells

    DEFF Research Database (Denmark)

    Andersen, H; Jensen, Ole N; Moiseeva, Elena P

    2003-01-01

    Prostate cancer cells metastasize to bone causing a predominantly osteosclerotic response. It has been shown that cells from the human prostate cancer cell line PC3 secrete factors that influence the behavior of osteoblast-like cells. Some of these factors with mitogenic activity have been found...... to be proteins with molecular weights between 20 and 30 kDa, but the identity of the osteoblastic mitogenic factor or factors produced by prostate cancer cells is still unknown. Therefore, the aim of this study was to characterize the protein profile of conditioned medium (CM) from PC3 cells in the molecular......BMS) cells. Furthermore, we tested whether adhesion of PC3 cells to plastic, laminin, fibronectin, and collagen type I was influenced by lactose, which inhibits galectin-1. Galectin-1 (1000 ng/ml) inhibited the proliferation of hBMS cells up to 70 +/- 12% (treated/control) of control in contrast to PC3 CM...

  13. Development of Raman spectral markers to assess metastatic bone in breast cancer

    Science.gov (United States)

    Ding, Hao; Nyman, Jeffry S.; Sterling, Julie A.; Perrien, Daniel S.; Mahadevan-Jansen, Anita; Bi, Xiaohong

    2014-11-01

    Bone is the most common site for breast cancer metastases. One of the major complications of bone metastasis is pathological bone fracture caused by chronic bone loss and degeneration. Current guidelines for the prediction of pathological fracture mainly rely on radiographs or computed tomography, which are limited in their ability to predict fracture risk. The present study explored the feasibility of using Raman spectroscopy to estimate pathological fracture risk by characterizing the alterations in the compositional properties of metastatic bones. Tibiae with evident bone destruction were investigated using Raman spectroscopy. The carbonation level calculated by the ratio of carbonate/phosphate ν1 significantly increased in the tumor-bearing bone at all the sampling regions at the proximal metaphysis and diaphysis, while tumor-induced elevation in mineralization and crystallinity was more pronounced in the metaphysis. Furthermore, the increased carbonation level is positively correlated to bone lesion size, indicating that this parameter could serve as a unique spectral marker for tumor progression and bone loss. With the promising advances in the development of spatially offset Raman spectroscopy for deep tissue measurement, this spectral marker can potentially be used for future noninvasive evaluation of metastatic bone and prediction of pathological fracture risk.

  14. 3D printing of high-strength bioscaffolds for the synergistic treatment of bone cancer

    Science.gov (United States)

    Ma, Hongshi; Li, Tao; Huan, Zhiguang; Zhang, Meng; Yang, Zezheng; Wang, Jinwu; Chang, Jiang; Wu, Chengtie

    2018-04-01

    The challenges in bone tumor therapy are how to repair the large bone defects induced by surgery and kill all possible residual tumor cells. Compared to cancellous bone defect regeneration, cortical bone defect regeneration has a higher demand for bone substitute materials. To the best of our knowledge, there are currently few bifunctional biomaterials with an ultra-high strength for both tumor therapy and cortical bone regeneration. Here, we designed Fe-CaSiO3 composite scaffolds (30CS) via 3D printing technique. First, the 30CS composite scaffolds possessed a high compressive strength that provided sufficient mechanical support in bone cortical defects; second, synergistic photothermal and ROS therapies achieved an enhanced tumor therapeutic effect in vitro and in vivo. Finally, the presence of CaSiO3 in the composite scaffolds improved the degradation performance, stimulated the proliferation and differentiation of rBMSCs, and further promoted bone formation in vivo. Such 30CS scaffolds with a high compressive strength can function as versatile and efficient biomaterials for the future regeneration of cortical bone defects and the treatment of bone cancer.

  15. Differential profiling of breast cancer plasma proteome by isotope-coded affinity tagging method reveals biotinidase as a breast cancer biomarker

    International Nuclear Information System (INIS)

    Kang, Un-Beom; Ahn, Younghee; Lee, Jong Won; Kim, Yong-Hak; Kim, Joon; Yu, Myeong-Hee; Noh, Dong-Young; Lee, Cheolju

    2010-01-01

    Breast cancer is one of the leading causes of women's death worldwide. It is important to discover a reliable biomarker for the detection of breast cancer. Plasma is the most ideal source for cancer biomarker discovery since many cells cross-communicate through the secretion of soluble proteins into blood. Plasma proteomes obtained from 6 breast cancer patients and 6 normal healthy women were analyzed by using the isotope-coded affinity tag (ICAT) labeling approach and tandem mass spectrometry. All the plasma samples used were depleted of highly abundant 6 plasma proteins by immune-affinity column chromatography before ICAT labeling. Several proteins showing differential abundance level were selected based on literature searches and their specificity to the commercially available antibodies, and then verified by immunoblot assays. A total of 155 proteins were identified and quantified by ICAT method. Among them, 33 proteins showed abundance changes by more than 1.5-fold between the plasmas of breast cancer patients and healthy women. We chose 5 proteins for the follow-up confirmation in the individual plasma samples using immunoblot assay. Four proteins, α1-acid glycoprotein 2, monocyte differentiation antigen CD14, biotinidase (BTD), and glutathione peroxidase 3, showed similar abundance ratio to ICAT result. Using a blind set of plasmas obtained from 21 breast cancer patients and 21 normal healthy controls, we confirmed that BTD was significantly down-regulated in breast cancer plasma (Wilcoxon rank-sum test, p = 0.002). BTD levels were lowered in all cancer grades (I-IV) except cancer grade zero. The area under the receiver operating characteristic curve of BTD was 0.78. Estrogen receptor status (p = 0.940) and progesterone receptor status (p = 0.440) were not associated with the plasma BTD levels. Our study suggests that BTD is a potential serological biomarker for the detection of breast cancer

  16. Lung, liver and bone cancer mortality after plutonium exposure in beagle dogs and nuclear workers.

    Science.gov (United States)

    Wilson, Dulaney A; Mohr, Lawrence C; Frey, G Donald; Lackland, Daniel; Hoel, David G

    2010-01-01

    The Mayak Production Association (MPA) worker registry has shown evidence of plutonium-induced health effects. Workers were potentially exposed to plutonium nitrate [(239)Pu(NO(3))(4)] and plutonium dioxide ((239)PuO(2)). Studies of plutonium-induced health effects in animal models can complement human studies by providing more specific data than is possible in human observational studies. Lung, liver, and bone cancer mortality rate ratios in the MPA worker cohort were compared to those seen in beagle dogs, and models of the excess relative risk of lung, liver, and bone cancer mortality from the MPA worker cohort were applied to data from life-span studies of beagle dogs. The lung cancer mortality rate ratios in beagle dogs are similar to those seen in the MPA worker cohort. At cumulative doses less than 3 Gy, the liver cancer mortality rate ratios in the MPA worker cohort are statistically similar to those in beagle dogs. Bone cancer mortality only occurred in MPA workers with doses over 10 Gy. In dogs given (239)Pu, the adjusted excess relative risk of lung cancer mortality per Gy was 1.32 (95% CI 0.56-3.22). The liver cancer mortality adjusted excess relative risk per Gy was 55.3 (95% CI 23.0-133.1). The adjusted excess relative risk of bone cancer mortality per Gy(2) was 1,482 (95% CI 566.0-5686). Models of lung cancer mortality based on MPA worker data with additional covariates adequately described the beagle dog data, while the liver and bone cancer models were less successful.

  17. Stem cell targets and dosimetry for radiation-induced leukaemia and bone cancer

    International Nuclear Information System (INIS)

    Richardson, R.B.

    2007-01-01

    The ICRP are proposing changes to the assumed targets for the induction of bone cancer and leukaemias as described by Harrison et al in an accompanying article. This study of radiation targets in the skeleton finds that the endosteum of the long bone medullary cavities is not an important target, especially in the adult, as it supports a very low stem cell population associated with high adiposity, whereas the periosteum has a strong mesenchymal stem cell population throughout lifetime. Quiescent stem cells are found to be preferentially located close to the trabecular bone surface in the osteoblastic niche, whereas progenitors of stem cells prefer to reside in perivascular niches. Evidence is given in support of the suggestion that the absence of excess bone-cancer in atomic bomb survivors may be related to the extremely low prevalence of Paget's disease in Japan. The hypoxic conditions of the endosteum adjacent to quiescent bone surfaces provide a radioprotective stem cell microenvironment by a factor of 2-3 fold, whereas greater radiosensitivity is prevalent in the young and individuals with benign diseases of bone. Increasing the volume of the bone cancer target from a 10 μm thick endosteum to a 50 μm peripheral marrow layer will result in an approximately three-fold decline in the mean dose from alpha-emitters in bone. These new observations are shown to go some way in explaining the low incidences for leukaemia and especially bone cancer in radium dial painters, Thorotrast patients and Mayak nuclear workers. (author)

  18. F-8 sodium fluoride position emission tomography/computed tomography for detection of thyroid cancer bone metastasis compared with bone scintigraphy

    Energy Technology Data Exchange (ETDEWEB)

    Lee, Hyun Jong; Lee, Won Woo; Park, So Yeon; Kim, Sang Eun [Seoul National University Bundang Hospital, Seoul National University College of Medicine, Seoul (Korea, Republic of)

    2016-04-15

    The aim of the study was to compare the diagnostic performances of F-18 sodium fluoride positron emission tomography/computed tomography (bone PET/CT) and bone scintigraphy (BS) for the detection of thyroid cancer bone metastasis. We retrospectively enrolled 6 thyroid cancer patients (age = 44.7 ± 9.8 years, M:F = 1:5, papillary:follicular = 2:4) with suspected bone metastatic lesions in the whole body iodine scintigraphy or BS, who subsequently underwent bone PET/CT. Pathologic diagnosis was conducted for 4 lesions of 4 patients. Of the 17 suspected bone lesions, 10 were metastatic and 7 benign. Compared to BS, bone PET/CT exhibited superior sensitivity (10/10 = 100% vs. 2/10 = 20%, p = 0.008), and accuracy (14/17 = 82.4% vs. 7/17 = 41.2%, p < 0.025). The specificity (4/7 = 57.1%) of bone PET/CT was not significantly different from that of BS (5/7 = 71.4%, p > 0.05). Bone PET/CT may be more sensitive and accurate than BS for the detection of thyroid cancer bone metastasis.

  19. Quantitative evaluation of bone metastases in patients with advanced prostate cancer during endocrine therapy

    International Nuclear Information System (INIS)

    Yahara, Jyunro

    2003-01-01

    A well-recognized difficulty in assessing the response to therapy for advanced prostate cancer is the infrequency of measurable metastatic disease. The most common metastatic site is bone, and it is manifested by diffuse ostoblastic lesions that cannot be measured reliably to allow for assessments of therapeutic benefits. We assessed the clinical usefulness of quantifying the extent of disease on bone scans in monitoring treatment response in patients with advance prostate cancer using computer-assisted image analysis. Percentage of the positive area on the bone scan (%PABS) was quantified automatically using a personal computer with the NIH Image program. Serial measurements of %PABS in 44 patients with bone metastasis from prostate cancer followed for a mean of 33 month (range 4 to 72) with hormonal therapy were compared with those of the extent of disease (EOD) grades in bone lesions and serum prostate specific antigen (PSA) levels according to treatment response. Serial measurements of EOD grades and %PABS in 13 patients with partial response (PR) disease and those in 12 patients with progressive disease (PD) who did not show bone metastasis progression demonstrated a downward trend during the treatment. On the other hand, changes of EOD grades and %PABS in the remaining 19 patients with PD who showed bone metastasis progression demonstrated an upward trend. Estimated survival curves showed that %PABS was a useful prognostic indicator, with the patients who showed a 25% decline in %PABS surviving longer than the patients who showed a less than 25% decline in %PABS after treatment (p=0.0207). The %PABS is a simple and reproducible estimate of the percentage of the skeleton involving tumors in patients with advanced prostate cancer, and serial measurements of %PABS can assist in monitoring the treatment response in patients with bone metastatic prostate cancer. (author)

  20. Towards an animal model of ovarian cancer: cataloging chicken blood proteins using combinatorial peptide ligand libraries coupled with shotgun proteomic analysis for translational research.

    Science.gov (United States)

    Ma, Yingying; Sun, Zeyu; de Matos, Ricardo; Zhang, Jing; Odunsi, Kunle; Lin, Biaoyang

    2014-05-01

    Epithelial ovarian cancer is the most deadly gynecological cancer around the world, with high morbidity in industrialized countries. Early diagnosis is key in reducing its morbidity rate. Yet, robust biomarkers, diagnostics, and animal models are still limited for ovarian cancer. This calls for broader omics and systems science oriented diagnostics strategies. In this vein, the domestic chicken has been used as an ovarian cancer animal model, owing to its high rate of developing spontaneous epithelial ovarian tumors. Chicken blood has thus been considered a surrogate reservoir from which cancer biomarkers can be identified. However, the presence of highly abundant proteins in chicken blood has compromised the applicability of proteomics tools to study chicken blood owing to a lack of immunodepletion methods. Here, we demonstrate that a combinatorial peptide ligand library (CPLL) can efficiently remove highly abundant proteins from chicken blood samples, consequently doubling the number of identified proteins. Using an integrated CPLL-1DGE-LC-MSMS workflow, we identified a catalog of 264 unique proteins. Functional analyses further suggested that most proteins were coagulation and complement factors, blood transport and binding proteins, immune- and defense-related proteins, proteases, protease inhibitors, cellular enzymes, or cell structure and adhesion proteins. Semiquantitative spectral counting analysis identified 10 potential biomarkers from the present chicken ovarian cancer model. Additionally, many human homologs of chicken blood proteins we have identified have been independently suggested as diagnostic biomarkers for ovarian cancer, further triangulating our novel observations reported here. In conclusion, the CPLL-assisted proteomic workflow using the chicken ovarian cancer model provides a feasible platform for translational research to identify ovarian cancer biomarkers and understand ovarian cancer biology. To the best of our knowledge, we report here

  1. The relationship between biological marker factors and the bone metastasis in breast cancer

    International Nuclear Information System (INIS)

    Xiong Lingjing; Liang Changhua; Li Xinhui; Deng Haoyu; Hu Shuo; Duan Huaxin

    2003-01-01

    Objective: To investigate the relationship between biological marker factors and the bone metastasis in breast cancer to instruct the follow-up of breast cancer patients. Methods: One hundred and fifteen breast cancer patients proved by histological examination after surgery were involved. To detect nm23 protein, C-erbB-2 protein, estrogen receptor (ER), progestogen receptor (PR) expression of their excised breast cancer tissue, immunohistochemical procedures were used. The relationship between biological marker factors and the bone metastasis in breast cancer was analyzed. All patients were examined by radioisotope whole body bone imaging during the follow-up. Results: The results were that the clinical staging, the status of axillary lymph nodes, the expression of nm23 protein, C-erbB-2 protein, ER were related to the bone metastasis in breast cancer, while the age, the mode of operation and the expression of PR were not. Conclusion: Colligating analysis of clinical, pathological status and biological marker factors is very important for the prediction of the prognosis and the direction of the follow-up in breast cancer patients after surgery

  2. Quantitative proteomic analysis by iTRAQ® for the identification of candidate biomarkers in ovarian cancer serum

    Directory of Open Access Journals (Sweden)

    Higgins LeeAnn

    2010-06-01

    Full Text Available Abstract Background Ovarian cancer is the most lethal gynecologic malignancy, with the majority of cases diagnosed at an advanced stage when treatments are less successful. Novel serum protein markers are needed to detect ovarian cancer in its earliest stage; when detected early, survival rates are over 90%. The identification of new serum biomarkers is hindered by the presence of a small number of highly abundant proteins that comprise approximately 95% of serum total protein. In this study, we used pooled serum depleted of the most highly abundant proteins to reduce the dynamic range of proteins, and thereby enhance the identification of serum biomarkers using the quantitative proteomic method iTRAQ®. Results Medium and low abundance proteins from 6 serum pools of 10 patients each from women with serous ovarian carcinoma, and 6 non-cancer control pools were labeled with isobaric tags using iTRAQ® to determine the relative abundance of serum proteins identified by MS. A total of 220 unique proteins were identified and fourteen proteins were elevated in ovarian cancer compared to control serum pools, including several novel candidate ovarian cancer biomarkers: extracellular matrix protein-1, leucine-rich alpha-2 glycoprotein-1, lipopolysaccharide binding protein-1, and proteoglycan-4. Western immunoblotting validated the relative increases in serum protein levels for several of the proteins identified. Conclusions This study provides the first analysis of immunodepleted serum in combination with iTRAQ® to measure relative protein expression in ovarian cancer patients for the pursuit of serum biomarkers. Several candidate biomarkers were identified which warrant further development.

