New study reveals relatively few mutations in AML genomes - TCGA

Cancer.gov

Investigators for The Cancer Genome Atlas (TCGA) Research Network have detailed and broadly classified the genomic alterations that frequently underlie the development of acute myeloid leukemia (AML).

Early Tracking or Finally Leaving? Determinants of Early Study Success in First-Year University Students

ERIC Educational Resources Information Center

Brouwer, Jasperina; Jansen, Ellen; Hofman, Adriaan; Flache, Andreas

2016-01-01

Two theoretical approaches underlie this investigation of the determinants of early study success among first-year university students. Specifically, to extend Walberg's educational productivity model, this study draws on the expectancy-value theory of achievement motivation in a contemporary university context. The survey data came from 407…

Purine Analog-Like Properties of Bendamustine Underlie Rapid Activation of DNA Damage Response and Synergistic Effects with Pyrimidine Analogues in Lymphoid Malignancies

PubMed Central

Hiraoka, Nobuya; Kikuchi, Jiro; Yamauchi, Takahiro; Koyama, Daisuke; Wada, Taeko; Uesawa, Mitsuyo; Akutsu, Miyuki; Mori, Shigehisa; Nakamura, Yuichi; Ueda, Takanori; Kano, Yasuhiko; Furukawa, Yusuke

2014-01-01

Bendamustine has shown considerable clinical activity against indolent lymphoid malignancies as a single agent or in combination with rituximab, but combination with additional anti-cancer drugs may be required for refractory and/or relapsed cases as well as other intractable tumors. In this study, we attempted to determine suitable anti-cancer drugs to be combined with bendamustine for the treatment of mantle cell lymphoma, diffuse large B-cell lymphoma, aggressive lymphomas and multiple myeloma, all of which are relatively resistant to this drug, and investigated the mechanisms underlying synergism. Isobologram analysis revealed that bendamustine had synergistic effects with alkylating agents (4-hydroperoxy-cyclophosphamide, chlorambucil and melphalan) and pyrimidine analogues (cytosine arabinoside, gemcitabine and decitabine) in HBL-2, B104, Namalwa and U266 cell lines, which represent the above entities respectively. In cell cycle analysis, bendamustine induced late S-phase arrest, which was enhanced by 4-hydroperoxy-cyclophosphamide, and potentiated early S-phase arrest by cytosine arabinoside (Ara-C), followed by a robust increase in the size of sub-G1 fractions. Bendamustine was able to elicit DNA damage response and subsequent apoptosis faster and with shorter exposure than other alkylating agents due to rapid intracellular incorporation via equilibrative nucleoside transporters (ENTs). Furthermore, bendamustine increased the expression of ENT1 at both mRNA and protein levels and enhanced the uptake of Ara-C and subsequent increase in Ara-C triphosphate (Ara-CTP) in HBL-2 cells to an extent comparable with the purine analog fludarabine. These purine analog-like properties of bendamustine may underlie favorable combinations with other alkylators and pyrimidine analogues. Our findings may provide a theoretical basis for the development of more effective bendamustine-based combination therapies. PMID:24626203

Gene–environment interplay in Drosophila melanogaster: Chronic food deprivation in early life affects adult exploratory and fitness traits

PubMed Central

Burns, James Geoffrey; Svetec, Nicolas; Rowe, Locke; Mery, Frederic; Dolan, Michael J.; Boyce, W. Thomas; Sokolowski, Marla B.

2012-01-01

Early life adversity has known impacts on adult health and behavior, yet little is known about the gene–environment interactions (GEIs) that underlie these consequences. We used the fruit fly Drosophila melanogaster to show that chronic early nutritional adversity interacts with rover and sitter allelic variants of foraging (for) to affect adult exploratory behavior, a phenotype that is critical for foraging, and reproductive fitness. Chronic nutritional adversity during adulthood did not affect rover or sitter adult exploratory behavior; however, early nutritional adversity in the larval period increased sitter but not rover adult exploratory behavior. Increasing for gene expression in the mushroom bodies, an important center of integration in the fly brain, changed the amount of exploratory behavior exhibited by sitter adults when they did not experience early nutritional adversity but had no effect in sitters that experienced early nutritional adversity. Manipulation of the larval nutritional environment also affected adult reproductive output of sitters but not rovers, indicating GEIs on fitness itself. The natural for variants are an excellent model to examine how GEIs underlie the biological embedding of early experience. PMID:23045644

Decision making for breast cancer prevention among women at elevated risk.

PubMed

Padamsee, Tasleem J; Wills, Celia E; Yee, Lisa D; Paskett, Electra D

2017-03-24

Several medical management approaches have been shown to be effective in preventing breast cancer and detecting it early among women at elevated risk: 1) prophylactic mastectomy; 2) prophylactic oophorectomy; 3) chemoprevention; and 4) enhanced screening routines. To varying extents, however, these approaches are substantially underused relative to clinical practice recommendations. This article reviews the existing research on the uptake of these prevention approaches, the characteristics of women who are likely to use various methods, and the decision-making processes that underlie the differing choices of women. It also highlights important areas for future research, detailing the types of studies that are particularly needed in four key areas: documenting women's perspectives on their own perceptions of risk and prevention decisions; explicit comparisons of available prevention pathways and their likely health effects; the psychological, interpersonal, and social processes of prevention decision making; and the dynamics of subgroup variation. Ultimately, this research could support the development of interventions that more fully empower women to make informed and values-consistent decisions, and to move towards favorable health outcomes.

NCI RNA Biology 2017 symposium recap | Center for Cancer Research

Cancer.gov

The recent discovery of new classes of RNAs and the demonstration that alterations in RNA metabolism underlie numerous human cancers have resulted in enormous interest among CCR investigators in RNA biology. In order to share the latest research in this exciting field, the CCR Initiative in RNA Biology held its second international symposium April 23-24, 2017, in Natcher

Induction of cyclooxygenase-2 expression by prostaglandin E2 stimulation of the prostanoid EP4 receptor via coupling to Gαi and transactivation of the epidermal growth factor receptor in HCA-7 human colon cancer cells.

PubMed

Yoshida, Kenji; Fujino, Hiromichi; Otake, Sho; Seira, Naofumi; Regan, John W; Murayama, Toshihiko

2013-10-15

Increased expressions of cyclooxygenase-2 (COX-2) and its downstream metabolite, prostaglandin E2 (PGE2), are well documented events in the development of colorectal cancer. Interestingly, PGE2 itself can induce the expression of COX-2 thereby creating the potential for positive feedback. Although evidence for such a positive feedback has been previously described, the specific E-type prostanoid (EP) receptor subtype that mediates this response, as well as the relevant signaling pathways, remain unclear. We now report that the PGE2 stimulated induction of COX-2 expression in human colon cancer HCA-7 cells is mediated by activation of the prostanoid EP4 receptor subtype and is followed by coupling of the receptor to Gαi and the activation of phosphatidylinositol 3-kinase. Subsequent activation of metalloproteinases releases membrane bound heparin-binding epidermal growth factor-like growth factor resulting in the transactivation of epidermal growth factor receptors and the activation of the extracellular signal-regulated kinases and induction of COX-2 expression. This induction of COX-2 expression by PGE2 stimulation of the prostanoid EP4 receptor may underlie the upregulation of COX-2 during colorectal cancer and appears to be an early event in the process of tumorigenesis. © 2013 Elsevier B.V. All rights reserved.

75 FR 78259 - Draft Guidance for Industry on Codevelopment of Two or More Unmarketed Investigational Drugs for...

Federal Register 2010, 2011, 2012, 2013, 2014

2010-12-15

... that underlie many complex diseases, such as cancer, cardiovascular disease, and infectious diseases... used in combination to treat a disease or condition. This guidance provides recommendations and advice...

Early Combinations of Words and Actions.

ERIC Educational Resources Information Center

Shore, Cecilia

Previous research has shown a similar starting time for early combinations of words and play actions in children and has suggested that similar cognitive processes underlie the transition to combining activities in language, symbolic play, and manipulative play. A study was undertaken to investigate combining activities in these three domains and…

NCI RNA Biology 2017 symposium recap | Center for Cancer Research

Cancer.gov

The recent discovery of new classes of RNAs and the demonstration that alterations in RNA metabolism underlie numerous human cancers have resulted in enormous interest among CCR investigators in RNA biology. In order to share the latest research in this exciting field, the CCR Initiative in RNA Biology held its second international symposium April 23-24, 2017, in Natcher Auditorium. Learn more...

Identifying DNA Methylation Features that Underlie Prostate Cancer Disparities

DTIC Science & Technology

2016-10-01

Report We will continue to recruit African American patients and bank their prostate tissue . We will continue dissecting tumor samples into tumor...in prostate tumors and adjacent normal tissue derived from both AA and EA individuals. We will determine if DNA methylation patterns in prostate... tissue (both cancerous and normal tissue ) differ between AA and EA individuals. We will also identify methylation features that differ between tumor

Music in the Early Years: Pathways into the Social World

ERIC Educational Resources Information Center

Ilari, Beatriz

2016-01-01

Two assumptions that underlie much research in early childhood music education are that music is a social endeavor and musical participation is beneficial to children's overall social development. As members of cultural and social groups, young children engage with music in a multitude of ways and with different companions. This article examines…

Comparison against 186 canid whole-genome sequences reveals survival strategies of an ancient clonally transmissible canine tumor

PubMed Central

Decker, Brennan; Davis, Brian W.; Rimbault, Maud; Long, Adrienne H.; Karlins, Eric; Jagannathan, Vidhya; Reiman, Rebecca; Parker, Heidi G.; Drögemüller, Cord; Corneveaux, Jason J.; Chapman, Erica S.; Trent, Jeffery M.; Leeb, Tosso; Huentelman, Matthew J.; Wayne, Robert K.; Karyadi, Danielle M.; Ostrander, Elaine A.

2015-01-01

Canine transmissible venereal tumor (CTVT) is a parasitic cancer clone that has propagated for thousands of years via sexual transfer of malignant cells. Little is understood about the mechanisms that converted an ancient tumor into the world's oldest known continuously propagating somatic cell lineage. We created the largest existing catalog of canine genome-wide variation and compared it against two CTVT genome sequences, thereby separating alleles derived from the founder's genome from somatic mutations that must drive clonal transmissibility. We show that CTVT has undergone continuous adaptation to its transmissible allograft niche, with overlapping mutations at every step of immunosurveillance, particularly self-antigen presentation and apoptosis. We also identified chronologically early somatic mutations in oncogenesis- and immune-related genes that may represent key initiators of clonal transmissibility. Thus, we provide the first insights into the specific genomic aberrations that underlie CTVT's dogged perseverance in canids around the world. PMID:26232412

Heat Shock Proteins Promote Cancer: It's a Protection Racket.

PubMed

Calderwood, Stuart K; Gong, Jianlin

2016-04-01

Heat shock proteins (HSP) are expressed at high levels in cancer and form a fostering environment that is essential for tumor development. Here, we review the recent data in this area, concentrating mainly on Hsp27, Hsp70, and Hsp90. The overriding role of HSPs in cancer is to stabilize the active functions of overexpressed and mutated cancer genes. Thus, elevated HSPs are required for many of the traits that underlie the morbidity of cancer, including increased growth, survival, and formation of secondary cancers. In addition, HSPs participate in the evolution of cancer treatment resistance. HSPs are also released from cancer cells and influence malignant properties by receptor-mediated signaling. Current data strongly support efforts to target HSPs in cancer treatment. Copyright © 2016 Elsevier Ltd. All rights reserved.

EMERGING BIOLOGICAL PRINCIPLES OF METASTASIS

PubMed Central

Lambert, Arthur W.; Pattabiraman, Diwakar R.; Weinberg, Robert A.

2016-01-01

Metastases account for the great majority of cancer-associated deaths, yet this complex process remains the least understood aspect of cancer biology. As the body of research concerning metastasis continues to grow at a rapid rate, the biological programs that underlie the dissemination and metastatic outgrowth of cancer cells are beginning to come into view. In this review we summarize the cellular and molecular mechanisms involved in metastasis, with a focus on carcinomas where the most is known, and highlight the general principles of metastasis that have begun to emerge. PMID:28187288

Crossing the endothelial barrier during metastasis.

PubMed

Reymond, Nicolas; d'Água, Bárbara Borda; Ridley, Anne J

2013-12-01

During metastasis, cancer cells disseminate to other parts of the body by entering the bloodstream in a process that is called intravasation. They then extravasate at metastatic sites by attaching to endothelial cells that line blood vessels and crossing the vessel walls of tissues or organs. This Review describes how cancer cells cross the endothelial barrier during extravasation and how different receptors, signalling pathways and circulating cells such as leukocytes and platelets contribute to this process. Identification of the mechanisms that underlie cancer cell extravasation could lead to the development of new therapies to reduce metastasis.

Identifying DNA Methylation Features that Underlie Prostate Cancer Disparities

DTIC Science & Technology

2017-10-01

Army position, policy or decision unless so designated by other documentation. REPORT DOCUMENTATION PAGE Form Approved OMB No. 0704- 0188 Public...failing to comply with a collection of information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE...men are more likely to die from prostate cancer than EA men. We hypothesize that differences in DNA methylation patterns across ethnic groups may

Epigenetics of prostate cancer and the prospect of identification of novel drug targets by RNAi screening of epigenetic enzymes.

PubMed

Björkman, Mari; Rantala, Juha; Nees, Matthias; Kallioniemi, Olli

2010-10-01

Alterations in epigenetic processes probably underlie most human malignancies. Novel genome-wide techniques, such as chromatin immunoprecipitation and high-throughput sequencing, have become state-of-the-art methods to map the epigenomic landscape of development and disease, such as in cancers. Despite these advances, the functional significance of epigenetic enzymes in cancer progression, such as prostate cancer, remain incompletely understood. A comprehensive mapping and functional understanding of the cancer epigenome will hopefully help to facilitate development of novel cancer therapy targets and improve future diagnostics. The authors have developed a novel cell microarray-based high-content siRNA screening technique suitable to address the putative functional role and impact of all known putative and novel epigenetic enzymes in cancer, including prostate cancer.

Early-Stage Chunking of Finger Tapping Sequences by Persons Who Stutter and Fluent Speakers

ERIC Educational Resources Information Center

Smits-Bandstra, Sarah; De Nil, Luc F.

2013-01-01

This research note explored the hypothesis that chunking differences underlie the slow finger-tap sequencing performance reported in the literature for persons who stutter (PWS) relative to fluent speakers (PNS). Early-stage chunking was defined as an immediate and spontaneous tendency to organize a long sequence into pauses, for motor planning,…

The rise of genomic profiling in ovarian cancer

PubMed Central

Previs, Rebecca A.; Sood, Anil K.; Mills, Gordon B.; Westin, Shannon N.