  3. Proteomic profiling identifies PTK2/FAK as a driver of radioresistance in HPV-negative head and neck cancer

    Science.gov (United States)

    Skinner, Heath D.; Giri, Uma; Yang, Liang P.; Woo, Sang Hyeok; Story, Michael; Pickering, Curtis; Byers, Lauren; Williams, Michelle; El Naggar, Adel; Wang, Jing; Diao, Lixia; Shen, Li; Fan, You Hong; Molkentine, David; Beadle, Beth; Meyn, Raymond; Myers, Jeffrey; Heymach, John

    2016-01-01

    Purpose Head and neck squamous cell carcinoma (HNSCC) is commonly treated with radiotherapy, and local failure after treatment remains the major cause of disease-related mortality. To date human papillomavirus (HPV) is the only known clinically validated, targetable biomarkers of response to radiation in HNSCC. Experimental Design We performed proteomic and transcriptomic analysis of targetable biomarkers of radioresistance in HPV-negative HNSCC cell lines in vitro, and tested whether pharmacologic blockade of candidate biomarkers sensitized cells to radiotherapy. Candidate biomarkers were then investigated in several independent cohorts of patients with HNSCC. Results Increased expression of several targets was associated with radioresistance, including FGFR, ERK1, EGFR, and focal adhesion kinase (FAK), also known as PTK2. Chemical inhibition of PTK2/FAK, but not FGFR, led to significant radiosensitization with increased G2/M arrest and potentiated DNA damage. PTK2/FAK overexpression was associated with gene amplification in HPV-negative HNSCC cell lines and clinical tumors. In two independent cohorts of patients with locally advanced HPV-negative HNSCC, PTK2/FAK amplification was highly associated with poorer disease-free survival (DFS) (P=0.012 and P=0.034). PTK2/FAK mRNA expression was also associated with worse DFS (P=0.03). Moreover, both PTK2/FAK mRNA (P=0.021) and copy number (P=0.063) were associated with DFS in the Head and Neck Cancer subgroup of The Cancer Genome Atlas. Conclusion Proteomic analysis identified PTK2/FAK overexpression is a biomarker of radioresistance in locally advanced HNSCC, and PTK2/FAK inhibition radiosensitized HNSCC cells. Combinations of PTK2/FAK inhibition with radiotherapy merit further evaluation as a therapeutic strategy for improving local control in HPV-negative HNSCC. PMID:27036135

  4. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    Energy Technology Data Exchange (ETDEWEB)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun, E-mail: biochelab@yuhs.ac; Chung, Won-Yoon, E-mail: wychung@yuhs.ac

    2014-03-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  5. Betulinic acid, a bioactive pentacyclic triterpenoid, inhibits skeletal-related events induced by breast cancer bone metastases and treatment

    International Nuclear Information System (INIS)

    Park, Se Young; Kim, Hyun-Jeong; Kim, Ki Rim; Lee, Sun Kyoung; Lee, Chang Ki; Park, Kwang-Kyun; Chung, Won-Yoon

    2014-01-01

    Many breast cancer patients experience bone metastases and suffer skeletal complications. The present study provides evidence on the protective and therapeutic potential of betulinic acid on cancer-associated bone diseases. Betulinic acid is a naturally occurring triterpenoid with the beneficial activity to limit the progression and severity of cancer, diabetes, cardiovascular diseases, atherosclerosis, and obesity. We first investigated its effect on breast cancer cells, osteoblastic cells, and osteoclasts in the vicious cycle of osteolytic bone metastasis. Betulinic acid reduced cell viability and the production of parathyroid hormone-related protein (PTHrP), a major osteolytic factor, in MDA-MB-231 human metastatic breast cancer cells stimulated with or without tumor growth factor-β. Betulinic acid blocked an increase in the receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin ratio by downregulating RANKL protein expression in PTHrP-treated human osteoblastic cells. In addition, betulinic acid inhibited RANKL-induced osteoclastogenesis in murine bone marrow macrophages and decreased the production of resorbed area in plates with a bone biomimetic synthetic surface by suppressing the secretion of matrix metalloproteinase (MMP)-2, MMP-9, and cathepsin K in RANKL-induced osteoclasts. Furthermore, oral administration of betulinic acid inhibited bone loss in mice intra-tibially inoculated with breast cancer cells and in ovariectomized mice causing estrogen deprivation, as supported by the restored bone morphometric parameters and serum bone turnover markers. Taken together, these findings suggest that betulinic acid may have the potential to prevent bone loss in patients with bone metastases and cancer treatment-induced estrogen deficiency. - Highlights: • Betulinic acid reduced PTHrP production in human metastatic breast cancer cells. • Betulinic acid blocked RANKL/OPG ratio in PTHrP-stimulated human osteoblastic cells. • Betulinic

  6. Skeletal-related events in urological cancer patients with bone metastasis. A multicenter study in Japan

    International Nuclear Information System (INIS)

    Yokomizo, Akira; Koga, Hirofumi; Shinohara, Nobuo

    2010-01-01

    The objective of this study was to investigate the incidence of skeletal-related events (SRE) in urological cancer patients with bone metastases in Japan. Five hundred eleven patients with urological cancer and documented bone metastases treated from January 2003 to April 2008 in ten Japanese institutions were included in a retrospective analysis. Type and incidence of SRE (fracture, radiotherapy, spinal cord compression, surgery, hypercalcemia, and bone pain) were determined from patient medical records. The overall incidence of SRE, including 'pain', was 61%. The most common event was radiotherapy for bone metastases, with an incidence of 31%. The overall incidence of events seemed to be similar among Japanese and Western patients with prostate cancer and renal cell carcinoma when comparing data with previously published reports. Nevertheless, a much lower incidence of fracture (19.1%) was observed in Japanese renal cell carcinoma patients. The overall incidence of SRE in Japanese urological cancer patients with bone metastasis was similar to that in Western patients, but the incidence of fracture was lower in Japanese renal cancer patients. (author)

  7. [A comparison of proteomic analysis of Helicobacter pylori in patients with gastritis and gastric cancer between areas of high and low incidence of gastric cancer].

    Science.gov (United States)

    Liu, Lin-na; Zhang, Jing; Ding, Shi-gang; Zhong, Li Jun; Li, Guang-chuan; Shi, Yan-yan; Wang, Ye

    2011-12-18

    To identify the differentially expressed proteins of Helicobacter pylori (Hp) in patients with gastritis and gastric cancer from areas of high and low incidence of gastric cancer by 2-dimensional electrophoresis (2-DE), and to discuss the role of bacterial factor in pathogenesis. Hp in the endoscopic biopsy specimens of gastric mucosa of patients with gastritis and gastric cancer from areas of high (Xining) and low (Beijing) incidence of gastric cancer, were separated, cultured and saved at -80°C. The bacteria were recovered. Then the whole-cell protein of the Hp were extracted and characterized by 2-DE. The different protein spots were analyzed by PDQuest analysis software and identified by electrospray ionization quadruple time-of-flight mass spectrometry (ESI-Q-TOF-MS), and searched by the Mascot database. Nine differentially expressed proteins were identified, and four protein spots were over expressed in the protein maps from gastric cancer in both areas, which were: Urease subunit alpha, chaperone protein dnaK, superoxide dismutase, DNA-directed RNA polymerase subunit alpha; two protein spots were over expressed in the protein maps from gastritis in both areas, which were: Probablethiol peroxidase, nucleoside diphosphate kinase; 60×10(3) chaperonin, and inorganic pyrophosphatase were over expressed only in the protein map from gastric cancer in Xining; S-ribosyl homocysteinelyase was over expressed only in the protein map from gastric cancer in Beijing. There are differences between proteomic analyses of Hp in patients with gastritis and gastric cancer in areas of high and low incidents of gastric cancer, but 2/3 of the protein spots over expressed in the areas are consistent. The protein spots over expressed from gastric cancer in the area with high incidence of gastric cancer are more than in the area with low incidence of gastric cancer. For the Hp extracted from patients with gastric cancer, the mechanism of gastric cancer may be similar, but the role

  8. Palliation of bone cancer pain by antagonists of platelet-activating factor receptors.

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    Katsuya Morita

    Full Text Available Bone cancer pain is the most severe among cancer pain and is often resistant to current analgesics. Thus, the development of novel analgesics effective at treating bone cancer pain are desired. Platelet-activating factor (PAF receptor antagonists were recently demonstrated to have effective pain relieving effects on neuropathic pain in several animal models. The present study examined the pain relieving effect of PAF receptor antagonists on bone cancer pain using the femur bone cancer (FBC model in mice. Animals were injected with osteolytic NCTC2472 cells into the tibia, and subsequently the effects of PAF receptor antagonists on pain behaviors were evaluated. Chemical structurally different type of antagonists, TCV-309, BN 50739 and WEB 2086 ameliorated the allodynia and improved pain behaviors such as guarding behavior and limb-use abnormalities in FBC model mice. The pain relieving effects of these antagonists were achieved with low doses and were long lasting. Blockade of spinal PAF receptors by intrathecal injection of TCV-309 and WEB 2086 or knockdown of the expression of spinal PAF receptor protein by intrathecal transfer of PAF receptor siRNA also produced a pain relieving effect. The amount of an inducible PAF synthesis enzyme, lysophosphatidylcholine acyltransferase 2 (LPCAT2 protein significantly increased in the spinal cord after transplantation of NCTC 2472 tumor cells into mouse tibia. The combination of morphine with PAF receptor antagonists develops marked enhancement of the analgesic effect against bone cancer pain without affecting morphine-induced constipation. Repeated administration of TCV-309 suppressed the appearance of pain behaviors and prolonged survival of FBC mice. The present results suggest that PAF receptor antagonists in combination with, or without, opioids may represent a new strategy for the treatment of persistent bone cancer pain and improve the quality of life of patients.

  9. Systemic effects of ionizing radiation at the proteome and metabolome levels in the blood of cancer patients treated with radiotherapy: the influence of inflammation and radiation toxicity.

    Science.gov (United States)

    Jelonek, Karol; Pietrowska, Monika; Widlak, Piotr

    2017-07-01

    Blood is the most common replacement tissue used to study systemic responses of organisms to different types of pathological conditions and environmental insults. Local irradiation during cancer radiotherapy induces whole body responses that can be observed at the blood proteome and metabolome levels. Hence, comparative blood proteomics and metabolomics are emerging approaches used in the discovery of radiation biomarkers. These techniques enable the simultaneous measurement of hundreds of molecules and the identification of sets of components that can discriminate different physiological states of the human body. Radiation-induced changes are affected by the dose and volume of irradiated tissues; hence, the molecular composition of blood is a hypothetical source of biomarkers for dose assessment and the prediction and monitoring of systemic responses to radiation. This review aims to provide a comprehensive overview on the available evidence regarding molecular responses to ionizing radiation detected at the level of the human blood proteome and metabolome. It focuses on patients exposed to radiation during cancer radiotherapy and emphasizes effects related to radiation-induced toxicity and inflammation. Systemic responses to radiation detected at the blood proteome and metabolome levels are primarily related to the intensity of radiation-induced toxicity, including inflammatory responses. Thus, several inflammation-associated molecules can be used to monitor or even predict radiation-induced toxicity. However, these abundant molecular features have a rather limited applicability as universal biomarkers for dose assessment, reflecting the individual predisposition of the immune system and tissue-specific mechanisms involved in radiation-induced damage.

  10. Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer.

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    Schroll, Monica M; Ludwig, Katelyn R; Bauer, Kerry M; Hummon, Amanda B

    2018-01-11

    Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side) colon is different from cancer of the descending (left side) colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.

  11. Calcitriol Supplementation Causes Decreases in Tumorigenic Proteins and Different Proteomic and Metabolomic Signatures in Right versus Left-Sided Colon Cancer

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    Monica M. Schroll

    2018-01-01

    Full Text Available Vitamin D deficiency is a common problem worldwide. In particular, it is an issue in the Northern Hemisphere where UVB radiation does not penetrate the atmosphere as readily. There is a correlation between vitamin D deficiency and colorectal cancer incidence and mortality. Furthermore, there is strong evidence that cancer of the ascending (right side colon is different from cancer of the descending (left side colon in terms of prognosis, tumor differentiation, and polyp type, as well as at the molecular level. Right-side tumors have elevated Wnt signaling and are more likely to relapse, whereas left-side tumors have reduced expression of tumor suppressor genes. This study seeks to understand both the proteomic and metabolomic changes resulting from treatment of the active metabolite of vitamin D, calcitriol, in right-sided and left-sided colon cancer. Our results show that left-sided colon cancer treated with calcitriol has a substantially greater number of changes in both the proteome and the metabolome than right-sided colon cancer. We found that calcitriol treatment in both right-sided and left-sided colon cancer causes a downregulation of ribosomal protein L37 and protein S100A10. Both of these proteins are heavily involved in tumorigenesis, suggesting a possible mechanism for the correlation between low vitamin D levels and colon cancer.

  12. Combining phenotypic and proteomic approaches to identify membrane targets in a ‘triple negative’ breast cancer cell type

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    Rust Steven

    2013-02-01

    Full Text Available Abstract Background The continued discovery of therapeutic antibodies, which address unmet medical needs, requires the continued discovery of tractable antibody targets. Multiple protein-level target discovery approaches are available and these can be used in combination to extensively survey relevant cell membranomes. In this study, the MDA-MB-231 cell line was selected for membranome survey as it is a ‘triple negative’ breast cancer cell line, which represents a cancer subtype that is aggressive and has few treatment options. Methods The MDA-MB-231 breast carcinoma cell line was used to explore three membranome target discovery approaches, which were used in parallel to cross-validate the significance of identified antigens. A proteomic approach, which used membrane protein enrichment followed by protein identification by mass spectrometry, was used alongside two phenotypic antibody screening approaches. The first phenotypic screening approach was based on hybridoma technology and the second was based on phage display technology. Antibodies isolated by the phenotypic approaches were tested for cell specificity as well as internalisation and the targets identified were compared to each other as well as those identified by the proteomic approach. An anti-CD73 antibody derived from the phage display-based phenotypic approach was tested for binding to other ‘triple negative’ breast cancer cell lines and tested for tumour growth inhibitory activity in a MDA-MB-231 xenograft model. Results All of the approaches identified multiple cell surface markers, including integrins, CD44, EGFR, CD71, galectin-3, CD73 and BCAM, some of which had been previously confirmed as being tractable to antibody therapy. In total, 40 cell surface markers were identified for further study. In addition to cell surface marker identification, the phenotypic antibody screening approaches provided reagent antibodies for target validation studies. This is illustrated

  13. Mint3 in bone marrow-derived cells promotes lung metastasis in breast cancer model mice.

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    Hara, Toshiro; Murakami, Yoshinori; Seiki, Motoharu; Sakamoto, Takeharu

    2017-08-26

    Breast cancer is one of the most common cancers in women in the world. Although breast cancer is well treatable at the early stage, patients with distant metastases show a poor prognosis. Data from recent studies using transplantation models indicate that Mint3/APBA3 might promote breast cancer malignancy. However, whether Mint3 indeed contributes to tumor development, progression, or metastasis in vivo remains unclear. To address this, here we examined whether Mint3 depletion affects tumor malignancy in MMTV-PyMT breast cancer model mice. In MMTV-PyMT mice, Mint3 depletion did not affect tumor onset and tumor growth, but attenuated lung metastases. Experimental lung metastasis of breast cancer Met-1 cells derived from MMTV-PyMT mice also decreased in Mint3-depleted mice, indicating that host Mint3 expression affected lung metastasis of MMTV-PyMT-derived breast cancer cells. Further bone marrow transplant experiments revealed that Mint3 in bone marrow-derived cells promoted lung metastasis in MMTV-PyMT mice. Thus, targeting Mint3 in bone marrow-derived cells might be a good strategy for preventing metastasis and improving the prognosis of breast cancer patients. Copyright © 2017 Elsevier Inc. All rights reserved.

  14. Proteomic-based identification of multiple pathways underlying n-butylidenephthalide-induced apoptosis in LNCaP human prostate cancer cells.

    Science.gov (United States)

    Pang, Cheng-Yoong; Chiu, Sheng-Chun; Harn, Horng-Jyh; Zhai, Wei-Jun; Lin, Shinn-Zong; Yang, Hsueh-Hui

    2013-09-01

    Although numerous studies have shown the cancer-preventive properties of butylidenephthalide (BP), there is little report of BP affecting human prostate cancer cells. In the present study, proteomic-based approaches were used to elucidate the anticancer mechanism of BP in LNCaP human prostate cancer cells. BP treatment decreased the viability of LNCaP human prostate cancer cells in a concentration- and time-dependent manner, which was correlated with G0/G1 phase cell cycle arrest. Increased cell cycle arrest was associated with a decrease in the level of CCND1, CDK2, and PCNA proteins and an increase in the level of CDKN2A, CDKN1A, and SFN proteins. Proteomic studies revealed that among 48 differentially expressed proteins, 25 proteins were down-regulated and 23 proteins were up-regulated and these proteins fall into one large protein protein interaction network. Among these proteins, FAS, AIFM1, BIK, CYCS, SFN, PPP2R1A, CALR, HSPA5, DDIT3, and ERN1 are apoptosis and endoplasmic reticulum (ER) stress associated proteins. Proteomic data suggested that multiple signaling pathways including FAS-dependent pathway, mitochondrial pathway, and ER stress pathway are involved in the apoptosis induced by BP. Copyright © 2013 Elsevier Ltd. All rights reserved.

  15. F-18 Sodium Fluoride Positron Emission Tomography/Computed Tomography for Detection of Thyroid Cancer Bone Metastasis Compared with Bone Scintigraphy.

    Science.gov (United States)

    Lee, Hyunjong; Lee, Won Woo; Park, So Yeon; Kim, Sang Eun

    2016-01-01

    The aim of the study was to compare the diagnostic performances of F-18 sodium fluoride positron emission tomography/computed tomography (bone PET/CT) and bone scintigraphy (BS) for the detection of thyroid cancer bone metastasis. We retrospectively enrolled 6 thyroid cancer patients (age = 44.7 ± 9.8 years, M:F = 1:5, papillary:follicular = 2:4) with suspected bone metastatic lesions in the whole body iodine scintigraphy or BS, who subsequently underwent bone PET/CT. Pathologic diagnosis was conducted for 4 lesions of 4 patients. Of the 17 suspected bone lesions, 10 were metastatic and 7 benign. Compared to BS, bone PET/CT exhibited superior sensitivity (10/10 = 100% vs. 2/10 = 20%, p = 0.008), and accuracy (14/17 = 82.4% vs. 7/17 = 41.2%, p 0.05). Bone PET/CT may be more sensitive and accurate than BS for the detection of thyroid cancer bone metastasis.

  16. Increased circulating rather than spinal cytokines accompany chronic pain behaviors in experimental bone cancer and arthritis

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    Line Pourtau

    2014-12-01

    Full Text Available Aim: Peripheral cytokines contribute to arthritis and bone cancer pain through sensory nerve actions. However, increased spinal cytokine and glial filament expression, coined neuroinflammation, has also been proposed to play a part in chronic pain. Therefore, spinal cord, dorsal root ganglia and circulating cytokines were compared in murine arthritis and bone cancer models in relationship to behavioral signs of pain. Methods: Exploratory behaviors were studied after intra-articular complete Freund's adjuvant or bone intramedullary sarcoma cell injection. Nervous tissue and blood cytokine expression were determined by real-time polymerase chain reaction (PCR and multiplex immunoassays, respectively. Results: PCR analysis did not reveal any hallmark of spinal neuroinflammation in spontaneously-behaving mice with cartilage or bone lesions. However, imposed paw stimulation during joint inflammation increased spinal interleukin-1β (IL-1β expression. Spontaneous paw guarding during rearing was displayed by animals with joint inflammation and bone destruction and was accompanied by increased circulating IL-6 and monocyte chemoattractant protein-1, respectively. In addition, dorsal root ganglia were found to constitutively express receptors for this chemotactic cytokine. Conclusion: Our findings indicate that spinal neuroinflammation is not a necessary condition for chronic pain and suggest that circulating cytokine action in dorsal root ganglia may contribute to experimental joint inflammation and bone cancer pain.