2017-01-01

Introduction Next-generation sequencing and advances in ‘omics technology have rapidly increased our understanding of the molecular landscape of epithelial ovarian cancers. Areas covered Once characterized only by histologic appearance and clinical behavior, we now understand many of the molecular phenotypes that underlie the different ovarian cancer subtypes. While the current approach to treatment involves standard cytotoxic therapies after cytoreductive surgery for all ovarian cancers regardless of histologic or molecular characteristics, focus has shifted beyond a ‘one size fits all’ approach to ovarian cancer. Expert commentary Genomic profiling offers potentially ‘actionable’ opportunities for development of targeted therapies and a more individualized approach to treatment with concomitant improved outcomes and decreased toxicity. PMID:27828713

Fragmentation and Unpredictability of Early-Life Experience in Mental Disorders

PubMed Central

Baram, Tallie Z.; Solodkin, Ana; Davis, Elysia P.; Stern, Hal; Obenaus, Andre; Sandman, Curt A.; Small, Steven L.

2012-01-01

Maternal sensory signals in early life play a crucial role in programming the structure and function of the developing brain, promoting vulnerability or resilience to emotional and cognitive disorders. In rodent models of early-life stress, fragmentation and unpredictability of maternally derived sensory signals provoke persistent cognitive and emotional dysfunction in offspring. Similar variability and inconsistency of maternal signals during both gestation and early postnatal human life may influence development of emotional and cognitive functions, including those that underlie later depression and anxiety. PMID:22885631

Combining Cell Type-Restricted Adenoviral Targeting with Immunostaining and Flow Cytometry to Identify Cells-of-Origin of Lung Cancer.

PubMed

Best, Sarah A; Kersbergen, Ariena; Asselin-Labat, Marie-Liesse; Sutherland, Kate D

2018-01-01

Lung cancers display considerable intertumoral heterogeneity, leading to the classification of distinct tumor subtypes. Our understanding of the genetic aberrations that underlie tumor subtypes has been greatly enhanced by recent genomic sequencing studies and state-of-the-art gene targeting technologies, highlighting evidence that distinct lung cancer subtypes may be derived from different "cells-of-origin". Here, we describe the intra-tracheal delivery of cell type-restricted Ad5-Cre viruses into the lungs of adult mice, combined with immunohistochemical and flow cytometry strategies for the detection of lung cancer-initiating cells in vivo.

Contralateral pulmonary metastases in lung cancer

PubMed Central

Onuigbo, Wilson I. B.

1974-01-01

Onuigbo, W. I. B. (1974).Thorax, 29, 132-133. Contralateral pulmonary metastases in lung cancer. It has long been known that lung cancer may attack many organs and yet spare the opposite lung. In 100 cases of this tumour studied at necropsy, only 22 showed contralateral pulmonary spread. Contralateral deposits are generally small and may be related to damaged tissues. Although tissue unsuitability is supposed to underlie the limitation of metastases in recipient organs, this does not apply to the contralateral lung. Since lung tissue is readily accessible to bloodborne cancer cells, research should be directed towards explaining the paradoxical paucity of the metastases. PMID:4825544

Phenotypic chemical screening using a zebrafish neural crest EMT reporter identifies retinoic acid as an inhibitor of epithelial morphogenesis

PubMed Central

Jimenez, Laura; Wang, Jindong; Morrison, Monique A.; Whatcott, Clifford; Soh, Katherine K.; Warner, Steven; Bearss, David; Jette, Cicely A.; Stewart, Rodney A.

2016-01-01

ABSTRACT The epithelial-to-mesenchymal transition (EMT) is a highly conserved morphogenetic program essential for embryogenesis, regeneration and cancer metastasis. In cancer cells, EMT also triggers cellular reprogramming and chemoresistance, which underlie disease relapse and decreased survival. Hence, identifying compounds that block EMT is essential to prevent or eradicate disseminated tumor cells. Here, we establish a whole-animal-based EMT reporter in zebrafish for rapid drug screening, called Tg(snai1b:GFP), which labels epithelial cells undergoing EMT to produce sox10-positive neural crest (NC) cells. Time-lapse and lineage analysis of Tg(snai1b:GFP) embryos reveal that cranial NC cells delaminate from two regions: an early population delaminates adjacent to the neural plate, whereas a later population delaminates from within the dorsal neural tube. Treating Tg(snai1b:GFP) embryos with candidate small-molecule EMT-inhibiting compounds identified TP-0903, a multi-kinase inhibitor that blocked cranial NC cell delamination in both the lateral and medial populations. RNA sequencing (RNA-Seq) analysis and chemical rescue experiments show that TP-0903 acts through stimulating retinoic acid (RA) biosynthesis and RA-dependent transcription. These studies identify TP-0903 as a new therapeutic for activating RA in vivo and raise the possibility that RA-dependent inhibition of EMT contributes to its prior success in eliminating disseminated cancer cells. PMID:26794130

Infection in neutropenic patients with cancer.

PubMed

Bow, Eric J

2013-07-01

Neutropenic fever sepsis syndromes are common among patients with cancer who are receiving intensive cytotoxic systemic therapy. Recognition of the syndromes and timely initial antibacterial therapy is critical for survival and treatment success. Outcomes are linked to myeloid reconstitution and recovery from neutropenia, control of active comorbidities, and appropriate treatment of the infections that underlie the sepsis syndrome. Hematologists and oncologists must be clear about the prognosis and treatment goals to work effectively with critical care physicians toward the best outcomes for patients with cancer who develop neutropenic sepsis syndromes. Copyright © 2013 Elsevier Inc. All rights reserved.

From Fly Wings to Targeted Cancer Therapies: A Centennial for Notch Signaling

PubMed Central

Ntziachristos, Panagiotis; Lim, Jing Shan; Sage, Julien; Aifantis, Iannis

2014-01-01

Since Notch phenotypes in Drosophila melanogaster were identified 100 years, Notch signaling has been extensively characterized as a regulator of cell fate decisions in a variety of organisms and tissues. However, in the past 20 years, accumulating evidence has linked alterations in the Notch pathway to tumorigenesis. In this Perspective, we discuss the pro-tumorigenic and tumor suppressive functions of Notch signaling and dissect the molecular mechanisms that underlie these functions in hematopoietic cancers and solid tumors. Finally, we link these mechanisms and observations to possible therapeutic strategies targeting the Notch pathway in human cancers. PMID:24651013

The Mechanism by which Neurofibromin Suppresses Tumorigenesis

DTIC Science & Technology

2013-02-01

et al., 2011; Taichman et al., 2002; Zeelenberg et al., 2003; Zhou et al., 2002), as well as non-Hodgkin’s lymphoma (Bertolini et al., 2002), and...underlie the unique pattern of optic glioma growth in neurofibromatosis type Cancer Res 67, 8588-8595. Zeelenberg , I.S., Ruuls-Van Stalle, L., and

Global Epigenetic Changes May Underlie Ethnic Differences and Susceptibility to Prostate Cancer

DTIC Science & Technology

2013-09-01

malignancy and can often be found in non-cancerous tissues; in the prostate, hypermethylation of the GSTP1 CpG has been detected in PIA lesions [8]. DNA...methylcytosine (5-meC; [9, 10]). Since the recognition that the GSTP1 CpG island was frequently hypermethylated in PCa, more than 40 genes have been reported to...has also been identified for several genes. One study demonstrated that GSTP1 hypermethylation was significantly higher in PCa samples from AA men

Predictors of emotional distress a year or more after diagnosis of cancer: A systematic review of the literature.

PubMed

Cook, Sharon A; Salmon, Peter; Hayes, Gemma; Byrne, Angela; Fisher, Peter L

2018-03-01

Why some people recover emotionally after diagnosis and treatment of cancer and others do not is poorly understood. To identify factors around the time of diagnosis that predict longer-term distress is a necessary step in developing interventions to reduce patients' vulnerability. This review identified the demographic, clinical, social, and psychological factors available at or within 3 months of diagnosis that are reliable predictors of emotional distress at least 12 months later. A systematic search of literature for prospective studies addressing our research question and predicting a range of distress outcomes was conducted. Thirty-nine papers (reporting 36 studies) were subjected to narrative synthesis of the evidence. There was no consistent evidence that demographic, clinical, or social factors reliably predicted longer-term distress. Of the psychological factors examined, only baseline distress (significant in 26 of 30 relevant papers; 24 of 28 studies) and neuroticism (significant in all 5 papers/studies that examined it) consistently predicted longer-term distress. The heterogeneity of included studies, particularly in populations studied and methodology, precluded meta-analytic techniques. This review supports current clinical guidance advising early assessment of distress as a marker of vulnerability to persistent problems. Additionally, neuroticism is also indicated as a useful marker of vulnerability. However, the review also highlights that more sophisticated research designs, capable of identifying the psychological processes that underlie the association between these marker variables and persistent distress, are needed before more effective early interventions can be developed. © 2018 The Authors. Psycho-Oncology Published by John Wiley & Sons Ltd.

The Lesson of Hiroshima and Nagasaki--Part I: The Past.

ERIC Educational Resources Information Center

Kauffman, George B.

1985-01-01

Examines scientific discoveries which underlie the atomic bomb and its technological development in the United States during World War II. Changing views, super-weapon development, early American efforts, production/dropping the bombs, and the Oppenheimer case are considered. (DH)

78 FR 35940 - Guidance for Industry on Codevelopment of Two or More New Investigational Drugs for Use in...

Federal Register 2010, 2011, 2012, 2013, 2014

2013-06-14

... underlie many complex diseases, such as cancer, cardiovascular disease, and infectious diseases. This...., ``new investigational drugs'') to be used in combination to treat a disease or condition. The guidance... (i.e., ``new investigational drugs'') to be used in combination to treat a disease or condition...

Identifying DNA Methylation Features that Underlie Prostate Cancer Disparities

DTIC Science & Technology

2015-10-01

variant analysis U01 HG007601 (Pierce, B.) NIH/NHGRI 8/1/2014 - 5/31/2017 Direct Cost: $201,814 1 Cal. Month Telomere length and chromosomal...Month Telomere length and chromosomal instability across various tissue types R01 ES023834 (Pierce, B.) NIH/NCI 4/1/14 - 3/31/18 Direct Cost

Return of D4 Dopamine Receptor Antagonists in Drug Discovery.

PubMed

Lindsley, Craig W; Hopkins, Corey R

2017-09-14

The dopamine D 4 receptor garnered a great deal of interest in the early 1990s when studies showed the atypical antipsychotic clozapine possessed higher affinity for D 4 , relative to other dopamine receptor subtypes, and that this activity might underlie the unique clinical efficacy of clozapine. Unfortunately, D 4 antagonists that were developed for schizophrenia failed in the clinic. Thus, D 4 fell out of favor as a therapeutic target, and work in this area was silent for decades. Recently, D 4 ligands with improved selectivity for D 4 against not only D 1-3,5 but also other biogenic amine targets have emerged, and D 4 is once again in the spotlight as a novel target for both addiction and Parkinson's disease (PD), as well as other emerging diseases. This report will review the historical data for D 4 , review the known D 4 ligands, and then highlight new data supporting a role for D 4 inhibition in addiction, PD, and cancer.

Do Theory of Mind and Executive Function Deficits Underlie the Adverse Outcomes Associated with Profound Early Deprivation?: Findings from the English and Romanian Adoptees Study

ERIC Educational Resources Information Center

Colvert, Emma; Rutter, Michael; Kreppner, Jana; Beckett, Celia; Castle, Jenny; Groothues, Christine; Hawkins, Amanda; Stevens, Suzanne; Sonuga-Barke, Edmund J. S.

2008-01-01

Theory of Mind (ToM) and Executive Function (EF) have been associated with autism and with attention-deficit hyperactivity disorder (ADHD), and hence might play a role in similar syndromes found following profound early institutional deprivation. In order to examine this possibility the current study included a group of 165 Romanian adoptees, of…

Molecular Pathways: Cachexia Signaling-A Targeted Approach to Cancer Treatment.

PubMed

Miyamoto, Yuji; Hanna, Diana L; Zhang, Wu; Baba, Hideo; Lenz, Heinz-Josef

2016-08-15

Cancer cachexia is a multifactorial syndrome characterized by an ongoing loss of skeletal muscle mass, which negatively affects quality of life and portends a poor prognosis. Numerous molecular substrates and mechanisms underlie the dysregulation of skeletal muscle synthesis and degradation observed in cancer cachexia, including proinflammatory cytokines (TNFα, IL1, and IL6), and the NF-κB, IGF1/AKT/mTOR, and myostatin/activin-SMAD pathways. Recent preclinical and clinical studies have demonstrated that anti-cachexia drugs (such as MABp1 and soluble receptor antagonist of myostatin/activin) not only prevent muscle wasting but also may prolong overall survival. In this review, we focus on the significance of cachexia signaling in patients with cancer and highlight promising drugs targeting tumor cachexia in clinical development. Clin Cancer Res; 22(16); 3999-4004. ©2016 AACR. ©2016 American Association for Cancer Research.

Steps in Prostate Cancer Progression that lead to Bone Metastasis

PubMed Central

Jin, Jung-Kang; Dayyani, Farshid; Gallick, Gary E.

2011-01-01

Prostate cancer is a complex disease in which metastasis to the bone is the main cause of death. Initial stages of metastasis are generally similar to those for most solid tumors; however, the mechanisms that underlie the homing of prostate tumor cells to the bone remain incompletely understood. Prostate cancer bone metastasis is also a microenvironment-driven disease, involving bi-directional interactions between the tumor and the bone microenvironment. In this review, we discuss the current understanding of the biologic processes and regulatory factors involved in the metastasis of prostate cancer cells, and their specific properties that promote growth in bone. Although many of these processes still need to be fully elucidated, a better understanding of the complex tumor/microenvironment interplay is slowly leading to more effective therapies for patients with prostate cancer bone metastases. PMID:21365645

Core Geometry in Perspective

ERIC Educational Resources Information Center

Dillon, Moira R.; Spelke, Elizabeth S.

2015-01-01

Research on animals, infants, children, and adults provides evidence that distinct cognitive systems underlie navigation and object recognition. Here we examine whether and how these systems interact when children interpret 2D edge-based perspectival line drawings of scenes and objects. Such drawings serve as symbols early in development, and they…

Accounting for Change in Declarative Memory: A Cognitive Neuroscience Perspective

ERIC Educational Resources Information Center

Richmond, Jenny; Nelson, Charles A.

2007-01-01

The medial temporal lobe memory system matures relatively early and supports rudimentary declarative memory in young infants. There is considerable development, however, in the memory processes that underlie declarative memory performance during infancy. Here we consider age-related changes in encoding, retention, and retrieval in the context of…

Biological Components of Colour Preference in Infancy

ERIC Educational Resources Information Center

Franklin, Anna; Bevis, Laura; Ling, Yazhu; Hurlbert, Anya

2010-01-01

Adult colour preference has been summarized quantitatively in terms of weights on the two fundamental neural processes that underlie early colour encoding: the S-(L+M) ("blue-yellow") and L-M ("red-green") cone-opponent contrast channels ( Ling, Hurlbert & Robinson, 2006; Hurlbert & Ling, 2007). Here, we investigate whether colour preference in…

Age-Related Changes in Decision Making: Comparing Informed and Noninformed Situations

ERIC Educational Resources Information Center

Van Duijvenvoorde, Anna C. K.; Jansen, Brenda R. J.; Bredman, Joren C.; Huizenga, Hilde M.

2012-01-01

Advantageous decision making progressively develops into early adulthood, most specifically in complex and motivationally salient decision situations in which direct feedback on gains and losses is provided (Figner & Weber, 2011). However, the factors that underlie this developmental improvement in decision making are still not well understood.…

Rational Emotive Behavior Therapy with Troubled Students.