  17. Bone scintigraphy predicts the risk of spinal cord compression in hormone-refractory prostate cancer

    International Nuclear Information System (INIS)

    Soerdjbalie-Maikoe, Vidija; Pelger, Rob C.M.; Nijeholt, Guus A.B. Lycklama; Arndt, Jan-Willem; Zwinderman, Aeilko H.; Bril, Herman; Papapoulos, Socrates E.; Hamdy, Neveen A.T.

    2004-01-01

    In prostate cancer, confirmation of metastatic involvement of the skeleton has traditionally been achieved by bone scintigraphy, although the widespread availability of prostate-specific antigen (PSA) measurements has tended to eliminate the need for this investigation. The potential of bone scintigraphy to predict skeletal-related events, particularly spinal cord compression, after the onset of hormone refractoriness has never been investigated. The aim of this study was to establish whether a new method of evaluating bone scintigraphy would offer a better predictive value for this complication of the metastatic process than is achieved with currently available grading methods. We studied 84 patients with hormone-refractory prostate cancer who had undergone bone scintigraphy at the time of hormone escape. Tumour grading and parameters of tumour load (PSA and alkaline phosphatase activity) were available in all patients. The incidence of spinal cord compression was documented and all patients were followed up until death. Bone scintigraphy was evaluated by the conventional Soloway grading and by an additional analysis determining total or partial involvement of individual vertebrae. In contrast to the Soloway method, the new method was able to predict spinal cord compression at various spinal levels. Our data suggest that there is still a place for bone scintigraphy in the management of hormone-refractory prostate cancer. (orig.)

  18. Reproductive hormones in breast cancer bone metastasis: The role of inhibins

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    Caroline Wilson

    2016-09-01

    Full Text Available The spread of breast cancer cells to bone and survival in this new metastatic environment is influenced not only by the genetic signature of the cells, but also multiple host cells and soluble factors produced locally (paracrine or from distant sites (endocrine. Disrupting this metastatic process has been evaluated in clinical trials of the bone targeted agents bisphosphonates and denosumab and have shown that these agents reduce the recurrence of breast cancer in postmenopausal women only, suggesting the efficacy of the drugs are influenced by levels of reproductive endocrine hormones. The molecular mechanism driving this differential effect has not been definitively identified, however, there is evidence that both reproductive hormones and bisphosphonates can affect similar paracrine factors and cellular components of the bone metastatic niche. This review focuses on how the ovarian endocrine hormone, inhibin, interacts with the paracrine factors activin and follistatin, abundant in the primary tumour and bone microenvironment, with subsequent effects on tumour cell survival. Inhibin also affects the cellular components of the bone microenvironment primarily the osteoblastic niche. Recent evidence has shown that bisphosphonates also alter this niche, which may represent a common mechanism by which inhibin and bisphosphonates interact to influence disease outcomes in early breast cancer. Further research is needed to fully elucidate these molecular mechanisms to enable understanding and future development of alternative bone targeted treatments with anti-tumour efficacy in premenopausal women.

  19. Behavioral, medical imaging and histopathological features of a new rat model of bone cancer pain.

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    Louis Doré-Savard

    2010-10-01

    Full Text Available Pre-clinical bone cancer pain models mimicking the human condition are required to respond to clinical realities. Breast or prostate cancer patients coping with bone metastases experience intractable pain, which affects their quality of life. Advanced monitoring is thus required to clarify bone cancer pain mechanisms and refine treatments. In our model of rat femoral mammary carcinoma MRMT-1 cell implantation, pain onset and tumor growth were monitored for 21 days. The surgical procedure performed without arthrotomy allowed recording of incidental pain in free-moving rats. Along with the gradual development of mechanical allodynia and hyperalgesia, behavioral signs of ambulatory pain were detected at day 14 by using a dynamic weight-bearing apparatus. Osteopenia was revealed from day 14 concomitantly with disorganization of the trabecular architecture (µCT. Bone metastases were visualized as early as day 8 by MRI (T(1-Gd-DTPA before pain detection. PET (Na(18F co-registration revealed intra-osseous activity, as determined by anatomical superimposition over MRI in accordance with osteoclastic hyperactivity (TRAP staining. Pain and bone destruction were aggravated with time. Bone remodeling was accompanied by c-Fos (spinal and ATF3 (DRG neuronal activation, sustained by astrocyte (GFAP and microglia (Iba1 reactivity in lumbar spinal cord. Our animal model demonstrates the importance of simultaneously recording pain and tumor progression and will allow us to better characterize therapeutic strategies in the future.

  20. Bone scintigraphy in prostate cancer: a French national survey

    International Nuclear Information System (INIS)

    Boneu, A.; Corone, C.; Giammarile, F.; Lumbroso, J.; Resche, I.

    1997-01-01

    A national survey has been performed in France concerning bone scan in prostatic carcinoma. Its aim was to define methods of performing examinations, criteria of analysis of imaging results and indications of radionuclide imaging in initial evaluation and post-therapeutic follow-up of the disease. Replies are given and recommendations are proposed in order to improve imaging quality, optimize interpretation and rationalize prescription of bone scintigraphy in case of prostatic carcinoma. (authors)

  1. Bone cancer from radium: canine dose response explains data for mice and humans

    International Nuclear Information System (INIS)

    Raabe, O.G.; Book, S.A.; Parks, N.J.

    1980-01-01

    Analysis of lifetime studies of 243 beagles with skeletal burdens of radium-226 shows that the distribution of bone cancers clusters about a linear function of the logarithms of radiation dose rate to the skeleton and time from exposure until death. Similar relations displaced by species-dependent response ratios also provide satisfactory descriptions of the reported data on deaths from primary bone cancers in people and mice exposed to radium-226. The median cumulative doses (or times) leading to death from bone tumors are 2.9 times larger for dogs than for mice and 3.6 times larger for people than for dogs. These response ratios are well correlated with the normal life expectancies. The cumulative radiation dose required to give significant risk of bone cancer is found to be much less at lower dose rates than at higher rates, but the time required for the tumors to be manifested is longer. At low dose rates, this time exceeds the normal life-span and appears as a practical threshold, which for bone cancer is estimated to occur at an average cumulative radiation dose to the skeleton of about 50 to 110 rads for the three species

  2. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    International Nuclear Information System (INIS)

    Oue, Erika; Lee, Ji-Won; Sakamoto, Kei; Iimura, Tadahiro; Aoki, Kazuhiro; Kayamori, Kou; Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo; Yamaguchi, Akira

    2012-01-01

    Highlights: ► Oral cancer cells synthesize CXCL2. ► CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. ► CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. ► We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first report showing the role of CXCL2 in cancer-associated bone destruction.

  3. CXCL2 synthesized by oral squamous cell carcinoma is involved in cancer-associated bone destruction

    Energy Technology Data Exchange (ETDEWEB)

    Oue, Erika [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Lee, Ji-Won; Sakamoto, Kei [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Iimura, Tadahiro [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan); Aoki, Kazuhiro [Section of Pharmacology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Kayamori, Kou [Section of Diagnostic Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Department of Pathology, Ome Municipal General Hospital, Ome, Tokyo (Japan); Michi, Yasuyuki; Yamashiro, Masashi; Harada, Kiyoshi; Amagasa, Teruo [Section of Maxillofacial Surgery, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Yamaguchi, Akira, E-mail: akira.mpa@tmd.ac.jp [Section of Oral Pathology, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University (Japan); Global Center of Excellence (GCOE) Program, International Research Center for Molecular Science in Tooth and Bone Diseases, Tokyo Medical and Dental University, Tokyo (Japan)

    2012-08-03

    Highlights: Black-Right-Pointing-Pointer Oral cancer cells synthesize CXCL2. Black-Right-Pointing-Pointer CXCL2 synthesized by oral cancer is involved in osteoclastogenesis. Black-Right-Pointing-Pointer CXCL2-neutralizing antibody inhibited osteoclastogenesis induced by oral cancer cells. Black-Right-Pointing-Pointer We first report the role of CXCL2 in cancer-associated bone destruction. -- Abstract: To explore the mechanism of bone destruction associated with oral cancer, we identified factors that stimulate osteoclastic bone resorption in oral squamous cell carcinoma. Two clonal cell lines, HSC3-C13 and HSC3-C17, were isolated from the maternal oral cancer cell line, HSC3. The conditioned medium from HSC3-C13 cells showed the highest induction of Rankl expression in the mouse stromal cell lines ST2 and UAMS-32 as compared to that in maternal HSC3 cells and HSC3-C17 cells, which showed similar activity. The conditioned medium from HSC3-C13 cells significantly increased the number of osteoclasts in a co-culture with mouse bone marrow cells and UAMS-32 cells. Xenograft tumors generated from these clonal cell lines into the periosteal region of the parietal bone in athymic mice showed that HSC3-C13 cells caused extensive bone destruction and a significant increase in osteoclast numbers as compared to HSC3-C17 cells. Gene expression was compared between HSC3-C13 and HSC3-C17 cells by using microarray analysis, which showed that CXCL2 gene was highly expressed in HSC3-C13 cells as compared to HSC3-C17 cells. Immunohistochemical staining revealed the localization of CXCL2 in human oral squamous cell carcinomas. The increase in osteoclast numbers induced by the HSC3-C13-conditioned medium was dose-dependently inhibited by addition of anti-human CXCL2-neutralizing antibody in a co-culture system. Recombinant CXCL2 increased the expression of Rankl in UAMS-32 cells. These results indicate that CXCL2 is involved in bone destruction induced by oral cancer. This is the first

  4. Proteomic profiling of antibody-inducing immunogens in tumor tissue identifies PSMA1, LAP3, ANXA3, and maspin as colon cancer markers

    Science.gov (United States)

    Yang, Qian; Roehrl, Michael H.; Wang, Julia Y.

    2018-01-01

    We hypothesized that cancer tissue immunogens – antigens capable of inducing specific antibody production in patients – are promising targets for development of precision diagnostics and humoral immunotherapies. We developed an innovative immuno-proteomic strategy and identified new immunogenic markers of colon cancer. Proteins from cancers and matched normal tissues were separated by 2D gel electrophoresis and blotted with serum antibodies from the same patients. Antibody-reactive proteins were sequenced by mass spectrometry and validated by Western blotting and immunohistochemistry. 170 serum antibody-reactive proteins were identified only in cancerous but not matched normal. Among these, proteasome subunit alpha type 1 (PSA1), leucine aminopeptidase 3 (LAP3), annexin A3 (ANXA3), and maspin (serpin B5) were reproducibly found in tissues from three patients. Differential expression patterns were confirmed in samples from eight patients with various stages of colon adenocarcinoma and liver metastases. These tumor-resident proteins and/or their associated serum antibodies may be promising markers for colon cancer screening and early diagnosis. Furthermore, tumor tissue-specific antibodies could potentially be exploited as immunotherapeutic targets against cancer. More generally, proteomic profiling of antibody-inducing cancer-associated immunogens represents a powerful generic method for uncovering the tumor antigen-ome, i.e., the totality of immunogenic tumor-associated proteins. PMID:29423100

  5. Plumbagin elicits differential proteomic responses mainly involving cell cycle, apoptosis, autophagy, and epithelial-to-mesenchymal transition pathways in human prostate cancer PC-3 and DU145 cells

    Directory of Open Access Journals (Sweden)

    Qui JX

    2015-01-01

    Full Text Available Jia-Xuan Qiu,1,2 Zhi-Wei Zhou, 3,4 Zhi-Xu He,4 Ruan Jin Zhao,5 Xueji Zhang,6 Lun Yang,7 Shu-Feng Zhou,3,4 Zong-Fu Mao11School of Public Health, Wuhan University, Wuhan, Hubei, People’s Republic of China; 2Department of Oral and Maxillofacial Surgery, The First Affiliated Hospital of Nanchang University, Nanchang, Jiangxi, People’s Republic of China; 3Department of Pharmaceutical Sciences, College of Pharmacy, University of South Florida, Tampa, FL, USA; 4Guizhou Provincial Key Laboratory for Regenerative Medicine, Stem Cell and Tissue Engineering Research Center and Sino-US Joint Laboratory for Medical Sciences, Guiyang Medical University, Guiyang, Guizhou, People’s Republic of China; 5Center for Traditional Chinese Medicine, Sarasota, FL, USA; 6Research Center for Bioengineering and Sensing Technology, University of Science and Technology Beijing, Beijing, People’s Republic of China; 7Bio-X Institutes, Key Laboratory for the Genetics of Development and Neuropsychiatric Disorders (Ministry of Education, Shanghai Jiao Tong University, Shanghai, People’s Republic of ChinaAbstract: Plumbagin (PLB has exhibited a potent anticancer effect in preclinical studies, but the molecular interactome remains elusive. This study aimed to compare the quantitative proteomic responses to PLB treatment in human prostate cancer PC-3 and DU145 cells using the approach of stable-isotope labeling by amino acids in cell culture (SILAC. The data were finally validated using Western blot assay. First, the bioinformatic analysis predicted that PLB could interact with 78 proteins that were involved in cell proliferation and apoptosis, immunity, and signal transduction. Our quantitative proteomic study using SILAC revealed that there were at least 1,225 and 267 proteins interacting with PLB and there were 341 and 107 signaling pathways and cellular functions potentially regulated by PLB in PC-3 and DU145 cells, respectively. These proteins and pathways played a

  6. Acidosis-Induced Changes in Proteome Patterns of the Prostate Cancer-Derived Tumor Cell Line AT-1.

    Science.gov (United States)

    Ihling, Angelika; Ihling, Christian H; Sinz, Andrea; Gekle, Michael

    2015-09-04

    Under various pathological conditions, such as inflammation, ischemia and in solid tumors, physiological parameters (local oxygen tension or extracellular pH) show distinct tissue abnormalities (hypoxia and acidosis). For tumors, the prevailing microenvironment exerts a strong influence on the phenotype with respect to proliferation, invasion, and metastasis formation and therefore influences prognosis. In this study, we investigate the impact of extracellular metabolic acidosis (pH 7.4 versus 6.6) on the proteome patterns of a prostate cancer-derived tumor cell type (AT-1) using isobaric labeling and LC-MS/MS analysis. In total, 2710 proteins were identified and quantified across four biological replicates, of which seven were significantly affected with changes >50% and used for validation. Glucose transporter 1 and farnesyl pyrophosphatase were found to be down-regulated after 48 h of acidic treatment, and metallothionein 2A was reduced after 24 h and returned to control values after 48 h. After 24 and 48 h at pH 6.6, glutathione S transferase A3 and NAD(P)H dehydrogenase 1, cellular retinoic acid-binding protein 2, and Na-bicarbonate transporter 3 levels were found to be increased. The changes in protein levels were confirmed by transcriptome and functional analyses. In addition to the experimental in-depth investigation of proteins with changes >50%, functional profiling (statistical enrichment analysis) including proteins with changes >20% revealed that acidosis upregulates GSH metabolic processes, citric acid cycle, and respiratory electron transport. Metabolism of lipids and cholesterol biosynthesis were downregulated. Our data comprise the first comprehensive report on acidosis-induced changes in proteome patterns of a tumor cell line.

  7. A Comparative Proteomic Analysis of Erinacine A’s Inhibition of Gastric Cancer Cell Viability and Invasiveness

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    Hsing-Chun Kuo

    2017-08-01

    Full Text Available Background / Aims: Erinacine A, isolated from the ethanol extract of the Hericium erinaceus mycelium, has been demonstrated as a new alternative anticancer medicine. Drawing upon current research, this study presents an investigation of the molecular mechanism of erinacine A inhibition associated with gastric cancer cell growth. Methods: Cell viability was determined by Annexin V–FITC/propidium iodide staining and migration using a Boyden chamber assay to determine the effects of erinacine A treatment on the proliferation capacity and invasiveness of gastric cancer cells. A proteomic assay provided information that was used to identify the differentially-expressed proteins following erinacine A treatment, as well as the mechanism of its targets in the apoptotic induction of erinacine A. Results: Our results demonstrate that erinacine A treatment of TSGH 9201 cells increased cytotoxicity and the generation of reactive oxygen species (ROS, as well as decreased the invasiveness. Treatment of TSGH 9201 cells with erinacine A resulted in the activation of caspases and the expression of TRAIL. Erinacine A induction of apoptosis was accompanied by sustained phosphorylation of FAK/AKT/p70S6K and the PAK1 pathways, as well as the generation of ROS. Furthermore, the induction of apoptosis and anti-invasion properties by erinacine A could involve the differential expression of the 14-3-3 sigma protein (1433S and microtubule-associated tumor suppressor candidate 2 (MTUS2, with the activation of the FAK/AKT/p70S6K and PAK1 signaling pathways. Conclusions: These results lead us to speculate that erinacine A may generate an apoptotic cascade in TSGH 9201 cells by activating the FAK/AKT/p70S6K/PAK1 pathway and upregulating proteins 1433S and MTUS2, providing a new mechanism underlying the anti-cancer effects of erinacine A in human gastric cancer cells.

  8. Pain and Mean Absorbed Dose to the Pubic Bone After Radiotherapy Among Gynecological Cancer Survivors

    International Nuclear Information System (INIS)

    Waldenstroem, Ann-Charlotte; Olsson, Caroline; Wilderaeng, Ulrica; Dunberger, Gail; Lind, Helena; Al-Abany, Massoud; Palm, Asa; Avall-Lundqvist, Elisabeth; Johansson, Karl-Axel; Steineck, Gunnar

    2011-01-01

    Purpose: To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. Methods and Materials: In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. Results: We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses <52.5 Gy to the pubic bone and 5/12 (42%) to mean absorbed external beam doses ≥52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Conclusions: Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer.

  9. Risk of second bone sarcoma following childhood cancer: role of radiation therapy treatment.

    Science.gov (United States)

    Schwartz, Boris; Benadjaoud, Mohamed Amine; Cléro, Enora; Haddy, Nadia; El-Fayech, Chiraz; Guibout, Catherine; Teinturier, Cécile; Oberlin, Odile; Veres, Cristina; Pacquement, Hélène; Munzer, Martine; N'guyen, Tan Dat; Bondiau, Pierre-Yves; Berchery, Delphine; Laprie, Anne; Hawkins, Mike; Winter, David; Lefkopoulos, Dimitri; Chavaudra, Jean; Rubino, Carole; Diallo, Ibrahima; Bénichou, Jacques; de Vathaire, Florent

    2014-05-01

    Bone sarcoma as a second malignancy is rare but highly fatal. The present knowledge about radiation-absorbed organ dose-response is insufficient to predict the risks induced by radiation therapy techniques. The objective of the present study was to assess the treatment-induced risk for bone sarcoma following a childhood cancer and particularly the related risk of radiotherapy. Therefore, a retrospective cohort of 4,171 survivors of a solid childhood cancer treated between 1942 and 1986 in France and Britain has been followed prospectively. We collected detailed information on treatments received during childhood cancer. Additionally, an innovative methodology has been developed to evaluate the dose-response relationship between bone sarcoma and radiation dose throughout this cohort. The median follow-up was 26 years, and 39 patients had developed bone sarcoma. It was found that the overall incidence was 45-fold higher [standardized incidence ratio 44.8, 95 % confidence interval (CI) 31.0-59.8] than expected from the general population, and the absolute excess risk was 35.1 per 100,000 person-years (95 % CI 24.0-47.1). The risk of bone sarcoma increased slowly up to a cumulative radiation organ absorbed dose of 15 Gy [hazard ratio (HR) = 8.2, 95 % CI 1.6-42.9] and then strongly increased for higher radiation doses (HR for 30 Gy or more 117.9, 95 % CI 36.5-380.6), compared with patients not treated with radiotherapy. A linear model with an excess relative risk per Gy of 1.77 (95 % CI 0.6213-5.935) provided a close fit to the data. These findings have important therapeutic implications: Lowering the radiation dose to the bones should reduce the incidence of secondary bone sarcomas. Other therapeutic solutions should be preferred to radiotherapy in bone sarcoma-sensitive areas.

  10. Can tumour marker assays be a guide in the prescription of bone scan for breast and lung cancers?

    Energy Technology Data Exchange (ETDEWEB)

    Buffaz, P.-D.; Gauchez, A.S.; Caravel, J.P.; Vuillez, J.P.; Cura, C.; Agnius-Delord, C.; Fagret, D. [Service de Medecine Nucleaire, Centre Hospitalier Universitaire de Grenoble (France)

    1999-01-01

    Considering the current need to improve cost-effectiveness in cancer patient management, a prospective study was undertaken in order to define the optimal combination of bone scan and tumour marker assays in breast and lung cancer strategies, as has been done in the case of prostate cancer. All patients with breast or lung cancer referred to the Nuclear Medicine Department of the Grenoble Teaching Hospital between December 1995 and April 1997 were included. A blood sample was drawn in each case for marker assay (CA15-3 or CEA and CYFRA 21-1) on the same day as the bone scan. Two hundred and seventy-five patients were included: 118 with lung cancer and 157 with breast cancer. With regard to lung cancer, no information useful for guiding bone scan prescription was obtained through CEA and CYFRA 21-1 assays. For breast cancer, the results suggest that in asymptomatic patients, a CA15-3 level of less than 25 U/ml (upper normal value chosen as the threshold) is strongly predictive of a negative bone scan; by contrast, high tumour marker levels are predictive of neoplastic bone involvement. When a doubtful bone scan is obtained in a patient with breast cancer, a normal marker level makes it highly probable that bone scan abnormalities are not related to malignancy. (orig.) With 3 figs., 21 refs.

  11. Integrated proteomic and N-glycoproteomic analyses of doxorubicin sensitive and resistant ovarian cancer cells reveal glycoprotein alteration in protein abundance and glycosylation

    Science.gov (United States)

    Hou, Junjie; Zhang, Chengqian; Xue, Peng; Wang, Jifeng; Chen, Xiulan; Guo, Xiaojing; Yang, Fuquan

    2017-01-01

    Ovarian cancer is one of the most common cancer among women in the world, and chemotherapy remains the principal treatment for patients. However, drug resistance is a major obstacle to the effective treatment of ovarian cancers and the underlying mechanism is not clear. An increased understanding of the mechanisms that underline the pathogenesis of drug resistance is therefore needed to develop novel therapeutics and diagnostic. Herein, we report the comparative analysis of the doxorubicin sensitive OVCAR8 cells and its doxorubicin-resistant variant NCI/ADR-RES cells using integrated global proteomics and N-glycoproteomics. A total of 1525 unique N-glycosite-containing peptides from 740 N-glycoproteins were identified and quantified, of which 253 N-glycosite-containing peptides showed significant change in the NCI/ADR-RES cells. Meanwhile, stable isotope labeling by amino acids in cell culture (SILAC) based comparative proteomic analysis of the two ovarian cancer cells led to the quantification of 5509 proteins. As about 50% of the identified N-glycoproteins are low-abundance membrane proteins, only 44% of quantified unique N-glycosite-containing peptides had corresponding protein expression ratios. The comparison and calibration of the N-glycoproteome versus the proteome classified 14 change patterns of N-glycosite-containing peptides, including 8 up-regulated N-glycosite-containing peptides with the increased glycosylation sites occupancy, 35 up-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy, 2 down-regulated N-glycosite-containing peptides with the decreased glycosylation sites occupancy, 46 down-regulated N-glycosite-containing peptides with the unchanged glycosylation sites occupancy. Integrated proteomic and N-glycoproteomic analyses provide new insights, which can help to unravel the relationship of N-glycosylation and multidrug resistance (MDR), understand the mechanism of MDR, and discover the new diagnostic and

  12. Integration of genomic, transcriptomic and proteomic data identifies two biologically distinct subtypes of invasive lobular breast cancer.

    Science.gov (United States)

    Michaut, Magali; Chin, Suet-Feung; Majewski, Ian; Severson, Tesa M; Bismeijer, Tycho; de Koning, Leanne; Peeters, Justine K; Schouten, Philip C; Rueda, Oscar M; Bosma, Astrid J; Tarrant, Finbarr; Fan, Yue; He, Beilei; Xue, Zheng; Mittempergher, Lorenza; Kluin, Roelof J C; Heijmans, Jeroen; Snel, Mireille; Pereira, Bernard; Schlicker, Andreas; Provenzano, Elena; Ali, Hamid Raza; Gaber, Alexander; O'Hurley, Gillian; Lehn, Sophie; Muris, Jettie J F; Wesseling, Jelle; Kay, Elaine; Sammut, Stephen John; Bardwell, Helen A; Barbet, Aurélie S; Bard, Floriane; Lecerf, Caroline; O'Connor, Darran P; Vis, Daniël J; Benes, Cyril H; McDermott, Ultan; Garnett, Mathew J; Simon, Iris M; Jirström, Karin; Dubois, Thierry; Linn, Sabine C; Gallagher, William M; Wessels, Lodewyk F A; Caldas, Carlos; Bernards, Rene

    2016-01-05

    Invasive lobular carcinoma (ILC) is the second most frequently occurring histological breast cancer subtype after invasive ductal carcinoma (IDC), accounting for around 10% of all breast cancers. The molecular processes that drive the development of ILC are still largely unknown. We have performed a comprehensive genomic, transcriptomic and proteomic analysis of a large ILC patient cohort and present here an integrated molecular portrait of ILC. Mutations in CDH1 and in the PI3K pathway are the most frequent molecular alterations in ILC. We identified two main subtypes of ILCs: (i) an immune related subtype with mRNA up-regulation of PD-L1, PD-1 and CTLA-4 and greater sensitivity to DNA-damaging agents in representative cell line models; (ii) a hormone related subtype, associated with Epithelial to Mesenchymal Transition (EMT), and gain of chromosomes 1q and 8q and loss of chromosome 11q. Using the somatic mutation rate and eIF4B protein level, we identified three groups with different clinical outcomes, including a group with extremely good prognosis. We provide a comprehensive overview of the molecular alterations driving ILC and have explored links with therapy response. This molecular characterization may help to tailor treatment of ILC through the application of specific targeted, chemo- and/or immune-therapies.

  13. Profilin-1 overexpression in MDA-MB-231 breast cancer cells is associated with alterations in proteomics biomarkers of cell proliferation, survival, and motility as revealed by global proteomics analyses.

    Science.gov (United States)

    Coumans, Joëlle V F; Gau, David; Poljak, Anne; Wasinger, Valerie; Roy, Partha; Moens, Pierre D J

    2014-12-01

    Despite early screening programs and new therapeutic strategies, metastatic breast cancer is still the leading cause of cancer death in women in industrialized countries and regions. There is a need for novel biomarkers of susceptibility, progression, and therapeutic response. Global analyses or systems science approaches with omics technologies offer concrete ways forward in biomarker discovery for breast cancer. Previous studies have shown that expression of profilin-1 (PFN1), a ubiquitously expressed actin-binding protein, is downregulated in invasive and metastatic breast cancer. It has also been reported that PFN1 overexpression can suppress tumorigenic ability and motility/invasiveness of breast cancer cells. To obtain insights into the underlying molecular mechanisms of how elevating PFN1 level induces these phenotypic changes in breast cancer cells, we investigated the alteration in global protein expression profiles of breast cancer cells upon stable overexpression of PFN1 by a combination of three different proteome analysis methods (2-DE, iTRAQ, label-free). Using MDA-MB-231 as a model breast cancer cell line, we provide evidence that PFN1 overexpression is associated with alterations in the expression of proteins that have been functionally linked to cell proliferation (FKPB1A, HDGF, MIF, PRDX1, TXNRD1, LGALS1, STMN1, LASP1, S100A11, S100A6), survival (HSPE1, HSPB1, HSPD1, HSPA5 and PPIA, YWHAZ, CFL1, NME1) and motility (CFL1, CORO1B, PFN2, PLS3, FLNA, FLNB, NME2, ARHGDIB). In view of the pleotropic effects of PFN1 overexpression in breast cancer cells as suggested by these new findings, we propose that PFN1-induced phenotypic changes in cancer cells involve multiple mechanisms. Our data reported here might also offer innovative strategies for identification and validation of novel therapeutic targets and companion diagnostics for persons with, or susceptibility to, breast cancer.

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

    International Nuclear Information System (INIS)

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

    2007-01-01

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

  15. Doxorubicin-mediated bone loss in breast cancer bone metastases is driven by an interplay between oxidative stress and induction of TGFβ.

    Directory of Open Access Journals (Sweden)

    Tapasi Rana

    Full Text Available Breast cancer patients, who are already at increased risk of developing bone metastases and osteolytic bone damage, are often treated with doxorubicin. Unfortunately, doxorubicin has been reported to induce damage to bone. Moreover, we have previously reported that doxorubicin treatment increases circulating levels of TGFβ in murine pre-clinical models. TGFβ has been implicated in promoting osteolytic bone damage, a consequence of increased osteoclast-mediated resorption and suppression of osteoblast differentiation. Therefore, we hypothesized that in a preclinical breast cancer bone metastasis model, administration of doxorubicin would accelerate bone loss in a TGFβ-mediated manner. Administration of doxorubicin to 4T1 tumor-bearing mice produced an eightfold increase in osteolytic lesion areas compared untreated tumor-bearing mice (P = 0.002 and an almost 50% decrease in trabecular bone volume expressed in BV/TV (P = 0.0005, both of which were rescued by anti-TGFβ antibody (1D11. Doxorubicin, which is a known inducer of oxidative stress, decreased osteoblast survival and differentiation, which was rescued by N-acetyl cysteine (NAC. Furthermore, doxorubicin treatment decreased Cu-ZnSOD (SOD1 expression and enzyme activity in vitro, and treatment with anti-TGFβ antibody was able to rescue both. In conclusion, a combination therapy using doxorubicin and anti-TGFβ antibody might be beneficial for preventing therapy-related bone loss in cancer patients.

  16. Solitary bone metastasis to the tibia from colorectal cancer- A case report

    Directory of Open Access Journals (Sweden)

    Abdulsalam Alnajjar

    2014-12-01

    Full Text Available The onset of osseous metastases during the course of colorectal cancer is not common. Although rare, they usually appear in the axial skeleton. In our report, we refer to the case of a 48-year-old patient who presented with colon cancer and eventually developed a solitary bone metastasis in the upper end of left tibia. At the time of diagnosis and staging investigations, the patient had only a primary disease.------------------------------------------------Cite this article as:Alnajjar A, Mohanty AK. Solitary bone metastasis to the tibia from colorectal cancer- A case report. Int J Cancer Ther Oncol 2014; 2(4:02045. DOI: 10.14319/ijcto.0204.5

  17. Fibrous dysplasia mimicking bone metastasis on both bone scintigraphy and {sup 18}F FDG PET CT: Diagnostic dilemma in a patient with breast cancer

    Energy Technology Data Exchange (ETDEWEB)

    KC, Sud Hir Suman; Sharma, Punit; Singh, Har Man Deep; Bal, Chand Rasekhar; Kumar, Rake Sh [India Institute of Medical Sciences, New Delhi (India)

    2012-12-15

    Bone is the most common distant site to which breast cancer metastasizes. Commonly used imaging modalities for imaging bone metastasis are bone scintigraphy, plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Although bone scintigraphy gas high sensitivity for detecting bone metastasis, its specificity is low. This is because of the fact that bone scintigraphy images secondary changes in bone rather than just tumor cells {sup 18}F fluorodeoxyglucose ({sup 18}F FDG) PET CT, on the other hand, directly images the tumor cells' glucose metabolism. Unfortunately, similar to bone scintigraphy, benign bone conditions can also show increased {sup 18}F FDG uptake on PET CT, and PET positive asymptomatic fibrous dysplasia can be misinterpreted as a metastasis. Fibrous dysplasia of bone has wide skeletal distribution, with variability of {sup 18}F FDG uptake and CT appearance. It is therefore important to recognize the characteristics of this skeletal dysplasia, to allow differentiation from skeletal metastasis. Bone lesions with {sup 18}F FDG uptake need to be carefully interpreted when evaluating patients with known malignancy. In doubtful cases, fibrous dysplasia should be given as a differential diagnosis and histopathological diagnosis may be warranted, as highlighted in the present case.

  18. Fibrous dysplasia mimicking bone metastasis on both bone scintigraphy and 18F FDG PET CT: Diagnostic dilemma in a patient with breast cancer

    International Nuclear Information System (INIS)

    KC, Sud Hir Suman; Sharma, Punit; Singh, Har Man Deep; Bal, Chand Rasekhar; Kumar, Rake Sh

    2012-01-01

    Bone is the most common distant site to which breast cancer metastasizes. Commonly used imaging modalities for imaging bone metastasis are bone scintigraphy, plain radiography, computed tomography (CT), magnetic resonance imaging (MRI), and positron emission tomography (PET). Although bone scintigraphy gas high sensitivity for detecting bone metastasis, its specificity is low. This is because of the fact that bone scintigraphy images secondary changes in bone rather than just tumor cells 18 F fluorodeoxyglucose ( 18 F FDG) PET CT, on the other hand, directly images the tumor cells' glucose metabolism. Unfortunately, similar to bone scintigraphy, benign bone conditions can also show increased 18 F FDG uptake on PET CT, and PET positive asymptomatic fibrous dysplasia can be misinterpreted as a metastasis. Fibrous dysplasia of bone has wide skeletal distribution, with variability of 18 F FDG uptake and CT appearance. It is therefore important to recognize the characteristics of this skeletal dysplasia, to allow differentiation from skeletal metastasis. Bone lesions with 18 F FDG uptake need to be carefully interpreted when evaluating patients with known malignancy. In doubtful cases, fibrous dysplasia should be given as a differential diagnosis and histopathological diagnosis may be warranted, as highlighted in the present case

  19. The Cytotoxicity Mechanism of 6-Shogaol-Treated HeLa Human Cervical Cancer Cells Revealed by Label-Free Shotgun Proteomics and Bioinformatics Analysis

    Directory of Open Access Journals (Sweden)

    Qun Liu

    2012-01-01

    Full Text Available Cervical cancer is one of the most common cancers among women in the world. 6-Shogaol is a natural compound isolated from the rhizome of ginger (Zingiber officinale. In this paper, we demonstrated that 6-shogaol induced apoptosis and G2/M phase arrest in human cervical cancer HeLa cells. Endoplasmic reticulum stress and mitochondrial pathway were involved in 6-shogaol-mediated apoptosis. Proteomic analysis based on label-free strategy by liquid chromatography chip quadrupole time-of-flight mass spectrometry was subsequently proposed to identify, in a non-target-biased manner, the molecular changes in cellular proteins in response to 6-shogaol treatment. A total of 287 proteins were differentially expressed in response to 24 h treatment with 15 μM 6-shogaol in HeLa cells. Significantly changed proteins were subjected to functional pathway analysis by multiple analyzing software. Ingenuity pathway analysis (IPA suggested that 14-3-3 signaling is a predominant canonical pathway involved in networks which may be significantly associated with the process of apoptosis and G2/M cell cycle arrest induced by 6-shogaol. In conclusion, this work developed an unbiased protein analysis strategy by shotgun proteomics and bioinformatics analysis. Data observed provide a comprehensive analysis of the 6-shogaol-treated HeLa cell proteome and reveal protein alterations that are associated with its anticancer mechanism.