ERIC Educational Resources Information Center

Zionts, Paul; Zionts, Laura

1997-01-01

Based on the early work of Albert Ellis, seeks to identify and challenge irrational beliefs that underlie behavior problems. Outlines concepts and methods of Rational Emotive Behavior Theory and describes the application both in counseling and as a mental health curriculum for troubled children and youth. Offers classroom techniques. (RJM)

Characterizing biomarkers in osteosarcoma metastasis based on an ego-network.

PubMed

Liu, Zhen; Song, Yan

2017-06-01

To characterize biomarkers that underlie osteosarcoma (OS) metastasis based on an ego-network. From the microarray data, we obtained 13,326 genes. By combining PPI data and microarray data, 10,520 shared genes were found and constructed into ego-networks. 17 significant ego-networks were identified with p < 0.05. In the pathway enrichment analysis, seven ego-networks were identified with the most significant pathway. These significant ego-modules were potential biomarkers that reveal the potential mechanisms in OS metastasis, which may contribute to understanding cancer prognoses and providing new perspectives in the treatment of cancer.

Age differences in dual information-processing modes: implications for cancer decision making.

PubMed

Peters, Ellen; Diefenbach, Michael A; Hess, Thomas M; Västfjäll, Daniel

2008-12-15

Age differences in affective/experiential and deliberative processes have important theoretical implications for cancer decision making, as cancer is often a disease of older adulthood. The authors examined evidence for adult age differences in affective and deliberative information processes, reviewed the sparse evidence about age differences in decision making, and introduced how dual process theories and their findings might be applied to cancer decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age, particularly when decisions are unfamiliar and the information is numeric. However, age-related adaptive processes, including an increased focus on emotional goals and greater experience, can influence decision making and potentially offset age-related declines. A better understanding of the mechanisms that underlie cancer decision processes in our aging population should ultimately allow us to help older adults to better help themselves.

Age Differences in Dual Information-Processing Modes: Implications for Cancer Decision Making

PubMed Central

Peters, Ellen; Diefenbach, Michael A.; Hess, Thomas M.; Västfjäll, Daniel

2008-01-01

Age differences in affective/experiential and deliberative processes have important theoretical implications for cancer decision making as cancer is often a disease of older adulthood. We examine evidence for adult age differences in affective and deliberative information processes, review the sparse evidence about age differences in decision making and introduce how dual process theories and their findings might be applied to cancer decision making. Age-related declines in the efficiency of deliberative processes predict poorer-quality decisions as we age, particularly when decisions are unfamiliar and the information is numeric. However, age-related adaptive processes, including an increased focus on emotional goals and greater experience, can influence decision making and potentially offset age-related declines. A better understanding of the mechanisms that underlie cancer decision processes in our aging population should ultimately allow us to help older adults to better help themselves. PMID:19058148

The role of epithelial plasticity in prostate cancer dissemination and treatment resistance

PubMed Central

Bitting, Rhonda L.; Schaeffer, Daneen; Somarelli, Jason A.; Garcia-Blanco, Mariano A.

2014-01-01

Nearly 30,000 men die annually in the USA of prostate cancer, nearly uniformly from metastatic dissemination. Despite recent advances in hormonal, immunologic, bone-targeted, and cytotoxic chemotherapies, treatment resistance and further dissemination are inevitable in men with metastatic disease. Emerging data suggests that the phenomenon of epithelial plasticity, encompassing both reversible mesenchymal transitions and acquisition of stemness traits, may underlie this lethal biology of dissemination and treatment resistance. Understanding the molecular underpinnings of this cellular plasticity from preclinical models of prostate cancer and from biomarker studies of human metastatic prostate cancer has provided clues to novel therapeutic approaches that may delay or prevent metastatic disease and lethality over time. This review will discuss the preclinical and clinical evidence for epithelial plasticity in this rapidly changing field and relate this to clinical phenotype and resistance in prostate cancer while suggesting novel therapeutic approaches. PMID:24414193

Epigenetic Regulation of Centromere Chromatin Stability by Dietary and Environmental Factors.

PubMed

Hernández-Saavedra, Diego; Strakovsky, Rita S; Ostrosky-Wegman, Patricia; Pan, Yuan-Xiang

2017-11-01

The centromere is a genomic locus required for the segregation of the chromosomes during cell division. This chromosomal region together with pericentromeres has been found to be susceptible to damage, and thus the perturbation of the centromere could lead to the development of aneuploidic events. Metabolic abnormalities that underlie the generation of cancer include inflammation, oxidative stress, cell cycle deregulation, and numerous others. The micronucleus assay, an early clinical marker of cancer, has been shown to provide a reliable measure of genotoxic damage that may signal cancer initiation. In the current review, we will discuss the events that lead to micronucleus formation and centromeric and pericentromeric chromatin instability, as well transcripts emanating from these regions, which were previously thought to be inactive. Studies were selected in PubMed if they reported the effects of nutritional status (macro- and micronutrients) or environmental toxicant exposure on micronucleus frequency or any other chromosomal abnormality in humans, animals, or cell models. Mounting evidence from epidemiologic, environmental, and nutritional studies provides a novel perspective on the origination of aneuploidic events. Although substantial evidence exists describing the role that nutritional status and environmental toxicants have on the generation of micronuclei and other nuclear aberrations, limited information is available to describe the importance of macro- and micronutrients on centromeric and pericentromeric chromatin stability. Moving forward, studies that specifically address the direct link between nutritional status, excess, or deficiency and the epigenetic regulation of the centromere will provide much needed insight into the nutritional and environmental regulation of this chromosomal region and the initiation of aneuploidy. © 2017 American Society for Nutrition.

Effects of Alcohol on Tumor Growth, Metastasis, Immune Response, and Host Survival

PubMed Central

Meadows, Gary G.; Zhang, Hui

2015-01-01

Most research involving alcohol and cancer concerns the relationship between alcohol consumption and cancer risk and the mechanisms of carcinogenesis. This review relates the amount and duration of alcohol intake in humans and in animal models of cancer to tumor growth, angiogenesis, invasion, metastasis, immune response, and host survival in specific types and subtypes of cancer. Research on the influence of alcohol drinking on human cancer patients is limited. Although there is more information in animal models of cancer, many aspects still are ill defined. More research is needed to define the mechanisms that underlie the role of alcohol on cancer progression in both animals and humans. Activation of the immune system can play a positive role in keeping cancer under control, but this also can facilitate cancer progression. Additionally, a functional immune system is required for cancer patients to achieve an optimal response to conventional chemotherapy. Insight into the underlying mechanisms of these interactions could lead to effective immunotherapeutic approaches to treat alcoholics with cancer. Defining the epigenetic mechanisms that modulate cancer progression also has great potential for the development of new treatment options not only for treating alcoholics with cancer but also for treating other alcohol-induced diseases. PMID:26695753

The Relation Between Antisocial and Borderline Personality Symptoms and Early Maladaptive Schemas in a Treatment Seeking Sample of Male Substance Users

PubMed Central

Shorey, Ryan C.; Anderson, Scott; Stuart, Gregory L.

2014-01-01

Individuals with substance use disorders are more likely to have antisocial and borderline personality disorder than non-substance abusers. Recently, research has examined the relations between early maladaptive schemas and personality disorders, as early maladaptive schemas are believed to underlie personality disorders. However, there is a dearth of research on the relations between early maladaptive schemas and personality disorders among individuals seeking treatment for substance abuse. The current study examined the relations among early maladaptive schemas and antisocial and borderline personality within in a sample of men seeking substance abuse treatment (n = 98). Results demonstrated that early maladaptive schema domains were associated with antisocial and borderline personality symptoms. Implications of these findings for substance use treatment and research are discussed. PMID:23650153

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer.

PubMed

Bailey, Swneke D; Desai, Kinjal; Kron, Ken J; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A; Treloar, Aislinn E; Dowar, Mark; Thu, Kelsie L; Cescon, David W; Silvester, Jennifer; Yang, S Y Cindy; Wu, Xue; Pezo, Rossanna C; Haibe-Kains, Benjamin; Mak, Tak W; Bedard, Philippe L; Pugh, Trevor J; Sallari, Richard C; Lupien, Mathieu

2016-10-01

Sustained expression of the estrogen receptor-α (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon estrogen stimulation to establish an oncogenic expression program. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers, suggesting that other mechanisms underlie the persistent expression of ESR1. We report significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by rs9383590, a functional inherited single-nucleotide variant (SNV) that accounts for several breast cancer risk-associated loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer.

The interplay between obesity and cancer: a fly view

PubMed Central

2016-01-01

ABSTRACT Accumulating epidemiological evidence indicates a strong clinical association between obesity and an increased risk of cancer. The global pandemic of obesity indicates a public health trend towards a substantial increase in cancer incidence and mortality. However, the mechanisms that link obesity to cancer remain incompletely understood. The fruit fly Drosophila melanogaster has been increasingly used to model an expanding spectrum of human diseases. Fly models provide a genetically simpler system that is ideal for use as a first step towards dissecting disease interactions. Recently, the combining of fly models of diet-induced obesity with models of cancer has provided a novel model system in which to study the biological mechanisms that underlie the connections between obesity and cancer. In this Review, I summarize recent advances, made using Drosophila, in our understanding of the interplay between diet, obesity, insulin resistance and cancer. I also discuss how the biological mechanisms and therapeutic targets that have been identified in fly studies could be utilized to develop preventative interventions and treatment strategies for obesity-associated cancers. PMID:27604692

Molecular targeted therapy for the treatment of gastric cancer.

PubMed

Xu, Wenting; Yang, Zhen; Lu, Nonghua

2016-01-04

Despite the global decline in the incidence and mortality of gastric cancer, it remains one of the most common malignant tumors of the digestive system. Although surgical resection is the preferred treatment for gastric cancer, chemotherapy is the preferred treatment for recurrent and advanced gastric cancer patients who are not candidates for reoperation. The short overall survival and lack of a standard chemotherapy regimen make it important to identify novel treatment modalities for gastric cancer. Within the field of tumor biology, molecular targeted therapy has attracted substantial attention to improve the specificity of anti-cancer efficacy and significantly reduce non-selective resistance and toxicity. Multiple clinical studies have confirmed that molecular targeted therapy acts on various mechanisms of gastric cancer, such as the regulation of epidermal growth factor, angiogenesis, immuno-checkpoint blockade, the cell cycle, cell apoptosis, key enzymes, c-Met, mTOR signaling and insulin-like growth factor receptors, to exert a stronger anti-tumor effect. An in-depth understanding of the mechanisms that underlie molecular targeted therapies will provide new insights into gastric cancer treatment.

Associations between Drug Use and Deviant Behavior in Teenagers. Health Sciences Program Reprint Series, 96-23D.

ERIC Educational Resources Information Center

Hays, Ron D.; Ellickson, Phyllis L.

1996-01-01

Drug use and delinquency share many common antecedents: early antisocial behavior, difficulties in school, impaired family relationships, delinquent or drug-using peers, and rebelliousness. But these common factors could underlie a cluster of problem behaviors or lead to distinctly different behavioral manifestations. Using data from 1,363 West…

Annual Research Review: Epigenetic Mechanisms and Environmental Shaping of the Brain during Sensitive Periods of Development

ERIC Educational Resources Information Center

Roth, Tania L.; Sweatt, J. David

2011-01-01

Experiences during early development profoundly affect development of the central nervous system (CNS) to impart either risk for or resilience to later psychopathology. Work in the developmental neuroscience field is providing compelling data that epigenetic marking of the genome may underlie aspects of this process. Experiments in rodents…

State Actions To Restructure Schools: First Steps. Results in Education Series.

ERIC Educational Resources Information Center

David, Jane L.; And Others

The widening mismatch between the skills of the work force and the skill demands of the work place underlie the need for school restructuring. Fourth in a series, this document builds on and extends the issues discussed in the National Governors' Association's (NGA) previous publications and reports on case studies of early restructuring efforts…

Phase Transitions: In the Brain, Socio-­Dramatic Play and Meaningful Early Learning

ERIC Educational Resources Information Center

Fromberg, Doris Pronin

2017-01-01

There are similar, non-linear complex dynamical systems that underlie the epigenetic development of young children. This paper discusses the confluence of research on brain functions; a body or research that informs the characteristics of young children's play and imagination; and the ways in which young children acquire fresh perceptions and…

Supporting and Developing Self-Regulatory Behaviours in Early Childhood in Young Children with High Levels of Impulsive Behaviour

ERIC Educational Resources Information Center

Dan, Aviva

2016-01-01

Deficits in self-regulatory skills underlie or contribute to a range of adverse developmental problems and disorders, including ADHD (Barkley, 1997), eating disorders (Attie & Brooks-Gunn, 1995) and risk -taking behaviour (Cantor & Sanderson 1998; Eisenberg et al., 2005). Self-regulation has been recognised as an important factor in aiding…

Remembering Kinds: New Evidence that Categories are Privileged in Children's Thinking

ERIC Educational Resources Information Center

Cimpian, Andrei; Erickson, Lucy C.

2012-01-01

What are the representations and learning mechanisms that underlie conceptual development? The present research provides evidence in favor of the claim that this process is guided by an early-emerging predisposition to think and learn about abstract kinds. Specifically, three studies (N=192) demonstrated that 4- to 7-year-old children have better…

Epidemiological transition of colorectal cancer in developing countries: Environmental factors, molecular pathways, and opportunities for prevention

PubMed Central

Bishehsari, Faraz; Mahdavinia, Mahboobeh; Vacca, Michele; Malekzadeh, Reza; Mariani-Costantini, Renato

2014-01-01

Colorectal cancer (CRC) is one of the leading causes of cancer and cancer-related mortality worldwide. The disease has been traditionally a major health problem in industrial countries, however the CRC rates are increasing in the developing countries that are undergoing economic growth. Several environmental risk factors, mainly changes in diet and life style, have been suggested to underlie the rise of CRC in these populations. Diet and lifestyle impinge on nuclear receptors, on the intestinal microbiota and on crucial molecular pathways that are implicated in intestinal carcinogenesis. In this respect, the epidemiological transition in several regions of the world offers a unique opportunity to better understand CRC carcinogenesis by studying the disease phenotypes and their environmental and molecular associations in different populations. The data from these studies may have important implications for the global prevention and treatment of CRC. PMID:24876728

Improving outcomes from breast cancer in a low-income country: lessons from bangladesh.

PubMed

Story, H L; Love, R R; Salim, R; Roberto, A J; Krieger, J L; Ginsburg, O M

2012-01-01

Women in low- and middle-income countries (LMICs) have yet to benefit from recent advances in breast cancer diagnosis and treatment now experienced in high-income countries. Their unique sociocultural and health system circumstances warrant a different approach to breast cancer management than that applied to women in high-income countries. Here, we present experience from the last five years working in rural Bangladesh. Case and consecutive series data, focus group and individual interviews, and clinical care experience provide the basis for this paper. These data illustrate a complex web of sociocultural, economic, and health system conditions which affect womens' choices to seek and accept care and successful treatment. We conclude that health system, human rights, and governance issues underlie high mortality from this relatively rare disease in Bangladesh.

Profound Tissue Specificity in Proliferation Control Underlies Cancer Drivers and Aneuploidy Patterns.

PubMed

Sack, Laura Magill; Davoli, Teresa; Li, Mamie Z; Li, Yuyang; Xu, Qikai; Naxerova, Kamila; Wooten, Eric C; Bernardi, Ronald J; Martin, Timothy D; Chen, Ting; Leng, Yumei; Liang, Anthony C; Scorsone, Kathleen A; Westbrook, Thomas F; Wong, Kwok-Kin; Elledge, Stephen J

2018-04-05

Genomics has provided a detailed structural description of the cancer genome. Identifying oncogenic drivers that work primarily through dosage changes is a current challenge. Unrestrained proliferation is a critical hallmark of cancer. We constructed modular, barcoded libraries of human open reading frames (ORFs) and performed screens for proliferation regulators in multiple cell types. Approximately 10% of genes regulate proliferation, with most performing in an unexpectedly highly tissue-specific manner. Proliferation drivers in a given cell type showed specific enrichment in somatic copy number changes (SCNAs) from cognate tumors and helped predict aneuploidy patterns in those tumors, implying that tissue-type-specific genetic network architectures underlie SCNA and driver selection in different cancers. In vivo screening confirmed these results. We report a substantial contribution to the catalog of SCNA-associated cancer drivers, identifying 147 amplified and 107 deleted genes as potential drivers, and derive insights about the genetic network architecture of aneuploidy in tumors. Copyright © 2018 Elsevier Inc. All rights reserved.

Myosin Heads Are Displaced from Actin Filaments in the In Situ Beating Rat Heart in Early Diabetes

PubMed Central

Jenkins, Mathew J.; Pearson, James T.; Schwenke, Daryl O.; Edgley, Amanda J.; Sonobe, Takashi; Fujii, Yutaka; Ishibashi-Ueda, Hatsue; Kelly, Darren J.; Yagi, Naoto; Shirai, Mikiyasu

2013-01-01

Diabetes is independently associated with a specific cardiomyopathy, characterized by impaired cardiac muscle relaxation and force development. Using synchrotron radiation small-angle x-ray scattering, this study investigated in the in situ heart and in real-time whether changes in cross-bridge disposition and myosin interfilament spacing underlie the early development of diabetic cardiomyopathy. Experiments were conducted using anesthetized Sprague-Dawley rats 3 weeks after treatment with either vehicle (control) or streptozotocin (diabetic). Diffraction patterns were recorded during baseline and dobutamine infusions simultaneous with ventricular pressure-volumetry. From these diffraction patterns myosin mass transfer to actin filaments was assessed as the change in intensity ratio (I1,0/I1,1). In diabetic hearts cross-bridge disposition was most notably abnormal in the diastolic phase (p < 0.05) and to a lesser extent the systolic phase (p < 0.05). In diabetic rats only, there was a transmural gradient of contractile depression. Elevated diabetic end-diastolic intensity ratios were correlated with the suppression of diastolic function (p < 0.05). Furthermore, the expected increase in myosin head transfer by dobutamine was significantly blunted in diabetic animals (p < 0.05). Interfilament spacing did not differ between groups. We reveal that impaired cross-bridge disposition and radial transfer may thus underlie the early decline in ventricular function observed in diabetic cardiomyopathy. PMID:23473489

Downregulation of PI3-K/Akt/PTEN pathway and activation of mitochondrial intrinsic apoptosis by Diclofenac and Curcumin in colon cancer.

PubMed

Rana, Chandan; Piplani, Honit; Vaish, Vivek; Nehru, Bimla; Sanyal, S N

2015-04-01

Phosphatidylinositol 3-kinase (PI3-K)/PTEN/Akt signaling is over activated in various tumors including colon cancer. Activation of this pathway regulates multiple biological processes such as apoptosis, metabolism, cell proliferation, and cell growth that underlie the biology of a cancer cell. In the present study, the chemopreventive effects have been observed of Diclofenac, a preferential COX-2 inhibitory non-steroidal anti-inflammatory drugs, and Curcumin, a natural anti-inflammatory agent, in the early stage of colorectal carcinogenesis induced by 1,2-dimethylhydrazine dihydrochloride in rats. The tumor-promoting role of PI3-K/Akt/PTEN signal transduction pathway and its association with anti-apoptotic family of proteins are also observed. Both Diclofenac and Curcumin downregulated the PI3-K and Akt expression while promoting the apoptotic mechanism. Diclofenac and Curcumin administration significantly increased the expression of pro-apoptotic Bcl-2 family members (Bad and Bax) while decreasing the anti-apoptotic Bcl-2 protein. An up-regulation of cysteine protease family apoptosis executioner, such as caspase-3 and -9, is seen. Diclofenac and Curcumin inhibited the Bcl-2 protein by directly interacting at the active site by multiple hydrogen bonding, as also evident by negative glide score of Bcl-2. These drugs stimulated apoptosis by increasing reactive oxygen species (ROS) generation and simultaneously decreasing the mitochondrial membrane potential (ΔΨ M). Diclofenac and Curcumin showed anti-neoplastic effects by downregulating PI3-K/Akt/PTEN pathway, inducing apoptosis, increasing ROS generation, and decreasing ΔΨ M. The anti-neoplastic and apoptotic effects were found enhanced when both Diclofenac and Curcumin were administered together, rather than individually.

Medical conditions associated with the use of CT in children and young adults, Great Britain, 1995–2008

PubMed Central

McHugh, Kieran; Harbron, Richard W; Pearce, Mark S; Berrington De Gonzalez, Amy

2016-01-01

Objective: To describe the medical conditions associated with the use of CT in children or young adults with no previous cancer diagnosis. Methods: Radiologist reports for scans performed in 1995–2008 in non-cancer patients less than 22 years of age were collected from the radiology information system in 44 hospitals of Great Britain. By semantic search, an automated procedure identified 185 medical conditions within the radiologist reports. Manual validation of a subsample by a paediatric radiologist showed a satisfactory performance of the automatic coding procedure. Results: Medical information was extracted for 37,807 scans; 19.5% scans were performed in children less than 5 years old; 52.0% scans were performed in 2000 or after. Trauma, diseases of the nervous (mainly hydrocephalus) or the circulatory system were each mentioned in 25–30% of scans. Hydrocephalus was mentioned in 19% of all scans, 59% of scans repeated ≥5 times in a year, and was the most frequent condition in children less than 5 years of age. Congenital diseases/malformations, disorders of the musculoskeletal system/connective tissues and infectious or respiratory diseases were each mentioned in 5–10% of scans. Suspicionor diagnosis of benign or malignant tumour was identified in 5% of scans. Conclusion: This study describes the medical conditions that likely underlie the use of CT in children in Great Britain. It shows that patients with hydrocephalus may receive high cumulative radiation exposures from CT in early life, i.e. at ages when they are most sensitive to radiation. Advances in knowledge: The majority of scans were unrelated to cancer suspicion. Repeated scans over time were mainly associated with the management of hydrocephalus. PMID:27767331

Medical conditions associated with the use of CT in children and young adults, Great Britain, 1995-2008.

PubMed

Journy, Neige M; McHugh, Kieran; Harbron, Richard W; Pearce, Mark S; Berrington De Gonzalez, Amy

2016-12-01

To describe the medical conditions associated with the use of CT in children or young adults with no previous cancer diagnosis. Radiologist reports for scans performed in 1995-2008 in non-cancer patients less than 22 years of age were collected from the radiology information system in 44 hospitals of Great Britain. By semantic search, an automated procedure identified 185 medical conditions within the radiologist reports. Manual validation of a subsample by a paediatric radiologist showed a satisfactory performance of the automatic coding procedure. Medical information was extracted for 37,807 scans; 19.5% scans were performed in children less than 5 years old; 52.0% scans were performed in 2000 or after. Trauma, diseases of the nervous (mainly hydrocephalus) or the circulatory system were each mentioned in 25-30% of scans. Hydrocephalus was mentioned in 19% of all scans, 59% of scans repeated ≥5 times in a year, and was the most frequent condition in children less than 5 years of age. Congenital diseases/malformations, disorders of the musculoskeletal system/connective tissues and infectious or respiratory diseases were each mentioned in 5-10% of scans. Suspicionor diagnosis of benign or malignant tumour was identified in 5% of scans. This study describes the medical conditions that likely underlie the use of CT in children in Great Britain. It shows that patients with hydrocephalus may receive high cumulative radiation exposures from CT in early life, i.e. at ages when they are most sensitive to radiation. Advances in knowledge: The majority of scans were unrelated to cancer suspicion. Repeated scans over time were mainly associated with the management of hydrocephalus.

How Does Your Garden Grow? Early Conceptualization of Seeds and Their Place in the Plant Growth Cycle.

ERIC Educational Resources Information Center

Hickling, Anne K.; Gelman, Susan A.

1995-01-01

Examined young children's understanding of seed origins and growth preconditions and the stages of plant growth. Found that, by 4.5 years, children realized that natural causal mechanisms underlie plant growth and appreciated the relationship of seeds to plants. Results suggest that preschoolers hold theory-like understandings of plants similar to…

Understanding Perceived Benefit of Early Cancer Detection: Community-Partnered Research with African American Women in South Los Angeles.

PubMed

Bazargan, Mohsen; Lucas-Wright, Anna; Jones, Loretta; Vargas, Roberto; Vadgama, Jaydutt V; Evers-Manly, Shirley; Maxwell, Annette E

2015-09-01

African American women have lower 5-year cancer survival rates than non-Latino White women. Differences in perceived benefits of early cancer detection among racial/ethnic groups may affect cancer-screening behaviors. This study assessed correlates of perceived benefits of early breast, cervical and colorectal cancer detection among 513 African American women. Using a community-partnered participatory research approach, we conducted a survey on cancer screening, risk behaviors, and related knowledge and attitudes among African American parishioners at 11 churches in South Los Angeles, a neighborhood that experiences one of the highest cancer mortality rates in California. African American women who participated in this study were more likely to believe that chances for survival are very good or good after early detection of breast cancer (74%) than after early detection of colorectal (51%) and cervical cancer (52%). Multivariate analyses show that perceived benefit of early cancer detection is associated with higher cancer knowledge and having discussed one's cancer risk with a doctor. Given that 5-year survival rates for early stage breast, cervical, and colorectal cancer range from 84% to 93%, our data suggest that a substantial proportion of African American women in South Los Angeles are not aware of the benefits of early detection, particularly of colorectal and cervical cancers. Programs that increase cancer knowledge and encourage a discussion of individual's cancer risk with a doctor may be able to increase perceived benefit of early detection, a construct that has been shown to be associated with cancer screening in some studies.

A construct divided: prosocial behavior as helping, sharing, and comforting subtypes.

PubMed

Dunfield, Kristen A

2014-01-01

The development and maintenance of prosocial, other-oriented behaviors has been of considerable recent interest. Though it is clear that prosocial behaviors emerge early and play a uniquely important role in the social lives of humans, there is less consensus regarding the mechanisms that underlie and maintain these fundamental acts. The goal of this paper is to clarify inconsistencies in our understanding of the early emergence and development of prosocial behavior by proposing a taxonomy of prosocial behavior anchored in the social-cognitive constraints that underlie the ability to act on behalf of others. I will argue that within the general domain of prosocial behavior, other-oriented actions can be categorized into three distinct types (helping, sharing, and comforting) that reflect responses to three distinct negative states (instrumental need, unmet material desire, and emotional distress). In support of this proposal, I will demonstrate that the three varieties of prosocial behavior show unique ages of onset, uncorrelated patterns of production, and distinct patterns of individual differences. Importantly, by differentiating specific varieties of prosocial behavior within the general category, we can begin to explain inconsistencies in the past literature and provide a framework for directing future research into the ontogenetic origins of these essential social behaviors.

Current role of minimally invasive approaches in the treatment of early gastric cancer

PubMed Central

El-Sedfy, Abraham; Brar, Savtaj S; Coburn, Natalie G

2014-01-01

Despite declining incidence, gastric cancer remains one of the most common cancers worldwide. Early detection in population-based screening programs has increased the number of cases of early gastric cancer, representing approximately 50% of newly detected gastric cancer cases in Asian countries. Endoscopic mucosal resection and endoscopic submucosal dissection have become the preferred therapeutic techniques in Japan and Korea for the treatment of early gastric cancer patients with a very low risk of lymph node metastasis. Laparoscopic and robotic resections for early gastric cancer, including function-preserving resections, have propagated through advances in technology and surgeon experience. The aim of this paper is to discuss the recent advances in minimally invasive approaches in the treatment of early gastric cancer. PMID:24833843

Noncoding somatic and inherited single-nucleotide variants converge to promote ESR1 expression in breast cancer

PubMed Central

Bailey, Swneke D.; Desai, Kinjal; Kron, Ken J.; Mazrooei, Parisa; Sinnott-Armstrong, Nicholas A.; Treloar, Aislinn E.; Dowar, Mark; Thu, Kelsie L.; Cescon, David W.; Silvester, Jennifer; Yang, S. Y. Cindy; Wu, Xue; Pezo, Rossanna C.; Haibe-Kains, Benjamin; Mak, Tak W.; Bedard, Philippe L.; Pugh, Trevor J.; Sallari, Richard C.; Lupien, Mathieu

2016-01-01

Sustained expression of the oestrogen receptor alpha (ESR1) drives two-thirds of breast cancer and defines the ESR1-positive subtype. ESR1 engages enhancers upon oestrogen stimulation to establish an oncogenic expression program1. Somatic copy number alterations involving the ESR1 gene occur in approximately 1% of ESR1-positive breast cancers2–5, implying that other mechanisms underlie the persistent expression of ESR1. We report the significant enrichment of somatic mutations within the set of regulatory elements (SRE) regulating ESR1 in 7% of ESR1-positive breast cancers. These mutations regulate ESR1 expression by modulating transcription factor binding to the DNA. The SRE includes a recurrently mutated enhancer whose activity is also affected by a functional inherited single nucleotide variant (SNV) rs9383590 that accounts for several breast cancer risk-loci. Our work highlights the importance of considering the combinatorial activity of regulatory elements as a single unit to delineate the impact of noncoding genetic alterations on single genes in cancer. PMID:27571262

Paclitaxel sensitivity in relation to ABCB1 expression, efflux and single nucleotide polymorphisms in ovarian cancer.

PubMed

Gao, Bo; Russell, Amanda; Beesley, Jonathan; Chen, Xiao Qing; Healey, Sue; Henderson, Michelle; Wong, Mark; Emmanuel, Catherine; Galletta, Laura; Johnatty, Sharon E; Bowtell, David; Haber, Michelle; Norris, Murray; Harnett, Paul; Chenevix-Trench, Georgia; Balleine, Rosemary L; deFazio, Anna

2014-05-09

ABCB1 (adenosine triphosphate-binding cassette transporter B1) mediates cellular elimination of many chemotherapeutic agents including paclitaxel, which is commonly used to treat ovarian cancer. A significant association between common single nucleotide polymorphisms (SNPs) in ABCB1 and progression-free survival has been reported in patients with ovarian cancer. Variable paclitaxel clearance due to genotype specific differences in ABCB1 activity in cancer cells and/or normal tissues may underlie the association. Using cell-based models, we evaluated the correlations between ABCB1 expression, polymorphisms, transporter activity and paclitaxel sensitivity in ovarian cancer (n = 10) and lymphoblastoid (n = 19) cell lines. Close associations between ABCB1 expression, transporter function and paclitaxel sensitivity were found in lymphoblastoid cell lines, although we could not demonstrate an association with common SNPs. In ovarian cancer cell lines, ABCB1 expression was low and the association between expression and function was lost. These results suggest that ABCB1 related survival difference in ovarian cancer patients is more likely to be due to differential whole body paclitaxel clearance mediated by normal cells rather than a direct effect on cancer cells.