  20. Anemia and thrombocytopenia as initial symptoms of occult breast cancer with bone marrow metastasis

    OpenAIRE

    Liu, Lulu; Zhang, Jingjing; Chen, Mingtai; Ren, Saisai; Liu, Haihui; Zhang, Hao

    2017-01-01

    Abstract Rationale: Occult breast cancer (OBC) is a rare type of breast cancer without any symptoms in the breast and is often presented with initial symptoms of axillary lymph node metastasis or other metastases. The low incidence rates of OBC make it a great challenge to diagnose and cure. Patient concerns: Our case was a 58-year-old female affected by dizziness and fatigue for nearly a month. Blood tests revealed anemia and thrombocytopenia, and pathological results of a bone marrow biopsy...

  1. Comparison of bone mineral density in young patients with breast cancer and healthy women

    Directory of Open Access Journals (Sweden)

    Sousan Kolahi

    2014-05-01

    Full Text Available BACKGROUND: Almost 1 in 8 women will have breast cancer during their lifetime. Several risk factors were identified; however, 70% of females with breast cancer have no risk factors. Many risk factors are associated with sex steroid hormones. Some studies have been focused on identification of the indices of cumulative exposures to estrogen during the patients’ life. One of these indicators is bone mineral density (BMD. Our aim was the comparison of BMD in young patients with and without breast cancer, and finding a relationship between breast cancer and bone density. METHODS: In this case-control study, 120 people were enrolled; 40 patients with breast cancer and 80 normal healthy persons as control group. Measurement of BMD was performed in both groups and compared. RESULTS: Both groups were matched in age, weight, age at menarche, age at first marriage and first pregnancy, number of pregnancies over 32 weeks and lactation period, and taking supplemental calcium and vitamin D. However, there was a significant difference between the two groups in terms of estrogen intake, family history of breast cancer, and history of breast masses (P = 0.03, P = 0.03, P ≤ 0.01, respectively. A significant difference was found between BMD, bone mineral content (BMC, and t-scores of lumbar spine of the two groups; they were higher in the control group (P = 0.08, P ≤ 0.01, P = 0.06, respectively. CONCLUSIONS: This study shows that bone mineral density of young patients with breast cancer is not higher than normal similar age females; thus, BMD is not directly a risk factor for breast cancer.

  2. Evaluation of follow-up bone scintigraphy for assessing the effects of hormone and chemotherapy of bone metastases from prostatic cancer

    Energy Technology Data Exchange (ETDEWEB)

    Otsuka, Nobuaki; Ito, Yasuhiko; Morita, Rikushi; Yoneda, Masaya; Muranaka, Akira [Kawasaki Medical School, Kurashiki, Okayama (Japan)

    1983-08-01

    To assess the clinical usefulness of bone scintigraphy for the osseous metastases of prostatic cancer after treatment, we attempted the correlative studies on laboratory data (TAP, PAP, ALP, and LDH) and scintigraphy. In 77 patients with prostatic cancer, bone scintigraphies were performed with sup(99m)Tc-phosphorous compounds to detect bone metastases. In 34 cases (44 %) bone metastases were detected. In 21 patients out of them, we assessed the effects of hormone and chemotherapy for bone metastases using serial bone scintigraphy. In 19 cases (24.7 %) of the bone scintigraphy showed equivocal results. Of 21 patients with bone metastases, 15 patients showed improvement on scintigram after hormone or chemotherapy. In much improved group (5 patients) and moderately improved group (5 patients), TAP and PAP levels were low and stable. On the other hand, in slightly improved group (5 patients) which showed partially effective on scintigram after treatment, serum TAP and PAP level were unstable. Some cases in the group of which the 1st scintigrams showed normal were turned to positive on scintigram, while TAP, PAP, ALP and LDH level were not elevated. Therefore, follow-up bone scintigraphies have value in evaluating the disease extent in patients with prostatic carcinoma.

  3. A novel method for sample preparation of fresh lung cancer tissue for proteomics analysis by tumor cell enrichment and removal of blood contaminants

    Directory of Open Access Journals (Sweden)

    Orre Lotta

    2010-02-01

    Full Text Available Abstract Background In-depth proteomics analyses of tumors are frequently biased by the presence of blood components and stromal contamination, which leads to large experimental variation and decreases the proteome coverage. We have established a reproducible method to prepare freshly collected lung tumors for proteomics analysis, aiming at tumor cell enrichment and reduction of plasma protein contamination. We obtained enriched tumor-cell suspensions (ETS from six lung cancer cases (two adenocarcinomas, two squamous-cell carcinomas, two large-cell carcinomas and from two normal lung samples. The cell content of resulting ETS was evaluated with immunocytological stainings and compared with the histologic pattern of the original specimens. By means of a quantitative mass spectrometry-based method we evaluated the reproducibility of the sample preparation protocol and we assessed the proteome coverage by comparing lysates from ETS samples with the direct lysate of corresponding fresh-frozen samples. Results Cytological analyses on cytospin specimens showed that the percentage of tumoral cells in the ETS samples ranged from 20% to 70%. In the normal lung samples the percentage of epithelial cells was less then 10%. The reproducibility of the sample preparation protocol was very good, with coefficient of variation at the peptide level and at the protein level of 13% and 7%, respectively. Proteomics analysis led to the identification of a significantly higher number of proteins in the ETS samples than in the FF samples (244 vs 109, respectively. Albumin and hemoglobin were among the top 5 most abundant proteins identified in the FF samples, showing a high contamination with blood and plasma proteins, whereas ubiquitin and the mitochondrial ATP synthase 5A1 where among the top 5 most abundant proteins in the ETS samples. Conclusion The method is feasible and reproducible. We could obtain a fair enrichment of cells but the major benefit of the method

  4. Micrometastatic cancer cells in lymph nodes, bone marrow, and blood: Clinical significance and biologic implications.

    Science.gov (United States)

    Leong, Stanley P L; Tseng, William W

    2014-01-01

    Cancer metastasis may be regarded as a progressive process from its inception in the primary tumor microenvironment to distant sites by way of the lymphovascular system. Although this type of tumor dissemination often occurs in an orderly fashion via the sentinel lymph node (SLN), acting as a possible gateway to the regional lymph nodes, bone marrow, and peripheral blood and ultimately to distant metastatic sites, this is not a general rule as tumor cells may enter the blood and spread to distant sites, bypassing the SLN. Methods of detecting micrometastatic cancer cells in the SLN, bone marrow, and peripheral blood of patients have been established. Patients with cancer cells in their SLN, bone marrow, or peripheral blood have worse clinical outcomes than patients with no evidence of spread to these compartments. The presence of these cells also has important biologic implications for disease progression and the clinician's understanding of the process of cancer metastasis. Further characterization of these micrometastatic cancer cells at each stage and site of metastasis is needed to design novel selective therapies for a more "personalized" treatment. © 2014 American Cancer Society, Inc.

  5. Clinical proteomics

    DEFF Research Database (Denmark)

    Albrethsen, Jakob; Frederiksen, Hanne; Johannsen, Trine Holm

    2018-01-01

    Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS)-platforms...... standards and calibrants. The present challenge is to examine if targeted proteomics of IGF-I can truly measure up to the routine performance that must be expected from a clinical testing platform.......Clinical proteomics aims to deliver cost-effective multiplexing of potentially hundreds of diagnostic proteins, including distinct protein isoforms. The analytical strategy known as targeted proteomics is particularly promising because it is compatible with robust mass spectrometry (MS......)-platforms already implemented in many clinical laboratories for routine quantitation of small molecules (i.e. uHPLC coupled to triple-quadrupole MS). Progress in targeted proteomics of circulating insulin-like growth factor 1 (IGF-I) have provided valuable insights about tryptic peptides, transitions, internal...

  6. Application of proteomics in the study of rodent models of cancer

    DEFF Research Database (Denmark)

    Terp, Mikkel Green; Ditzel, Henrik J

    2014-01-01

    The molecular and cellular mechanisms underlying the multistage processes of cancer progression and metastasis are complex and strictly depend on the interplay between tumor cells and surrounding tissues. Identification of protein aberrations in cancer pathophysiology requires a physiologically r......, and monitoring of cancer progression and treatment response. Central to such studies is the ability to ensure at an early stage that the identified proteins are of clinical relevance by examining relevant specimens from larger cohorts of cancer patients.......The molecular and cellular mechanisms underlying the multistage processes of cancer progression and metastasis are complex and strictly depend on the interplay between tumor cells and surrounding tissues. Identification of protein aberrations in cancer pathophysiology requires a physiologically...... relevant experimental model. The mouse offers such a model to identify protein changes associated with tumor initiation and progression, metastasis development, tumor/microenvironment interplay, and treatment responses. Furthermore, the mouse model offers the ability to collect samples at any stage...

  7. Targeting a novel bone degradation pathway in primary bone cancer by inactivation of the collagen receptor uPARAP/Endo180

    DEFF Research Database (Denmark)

    Engelholm, Lars H; Carlsen Melander, Eva Maria; Hald, Andreas

    2016-01-01

    metastases of carcinoma origin. This opened the possibility that sarcoma cells might directly mediate bone degeneration. To examine this question, we utilized a syngeneic, osteolytic bone tumour model with transplanted NCTC-2472 sarcoma cells in mice. When analysed in vitro, these cells were capable......In osteosarcoma, a primary mesenchymal bone cancer occurring predominantly in younger patients, invasive tumour growth leads to extensive bone destruction. This process is insufficiently understood, cannot be efficiently counteracted and calls for novel means of treatment. The endocytic collagen...... receptor, uPARAP/Endo180, is expressed on various mesenchymal cell types and is involved in bone matrix turnover during normal bone growth. Human osteosarcoma specimens showed strong expression of this receptor on tumour cells, along with the collagenolytic metalloprotease, MT1-MMP. In advanced tumours...

  8. Gap Junctional Intercellular Communication and Breast Cancer Metastasis to Bone

    National Research Council Canada - National Science Library

    Donahue, Henry

    2001-01-01

    .... We found that: 1) expressing the metastasis suppressing gene BRMS1 in diverse cancer cell lines, including breast and melanoma, restores homotypic gap junctional intercellular communication (GJIC); 2...

  9. Scanning usefulness for bone metastases diagnosis in the breast cancer follow-up

    International Nuclear Information System (INIS)

    Guillen, G.; Martinez, P.; Garcia, F.; Tres, A.

    1988-01-01

    It is studied the incidence of osseus metastases and the usefulness of 179 bone scanning realized in the diagnosis and follow-up (average: 23,6 months) of 87 patients operated by breast cancer. It is obvious the scan sensitivity and its unspecificity (15,08% phase-positives). In 13 (14,9%) patients who showed them, during the follow-up, scan was pathological at the moment of the osseus metastases diagnosis or a bit later; there were other clinical data or abnormal analytical ones of suspicion in 77% of them. The time average of appearance is 27 months after surgery. We concluded that the bone scan in the follow-up of breast cancer will be realized only when clinical or analytical suspicion of bone metastases. (Author)

  10. Correlation between PSA, bone scan and Gleason score in patients with prostate cancer

    International Nuclear Information System (INIS)

    Mendoza, G.; Cano, R.; Morales, R.; Munoz, L.; Saavedra, P.; Aguilar, C.

    2004-01-01

    Full text: Prostate cancer is the third most common cancer among Peruvian males. Although radionuclide bone scans (BS) are frequently recommended as part of the staging evaluation for newly diagnosed prostate cancer, most scans are negative for metastases. It has been suggested that a routine bone scan is unnecessary in recently diagnosed prostate cancer if serum PSA is under 10 ng/mL. We hypothesized that Gleason score plus prostate-specific antigen (PSA), could predict for a positive bone scan (better that PSA alone), and that a low - risk group of patients could be identified in whom BS might be omitted. All patients who had both pathologic review of their prostate cancer biopsies and radionuclide BS at our institution from 1/93 to 12/95 were studied. Gleason score, PSA, and bone scan (Soloway Index) were determined in 165 patients. Bivariate analysis using chi (x2) was performed. The mean age of the 165 patients was 71.3 years, 109/165 (66.1%) had a 7-9 Gleason score and only 9/165 (5.5%) were well differentiated prostrate cancer. 82/165 (49.7%) had negative BS. When classifying patients according to their histological grade, the PSA median values were 11.8 ng/mL, 74.8 ng/mL and 116.4 ng/mL in well, median and poorly differentiated prostate cancer respectively. Using a cut off point of 10 ng/mL of PSA, the probability of having a positive BS in Gleason 7, 8 and 9 tumors were 0.109, 0.121 and 0.133 respectively. By using a cut off point of 20 ng/mL of PSA the possibility to have a positive BS in Gleason 7, 8 and 9 tumours were 0.182, 0.206 and 0.224 respectively. Gleason score plus PSA were independent predictors for a positive radionuclide BS in newly diagnosed prostate cancer patients. Considering that most of our patients have Gleason 7-9, the risk of bone metastases despite PSA levels between 10 - 20 ng/mL is not negligible. In our opinion, it is important to continue including bone scan in the staging assessment of prostate cancer. (author)

  11. Enhancing Quality of Life for Breast Cancer Patients with Bone Metastases

    Science.gov (United States)

    2008-04-01

    paclitaxel. British Journal of Cancer 84:1126-34; 2001. 46. Jilka, R. L., Weinstein , R. S., Bellido, T., Roberson, P., Parfitt, A. M., and Manolagas...D., and Harvey , W. J. Correlation of neoplasms with incidence and localization of skeletal metastases: An analysis of 1,355 diphosphonate bone scans

  12. Levo-Tetrahydropalmatine Attenuates Bone Cancer Pain by Inhibiting Microglial Cells Activation

    Directory of Open Access Journals (Sweden)

    Mao-yin Zhang

    2015-01-01

    Full Text Available Objective. The present study is to investigate the analgesic roles of L-THP in rats with bone cancer pain caused by tumor cell implantation (TCI. Methods. Thermal hyperalgesia and mechanical allodynia were measured at different time points before and after operation. L-THP (20, 40, and 60 mg/kg were administrated intragastrically at early phase of postoperation (before pain appearance and later phase of postoperation (after pain appearance, respectively. The concentrations of TNF-α, IL-1β, and IL-18 in spinal cord were measured by enzyme-linked immunosorbent assay. Western blot was used to test the activation of astrocytes and microglial cells in spinal cord after TCI treatment. Results. TCI treatment induced significant thermal hyperalgesia and mechanical allodynia. Administration of L-THP at high doses significantly prevented and/or reversed bone cancer-related pain behaviors. Besides, TCI-induced activation of microglial cells and the increased levels of TNF-α and IL-18 were inhibited by L-THP administration. However, L-THP failed to affect TCI-induced astrocytes activation and IL-1β increase. Conclusion. This study suggests the possible clinical utility of L-THP in the treatment of bone cancer pain. The analgesic effects of L-THP on bone cancer pain maybe underlying the inhibition of microglial cells activation and proinflammatory cytokines increase.

  13. Proteomic biomarkers predicting lymph node involvement in serum of cervical cancer patients. Limitations of SELDI-TOF MS

    Directory of Open Access Journals (Sweden)

    Van Gorp Toon

    2012-06-01

    Full Text Available Abstract Background Lymph node status is not part of the staging system for cervical cancer, but provides important information for prognosis and treatment. We investigated whether lymph node status can be predicted with proteomic profiling. Material & methods Serum samples of 60 cervical cancer patients (FIGO I/II were obtained before primary treatment. Samples were run through a HPLC depletion column, eliminating the 14 most abundant proteins ubiquitously present in serum. Unbound fractions were concentrated with spin filters. Fractions were spotted onto CM10 and IMAC30 surfaces and analyzed with surface-enhanced laser desorption time of flight (SELDI-TOF mass spectrometry (MS. Unsupervised peak detection and peak clustering was performed using MASDA software. Leave-one-out (LOO validation for weighted Least Squares Support Vector Machines (LSSVM was used for prediction of lymph node involvement. Other outcomes were histological type, lymphvascular space involvement (LVSI and recurrent disease. Results LSSVM models were able to determine LN status with a LOO area under the receiver operating characteristics curve (AUC of 0.95, based on peaks with m/z values 2,698.9, 3,953.2, and 15,254.8. Furthermore, we were able to predict LVSI (AUC 0.81, to predict recurrence (AUC 0.92, and to differentiate between squamous carcinomas and adenocarcinomas (AUC 0.88, between squamous and adenosquamous carcinomas (AUC 0.85, and between adenocarcinomas and adenosquamous carcinomas (AUC 0.94. Conclusions Potential markers related with lymph node involvement were detected, and protein/peptide profiling support differentiation between various subtypes of cervical cancer. However, identification of the potential biomarkers was hampered by the technical limitations of SELDI-TOF MS.

  14. Comparative proteomic analysis of colon cancer cell HCT-15 in response to all-trans retinoic acid treatment.

    Science.gov (United States)

    Zhao, Jie; Wen, Gaotian; Ding, Ming; Pan, Jian-Yi; Yu, Mei-Lan; Zhao, Fukun; Weng, Xia-Lian; Du, Jiang-Li

    2012-12-01

    Colon cancer is one of the most common malignances. In vitro and in vivo study show that retinoic acids inhibit a wide variety of cancer cells but the molecular mechanism of their anti-tumor effects are not yet fully understood. Alltrans retinoic acid (ATRA), an isomer of retinoic acid, can inhibit the proliferation of HCT-15 human colon cancer cell line. A proteomic analysis was performed using HCT-15 treated with ATRA to further elucidate the retinoic acid signaling pathway and its anti-tumor effect mechanism. MTT results showed that the growth of HCT-15 cells were significantly inhibited by ATRA. The alkaline phosphatase activity assay showed that ATRA failed to induce the differentiation of HCT-15. The DNA ladder detection showed that ATRA induced apoptosis in HCT-15. Two-dimensional gel electrophoresis coupled with MALDI-TOF/TOF mass spectrometry identified 13 differentially expressed proteins in HCT-15 cells after all-trans retinoic acid treatment. Among the identified differentially expressed proteins, there were four scaffold proteins (YWHAE, SFN, YWHAB, and YWHAZ), two ubiquitin modification related proteins (ISG-15 and UBE2N), two translational initiation factors (EIF1AX and EIF3K), two cytoskeleton related proteins (EZRI and CNN3), two proteinmodification related proteins (TXNDC17 and PIMT), and one enzyme related to phospholipid metabolism (PSP). Both EZRI and UBE2N were rendered to western-blot validation and the results were consistent with the two-dimension electrophoresis analysis. In this study, the differentially expressed proteins in HCT-15 treated by ATRA were identified, which will assist the further elucidation of the anti-tumor mechanism of retinoic acids.