Translational Control in Cancer Etiology

PubMed Central

Ruggero, Davide

2013-01-01

The link between perturbations in translational control and cancer etiology is becoming a primary focus in cancer research. It has now been established that genetic alterations in several components of the translational apparatus underlie spontaneous cancers as well as an entire class of inherited syndromes known as “ribosomopathies” associated with increased cancer susceptibility. These discoveries have illuminated the importance of deregulations in translational control to very specific cellular processes that contribute to cancer etiology. In addition, a growing body of evidence supports the view that deregulation of translational control is a common mechanism by which diverse oncogenic pathways promote cellular transformation and tumor development. Indeed, activation of these key oncogenic pathways induces rapid and dramatic translational reprogramming both by increasing overall protein synthesis and by modulating specific mRNA networks. These translational changes promote cellular transformation, impacting almost every phase of tumor development. This paradigm represents a new frontier in the multihit model of cancer formation and offers significant promise for innovative cancer therapies. Current research, in conjunction with cutting edge technologies, will further enable us to explore novel mechanisms of translational control, functionally identify translationally controlled mRNA groups, and unravel their impact on cellular transformation and tumorigenesis. PMID:22767671

Chronic restraint stress during early Theiler’s virus infection exacerbates the subsequent demyelinating disease in SJL mice: II. CNS disease severity

PubMed Central

Young, Erin E.; Sieve, Amy N.; Vichaya, Elisabeth G.; Carcoba, Luis M.; Young, Colin R.; Ambrus, Andrew; Storts, Ralph; Welsh, C. Jane R.; Meagher, Mary W.

2010-01-01

Theiler’s murine encephalomyelitis virus (TMEV) infection is a well-characterized model of multiple sclerosis (MS). Previous research has shown that chronic restraint stress (RS) during early TMEV infection exacerbates behavioral signs of disease. The present data suggest RS-induced increases in CNS inflammation, demyelination, and axonal degeneration may underlie this exacerbation. In addition, we report that males exhibit greater CNS inflammation and higher numbers of demyelinating lesions while females show greater susceptibility to RS-induced exacerbation. These findings indicate RS during early TMEV infection increases CNS lesion formation during the late phase and suggest the effects of RS are sex-dependent. PMID:20167380

Improving Outcomes from Breast Cancer in a Low-Income Country: Lessons from Bangladesh

PubMed Central

Story, H. L.; Love, R. R.; Salim, R.; Roberto, A. J.; Krieger, J. L.; Ginsburg, O. M.

2012-01-01

Women in low- and middle-income countries (LMICs) have yet to benefit from recent advances in breast cancer diagnosis and treatment now experienced in high-income countries. Their unique sociocultural and health system circumstances warrant a different approach to breast cancer management than that applied to women in high-income countries. Here, we present experience from the last five years working in rural Bangladesh. Case and consecutive series data, focus group and individual interviews, and clinical care experience provide the basis for this paper. These data illustrate a complex web of sociocultural, economic, and health system conditions which affect womens' choices to seek and accept care and successful treatment. We conclude that health system, human rights, and governance issues underlie high mortality from this relatively rare disease in Bangladesh. PMID:22295245

Radiation-induced genomic instability and its implications for radiation carcinogenesis

NASA Technical Reports Server (NTRS)

Huang, Lei; Snyder, Andrew R.; Morgan, William F.

2003-01-01

Radiation-induced genomic instability is characterized by an increased rate of genetic alterations including cytogenetic rearrangements, mutations, gene amplifications, transformation and cell death in the progeny of irradiated cells multiple generations after the initial insult. Chromosomal rearrangements are the best-characterized end point of radiation-induced genomic instability, and many of the rearrangements described are similar to those found in human cancers. Chromosome breakage syndromes are defined by chromosome instability, and individuals with these diseases are cancer prone. Consequently, chromosomal instability as a phenotype may underlie some fraction of those changes leading to cancer. Here we attempt to relate current knowledge regarding radiation-induced chromosome instability with the emerging molecular information on the chromosome breakage syndromes. The goal is to understand how genetic and epigenetic factors might influence the onset of chromosome instability and the role of chromosomal instability in carcinogenesis.

Early prostate cancer antigen expression in predicting presence of prostate cancer in men with histologically negative biopsies.

PubMed

Hansel, D E; DeMarzo, A M; Platz, E A; Jadallah, S; Hicks, J; Epstein, J I; Partin, A W; Netto, G J

2007-05-01

Early prostate cancer antigen is a nuclear matrix protein that was recently shown to be expressed in prostate adenocarcinoma and adjacent benign tissue. Previous studies have demonstrated early prostate cancer antigen expression in benign prostate tissue up to 5 years before a diagnosis of prostate carcinoma, suggesting that early prostate cancer antigen could be used as a potential predictive marker. We evaluated early prostate cancer antigen expression by immunohistochemistry using a polyclonal antibody (Onconome Inc., Seattle, Washington) on benign biopsies from 98 patients. Biopsies were obtained from 4 groups that included 39 patients with first time negative biopsy (group 1), 24 patients with persistently negative biopsies (group 2), 8 patients with initially negative biopsies who were subsequently diagnosed with prostate carcinoma (group 3) and negative biopsies obtained from 27 cases where other concurrent biopsies contained prostate carcinoma (group 4). Early prostate cancer antigen staining was assessed by 2 of the authors who were blind to the group of the examined sections. Staining intensity (range 0 to 3) and extent (range 1 to 3) scores were assigned. The presence of intensity 3 staining in any of the blocks of a biopsy specimen was considered as positive for early prostate cancer antigen for the primary outcome in the statistical analysis. In addition, as secondary outcomes we evaluated the data using the proportion of blocks with intensity 3 early prostate cancer antigen staining, the mean of the product of staining intensity and staining extent of all blocks within a biopsy, and the mean of the product of intensity 3 staining and extent. Primary outcome analysis revealed the proportion of early prostate cancer antigen positivity to be highest in group 3 (6 of 8, 75%) and lowest in group 2 (7 of 24, 29%, p=0.04 for differences among groups). A relatively higher than expected proportion of early prostate cancer antigen positivity was present in group 1 (23 of 39, 59%). Early prostate cancer antigen was negative in 41% of group 4 who were known to harbor prostate carcinoma. The proportion of early prostate cancer antigen positivity was statistically significantly lower in group 2 than in each of the other groups when compared pairwise. A lower proportion of early prostate cancer antigen positivity was encountered in older archival tissue blocks (p<0.0001) pointing to a potential confounding factor. Corrected for block age, group 3 was the only group to remain statistically significantly different in early prostate cancer antigen positivity compared to the reference group 2. Similar findings were obtained when adjustments for patient age were made and when analysis was based on secondary outcome measurements. Our study showed a higher proportion of early prostate cancer antigen expression in initial negative prostate biopsy of patients who were diagnosed with prostate carcinoma on subsequent followup biopsies. We found a relatively high proportion of early prostate cancer antigen positivity (59%) in the group with first time negative biopsies and a potential 41% rate of false-negative early prostate cancer antigen staining in benign biopsies from cases with documented prostate carcinoma on concurrent cores. The lower early prostate cancer antigen positivity in cases with older blocks raises the question of a confounding effect of block age. Additional studies on the antigenic properties of early prostate cancer antigen in archival material are required to further delineate the usefulness of early prostate cancer antigen immunostaining on biopsy material.

The Effect of Context on Training: Is Learning Situated?

DTIC Science & Technology

1994-09-13

not underlie the central processes of ordinary everyday cognition ? We think not." There are numerous examples where abstract instruction has been shown... instruction , concrete examples, and abstract rules and procedures. Claims made by proponents of Situated Learning Theory suggest that training must be... instruction . This argues against apprenticeship learning during early stages of acquisition for many skills. Further, too much fidelity in simulation may

Distinct Single but Not Necessarily Repeated Tetanization Is Required to Induce Hippocampal Late-LTP in the Rat CA1

ERIC Educational Resources Information Center

Sajikumar, Sreedharan; Navakkode, Sheeja; Frey, Julietta U.

2008-01-01

The protein synthesis-dependent form of hippocampal long-term potentiation (late-LTP) is thought to underlie memory. Its induction requires a distinct stimulation strength, and the common opinion is that only repeated tetani result in late-LTP whereas as single tetanus only reveals a transient early-LTP. Properties of LTP induction were compared…

The Effect of Shyness on Children's Formation and Retention of Novel Word-Object Mappings

ERIC Educational Resources Information Center

Hilton, Matt; Westermann, Gert

2017-01-01

This study set out to examine whether shyness, an aversion to novelty and unfamiliar social situations, can affect the processes that underlie early word learning. Twenty-four-month-old children (n = 32 ) were presented with sets of one novel and two familiar objects, and it was found that shyer children were less likely to select a novel object…

Sexual dysfunction and male infertility.

PubMed

Lotti, Francesco; Maggi, Mario

2018-05-01

Infertility affects up to 12% of all men, and sexual dysfunction occurs frequently in men of reproductive age, causing infertility in some instances. In infertile men, hypoactive sexual desire and lack of sexual satisfaction are the most prevalent types of sexual dysfunction, ranging from 8.9% to 68.7%. Erectile dysfunction and/or premature ejaculation, evaluated with validated tools, have a prevalence of one in six infertile men, and orgasmic dysfunction has a prevalence of one in ten infertile men. In addition, infertile men can experience a heavy psychological burden. Infertility and its associated psychological concerns can underlie sexual dysfunction. Furthermore, general health perturbations can lead to male infertility and/or sexual dysfunction. Erectile dysfunction and male infertility are considered proxies for general health, the former underlying cardiovascular disorders and the latter cancerous and noncancerous conditions. The concept that erectile dysfunction in infertile men might be an early marker of poor general health is emerging. Finally, medications used for general health problems can cause sperm abnormalities and sexual dysfunction. The treatment of some causes of male infertility might improve semen quality and reverse infertility-related sexual dysfunction. In infertile men, an investigation of sexual, general, and psychological health status is advisable to improve reproductive problems and general health.

Transgenerational neuroendocrine disruption of reproduction

PubMed Central

Walker, Deena M.; Gore, Andrea C.

2014-01-01

Exposure to endocrine disrupting chemicals (EDCs) is associated with dysfunctions of metabolism, energy balance, thyroid function and reproduction, and an increased risk of endocrine cancers. These multifactorial disorders can be ‘programmed’ through molecular epigenetic changes induced by exposure to EDCs early in life, the expression of which may not manifest until adulthood. In some cases, EDCs have detrimental effects on subsequent generations, which indicates that traits for disease predisposition may be passed to future generations by nongenomic inheritance. This Review discusses current understanding of the epigenetic mechanisms that underlie sexual differentiation of reproductive neuroendocrine systems in mammals and summarizes the literature on transgenerational epigenetic effects of representative EDCs: vinclozolin, diethylstilbesterol, bisphenol A and polychlorinated biphenyls. The article differentiates between context-dependent epigenetic transgenerational changes—namely, those that require environmental exposure, either via the EDC itself or through behavioral or physiological differences in parents—and germline-dependent epigenetic mechanisms. These processes, albeit discrete, are not mutually exclusive and can involve similar molecular mechanisms including DNA methylation and histone modifications and may predispose exposed individuals to transgenerational disruption of reproductive processes. New insights stress the crucial need to develop a clear understanding of how EDCs may program the epigenome of exposed individuals and their descendants. PMID:21263448

A new rapid methodological strategy to assess BRCA mutational status.

PubMed

Vuttariello, Emilia; Borra, Marco; Calise, Celeste; Mauriello, Elvira; Greggi, Stefano; Vecchione, Aldo; Biffali, Elio; Chiappetta, Gennaro

2013-07-01

Hereditary cancers account for approximately 10 % of breast and ovarian cancers. Mutations of the BRCA1 and BRCA2 genes, encoding two proteins involved in DNA repair, underlie most cases of such hereditary cancers. Women with BRCA mutations develop breast cancer in 50-80 % of cases and ovarian cancer in 10-40 % of cases. Assessing BRCA mutational status is needed to direct the clinical management of women with predisposition to these hereditary cancers. However, BRCA screening constitutes a bottleneck in terms of costs and time to deliver results. We developed a PCR-based assay using 73 primer pairs covering the entire coding regions of BRCA1 and BRCA2. PCR primers, containing at the 5' end the universal M13 primer sequences, were pre-spotted in 96-well plates. Following PCR, direct sequencing was performed using M13 primers, allowing to standardize the conditions. PCR amplification and sequencing were successful for each amplicon. We tested and validated the assay on 10 known gDNAs from patients with Hereditary breast and ovarian cancer (HBOC). Our strategy is a promising time and cost-effective method to detect BRCA mutations in the clinical setting, which is essential to formulate a personalized therapy for patients with HBOC.

Basal/HER2 breast carcinomas

PubMed Central

Martin-Castillo, Begoña; Oliveras-Ferraros, Cristina; Vazquez-Martin, Alejandro; Cufí, Silvia; Moreno, José Manuel; Corominas-Faja, Bruna; Urruticoechea, Ander; Martín, Ángel G.; López-Bonet, Eugeni; Menendez, Javier A.

2013-01-01

High rates of inherent primary resistance to the humanized monoclonal antibody trastuzumab (Herceptin) are frequent among HER2 gene-amplified breast carcinomas in both metastatic and adjuvant settings. The clinical efficacy of trastuzumab is highly correlated with its ability to specifically and efficiently target HER2-driven populations of breast cancer stem cells (CSCs). Intriguingly, many of the possible mechanisms by which cancer cells escape trastuzumab involve many of the same biomarkers that have been implicated in the biology of CS-like tumor-initiating cells. In the traditional, one-way hierarchy of CSCs in which all cancer cells descend from special self-renewing CSCs, HER2-positive CSCs can occur solely by self-renewal. Therefore, by targeting CSC self-renewal and resistance, trastuzumab is expected to induce tumor shrinkage and further reduce breast cancer recurrence rates when used alongside traditional therapies. In a new, alternate model, more differentiated non-stem cancer cells can revert to trastuzumab-refractory, CS-like cells via the activation of intrinsic or microenvironmental paths-to-stemness, such as the epithelial-to-mesenchymal transition (EMT). Alternatively, stochastic transitions of trastuzumab-responsive CSCs might also give rise to non-CSC cellular states that lack major attributes of CSCs and, therefore, can remain “hidden” from trastuzumab activity. Here, we hypothesize that a better understanding of the CSC/non-CSC social structure within HER2-overexpressing breast carcinomas is critical for trastuzumab-based treatment decisions in the clinic. First, we decipher the biological significance of CSC features and the EMT on the molecular effects and efficacy of trastuzumab in HER2-positive breast cancer cells. Second, we reinterpret the genetic heterogeneity that differentiates trastuzumab-responders from non-responders in terms of CSC cellular states. Finally, we propose that novel predictive approaches aimed at better forecasting early tumor responses to trastuzumab should identify biological determinants that causally underlie the intrinsic flexibility of HER2-positive CSCs to “enter” into or “exit” from trastuzumab-sensitive states. An accurate integration of CSC cellular states and EMT-related biomarkers with the currently available breast cancer molecular taxonomy may significantly improve our ability to make a priori decisions about whether patients belonging to HER2 subtypes differentially enriched with a “mesenchymal transition signature” (e.g., luminal/HER2 vs. basal/HER2) would distinctly benefit from trastuzumab-based therapy ab initio. PMID:23255137

Consensus guidelines for the detection of immunogenic cell death

PubMed Central

Kepp, Oliver; Senovilla, Laura; Vitale, Ilio; Vacchelli, Erika; Adjemian, Sandy; Agostinis, Patrizia; Apetoh, Lionel; Aranda, Fernando; Barnaba, Vincenzo; Bloy, Norma; Bracci, Laura; Breckpot, Karine; Brough, David; Buqué, Aitziber; Castro, Maria G.; Cirone, Mara; Colombo, Maria I.; Cremer, Isabelle; Demaria, Sandra; Dini, Luciana; Eliopoulos, Aristides G.; Faggioni, Alberto; Formenti, Silvia C.; Fučíková, Jitka; Gabriele, Lucia; Gaipl, Udo S.; Galon, Jérôme; Garg, Abhishek; Ghiringhelli, François; Giese, Nathalia A.; Guo, Zong Sheng; Hemminki, Akseli; Herrmann, Martin; Hodge, James W.; Holdenrieder, Stefan; Honeychurch, Jamie; Hu, Hong-Min; Huang, Xing; Illidge, Tim M.; Kono, Koji; Korbelik, Mladen; Krysko, Dmitri V.; Loi, Sherene; Lowenstein, Pedro R.; Lugli, Enrico; Ma, Yuting; Madeo, Frank; Manfredi, Angelo A.; Martins, Isabelle; Mavilio, Domenico; Menger, Laurie; Merendino, Nicolò; Michaud, Michael; Mignot, Gregoire; Mossman, Karen L.; Multhoff, Gabriele; Oehler, Rudolf; Palombo, Fabio; Panaretakis, Theocharis; Pol, Jonathan; Proietti, Enrico; Ricci, Jean-Ehrland; Riganti, Chiara; Rovere-Querini, Patrizia; Rubartelli, Anna; Sistigu, Antonella; Smyth, Mark J.; Sonnemann, Juergen; Spisek, Radek; Stagg, John; Sukkurwala, Abdul Qader; Tartour, Eric; Thorburn, Andrew; Thorne, Stephen H.; Vandenabeele, Peter; Velotti, Francesca; Workenhe, Samuel T.; Yang, Haining; Zong, Wei-Xing; Zitvogel, Laurence; Kroemer, Guido; Galluzzi, Lorenzo

2014-01-01

Apoptotic cells have long been considered as intrinsically tolerogenic or unable to elicit immune responses specific for dead cell-associated antigens. However, multiple stimuli can trigger a functionally peculiar type of apoptotic demise that does not go unnoticed by the adaptive arm of the immune system, which we named “immunogenic cell death” (ICD). ICD is preceded or accompanied by the emission of a series of immunostimulatory damage-associated molecular patterns (DAMPs) in a precise spatiotemporal configuration. Several anticancer agents that have been successfully employed in the clinic for decades, including various chemotherapeutics and radiotherapy, can elicit ICD. Moreover, defects in the components that underlie the capacity of the immune system to perceive cell death as immunogenic negatively influence disease outcome among cancer patients treated with ICD inducers. Thus, ICD has profound clinical and therapeutic implications. Unfortunately, the gold-standard approach to detect ICD relies on vaccination experiments involving immunocompetent murine models and syngeneic cancer cells, an approach that is incompatible with large screening campaigns. Here, we outline strategies conceived to detect surrogate markers of ICD in vitro and to screen large chemical libraries for putative ICD inducers, based on a high-content, high-throughput platform that we recently developed. Such a platform allows for the detection of multiple DAMPs, like cell surface-exposed calreticulin, extracellular ATP and high mobility group box 1 (HMGB1), and/or the processes that underlie their emission, such as endoplasmic reticulum stress, autophagy and necrotic plasma membrane permeabilization. We surmise that this technology will facilitate the development of next-generation anticancer regimens, which kill malignant cells and simultaneously convert them into a cancer-specific therapeutic vaccine. PMID:25941621

Colorectal cancer, screening and primary care: A mini literature review.

PubMed

Hadjipetrou, Athanasios; Anyfantakis, Dimitrios; Galanakis, Christos G; Kastanakis, Miltiades; Kastanakis, Serafim

2017-09-07

Colorectal cancer (CRC) is a common health problem, representing the third most commonly diagnosed cancer worldwide and causing a significant burden in terms of morbidity and mortality, with annual deaths estimated at 700000. The western way of life, that is being rapidly adopted in many regions of the world, is a well discussed risk factor for CRC and could be targeted in terms of primary prevention. Furthermore, the relatively slow development of this cancer permits drastic reduction of incidence and mortality through secondary prevention. These facts underlie primary care physicians (PCPs) being assigned a key role in health strategies that enhance prevention and prompt diagnosis. Herein, we review the main topics of CRC in the current literature, in order to better understand its pathogenesis, risk and protective factors, as well as screening techniques. Furthermore, we discuss preventive and screening policies to combat CRC and the crucial role served by PCPs in their successful implementation. Relevant articles were identified through electronic searches of MEDLINE and through manual searches of reference lists.

Circulating and intraprostatic sex steroid hormonal profiles in relation to male pattern baldness and chest hair density among men diagnosed with localized prostate cancers.

PubMed

Zhou, Cindy Ke; Stanczyk, Frank Z; Hafi, Muhannad; Veneroso, Carmela C; Lynch, Barlow; Falk, Roni T; Niwa, Shelley; Emanuel, Eric; Gao, Yu-Tang; Hemstreet, George P; Zolfghari, Ladan; Carroll, Peter R; Manyak, Michael J; Sesterhenn, Isabell A; Levine, Paul H; Hsing, Ann W; Cook, Michael B

2017-12-01

Prospective cohort studies of circulating sex steroid hormones and prostate cancer risk have not provided a consistent association, despite evidence from animal and clinical studies. However, studies using male pattern baldness as a proxy of early-life or cumulative androgen exposure have reported significant associations with aggressive and fatal prostate cancer risk. Given that androgens underlie the development of patterned hair loss and chest hair, we assessed whether these two dermatological characteristics were associated with circulating and intraprostatic concentrations of sex steroid hormones among men diagnosed with localized prostate cancer. We included 248 prostate cancer patients from the NCI Prostate Tissue Study, who answered surveys and provided a pre-treatment blood sample as well as fresh frozen adjacent normal prostate tissue. Male pattern baldness and chest hair density were assessed by trained nurses before surgery. General linear models estimated geometric means and 95% confidence intervals (95%CIs) of each hormone variable by dermatological phenotype with adjustment for potential confounding variables. Subgroup analyses were performed by Gleason score (<7 vs ≥7) and race (European American vs. African American). We found strong positive associations of balding status with serum testosterone, dihydrotestosterone (DHT), estradiol, and sex hormone-binding globulin (SHBG), and a weak association with elevated intraprostatic testosterone. Conversely, neither circulating nor intraprostatic sex hormones were statistically significantly associated with chest hair density. Age-adjusted correlation between binary balding status and three-level chest hair density was weak (r = 0.05). There was little evidence to suggest that Gleason score or race modified these associations. This study provides evidence that balding status assessed at a mean age of 60 years may serve as a clinical marker for circulating sex hormone concentrations. The weak-to-null associations between balding status and intraprostatic sex hormones reaffirm differences in organ-specific sex hormone metabolism, implying that other sex steroid hormone-related factors (eg, androgen receptor) play important roles in organ-specific androgenic actions, and that other overlapping pathways may be involved in associations between the two complex conditions. © 2017 Wiley Periodicals, Inc.

Adult age differences in subjective and objective measures of strategy use on a sequentially cued prediction task

PubMed Central

Seaman, Kendra L.; Howard, Darlene V.; Howard, James H.

2015-01-01

Differences in strategy use are thought to underlie age-related performance deficits on many learning and decision-making tasks. Recently, age-related differences in learning to make predictions were reported on the Triplets Prediction Task (TPT; Seaman, Howard & Howard, 2013). Notably, deficits appeared early in training and continued with experience. To assess if age differences were due to early strategy use, neural networks were used to objectively assess the strategies implemented by participants during Session 1. Then the relationship between these strategies and performance was examined. Results revealed that older adults were more likely to implement a disadvantageous strategy early in learning, and this led to poorer task performance. Importantly the relationship between age and task performance was partially mediated by early strategy use, suggesting that early strategy selection played a role in the lower quality of predictions in older adults. PMID:24673615

Molecular insights into cancer therapeutic effects of the dietary medicinal phytochemical withaferin A.

PubMed

Chirumamilla, Chandra Sekhar; Pérez-Novo, Claudina; Van Ostade, Xaveer; Vanden Berghe, Wim

2017-05-01

Despite the worldwide research efforts to combat cancer, it remains a leading cause of death. Although various specific kinase inhibitors already have been approved for clinical cancer treatment, occurrence of intrinsic or acquired resistance and intermittent response over longer periods limits long-term success of single kinase-targeted therapies. In this respect, there is a renewed interest in polypharmaceutical natural compounds, which simultaneously target various hyperactivated kinases involved in tumour-inflammation, angiogenesis, cell survival, proliferation, metastasis and angiogenesis. The dietary medicinal phytochemical withaferin A (WA), isolated from Withaferin somnifera (popular Indian name Ashwagandha), holds promise as a novel anti-cancer agent, which targets multiple cell survival kinase pathways, including IκB kinase/NF-κB, PI3 kinase/protein kinase B/mammalian target of rapamycin and mitogen-activated protein kinase/extracellular signal-regulated kinase amongst others. In this review, we propose a novel mechanism of WA-dependent kinase inhibition via electrophilic covalent targeting of cysteine residues in conserved kinase activation domains (kinase cysteinome), which could underlie its pleiotropic therapeutic effects in cancer signalling.

Global Epigenetic Changes May Underlie Ethnic Differences and susceptibility to Prostate Cancer

DTIC Science & Technology

2012-09-01

tissues; in the prostate, hypermethylation of the GSTP1 CpG has been detected in PIA lesions [8]. DNA methylation occurs at CpG sites in the human...that the GSTP1 CpG island was frequently hypermethylated in PCa, more than 40 genes have been reported to be targets of DNA hypermethylation-associated...One study demonstrated that GSTP1 hypermethylation was significantly higher in PCa samples from AA men in comparison with EA and Asians [12]. Another

Food-derived bioactive peptides on inflammation and oxidative stress.

PubMed

Chakrabarti, Subhadeep; Jahandideh, Forough; Wu, Jianping

2014-01-01

Chronic diseases such as atherosclerosis and cancer are now the leading causes of morbidity and mortality worldwide. Inflammatory processes and oxidative stress underlie the pathogenesis of these pathological conditions. Bioactive peptides derived from food proteins have been evaluated for various beneficial effects, including anti-inflammatory and antioxidant properties. In this review, we summarize the roles of various food-derived bioactive peptides in inflammation and oxidative stress and discuss the potential benefits and limitations of using these compounds against the burden of chronic diseases.

Trans-Agency Early-Life Exposures and Cancer Working Group

Cancer.gov

The Trans-Agency Early-Life Exposures and Cancer Working Group promotes integration of early-life events and exposures into public health cancer research, control, prevention, and policy strategies to reduce the cancer burden in the United States and globally.

Bioinformatic approaches to augment study of epithelial-to-mesenchymal transition in lung cancer

PubMed Central

Beck, Tim N.; Chikwem, Adaeze J.; Solanki, Nehal R.

2014-01-01

Bioinformatic approaches are intended to provide systems level insight into the complex biological processes that underlie serious diseases such as cancer. In this review we describe current bioinformatic resources, and illustrate how they have been used to study a clinically important example: epithelial-to-mesenchymal transition (EMT) in lung cancer. Lung cancer is the leading cause of cancer-related deaths and is often diagnosed at advanced stages, leading to limited therapeutic success. While EMT is essential during development and wound healing, pathological reactivation of this program by cancer cells contributes to metastasis and drug resistance, both major causes of death from lung cancer. Challenges of studying EMT include its transient nature, its molecular and phenotypic heterogeneity, and the complicated networks of rewired signaling cascades. Given the biology of lung cancer and the role of EMT, it is critical to better align the two in order to advance the impact of precision oncology. This task relies heavily on the application of bioinformatic resources. Besides summarizing recent work in this area, we use four EMT-associated genes, TGF-β (TGFB1), NEDD9/HEF1, β-catenin (CTNNB1) and E-cadherin (CDH1), as exemplars to demonstrate the current capacities and limitations of probing bioinformatic resources to inform hypothesis-driven studies with therapeutic goals. PMID:25096367

A construct divided: prosocial behavior as helping, sharing, and comforting subtypes

PubMed Central

Dunfield, Kristen A.

2014-01-01

The development and maintenance of prosocial, other-oriented behaviors has been of considerable recent interest. Though it is clear that prosocial behaviors emerge early and play a uniquely important role in the social lives of humans, there is less consensus regarding the mechanisms that underlie and maintain these fundamental acts. The goal of this paper is to clarify inconsistencies in our understanding of the early emergence and development of prosocial behavior by proposing a taxonomy of prosocial behavior anchored in the social-cognitive constraints that underlie the ability to act on behalf of others. I will argue that within the general domain of prosocial behavior, other-oriented actions can be categorized into three distinct types (helping, sharing, and comforting) that reflect responses to three distinct negative states (instrumental need, unmet material desire, and emotional distress). In support of this proposal, I will demonstrate that the three varieties of prosocial behavior show unique ages of onset, uncorrelated patterns of production, and distinct patterns of individual differences. Importantly, by differentiating specific varieties of prosocial behavior within the general category, we can begin to explain inconsistencies in the past literature and provide a framework for directing future research into the ontogenetic origins of these essential social behaviors. PMID:25228893

Multiple Biomarker Panels for Early Detection of Breast Cancer in Peripheral Blood

PubMed Central

Zhang, Fan; Deng, Youping; Drabier, Renee

2013-01-01

Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers. PMID:24371830

Multiple biomarker panels for early detection of breast cancer in peripheral blood.

PubMed

Zhang, Fan; Deng, Youping; Drabier, Renee

2013-01-01

Detecting breast cancer at early stages can be challenging. Traditional mammography and tissue microarray that have been studied for early breast cancer detection and prediction have many drawbacks. Therefore, there is a need for more reliable diagnostic tools for early detection of breast cancer due to a number of factors and challenges. In the paper, we presented a five-marker panel approach based on SVM for early detection of breast cancer in peripheral blood and show how to use SVM to model the classification and prediction problem of early detection of breast cancer in peripheral blood. We found that the five-marker panel can improve the prediction performance (area under curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the top four five-marker panels are associated with signaling, steroid hormones, metabolism, immune system, and hemostasis, which are consistent with previous findings. Our prediction model can serve as a general model for multibiomarker panel discovery in early detection of other cancers.