  15. Proteomics dataset

    DEFF Research Database (Denmark)

    Bennike, Tue Bjerg; Carlsen, Thomas Gelsing; Ellingsen, Torkell

    2017-01-01

    The datasets presented in this article are related to the research articles entitled “Neutrophil Extracellular Traps in Ulcerative Colitis: A Proteome Analysis of Intestinal Biopsies” (Bennike et al., 2015 [1]), and “Proteome Analysis of Rheumatoid Arthritis Gut Mucosa” (Bennike et al., 2017 [2])...... been deposited to the ProteomeXchange Consortium via the PRIDE partner repository with the dataset identifiers PXD001608 for ulcerative colitis and control samples, and PXD003082 for rheumatoid arthritis samples....

  16. Bone density as a marker for local response to radiotherapy of spinal bone metastases in women with breast cancer: a retrospective analysis

    International Nuclear Information System (INIS)

    Foerster, Robert; Eisele, Christian; Bruckner, Thomas; Bostel, Tilman; Schlampp, Ingmar; Wolf, Robert; Debus, Juergen; Rief, Harald

    2015-01-01

    We designed this study to quantify the effects of radiotherapy (RT) on bone density as a local response in spinal bone metastases of women with breast cancer and, secondly, to establish bone density as an accurate and reproducible marker for assessment of local response to RT in spinal bone metastases. We retrospectively assessed 135 osteolytic spinal metastases in 115 women with metastatic breast cancer treated at our department between January 2000 and January 2012. Primary endpoint was to compare bone density in the bone metastases before, 3 months after and 6 months after RT. Bone density was measured in Hounsfield units (HU) in computed tomography scans. We calculated mean values in HU and the standard deviation (SD) as a measurement of bone density before, 3 months and 6 months after RT. T-test was used for statistical analysis of difference in bone density as well as for univariate analysis of prognostic factors for difference in bone density 3 and 6 months after RT. Mean bone density was 194.8 HU ± SD 123.0 at baseline. Bone density increased significantly by a mean of 145.8 HU ± SD 139.4 after 3 months (p = .0001) and by 250.3 HU ± SD 147.1 after 6 months (p < .0001). Women receiving bisphosphonates showed a tendency towards higher increase in bone density in the metastases after 3 months (152.6 HU ± SD 141.9 vs. 76.0 HU ± SD 86.1; p = .069) and pathological fractures before RT were associated with a significantly higher increase in bone density after 3 months (202.3 HU ± SD 161.9 vs. 130.3 HU ± SD 129.2; p = .013). Concomitant chemotherapy (ChT) or endocrine therapy (ET), hormone receptor status, performance score, applied overall RT dose and prescription of a surgical corset did not correlate with a difference in bone density after RT. Bone density measurement in HU is a practicable and reproducible method for assessment of local RT response in osteolytic metastases in breast cancer. Our analysis demonstrated an excellent local response within

  17. Pain and mean absorbed dose to the pubic bone after radiotherapy among gynecological cancer survivors.

    Science.gov (United States)

    Waldenström, Ann-Charlotte; Olsson, Caroline; Wilderäng, Ulrica; Dunberger, Gail; Lind, Helena; al-Abany, Massoud; Palm, Åsa; Avall-Lundqvist, Elisabeth; Johansson, Karl-Axel; Steineck, Gunnar

    2011-07-15

    To analyze the relationship between mean absorbed dose to the pubic bone after pelvic radiotherapy for gynecological cancer and occurrence of pubic bone pain among long-term survivors. In an unselected, population-based study, we identified 823 long-term gynecological cancer survivors treated with pelvic radiotherapy during 1991-2003. For comparison, we used a non-radiation-treated control population of 478 matched women from the Swedish Population Register. Pain, intensity of pain, and functional impairment due to pain in the pubic bone were assessed with a study-specific postal questionnaire. We analyzed data from 650 survivors (participation rate 79%) with median follow-up of 6.3 years (range, 2.3-15.0 years) along with 344 control women (participation rate, 72 %). Ten percent of the survivors were treated with radiotherapy; ninety percent with surgery plus radiotherapy. Brachytherapy was added in 81%. Complete treatment records were recovered for 538/650 survivors, with dose distribution data including dose-volume histograms over the pubic bone. Pubic bone pain was reported by 73 survivors (11%); 59/517 (11%) had been exposed to mean absorbed external beam doses beam doses ≥ 52.5 Gy. Thirty-three survivors reported pain affecting sleep, a 13-fold increased prevalence compared with control women. Forty-nine survivors reported functional impairment measured as pain walking indoors, a 10-fold increased prevalence. Mean absorbed external beam dose above 52.5 Gy to the pubic bone increases the occurrence of pain in the pubic bone and may affect daily life of long-term survivors treated with radiotherapy for gynecological cancer. Copyright © 2011 Elsevier Inc. All rights reserved.

  18. Radiation Induced Rib Fractures on Bone Scan after Breast Cancer Surgery and Radiation Therapy

    International Nuclear Information System (INIS)

    Kim, Hae Won; Won, Kyoung Sook; Zeon, Seok Kil; Kim, Jin Hee

    2009-01-01

    This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest CT findings of rib fracture were analyzed. The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p=0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p=0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest CT, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p=0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p=0.001). Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis

  19. Radiation Induced Rib Fractures on Bone Scan after Breast Cancer Surgery and Radiation Therapy

    Energy Technology Data Exchange (ETDEWEB)

    Kim, Hae Won; Won, Kyoung Sook; Zeon, Seok Kil; Kim, Jin Hee [Keimyung University, School of Medicine, Daegu (Korea, Republic of)

    2009-08-15

    This study is to evaluate rib fractures on bone scan in breast cancer patients treated with breast cancer surgery and radiation therapy and to evaluate its relation with radiation therapy and operation modality. Two hundred seventy cases that underwent serial bone scan after breast cancer surgery and radiation therapy were enrolled. Bone scan and chest CT findings of rib fracture were analyzed. The rib uptake was seen in 74 of 270 cases (27.4%) on bone scan and 50 cases (18.5%) were confirmed to have rib fracture by chest CT. The rate of modified radical mastectomy in patients with rib fracture was significantly higher than that in patients without rib fracture (66.0% vs. 27.0%, p=0.000). The rate of additional radiation therapy to axillar or supraclavicular regions in patients with rib fracture was significantly higher than that in patients without rib fracture (62.0% vs. 28.6%, p=0.000). Rib fracture was seen most frequently at 1-2 years after radiation therapy (51.9%) and single rib fracture was seen most frequently (55.2%). Of total 106 rib fractures, focal rib uptake was seen in 94 ribs (88.7%) and diffuse rib uptake was seen in 12 ribs (11.3%). On one year follow-up bone scan, complete resolution of rib uptake was seen in 15 ribs (14.2%). On chest CT, the rate of fracture line in ribs with intense uptake was significantly higher than that in ribs with mild or moderate uptake (p=0.000). The rate of presence of fracture line in ribs with focal uptake was significantly higher than that in ribs with diffuse uptake (p=0.001). Rib fracture in breast cancer patients after radiation therapy was related to radiation portal and operation modality. It should be interpreted carefully as a differential diagnosis of bone metastasis.

  20. [Evaluation and classification of drug therapy for breast cancer with bone-only metastasis].

    Science.gov (United States)

    Meng, X Y; Song, S T

    2017-03-23

    Skeleton is one of the most common metastatic organs for breast cancer, which has a better prognosis than visceral metastases. Bone-only metastasis was defined"non-measurable" in the RECIST (Response Evaluation Criteria in Solid Tumors) criteria, and was excluded by clinical trials. However, patients with bone-only metastasis are also in need of effective treatment to prolong survival. Endocrine therapy is the most important treatment for bone metastatic patients. Tumor response of bone metastases can be determined objectively by bone-window CT. Effective treatment should be continued if the symptoms are relieved or osteogenesis is observed. Osteoblastic change in bone-window CT is a sign of improvement after treatment. Endocrine therapy is proper for ER-positive patients. The patients with initial osteoblastic metastasis should not be treated with salvage chemotherapy or anti-HER2 treatment, only if osteolytic metastasis or visceral metastasis is observed. Bishosphonates are just auxiliary drugs in bone metastasis, which should not be abused.

  1. Cancer cell-secreted IGF2 instigates fibroblasts and bone marrow-derived vascular progenitor cells to promote cancer progression.

    Science.gov (United States)

    Xu, Wen Wen; Li, Bin; Guan, Xin Yuan; Chung, Sookja K; Wang, Yang; Yip, Yim Ling; Law, Simon Y K; Chan, Kin Tak; Lee, Nikki P Y; Chan, Kwok Wah; Xu, Li Yan; Li, En Min; Tsao, Sai Wah; He, Qing-Yu; Cheung, Annie L M

    2017-02-10

    Local interactions between cancer cells and stroma can produce systemic effects on distant organs to govern cancer progression. Here we show that IGF2 secreted by inhibitor of differentiation (Id1)-overexpressing oesophageal cancer cells instigates VEGFR1-positive bone marrow cells in the tumour macroenvironment to form pre-metastatic niches at distant sites by increasing VEGF secretion from cancer-associated fibroblasts. Cancer cells are then attracted to the metastatic site via the CXCL5/CXCR2 axis. Bone marrow cells transplanted from nude mice bearing Id1-overexpressing oesophageal tumours enhance tumour growth and metastasis in recipient mice, whereas systemic administration of VEGFR1 antibody abrogates these effects. Mechanistically, IGF2 regulates VEGF in fibroblasts via miR-29c in a p53-dependent manner. Analysis of patient serum samples showed that concurrent elevation of IGF2 and VEGF levels may serve as a prognostic biomarker for oesophageal cancer. These findings suggest that the Id1/IGF2/VEGF/VEGFR1 cascade plays a critical role in tumour-driven pathophysiological processes underlying cancer progression.

  2. Oral Squamous Cell Carcinoma Mutational Profile in Taiwanese Population | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    Oral squamous cell carcinoma (OSCC) is a major oral cancer subtype that is the fourth most common cancer affecting Taiwanese men. Despite known risk behaviors such as cigarette smoking, alcohol drinking, and betel nut chewing often indulged by Taiwanese men, the genetic contribution to the incidence or progression of OSCC has yet been elucidated in the Taiwanese population.

  3. Molecular mechanisms in ageing and cancer : Redox signalling & proteome-wide protein turnover

    NARCIS (Netherlands)

    Visscher, M.

    2016-01-01

    Cells are exposed to reactive oxygen species (ROS) that derive both from internal and external sources. The formation of cellular ROS is linked to ageing and age-related diseases like cancer. Because of conflicting data, the link between ROS and ageing or cancer is not exactly clear. ROS are in some

  4. Proteomic analysis of human oral verrucous carcinoma

    African Journals Online (AJOL)

    Jane

    2011-10-05

    Oct 5, 2011 ... This study is about proteomic analysis of oral verrucous carcinoma (OVC). The total proteins ..... receptor protein (recoverin) through autoimmunity ..... chromosome 8q21.1 and overexpressed in human prostate cancer. Cancer ...

  5. Prognostic factors for survival of women with unstable spinal bone metastases from breast cancer

    International Nuclear Information System (INIS)

    Foerster, Robert; Bruckner, Thomas; Bostel, Tilman; Schlampp, Ingmar; Debus, Juergen; Rief, Harald

    2015-01-01

    Bone metastases are an important clinical issue in women with breast cancer. Particularly, unstable spinal bone metastases (SBM) are a major cause of severe morbidity and reduced quality of life (QoL) due to frequent immobilization. Radiotherapy (RT) is the major treatment modality and is capable of promoting re-ossification and improving stability. Since local therapy response is excellent, survival of these patients with unstable SBM is of high clinical importance. We therefore conducted this analysis to assess survival and to determine prognostic factors for bone survival (BS) in women with breast cancer and unstable SBM. A total population of 92 women with unstable SBM from breast cancer who were treated with RT at our department between January 2000 and January 2012 was retrospectively investigated. We calculated overall survival (OS) and BS (time between first diagnosis of bone metastases until death) with the Kaplan-Meier method and assessed prognostic factors for BS with a Cox regression model. Mean age at first diagnosis of breast cancer was 60.8 years ± SD 12.4 years. OS after 1, 2 and 5 years was 84.8, 66.3 and 50 %, respectively. BS after 1, 2 and 5 years was 62.0, 33.7 and 12 %, respectively. An age > 50 years (p < .001; HR 1.036 [CI 1.015–1.057]), the presence of a single bone metastasis (p = .002; HR 0.469 [CI 0.292–0.753]) and triple negative phenotype (p < .001; HR 1.068 [CI 0.933–1.125]) were identified as independent prognostic factors for BS. Our analysis demonstrated a short survival of women with breast cancer and unstable SBM. Age, presence of a solitary SBM and triple-negative phenotype correlated with survival. Our results may have an impact on therapeutic decisions in the future and offer a rationale for future prospective investigations

  6. 15-deoxy-δ12,14-prostaglandin j2 inhibits osteolytic breast cancer bone metastasis and estrogen deficiency-induced bone loss.

    Directory of Open Access Journals (Sweden)

    Ki Rim Kim

    Full Text Available Breast cancer is the major cause of cancer death in women worldwide. The most common site of metastasis is bone. Bone metastases obstruct the normal bone remodeling process and aberrantly enhance osteoclast-mediated bone resorption, which results in osteolytic lesions. 15-deoxy-Δ12,14-prostaglandin J2 (15d-PGJ2 is an endogenous ligand of peroxisome proliferator-activated receptor gamma (PPARγ that has anti-inflammatory and antitumor activity at micromolar concentrations through PPARγ-dependent and/or PPARγ-independent pathways. We investigated the inhibitory activity of 15d-PGJ2 on the bone loss that is associated with breast cancer bone metastasis and estrogen deficiency caused by cancer treatment. 15d-PGJ2 dose-dependently inhibited viability, migration, invasion, and parathyroid hormone-related protein (PTHrP production in MDA-MB-231 breast cancer cells. 15d-PGJ2 suppressed receptor activator of nuclear factor kappa-B ligand (RANKL mRNA levels and normalized osteoprotegerin (OPG mRNA levels in hFOB1.19 osteoblastic cells treated with culture medium from MDA-MB-231 cells or PTHrP, which decreased the RANKL/OPG ratio. 15d-PGJ2 blocked RANKL-induced osteoclastogenesis and inhibited the formation of resorption pits by decreasing the activities of cathepsin K and matrix metalloproteinases, which are secreted by mature osteoclasts. 15d-PGJ2 exerted its effects on breast cancer and bone cells via PPARγ-independent pathways. In Balb/c nu/nu mice that received an intracardiac injection of MDA-MB-231 cells, subcutaneously injected 15d-PGJ2 substantially decreased metastatic progression, cancer cell-mediated bone destruction in femora, tibiae, and mandibles, and serum PTHrP levels. 15d-PGJ2 prevented the destruction of femoral trabecular structures in estrogen-deprived ICR mice as measured by bone morphometric parameters and serum biochemical data. Therefore, 15d-PGJ2 may be beneficial for the prevention and treatment of breast cancer

  7. Mutations in Cancer Cause Gain of Cysteine, Histidine, and Tryptophan at the Expense of a Net Loss of Arginine on the Proteome Level

    Directory of Open Access Journals (Sweden)

    Viktoriia Tsuber

    2017-07-01

    Full Text Available Accumulation of somatic mutations is critical for the transition of a normal cell to become cancerous. Mutations cause amino acid substitutions that change properties of proteins. However, it has not been studied as to what extent the composition and accordingly chemical properties of the cell proteome is altered as a result of the increased mutation load in cancer. Here, we analyzed data on amino acid substitutions caused by mutations in about 2000 protein coding genes from the Cancer Cell Line Encyclopedia that contains information on nucleotide and amino acid alterations in 782 cancer cell lines, and validated the analysis with information on amino acid substitutions for the same set of proteins in the Catalogue of Somatic Mutations in Cancer (COSMIC; v78 in circa 18,000 tumor samples. We found that nonsynonymous single nucleotide substitutions in the analyzed proteome subset ultimately result in a net gain of cysteine, histidine, and tryptophan at the expense of a net loss of arginine. The extraordinary loss of arginine may be attributed to some extent to composition of its codons as well as to the importance of arginine in the functioning of prominent tumor suppressor proteins like p53.

  8. Contribution to the study of radiation induced bone tissue cancer

    International Nuclear Information System (INIS)

    Bouet, Monique.

    1975-01-01

    In this work four original observations of more or less long-delayed cancers induced by ionizing radiations are compared with 34 other cases in the literature, after which an attempt is made to establish a general and prognostic synthesis of the results; the indications to emerge are as follows: - Ionizing radiation-induced cancers are very rare, especially when compared with the extensive therapeutic use made of X-rays; - The probability of radio-cancer formation, though no figures are given in the many papers consulted, seems nevertheless to be higher in cases of benign lesion irradiation; - Induced cancers have been observed after treatments with all types of radiation, whether or not the lesion is tumoral or cancerous, whatever the patient's age at the time of irradiations; - As a general rule these neoplasms appear after a variable latency period but usually from the 6th post-radiotherapy year onwards, with a greater frequency range between 6 and 12 years; - These induced cancers are generally epitheliomas or sarcomas, the latter being noticeably more predominant than in the case of spontaneous cancers. Leukoses may also be observed [fr

  9. Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

    Directory of Open Access Journals (Sweden)

    Donna M. Sosnoski

    2012-01-01

    Full Text Available It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization.

  10. Changes in Cytokines of the Bone Microenvironment during Breast Cancer Metastasis

    International Nuclear Information System (INIS)

    Sosnoski, D.M.; Krishnan, V.; Mastro, A.M.; Kraemer, W.J.; Dunn-Lewis, C.