Genomic analysis and selected molecular pathways in rare cancers

NASA Astrophysics Data System (ADS)

Liu, Stephen V.; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J.; Eng, Cathy; Ramanathan, Ramesh K.; Von Hoff, Daniel D.; Barrett, Michael T.

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Genomic analysis and selected molecular pathways in rare cancers.

PubMed

Liu, Stephen V; Lenkiewicz, Elizabeth; Evers, Lisa; Holley, Tara; Kiefer, Jeffrey; Ruiz, Christian; Glatz, Katharina; Bubendorf, Lukas; Demeure, Michael J; Eng, Cathy; Ramanathan, Ramesh K; Von Hoff, Daniel D; Barrett, Michael T

2012-12-01

It is widely accepted that many cancers arise as a result of an acquired genomic instability and the subsequent evolution of tumor cells with variable patterns of selected and background aberrations. The presence and behaviors of distinct neoplastic cell populations within a patient's tumor may underlie multiple clinical phenotypes in cancers. A goal of many current cancer genome studies is the identification of recurring selected driver events that can be advanced for the development of personalized therapies. Unfortunately, in the majority of rare tumors, this type of analysis can be particularly challenging. Large series of specimens for analysis are simply not available, allowing recurring patterns to remain hidden. In this paper, we highlight the use of DNA content-based flow sorting to identify and isolate DNA-diploid and DNA-aneuploid populations from tumor biopsies as a strategy to comprehensively study the genomic composition and behaviors of individual cancers in a series of rare solid tumors: intrahepatic cholangiocarcinoma, anal carcinoma, adrenal leiomyosarcoma, and pancreatic neuroendocrine tumors. We propose that the identification of highly selected genomic events in distinct tumor populations within each tumor can identify candidate driver events that can facilitate the development of novel, personalized treatment strategies for patients with cancer.

Exposing a deadly alliance: novel insights into the biological links between COPD and lung cancer.

PubMed

Vermaelen, K; Brusselle, G

2013-10-01

Chronic obstructive pulmonary disease (COPD) affects more than 200 million people worldwide and is expected to become the third leading cause of death in 2020. COPD is characterized by progressive airflow limitation, due to a combination of chronic inflammation and remodeling of the small airways (bronchiolitis) and loss of elastic recoil caused by destruction of the alveolar walls (emphysema). Lung cancer is the most important cause of cancer-related death in the world. (Cigarette) smoking is the principal culprit causing both COPD and lung cancer; in addition, exposure to environmental tobacco smoke, biomass fuel smoke, coal smoke and outdoor air pollution have also been associated with an increased incidence of both diseases. Importantly, smokers with COPD--defined as either not fully reversible airflow limitation or emphysema--have a two- to four-fold increased risk to develop lung cancer. In this review, we highlight several of the genetic, epigenetic and inflammatory mechanisms, which link COPD and carcinogenesis in the lungs. Elucidating the biological pathways and networks, which underlie the increased susceptibility of lung cancer in patients with COPD, has important implications for screening, prevention, diagnosis and treatment of these two devastating pulmonary diseases. Copyright © 2013 Elsevier Ltd. All rights reserved.

Blueprint of quartz crystal microbalance biosensor for early detection of breast cancer through salivary autoantibodies against ATP6AP1.

PubMed

Arif, Sania; Qudsia, Syeda; Urooj, Samina; Chaudry, Nazia; Arshad, Aneeqa; Andleeb, Saadia

2015-03-15

Breast cancer represents a significant health problem because of its high prevalence. Tests like mammography, which are used abundantly for the detection of breast cancer, suffer from serious limitations. Mammography correctly detects malignancy about 80-90% of the times, failing in places when (1) the tumor is small at early stage, (2) breast tissue is dense or (3) in women of less than 40 years. Serum-based detection of biomarkers involves risk of disease transfer, along with other concerns. These techniques compromise in the early detection of breast cancer. Early detection of breast cancer is a crucial factor to enhance the survival rate of patient. Development of regular screening tests for early diagnosis of breast cancer is a challenge. This review highlights the design of a handy and household biosensor device aimed for self-screening and early diagnosis of breast cancer. The design makes use of salivary autoantibodies for specificity to develop a noninvasive procedure, breast cancer specific biomarkers for precision for the development of device, and biosensor technology for sensitivity to screen the early cases of breast cancer more efficiently. Copyright © 2014 Elsevier B.V. All rights reserved.

Breast cancer cells obtain an osteomimetic feature via epithelial-mesenchymal transition that have undergone BMP2/RUNX2 signaling pathway induction.

PubMed

Tan, Cong-Cong; Li, Gui-Xi; Tan, Li-Duan; Du, Xin; Li, Xiao-Qing; He, Rui; Wang, Qing-Shan; Feng, Yu-Mei

2016-11-29

Bone is one of the most common organs of breast cancer metastasis. Cancer cells that mimic osteoblasts by expressing bone matrix proteins and factors have a higher likelihood of metastasizing to bone. However, the molecular mechanisms of osteomimicry formation of cancer cells remain undefined. Herein, we identified a set of bone-related genes (BRGs) that are ectopically co-expressed in primary breast cancer tissues and determined that osteomimetic feature is obtained due to the osteoblast-like transformation of epithelial breast cancer cells that have undergone epithelial-mesenchymal transition (EMT) followed by bone morphogenetic protein-2 (BMP2) stimulation. Furthermore, we demonstrated that breast cancer cells that transformed into osteoblast-like cells with high expression of BRGs showed enhanced chemotaxis, adhesion, proliferation and multidrug resistance in an osteoblast-mimic bone microenvironment in vitro. During these processes, runt-related transcription factor 2 (RUNX2) functioned as a master mediator by suppressing or activating the transcription of BRGs that underlie the dynamic antagonism between the TGF-β/SMAD and BMP/SMAD signaling pathways in breast cancer cells. Our findings suggest a novel mechanism of osteomimicry formation that arises in primary breast tumors, which may explain the propensity of breast cancer to metastasize to the skeleton and contribute to potential strategies for predicting and targeting breast cancer bone metastasis and multidrug resistance.

Selection of Optimal Adjuvant Chemotherapy and Targeted Therapy for Early Breast Cancer: ASCO Clinical Practice Guideline Focused Update.

PubMed

Denduluri, Neelima; Chavez-MacGregor, Mariana; Telli, Melinda L; Eisen, Andrea; Graff, Stephanie L; Hassett, Michael J; Holloway, Jamie N; Hurria, Arti; King, Tari A; Lyman, Gary H; Partridge, Ann H; Somerfield, Mark R; Trudeau, Maureen E; Wolff, Antonio C; Giordano, Sharon H

2018-05-22

Purpose To update key recommendations of the ASCO guideline adaptation of the Cancer Care Ontario guideline on the selection of optimal adjuvant chemotherapy regimens for early breast cancer and adjuvant targeted therapy for breast cancer. Methods An Expert Panel conducted targeted systematic literature reviews guided by a signals approach to identify new, potentially practice-changing data that might translate to revised practice recommendations. Results The Expert Panel reviewed phase III trials that evaluated adjuvant capecitabine after completion of standard preoperative anthracycline- and taxane-based combination chemotherapy by patients with early-stage breast cancer HER2-negative breast cancer with residual invasive disease at surgery; the addition of 1 year of adjuvant pertuzumab to combination chemotherapy and trastuzumab for patients with early-stage, HER2-positive breast cancer; and the use of neratinib as extended adjuvant therapy for patients after combination chemotherapy and trastuzumab-based adjuvant therapy with early-stage, HER2-positive breast cancer. Recommendations Patients with early-stage HER2-negative breast cancer with pathologic, invasive residual disease at surgery following standard anthracycline- and taxane-based preoperative therapy may be offered up to six to eight cycles of adjuvant capecitabine. Clinicians may add 1 year of adjuvant pertuzumab to trastuzumab-based combination chemotherapy in patients with high-risk, early-stage, HER2-positive breast cancer. Clinicians may use extended adjuvant therapy with neratinib to follow trastuzumab in patients with early-stage, HER2-positive breast cancer. Neratinib causes substantial diarrhea, and diarrhea prophylaxis must be used. Additional information can be found at www.asco.org/breast-cancer-guidelines .

Early Life Exposures and Cancer

Cancer.gov

Early-life events and exposures have important consequences for cancer development later in life, however, epidemiological studies of early-life factors and cancer development later in life have had significant methodological challenges.

[Heredity in renal and prostatic neoplasia].

PubMed

Prayer Galetti, T; D'Arrigo, L; De Zorzi, L; Patarnello, T

1997-09-01

There is an ever growing report of data supporting the evidence that accumulated genetic changes underlie the development of neoplasia. The paradigma of this multistep process is colon cancer were cancer onset is associated, over decades, with at least seven genetic events. The number of genetic alterations increases moving from adenomatous lesions to colon cancer and, although the genetic alterations occur according to a preferred sequence, the total accumulation of changes rather than their sequential order is responsible of tumor biological behavior. It is noteworthy that, at least for this neoplasia, carcinogenesis appears to arise as a result of the mutational activation of oncogenes coupled with the mutational inactivation of tumor suppressor genes. In some cases mutant suppressor genes appear to exert a phenotypic effect even when present in the heterozygous state thus been non "recessive" at the cellular level. The general features of this model may apply also to renal cell cancer (RCC) and prostate cancer (CaP). Extensive literature exists on the cytogenetic and molecular findings in RCC. Only 2% of RCC are familiar, but molecular genetic studies of these cancers have provided important informations on RCC pathogenesis. As with other cancers, familiar RCC is characterized by an early age of onset and frequent multicentricity. A pathological classification useful in studying these patients subdivide renal cancers in papillary (pRCC) and non papillary (RCC) neoplasms. The most common cause of inherited RCC is the Von Hippel Lindau disease (VHL) a dominantly inherited multisystem disorder characterized by retinal and cerebellar hemangioblastomas, pheochromocytomas, pancreatic cysts and RCC. Over 70% of these patients will develop an RCC by their sixth decade. In 1993 the isolation of the tumor suppressor gene in VHL disease at the level of chromosome 3p25-p26 have lead to a better understanding of RCC. Most missense mutations are associated with high risk of RCC, but some are associated with high risk of pheochromocytoma and low risk of RCC. The VHL gene is evolutionary conserved and encodes for a specific protein (pVHL). VHL protein downregulates transcriptional elongation and so suppresses the expression of proto-oncogenes and growth factors. Recently reintroduction of wild-type, non mutant, VHL gene into VHL deficient RCC cell line 786-O had no demonstrable effect on their in vitro growth but inhibited their ability to form tumors in nude mice. So far, VHL mutations or hypermethylations have been found in 76% of sporadic RCC. On the contrary, up to now, no 3p allele loss or VHL mutations have been detected in pRCC. Preliminary studies in familiar pRCC are pointing on genetic changes on chromosomes 1, 7, 16 and 17. As far as prostate cancer is regarded, men with a family history of prostate cancer have an age dependent, significantly increased PCa risk. For familiar clustering, of PCa the two main factors are early age at onset of the disease and the number of multiple affected family members. Hereditary prostate cancer is a subset of familiar prostate cancer with a pattern of distribution consistent with Mendelian inheritance. Hereditary prostate cancer is clinically defined as a clustering of 3 or more relatives within any nuclear family; or the occurrence of prostate cancer in each of 3 generations in either the probands paternal or maternal lineage; or a cluster of 2 relatives affected within 55 years of age or less. Therefore, hereditary prostate cancer may be seen as a multistep carcinogenesis, and clustering may be explained by Mendelian inheritance of a rare (frequency in population 0.36%) dominant, highly penetrant, allele. The estimated cumulative risk of developing PCa, is 88% for carriers as compared with 5% for non carriers. There are conflicting reports of an associated increased incidence of breast cancer in female relatives of men with familiar prostate cancer. In conclusion, there is a clear associatio

Catalyzing Novel Approaches to Rapid, Accurate, and Affordable Early Cancer Detection.

PubMed

Dhar, Asif; Meagher, Beth; Ryscavage, Andrew

Inspired by the Cancer Moonshot, a dedicated team of professionals worked with leaders across the cancer ecosystem to look for an opportunity to radically reduce cancer mortality globally by focusing on early cancer detection. After an initial survey of cancer innovation, progress, and pitfalls, the team believed that if new rapid, affordable, and accurate early detection solutions were appropriately brought to market, it would be possible to intervene earlier when cancer is most treatable.An extensive process began, informed by dozens of experts in the cancer ecosystem. The Cancer XPRIZE team designed a prize competition where "the winning team will develop a means to rapidly, accurately, and affordably screen for early cancers where intervention can reduce human suffering."The following outlines the Cancer XPRIZE's experience using a powerful approach-the radical prize design-to catch more cancers in time to make a difference saving lives, dollars, and suffering.

Early Upper Paleolithic in Eastern Europe and implications for the dispersal of modern humans.

PubMed

Anikovich, M V; Sinitsyn, A A; Hoffecker, John F; Holliday, Vance T; Popov, V V; Lisitsyn, S N; Forman, Steven L; Levkovskaya, G M; Pospelova, G A; Kuz'mina, I E; Burova, N D; Goldberg, Paul; Macphail, Richard I; Giaccio, Biagio; Praslov, N D

2007-01-12

Radiocarbon and optically stimulated luminescence dating and magnetic stratigraphy indicate Upper Paleolithic occupation-probably representing modern humans-at archaeological sites on the Don River in Russia 45,000 to 42,000 years ago. The oldest levels at Kostenki underlie a volcanic ash horizon identified as the Campanian Ignimbrite Y5 tephra that is dated elsewhere to about 40,000 years ago. The occupation layers contain bone and ivory artifacts, including possible figurative art, and fossil shells imported more than 500 kilometers. Thus, modern humans appeared on the central plain of Eastern Europe as early as anywhere else in northern Eurasia.

[6]-Gingerol Induces Cell Cycle Arrest and Cell Death of Mutant p53-expressing Pancreatic Cancer Cells

PubMed Central

Park, Yon Jung; Wen, Jing; Bang, Seungmin; Park, Seung Woo

2006-01-01

[6]-Gingerol, a major phenolic compound derived from ginger, has anti-bacterial, anti-inflammatory and anti-tumor activities. While several molecular mechanisms have been described to underlie its effects on cells in vitro and in vivo, the underlying mechanisms by which [6]-gingerol exerts anti-tumorigenic effects are largely unknown. The purpose of this study was to investigate the action of [6]-gingerol on two human pancreatic cancer cell lines, HPAC expressing wild-type (wt) p53 and BxPC-3 expressing mutated p53. We found that [6]-gingerol inhibited the cell growth through cell cycle arrest at G1 phase in both cell lines. Western blot analyses indicated that [6]-gingerol decreased both Cyclin A and Cyclin-dependent kinase (Cdk) expression. These events led to reduction in Rb phosphorylation followed by blocking of S phase entry. p53 expression was decreased by [6]-gingerol treatment in both cell lines suggesting that the induction of Cyclin-dependent kinase inhibitor, p21cip1, was p53-independent. [6]-Gingerol induced mostly apoptotic death in the mutant p53-expressing cells, while no signs of early apoptosis were detected in wild type p53-expressing cells and this was related to the increased phosphorylation of AKT. These results suggest that [6]-gingerol can circumvent the resistance of mutant p53-expressing cells towards chemotherapy by inducing apoptotic cell death while it exerts cytostatic effect on wild type p53-expressing cells by inducing temporal growth arrest. PMID:17066513

Early Diagnosis of Breast Cancer.