    2012-01-01

    It is commonly accepted that cancer cells interact with host cells to create a microenvironment favoring malignant colonization. The complex bone microenvironment produces an ever changing array of cytokines and growth factors. In this study, we examined levels of MCP-1, IL-6, KC, MIP-2, VEGF, MIG, and eotaxin in femurs of athymic nude mice inoculated via intracardiac injection with MDA-MB-231GFP human metastatic breast cancer cells, MDA-MB-231 BRMS1GFP, a metastasis suppressed variant, or PBS. Animals were euthanized (day 3, 11, 19, 27 after injection) to examine femoral cytokine levels at various stages of cancer cell colonization. The epiphysis contained significantly more cytokines than the diaphysis except for MIG which was similar throughout the bone. Variation among femurs was evident within all groups. By day 27, MCP-1, MIG, VEGF and eotaxin levels were significantly greater in femurs of cancer cell-inoculated mice. These pro-osteoclastic and angiogenic cytokines may manipulate the bone microenvironment to enhance cancer cell colonization

  11. Quantitative proteomics reveals middle infrared radiation-interfered networks in breast cancer cells.

    Science.gov (United States)

    Chang, Hsin-Yi; Li, Ming-Hua; Huang, Tsui-Chin; Hsu, Chia-Lang; Tsai, Shang-Ru; Lee, Si-Chen; Huang, Hsuan-Cheng; Juan, Hsueh-Fen

    2015-02-06

    Breast cancer is one of the leading cancer-related causes of death worldwide. Treatment of triple-negative breast cancer (TNBC) is complex and challenging, especially when metastasis has developed. In this study, we applied infrared radiation as an alternative approach for the treatment of TNBC. We used middle infrared (MIR) with a wavelength range of 3-5 μm to irradiate breast cancer cells. MIR significantly inhibited cell proliferation in several breast cancer cells but did not affect the growth of normal breast epithelial cells. We performed iTRAQ-coupled LC-MS/MS analysis to investigate the MIR-triggered molecular mechanisms in breast cancer cells. A total of 1749 proteins were identified, quantified, and subjected to functional enrichment analysis. From the constructed functionally enriched network, we confirmed that MIR caused G2/M cell cycle arrest, remodeled the microtubule network to an astral pole arrangement, altered the actin filament formation and focal adhesion molecule localization, and reduced cell migration activity and invasion ability. Our results reveal the coordinative effects of MIR-regulated physiological responses in concentrated networks, demonstrating the potential implementation of infrared radiation in breast cancer therapy.

  12. Proteomics in uveal melanoma.

    LENUS (Irish Health Repository)

    Ramasamy, Pathma

    2014-01-01

    Uveal melanoma is the most common primary intraocular malignancy in adults, with an incidence of 5-7 per million per year. It is associated with the development of metastasis in about 50% of cases, and 40% of patients with uveal melanoma die of metastatic disease despite successful treatment of the primary tumour. The survival rates at 5, 10 and 15 years are 65%, 50% and 45% respectively. Unlike progress made in many other areas of cancer, uveal melanoma is still poorly understood and survival rates have remained similar over the past 25 years. Recently, advances made in molecular genetics have improved our understanding of this disease and stratification of patients into low risk and high risk for developing metastasis. However, only a limited number of studies have been performed using proteomic methods. This review will give an overview of various proteomic technologies currently employed in life sciences research, and discuss proteomic studies of uveal melanoma.

  13. Model for the induction of bone cancer by 224Ra

    International Nuclear Information System (INIS)

    Groer, P.G.; Marshall, J.H.

    1976-01-01

    A mathematical model for the transformation of normal endosteal cells into malignant tumor cells by α irradiation is applied to 224 Ra. The model postulates that a normal endosteal cell near the bone surface is transformed into a malignant cell by three consecutive events. The first two events are the initiation events. The probability of their occurrence is proportional to the absorbed endosteal dose and they generate dormant tumor cells. These dormant tumor cells are promoted by the third event, the promotion event. The probability of this last event is proportional to the rate of bone remodeling but independent of the radiation dose. In competition with these transforming events is the killing of any endosteal cell by α irradiation. Killing is balanced by replacement of killed endosteal cells by normal stem cells. This model provides the following interesting predictions for the human 224 Ra cases: after the decay of 224 Ra the tumor rate decreases exponentially at a rate proportional to the bone turnover rate; for exposure to the same dose the model predicts an increased number of tumors for protracted exposure (i.e., exposure at a lower dose rate). Implications of this model for the therapy of ankylosing spondylitis are discussed. Statistical procedures are suggested for comparison of this theoretical model with the existing data on the induction of osteosarcomas by 224 Ra in man

  14. Zoledronic acid preserves bone structure and increases survival but does not limit tumour incidence in a prostate cancer bone metastasis model.

    Directory of Open Access Journals (Sweden)

    Tzong-Tyng Hung

    Full Text Available BACKGROUND: The bisphosphonate, zoledronic acid (ZOL, can inhibit osteoclasts leading to decreased osteoclastogenesis and osteoclast activity in bone. Here, we used a mixed osteolytic/osteoblastic murine model of bone-metastatic prostate cancer, RM1(BM, to determine how inhibiting osteolysis with ZOL affects the ability of these cells to establish metastases in bone, the integrity of the tumour-bearing bones and the survival of the tumour-bearing mice. METHODS: The model involves intracardiac injection for arterial dissemination of the RM1(BM cells in C57BL/6 mice. ZOL treatment was given via subcutaneous injections on days 0, 4, 8 and 12, at 20 and 100 µg/kg doses. Bone integrity was assessed by micro-computed tomography and histology with comparison to untreated mice. The osteoclast and osteoblast activity was determined by measuring serum tartrate-resistant acid phosphatase 5b (TRAP 5b and osteocalcin, respectively. Mice were euthanased according to predetermined criteria and survival was assessed using Kaplan Meier plots. FINDINGS: Micro-CT and histological analysis showed that treatment of mice with ZOL from the day of intracardiac injection of RM1(BM cells inhibited tumour-induced bone lysis, maintained bone volume and reduced the calcification of tumour-induced endochondral osteoid material. ZOL treatment also led to a decreased serum osteocalcin and TRAP 5b levels. Additionally, treated mice showed increased survival compared to vehicle treated controls. However, ZOL treatment did not inhibit the cells ability to metastasise to bone as the number of bone-metastases was similar in both treated and untreated mice. CONCLUSIONS: ZOL treatment provided significant benefits for maintaining the integrity of tumour-bearing bones and increased the survival of tumour bearing mice, though it did not prevent establishment of bone-metastases in this model. From the mechanistic view, these observations confirm that tumour-induced bone lysis is not a

  15. Dietary Fish Oil in Reducing Bone Metastasis of Breast Cancer

    National Research Council Canada - National Science Library

    Ghosh-Choudhury, Nandini

    2006-01-01

    In a study of the mechanism behind the inhibitory effect of fish oil on the growth of breast cancer cells, the authors reported that fish oil, or w-3 polyunsaturated fatty acids (PUFAs), did the following: (1...

  16. Trafficking of Metastatic Breast Cancer Cells in Bone

    National Research Council Canada - National Science Library

    Mastro, Andrea M

    2004-01-01

    ... metaphyses. Human breast cancer cells that express green fluorescent protein (GFP-MDA-MB 231) will be inoculated into athymic mice by intracardiac injection and femurs harvested at various times from 1 hour to 6 weeks later...

  17. Quantitative proteomics of fractionated membrane and lumen exosome proteins from isogenic metastatic and nonmetastatic bladder cancer cells reveal differential expression of EMT factors

    DEFF Research Database (Denmark)

    Jeppesen, Dennis Kjølhede; Nawrocki, Arkadiusz; Jensen, Steffen Grann

    2014-01-01

    Cancer cells secrete soluble factors and various extracellular vesicles, including exosomes, into their tissue microenvironment. The secretion of exosomes is speculated to facilitate local invasion and metastatic spread. Here, we used an in vivo metastasis model of human bladder carcinoma cell line...... T24 without metastatic capacity and its two isogenic derivate cell lines SLT4 and FL3, which form metastases in the lungs and liver of mice, respectively. Cultivation in CLAD1000 bioreactors rather than conventional culture flasks resulted in a 13-16-fold increased exosome yield and facilitated...... quantitative proteomics of fractionated exosomes. Exosomes from T24, SLT4, and FL3 cells were partitioned into membrane and luminal fractions and changes in protein abundance related to the gain of metastatic capacity were identified by quantitative iTRAQ- proteomics. We identified several proteins linked...

  18. NCI Requests Targets for Monoclonal Antibody Production and Characterization | Office of Cancer Clinical Proteomics Research

    Science.gov (United States)

    In an effort to provide well-characterized monoclonal antibodies to the scientific community, NCI's Antibody Characterization Program requests cancer-related protein targets for affinity production and distribution. Submissions will be accepted through July 9, 2012.

  19. Identification of proteomic biomarkers predicting prostate cancer aggressiveness and lethality despite biopsy-sampling error

    OpenAIRE

    Shipitsin, M; Small, C; Choudhury, S; Giladi, E; Friedlander, S; Nardone, J; Hussain, S; Hurley, A D; Ernst, C; Huang, Y E; Chang, H; Nifong, T P; Rimm, D L; Dunyak, J; Loda, M

    2014-01-01

    Background: Key challenges of biopsy-based determination of prostate cancer aggressiveness include tumour heterogeneity, biopsy-sampling error, and variations in biopsy interpretation. The resulting uncertainty in risk assessment leads to significant overtreatment, with associated costs and morbidity. We developed a performance-based strategy to identify protein biomarkers predictive of prostate cancer aggressiveness and lethality regardless of biopsy-sampling variation. Methods: Prostatectom...

  20. Micellar Drug Delivery and Proteomics Analysis for Effective Treatment of Resistant Prostate Cancer

    Science.gov (United States)

    2015-12-01

    by a luminometer (Berthold, Bad Wildbad, Germany ). In Vivo Efficacy of Drug Loaded LHRH Conjugated Micelles in Ectopic Tumor Bearing Mice All...and metabolism) as well as the pathogenesis of several human diseases, including prostate cancers.11,12 Deregulated miRNAs are involved in initiation...signaling pathways and therefore can be more effective in treating cancers that are inherently heterogeneous and are resulted from the deregulation of

  1. P2X7 Receptor Function in Bone-Related Cancer

    Directory of Open Access Journals (Sweden)

    Elena Adinolfi

    2012-01-01

    Full Text Available Modulation of tumor microenvironment by different mediators is central in determining neoplastic formation and progression. Among these molecules extracellular ATP is emerging as a good candidate in promoting cell growth, neovascularization, tumor-host interactions, and metastatization. This paper summarizes recent findings on expression and function of P2X7 receptor for extracellular ATP in primary and metastatic bone cancers. Search of mRNA expression microchip databases and literature analysis demonstrate a high expression of P2X7 in primary bone tumors as well as in other malignancies such as multiple myeloma, neuroblastoma, breast, and prostate cancer. Evidence that P2X7 triggers NFATc1, PI3K/Akt, ROCK, and VEGF pathways in osteoblasts promoting either primary tumor development or osteoblastic lesions is also reported. Moreover, P2X7 receptor is involved in osteoclast differentiation, RANKL expression, matrix metalloproteases and cathepsin secretion thus promoting bone resorption and osteolytic lesions. Taken together these data point to a pivotal role for the P2X7 receptor in bone cancer biology.

  2. Combined serum and EPS-urine proteomic analysis using iTRAQ technology for discovery of potential prostate cancer biomarkers.

    Science.gov (United States)

    Zhang, Mo; Chen, Lizhu; Yuan, Zhengwei; Yang, Zeyu; Li, Yue; Shan, Liping; Yin, Bo; Fei, Xiang; Miao, Jianing; Song, Yongsheng

    2016-11-01

    Prostate cancer (PCa) is one of the most common malignant tumors and a major cause of cancer-related death for men worldwide. The aim of our study was to identify potential non-invasive serum and expressed prostatic secretion (EPS)-urine biomarkers for accurate diagnosis of PCa. Here, we performed a combined isobaric tags for relative and absolute quantification (iTRAQ) proteomic analysis to compare protein profiles using pooled serum and EPS-urine samples from 4 groups of patients: benign prostate hyperplasia (BPH), high grade prostatic intraepithelial neoplasia (HGPIN), localized PCa and metastatic PCa. The differentially expressed proteins were rigorously selected and further validated in a large and independent cohort using classical ELISA and Western blot assays. Finally, we established a multiplex biomarker panel consisting of 3 proteins (serum PF4V1, PSA, and urinary CRISP3) with an excellent diagnostic capacity to differentiate PCa from BPH [area under the receiver operating characteristic curve (AUC) of 0.941], which showed an evidently greater discriminatory ability than PSA alone (AUC, 0.757) (P<0.001). Importantly, even when PSA level was in the gray zone (4-10 ng/mL), a combination of PF4V1 and CRISP3 could achieve a relatively high diagnostic efficacy (AUC, 0.895). Furthermore, their combination also had the potential to distinguish PCa from HGPIN (AUC, 0.934). Our results demonstrated that the combined application of serum and EPS-urine biomarkers can improve the diagnosis of PCa and provide a new prospect for non-invasive PCa detection.

  3. Label-free Raman spectroscopy provides early determination and precise localization of breast cancer-colonized bone alterations.

    Science.gov (United States)

    Zhang, Chi; Winnard, Paul T; Dasari, Sidarth; Kominsky, Scott L; Doucet, Michele; Jayaraman, Swaathi; Raman, Venu; Barman, Ishan

    2018-01-21

    Breast neoplasms frequently colonize bone and induce development of osteolytic bone lesions by disrupting the homeostasis of the bone microenvironment. This degenerative process can lead to bone pain and pathological bone fracture, a major cause of cancer morbidity and diminished quality of life, which is exacerbated by our limited ability to monitor early metastatic disease in bone and assess fracture risk. Spurred by its label-free, real-time nature and its exquisite molecular specificity, we employed spontaneous Raman spectroscopy to assess and quantify early metastasis driven biochemical alterations to bone composition. As early as two weeks after intracardiac inoculations of MDA-MB-435 breast cancer cells in NOD-SCID mice, Raman spectroscopic measurements in the femur and spine revealed consistent changes in carbonate substitution, overall mineralization as well as crystallinity increase in tumor-bearing bones when compared with their normal counterparts. Our observations reveal the possibility of early stage detection of biochemical changes in the tumor-bearing bones - significantly before morphological variations are captured through radiographic diagnosis. This study paves the way for a better molecular understanding of altered bone remodeling in such metastatic niches, and for further clinical studies with the goal of establishing a non-invasive tool for early metastasis detection and prediction of pathological fracture risk in breast cancer.

  4. Crosstalk between bone niche and immune system: osteoimmunology signaling as a potential target for cancer treatment.

    Science.gov (United States)

    Criscitiello, Carmen; Viale, Giulia; Gelao, Lucia; Esposito, Angela; De Laurentiis, Michele; De Placido, Sabino; Santangelo, Michele; Goldhirsch, Aron; Curigliano, Giuseppe

    2015-02-01

    There is a well recognized link between the bone and the immune system and in recent years there has been a major effort to elucidate the multiple functions of the molecules expressed in both bone and immune cells. Several molecules that were initially identified and studied in the immune system have been shown to have essential functions also in the bone. An interdisciplinary field embracing immune and bone biology has been brought together and called "osteoimmunology". The co-regulation of the skeletal and immune systems strikingly exemplifies the extreme complexity of such an interaction. Their interdependency must be considered in designing therapeutic approaches for either of the two systems. In other words, it is necessary to think of the osteoimmune system as a complex physiological unit. Denosumab was originally introduced to specifically target bone resorption, but it is now under evaluation for its effect on the long term immune response. Similarly, our current and still growing knowledge of the intimate link between the immune system and bone will be beneficial for the safety of drugs targeting either of these integrated systems. Given the large number of molecules exerting functions on both the skeletal and immune systems, osteoimmunological understanding is becoming increasingly important. Both bone and immune systems are frequently disrupted in cancer; and they may be crucial in regulating tumor growth and progression. Some therapies - such as bisphosphonates and receptor activator of NF-κB ligand (RANKL) targeted drugs - that aim at reducing pathologic osteolysis in cancer may interact with the immune system, thus providing potential favorable effects on survival. Copyright © 2014 Elsevier Ltd. All rights reserved.

  5. A Technical Assessment of the Utility of Reverse Phase Protein Arrays for the Study of the Functional Proteome in Non-microdissected Human Breast Cancers.

    LENUS (Irish Health Repository)

    Hennessy, Bryan T

    2010-12-01

    INTRODUCTION: The lack of large panels of validated antibodies, tissue handling variability, and intratumoral heterogeneity potentially hamper comprehensive study of the functional proteome in non-microdissected solid tumors. The purpose of this study was to address these concerns and to demonstrate clinical utility for the functional analysis of proteins in non-microdissected breast tumors using reverse phase protein arrays (RPPA). METHODS: Herein, 82 antibodies that recognize kinase and steroid signaling proteins and effectors were validated for RPPA. Intraslide and interslide coefficients of variability were <15%. Multiple sites in non-microdissected breast tumors were analyzed using RPPA after intervals of up to 24 h on the benchtop at room temperature following surgical resection. RESULTS: Twenty-one of 82 total and phosphoproteins demonstrated time-dependent instability at room temperature with most variability occurring at later time points between 6 and 24 h. However, the 82-protein functional proteomic "fingerprint" was robust in most tumors even when maintained at room temperature for 24 h before freezing. In repeat samples from each tumor, intratumoral protein levels were markedly less variable than intertumoral levels. Indeed, an independent analysis of prognostic biomarkers in tissue from multiple tumor sites accurately and reproducibly predicted patient outcomes. Significant correlations were observed between RPPA and immunohistochemistry. However, RPPA demonstrated a superior dynamic range. Classification of 128 breast cancers using RPPA identified six subgroups with markedly different patient outcomes that demonstrated a significant correlation with breast cancer subtypes identified by transcriptional profiling. CONCLUSION: Thus, the robustness of RPPA and stability of the functional proteomic "fingerprint" facilitate the study of the functional proteome in non-microdissected breast tumors.

  6. Usefulness of 18F fluoride PET/CT in breast cancer patients with osteosclerotic bone metastases

    International Nuclear Information System (INIS)

    Yoon, Seok Ho; Kim, Ku Sang; Kang, Seok Yun; Song, Hee Sung; Jo, Kyung Sook; Lee, Su Jin; Yoon, Joon Kee; An, Young Sil; Choi, Bong Hoi

    2012-01-01

    Bone metastasis is an important factor for the treatment and prognosis of breast cancer patients. Whole body bone scintigraphy (WBBS) can evaluate skeletal metastases, and 18 F FDG PET/CT seems to exhibit high specificity and accuracy in detecting bone metastases. However, there is a limitation of 18 F FDG PET in assessing sclerotic bone metastases because some lesions may be undetectable. Recent studies showed that 18 F fluoride PET/CT is more sensitive than WBBS in detecting bone metastases. This study aims to evaluate the usefulness of 18 F fluoride PET/CT by comparing it with WBBS and 18 F FDG PET/CT in breast cancer patients with osteosclerotic skeletal metastases. Nine breast cancer patients with suspected bone metastases (9 females; mean age ± SD, 55.6±10.0 years) underwent 99m Tc MDP WBBS, 18 F FDG PET/CT and 18 F fluoride PET/CT. Lesion based analysis of five regions of the skeletons(skull, vertebral column, thoracic cage, pelvic bones and long bones of extremities) and patient based analysis were performed. 18 F fluoride PET/CT, 18 F FDG PET/CT and WBBS detected 49, 20 and 25 true metastases, respectively. Sensitivity, specificity, positive predictive value and negative predictive value of 18 F fluoride PET/CT were 94.2%, 46.3%, 57.7% and 91.2%, respectively. Most true metastatic lesions of 18 F fluoride PET/CT had osteosclerotic change (45/49, 91.8%), and only four lesions showed osteolytic change. Most lesions on 18 F FDG PET/CT also demonstrated osteosclerotic change (17/20, 85.0%) with three osteolytic lesions. All true metastatic lesions detected on WBBS and 18 F FDG PET/CT were identified on 18 F fluoride PET/CT. 18 F FDG PET/CT in detecting osteosclerotic metastatic lesions. 18 F fluoride PET/CT might be useful in evaluating osteosclerotic metastases in breast cancer patients

  7. Polyurethane foam scaffold as in vitro model for breast cancer bone metastasis.

    Science.gov (United States)

    Angeloni, Valentina; Contessi, Nicola; De Marco, Cinzia; Bertoldi, Serena; Tanzi, Maria Cristina; Daidone, Maria Grazia; Farè, Silvia

    2017-11-01

    Breast cancer (BC) represents the most incident cancer case in women (29%), with high mortality rate. Bone metastasis occurs in 20-50% cases and, despite advances in BC research, the interactions between tumor cells and the metastatic microenvironment are still poorly understood. In vitro 3D models gained great interest in cancer research, thanks to the reproducibility, the 3D spatial cues and associated low costs, compared to in vivo and 2D in vitro models. In this study, we investigated the suitability of a poly-ether-urethane (PU) foam as 3D in vitro model to study the interactions between BC tumor-initiating cells and the bone microenvironment. PU foam open porosity (>70%) appeared suitable to mimic trabecular bone structure. The PU foam showed good mechanical properties under cyclic compression (E=69-109kPa), even if lower than human trabecular bone. The scaffold supported osteoblast SAOS-2 cell line proliferation, with no cytotoxic effects. Human adipose derived stem cells (ADSC) were cultured and differentiated into osteoblast lineage on the PU foam, as shown by alizarin red staining and RT-PCR, thus offering a bone biomimetic microenvironment to the further co-culture with BC derived tumor-initiating cells (MCFS). Tumor aggregates were observed after three weeks of co-culture by e-cadherin staining and SEM; modification in CaP distribution was identified by SEM-EDX and associated to the presence of tumor cells. In conclusion, we demonstrated the suitability of the PU foam to reproduce a bone biomimetic microenvironment, useful for the co-culture of human osteoblasts/BC tumor-initiating cells and to investigate their interaction. 3D in vitro models represent an outstanding alternative in the study of tumor metastases development, compared to traditional 2D in vitro cultures, which oversimplify the 3D tissue microenvironment, and in vivo studies, affected by low reproducibility and ethical issues. Several scaffold-based 3D in vitro models have been proposed

  8. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    Energy Technology Data Exchange (ETDEWEB)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui, E-mail: baohuihan1@163.com

    2014-01-17

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC.

  9. Lung cancer-derived Dickkopf1 is associated with bone metastasis and the mechanism involves the inhibition of osteoblast differentiation

    International Nuclear Information System (INIS)

    Chu, Tianqing; Teng, Jiajun; Jiang, Liyan; Zhong, Hua; Han, Baohui

    2014-01-01

    Highlights: •DKK1 level was associated with NSCLC bone metastases. •Lung tumor cells derived DKK1 inhibited osteoblast differentiation. •Lung tumor cells derived DKK1 modulates β-catenin and RUNX2. -- Abstract: Wnt/β-catenin signaling and Dickkopf1 (DKK1) play important roles in the progression of lung cancer, which preferably metastasizes to skeleton. But the role of them in bone dissemination is poorly understood. This study aims to define the role of DKK1 in lung cancer bone metastases and investigate the underlying mechanism. Our results demonstrated that DKK1 over-expression was a frequent event in non-small-cell lung cancer (NSCLC) blood samples, and serous DKK1 level was much higher in bone metastatic NSCLC compared to non-bone metastatic NSCLC. We also found that conditioned medium from DKK1 over-expressing lung cancer cells inhibited the differentiation of osteoblast, determined by alkaline phosphatase activity and osteocalcin secretion, whereas the conditioned medium from DKK1 silencing lung cancer cells exhibited the opposite effects. Mechanistically, DKK1 reduced the level of β-catenin and RUNX2, as well as inhibiting the nuclear translocation of β-catenin. Taken together, these results suggested that lung cancer-produced DKK1 may be an important mechanistic link between NSCLC and bone metastases, and targeting DKK1 may be an effective method to treat bone metastase of NSCLC

  10. [Effect of intravenous treatment with OK-432 on the bone marrow in patients with lung cancer].

    Science.gov (United States)

    Fujii, M; Ishikawa, M; Toki, H

    1984-03-01

    We studied effects of OK-432 on the bone marrow and peripheral blood cells of lung cancer patients. The nuclear cell count of bone marrow increased in 5 to 7 patients upon intravenous treatment with OK-432 compared with 3 of 6 patients who were intramuscularly treated with OK-432. Serial neutrophil counts of bone marrow increased in all 7 patients treated intravenously compared with 3 of 6 patients treated intramuscularly. The mean nuclear cell count or the serial neutrophil count of bone marrow in intravenously treated patients was significantly higher than the pretreatment values (p less than 0.001). In the peripheral blood picture, the difference in white blood cells or neutrophils before and after intravenous treatment was also statistically significant (p less than 0.01). There was no change in the erythrocytic series count of bone marrow and the hemoglobin count. Our results support the superiority of intravenous OK-432 treatment over intramuscular treatment in the growth-accelerating effect on bone marrow cells, especially regarding the neutrophil series.

  11. XCR1 promotes cell growth and migration and is correlated with bone metastasis in non-small cell lung cancer

    Energy Technology Data Exchange (ETDEWEB)

    Wang, Ting; Han, Shuai; Wu, Zhipeng; Han, Zhitao; Yan, Wangjun; Liu, Tielong; Wei, Haifeng; Song, Dianwen; Zhou, Wang, E-mail: brilliant212@163.com; Yang, Xinghai, E-mail: cnspineyang@163.com; Xiao, Jianru, E-mail: jianruxiao83@163.com

    2015-08-21

    Bone metastasis occurs in approximately 30–40% patients with advanced non-small cell lung cancer (NSCLC), but the mechanism underlying this bone metastasis remains poorly understood. The chemokine super family is believed to play an important role in tumor metastasis in lung cancer. The chemokine receptor XCR1 has been identified to promote cell proliferation and migration in oral cancer and ovarian carcinoma, but the role of XCR1 in lung cancer has not been reported. In this study, we demonstrated for the first time that XCR1 was overexpressed in lung cancer bone metastasis as compared with that in patients with primary lung cancer. In addition, the XCR1 ligand XCL1 promoted the proliferation and migration of lung cancer cells markedly, and knockdown of XCR1 by siRNA abolished the effect of XCL1 in cell proliferation and migration. Furthermore, we identified JAK2/STAT3 as a novel downstream pathway of XCR1, while XCL1/XCR1 increased the mRNA level of the downstream of JAK2/STAT3 including PIM1, JunB, TTP, MMP2 and MMP9. These results indicate that XCR1 is a new potential therapeutic target for the treatment of lung cancer bone metastasis. - Highlights: • XCR1 is overexpressed in bone metastasis compared with primary NSCLC. • XCR1 activation by XCL1 promotes lung cancer cell proliferation and migration. • JAK2/STAT3 is a novel potential downstream pathway of XCR1.

  12. Synthetic bone substitute material comparable with xenogeneic material for bone tissue regeneration in oral cancer patients: First and preliminary histological, histomorphometrical and clinical results.

    Science.gov (United States)

    Ghanaati, Shahram; Barbeck, Mike; Lorenz, Jonas; Stuebinger, Stefan; Seitz, Oliver; Landes, Constantin; Kovács, Adorján F; Kirkpatrick, Charles J; Sader, Robert A

    2013-07-01

    The present study was first to evaluate the material-specific cellular tissue response of patients with head and neck cancer to a nanocrystalline hydroxyapatite bone substitute NanoBone (NB) in comparison with a deproteinized bovine bone matrix Bio-Oss (BO) after implantation into the sinus cavity. Eight patients with tumor resection for oral cancer and severely resorbed maxillary bone received materials according to a split mouth design for 6 months. Bone cores were harvested prior to implantation and analyzed histologically and histomorphometrically. Implant survival was followed-up to 2 years after placement. Histologically, NB underwent a higher vascularization and induced significantly more tartrate-resistant acid phosphatase-positive (TRAP-positive) multinucleated giant cells when compared with BO, which induced mainly mononuclear cells. No significant difference was observed in the extent of new bone formation between both groups. The clinical follow-up showed undisturbed healing of all implants in the BO-group, whereas the loss of one implant was observed in the NB-group. Within its limits, the present study showed for the first time that both material classes evaluated, despite their induction of different cellular tissue reactions, may be useful as augmentation materials for dental and maxillofacial surgical applications, particularly in patients who previously had oral cancer.

  13. Effect of music therapy on pain behaviors in rats with bone cancer pain.

    Science.gov (United States)

    Gao, Ji; Chen, Shaoqin; Lin, Suyong; Han, Hongjing

    2016-01-01

    To investigate the effects of music therapy on the pain behaviors and survival of rats with bone cancer pain and analyze the mediating mechanism of mitogen activated protein kinase (MAPK) signal transduction pathway. Male Wistar rats aged 5-8 weeks and weighing 160-200 g were collected. The rat models of colorectal cancer bone cancer pain was successfully established. Animals were divided into experimental and control group, each with 10 rats. The animals in the observation group were given Mozart K448 sonata, sound intensity of 60 db, played the sonata once every 1 hr in the daytime, stopped playing during the night, and this cycle was kept for 2 weeks. On the other hand, rats in the control group were kept under the same environment without music. Animals in the experimental group consumed more feed and gained significant weight in comparison to the control group. The tumor volume of the experimental group was significantly smaller than that of the control group (pMusic therapy may improve the pain behaviors in rats with bone cancer pain, which might be related with low expression of p38á and p38β in the MAPK signal transduction pathway.

  14. Chromosomal aberration in peripheral lymphocytes and doses to the active bone marrow in radiotherapy of prostate cancer

    International Nuclear Information System (INIS)

    Gershkevitsh, E.; Trott, K.R.

    2002-01-01

    Purpose: Radiotherapy plays an important role in the management of prostate cancer. Epidemiological data indicate a small but significant risk of radiation-induced leukemia after radiotherapy which might be related to the high mean bone marrow dose associated with radiotherapy of prostate cancer. The purpose of the study was to investigate the relation between the mean bone marrow dose and unstable chromosome aberrations in peripheral blood lymphocytes in patients undergoing conformal radiotherapy for prostate cancer as a possible indicator of risk. Endometrial cancer patients were also included for comparison. Patients and Methods: Nine patients, six with prostate cancer (60-73 years old) and three with endometrial cancer (61-81 years old) treated with radiotherapy were included in the study. The non-bony spaces inside the pelvic bones were outlined on every CT slice using the treatment planning system and mean doses to the bone marrow calculated. Blood samples of the patients were obtained at different times before, during and at the end of treatment. Lymphocytes were cultured in the usual way and metaphases scored for dicentric aberrations. Results: 46 samples from nine patients were obtained. The mean number of metaphases analyzed per sample was 180 with a range from 52 to 435. The mean bone marrow doses for prostate cancer patients ranged from 2.8 to 4.2 Gy and for endometrial cancer patients from 12.8 to 14.8 Gy. The aberration yield increased with the planning target volume and the mean bone marrow dose. Conclusion: The yield of dicentric aberrations for prostate cancer patients correlated closely with the mean bone marrow dose albeit the induction of dicentrics occurred in mature T lymphocytes most of which were probably in transit through the irradiated volumes. Therefore, the observed relationship between dicentrics and mean bone marrow doses are indirect. (orig.) [de

  15. Quantitative Mass Spectrometry-Based Proteomic Profiling for Precision Medicine in Prostate Cancer

    DEFF Research Database (Denmark)

    Flores-Morales, Amilcar; Iglesias-Gato, Diego

    2017-01-01

    are proteins, including the widely-used prostate-specific antigen (PSA). Recent developments in mass spectrometry allow the identification and quantification of thousands of proteins and posttranslational modifications from small amounts of biological material, including formalin-fixed paraffin......Prostate cancer (PCa) is one of the most frequently diagnosed cancer among men in the western societies. Many PCa patients bear tumors that will not threat their lives if left untreated or if treatment is delayed. Our inability for early identification of these patients has resulted in massive...

  16. Study on {sup 41}Ca-AMS for diagnosis and assessment of cancer bone metastasis in rats

    Energy Technology Data Exchange (ETDEWEB)

    Shen, Hongtao; Pang, Fangfang [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Jiang, Shan; He, Ming; Dong, Kejun; Dou, Liang [China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Pang, Yijun [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); China Institute of Atomic Energy, P.O. Box 275-50, Beijing 102413 (China); Yang, Xianlin [College of Physics and Technology, Guangxi Normal University, Guilin 541004 (China); Ruan, Xiangdong [College of Physics, Guangxi University, Nanning 530004 (China); Liu, Manjun; Xia, Chunbo [Guiin Medical University, Guilin 541004 (China)

    2015-10-15

    The annual incidence of new cancer patients in China is about 2 million, 30–40% of which will end up with bone metastasis. Profound study on the preclinical model and early diagnosis of cancer bone metastasis in rats are very significant for the drug development, better understanding and treatment of bone metastases. In order to monitor the process of bone metabolism and early detection of bone metastasis of cancer cells, a technique of {sup 41}Ca isotope tracer combined with AMS has been developed and applied in the study on the bone metastasis of cancer cells by rat model. In this work, 3-month-old female Sprague–Dawley (SD) rats were randomly divided into different groups, and tumor cells injected respectively into the tail vein, femoral artery, femoral cavity and the thigh muscle to establish the rat models for bone metastases. The most appropriate model, i.e., the thigh muscle group, was finally adopted in our real metastases experiment. Each rat in this group was intramuscularly (i.m.) injected with 250 μl CaCl{sub 2} solution (containing 1.4 mg Ca and 5nCi {sup 41}Ca). About 40 days later, the rat mammary gland carcinoma cells (Walker 256) were injected into these rats following the established protocol. After bone metastasis, medicine interventions were performed. The sequential urine and blood samples were collected and analyzed for {sup 41}Ca (by AMS) and N-terminal telopeptide (Ntx), respectively. Bone Mineral Density (BMD) values in the femur and the tibia were measured by CT scan. The results of {sup 41}Ca/Ca in longitudinal urinary samples can sensitively reveal the skeletal perturbations caused by bone metastasis of rats, suggests that {sup 41}Ca might be similarly developed for human use and improve clinical management through the assessment of the curative effect and non-invasive detection of the earliest stages of cancer growth in bone.

  17. A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic Biomarker and Novel Therapeutic Mitochondrial Target

    Science.gov (United States)

    2017-10-01

    goal of this application is to identify targets for the treatment of androgen receptor null castration-resistant prostate cancer in in vitro and pre...AWARD NUMBER: W81XWH-16-1-0584 TITLE : A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases: Novel Opportunity for Genetic...Missense Mutation in 77% of Prostate Cancer Bone Metastases: 5a. CONTRACT NUMBER A Single Missense Mutation in 77% of Prostate Cancer Bone Metastases

  18. A Dual-Action Armed Replicating Adenovirus for the Treatment of Osteoblastic Bone Metastases of Prostate Cancer

    Science.gov (United States)

    2007-03-01

    that bone metastases of prostate cancer have an extensive bone resorptive component mediated by osteoclasts: resorption of the bone matrix provides...enhances protection by parenteral Mycobac- 795 terium bovis BCG immunization against pulmonary tuberculosis. 796 Infection and Immunity, 74, 4634–4643. 797...oncolysis; replicating adeno- virus; TIMP-2; tumor growth ABBReviATionS MMP matrix metalloproteinase TIMP-2 tissue inhibitor of metalloproteinases-2

  19. Prolonged Hypocalcemia Following a Single Dose of Denosumab for Diffuse Bone Metastasis of Gastric Cancer after Total Gastrectomy.

    Science.gov (United States)

    Iizumi, Sakura; Shimoi, Tatsunori; Nishikawa, Tadaaki; Kit