PubMed

Wang, Lulu

2017-07-05

Early-stage cancer detection could reduce breast cancer death rates significantly in the long-term. The most critical point for best prognosis is to identify early-stage cancer cells. Investigators have studied many breast diagnostic approaches, including mammography, magnetic resonance imaging, ultrasound, computerized tomography, positron emission tomography and biopsy. However, these techniques have some limitations such as being expensive, time consuming and not suitable for young women. Developing a high-sensitive and rapid early-stage breast cancer diagnostic method is urgent. In recent years, investigators have paid their attention in the development of biosensors to detect breast cancer using different biomarkers. Apart from biosensors and biomarkers, microwave imaging techniques have also been intensely studied as a promising diagnostic tool for rapid and cost-effective early-stage breast cancer detection. This paper aims to provide an overview on recent important achievements in breast screening methods (particularly on microwave imaging) and breast biomarkers along with biosensors for rapidly diagnosing breast cancer.

Total colonoscopy detects early colorectal cancer more frequently than advanced colorectal cancer in patients with fecal occult blood.

PubMed

Ozaki, Takuji; Tokunaga, Akira; Chihara, Naoto; Yoshino, Masanori; Bou, Hideki; Ogata, Masao; Watanabe, Masanori; Suzuki, Hideyuki; Uchida, Eiji

2010-08-01

The efficacy of total colonoscopy following a positive result of the fecal occult blood test (FOBT) for the early detection of colorectal cancer and polyps was evaluated. A total of 1,491 patients with positive FOBT results underwent total colonoscopy at the Institute of Gastroenterology, Nippon Medical School, Musashi Kosugi Hospital, from April 2002 through July 2009. Abnormalities were found in 1,312 of the 1,491 patients (88.0%). Ninety-six of the 1,491 patients (6.4%) were found to have early cancer, but 59 patients (4.0%) were found to have advanced cancer. The early cancers were treated with endoscopic mucosal resection or endoscopic submucosal dissection in 81 patients, with laparoscopy-assisted colectomy in 10 patients, and with open surgery in 5 patients. Fifty-one of the 59 patients with advanced colorectal cancer underwent conventional open surgery, and 8 patients underwent laparoscopic surgery. The cancers detected were more likely to be early cancers than advanced cancers. In addition to malignancies, other abnormalities found included inner or external hemorrhoids, diverticula of the colon, ulcerative colitis, ischemic colitis, infectious colitis, and colorectal polyps. Our results show that a high percentage of lesions detected with total colonoscopy following a positive FOBT result are early colorectal cancers and polyps.

The African Organisation for Research and Training in Cancer and its conferences: a historical perspective and highlights of the Ninth International Conference, Durban, South Africa, 21-24 November 2013.

PubMed

Williams, Christopher Ko; Cristina Stefan, D; Rawlinson, Fiona; Simbiri, Kenneth; Mbulaiteye, Sam M

2014-01-01

The objectives of the African Organisation for Research and Training in Cancer (AORTIC), both at its inception in the early 1980s, and at its reactivation in 2000 following a decade of inactivity, included bringing the products of decades of advances in cancer research to African populations through international collaboration. The historical perspective provided in this report illustrates progress in achieving these objectives through successive continent-wide activities over a period of 30 years, culminating in the organisation's most recent conference held in Durban, South Africa, 21-24 November 2013. The constant growth in the number of attendants and increasing diversity of the nations of their origin are consistent with advances, whereby the number of participants and the nations of their origin have grown from 24 in 1983 to almost 1000 in 2013, and from 14 to 70, respectively. While earlier AORTIC conferences used to assume the atmosphere of 'jamborees', more recent ones have morphed to problem-solving events, with the concerted collaboration of international organisations, including the World Health Organisation (WHO), International Union Against Cancer (UICC), the Africa Union (AU), the US National Cancer Institute (NCI), the International Psycho-Oncology Society (IPOS), and others. The topics of discussion at the Ninth AORTIC International Conference on Cancer in Africa in Durban were those of paramount importance for low- and middle-income countries: childhood cancers, cancers of the cervix, breast, and prostate, as well as cancer care challenges resulting from ignorance, neglect, and economic deprivation. The role of environmental factors that underlie Burkitt's lymphoma was the subject of the Epidemiology of Burkitt Lymphoma in East-African Children and Minors Workshop, highlighting the NCI research programme in East Africa, while the Workshop on Cost Effectiveness of Treatment of Cancer in Africa surmised that treating childhood cancers is affordable in Africa in spite of widespread economic deprivation. WHO representatives emphasised the organisation's commitment to the global control of non-communicable diseases (NCDs), including cancer, and promoted the new initiatives for the control of cervical cancer, one of the commonest and deadliest cancers in adult Africans. AU representative proffered the principles of 'demographic dividends' for Africa to be able to tackle its burden of NCDs. UICC, represented by its President, provided guidelines for cancer diagnosis and staging, and advised on its effort to improve global access to radiotherapy, especially in Africa, while IPOS led the discussions on mitigating the suffering that is associated with the late presentation of cancer in the region. Oral and poster presentations from various parts of the continent indicate the growth of basic science of cancer in the region, with studies revealing regional diversity in the frequencies of the triple-negative breast cancer. They also suggest a need for genome-wide association studies as well as the evaluation of single nucleotide polymorphisms that may be responsible for variable susceptibility in breast and prostate cancer in people of African descent. Finally, the AORTIC leadership announced its plan for the advancement of cancer control by intensifying cancer advocacy at all levels of governance in the region.

Gastrointestinal Cancers: Screening and Early Detection.

PubMed

Griffin-Sobel, Joyce P

2017-05-01

To present an overview of current practices in the screening and early detection of gastrointestinal cancers. Literature reviews. Screening for gastrointestinal cancers is less than desirable, particularly in underserved populations. There are inadequate methods of screening for early detection of esophageal and gastric cancers. Education of patients is needed to reinforce the importance of screening for gastrointestinal cancers. Copyright © 2017 Elsevier Inc. All rights reserved.

Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation

DTIC Science & Technology

2008-03-01

CONTRACT NUMBER Detection and Evaluation of Early Breast Cancer via Magnetic Resonance Imaging: Studies of Mouse Models and Clinical Implementation...research proposed here can directly lead to clinical improvements in both early breast cancer detection, as well as effective breast cancer therapy. To date... cancer is a major prognostic factor in the management of the disease. In particular, detecting breast cancer in its pre-invasive form as ductal carcinoma

Differential adaptation to a harsh granite outcrop habitat between sympatric Mimulus species.

PubMed

Ferris, Kathleen G; Willis, John H

2018-03-31

Understanding which environmental variables and traits underlie adaptation to harsh environments is difficult because many traits evolve simultaneously as populations or species diverge. Here, we investigate the ecological variables and traits that underlie Mimulus laciniatus' adaptation to granite outcrops compared to its sympatric, mesic-adapted progenitor, Mimulus guttatus. We use fine-scale measurements of soil moisture and herbivory to examine differences in selective forces between the species' habitats, and measure selection on flowering time, flower size, plant height, and leaf shape in a reciprocal transplant using M. laciniatus × M. guttatus F 4 hybrids. We find that differences in drought and herbivory drive survival differences between habitats, that M. laciniatus and M. guttatus are each better adapted to their native habitat, and differential habitat selection on flowering time, plant stature, and leaf shape. Although early flowering time, small stature, and lobed leaf shape underlie plant fitness in M. laciniatus' seasonally dry environment, increased plant size is advantageous in a competitive mesic environment replete with herbivores like M. guttatus'. Given that we observed divergent selection between habitats in the direction of species differences, we conclude that adaptation to different microhabitats is an important component of reproductive isolation in this sympatric species pair. © 2018 The Author(s). Evolution © 2018 The Society for the Study of Evolution.

Interventions to promote cancer awareness and early presentation: systematic review

PubMed Central

Austoker, J; Bankhead, C; Forbes, L J L; Atkins, L; Martin, F; Robb, K; Wardle, J; Ramirez, A J

2009-01-01

Background: Low cancer awareness contributes to delay in presentation for cancer symptoms and may lead to delay in cancer diagnosis. The aim of this study was to review the evidence for the effectiveness of interventions to raise cancer awareness and promote early presentation in cancer to inform policy and future research. Methods: We searched bibliographic databases and reference lists for randomised controlled trials of interventions delivered to individuals, and controlled or uncontrolled studies of interventions delivered to communities. Results: We found some evidence that interventions delivered to individuals modestly increase cancer awareness in the short term and insufficient evidence that they promote early presentation. We found limited evidence that public education campaigns reduce stage at presentation of breast cancer, malignant melanoma and retinoblastoma. Conclusions: Interventions delivered to individuals may increase cancer awareness. Interventions delivered to communities may promote cancer awareness and early presentation, although the evidence is limited. PMID:19956160

Early Nutrition and Physical Activity Interventions in Childhood Cancer Survivors

PubMed Central

Zhang, Fang Fang; Kelly, Michael J.; Must, Aviva

2017-01-01

Purpose of review Childhood cancer survivors experience excessive weight gain early in treatment. Lifestyle interventions need to be initiated early in cancer care to prevent the early onset of obesity and cardiovascular disease (CVD). We reviewed the existing literature on early lifestyle interventions in childhood cancer survivors and consider implications for clinical care. Recent findings Few lifestyle interventions focus on improving nutrition in childhood cancer survivors. A consistent effect on reducing obesity and CVD risk factors is not evident from the limited number of studies with heterogeneous intervention characteristics, although interventions with a longer duration and follow-up show more promising trends. Summary Future lifestyle interventions should be of a longer duration and include a nutrition component. Interventions with a longer duration and follow-up are needed to assess the timing and sustainability of the intervention effect. Lifestyle interventions introduced early in cancer care are both safe and feasible. PMID:28455678

Screening and Biosensor-Based Approaches for Lung Cancer Detection

PubMed Central

Wang, Lulu

2017-01-01

Early diagnosis of lung cancer helps to reduce the cancer death rate significantly. Over the years, investigators worldwide have extensively investigated many screening modalities for lung cancer detection, including computerized tomography, chest X-ray, positron emission tomography, sputum cytology, magnetic resonance imaging and biopsy. However, these techniques are not suitable for patients with other pathologies. Developing a rapid and sensitive technique for early diagnosis of lung cancer is urgently needed. Biosensor-based techniques have been recently recommended as a rapid and cost-effective tool for early diagnosis of lung tumor markers. This paper reviews the recent development in screening and biosensor-based techniques for early lung cancer detection. PMID:29065541

CEACAM6 is upregulated by Helicobacter pylori CagA and is a biomarker for early gastric cancer

PubMed Central

Srivastava, Supriya; Samanta, Animesh; Sharma, Neel; Tan, Kar Tong; Yang, Henry; Voon, Dominic C.; Pang, Brendan; Teh, Ming; Murata-Kamiya, Naoko; Hatakeyama, Masanori; Chang, Young-Tae; Yong, Wei Peng; Ito, Yoshiaki; Ho, Khek Yu; Tan, Patrick; Soong, Richie; Koeffler, Phillip H.; Yeoh, Khay Guan; Jeyasekharan, Anand D.

2016-01-01

Early detection of gastric cancers saves lives, but remains a diagnostic challenge. In this study, we aimed to identify cell-surface biomarkers of early gastric cancer. We hypothesized that a subset of plasma membrane proteins induced by the Helicobacter pylori oncoprotein CagA will be retained in early gastric cancers through non-oncogene addiction. An inducible system for expression of CagA was used to identify differentially upregulated membrane protein transcripts in vitro. The top hits were then analyzed in gene expression datasets comparing transcriptome of gastric cancer with normal tissue, to focus on markers retained in cancer. Among the transcripts enriched upon CagA induction in vitro, a significant elevation of CEACAM6 was noted in gene expression datasets of gastric cancer. We used quantitative digital immunohistochemistry to measure CEACAM6 protein levels in tissue microarrays of gastric cancer. We demonstrate an increase in CEACAM6 in early gastric cancers, when compared to matched normal tissue, with an AUC of 0.83 for diagnostic validity. Finally, we show that a fluorescently conjugated CEACAM6 antibody binds avidly to freshly resected gastric cancer xenograft samples and can be detected by endoscopy in real time. Together, these results suggest that CEACAM6 upregulation is a cell surface response to H. pylori CagA, and is retained in early gastric cancers. They highlight a novel link between CEACAM6 expression and CagA in gastric cancer, and suggest CEACAM6 to be a promising biomarker to aid with the fluorescent endoscopic diagnosis of early neoplastic lesions in the stomach. PMID:27421133

Glycomics Laboratory for the Early Detection of Epithelial Ovarian Cancer | Division of Cancer Prevention

Cancer.gov

Ovarian cancer is a silent killer with few early symptoms and advanced disease present at the time of diagnosis. This cancer is the most lethal of all gynecologic malignancies with over 20,000 new cases diagnosed each year. The 5 year survival rates for ovarian cancer dramatically improve when the disease is diagnosed at an early stage. Therefore, the long term goal of the

The Early Detection of Pancreatic Cancer: What Will it Take to Diagnose and Treat Curable Pancreatic Neoplasia?

PubMed Central

Lennon, Anne Marie; Wolfgang, Christopher L.; Canto, Marcia Irene; Klein, Alison P.; Herman, Joseph M.; Goggins, Michael; Fishman, Elliot K.; Kamel, Ihab; Weiss, Matthew J.; Diaz, Luis A.; Papadopoulos, Nickolas; Kinzler, Kenneth W.; Vogelstein, Bert; Hruban, Ralph H.

2014-01-01

Pancreatic cancer is the deadliest of all solid malignancies. Early detection offers the best hope for a cure, but characteristics of this disease such as the lack of early clinical symptoms, make the early detection difficult. Recent genetic mapping of the molecular evolution of pancreatic cancer suggests that a large window of opportunity exists for the early detection of pancreatic neoplasia, and developments in cancer genetics offer new, potentially highly specific, approaches for screening for curable pancreatic neoplasia. We review the challenges of screening for early pancreatic neoplasia, as well as opportunities presented by incorporating molecular genetics into these efforts. PMID:24924775

Sexual dysfunction and infertility as late effects of cancer treatment

PubMed Central

Schover, Leslie R.; van der Kaaij, Marleen; van Dorst, Eleonora; Creutzberg, Carien; Huyghe, Eric; Kiserud, Cecilie E.

2014-01-01

Sexual dysfunction is a common consequence of cancer treatment, affecting at least half of men and women treated for pelvic malignancies and over a quarter of people with other types of cancer. Problems are usually linked to damage to nerves, blood vessels, and hormones that underlie normal sexual function. Sexual dysfunction also may be associated with depression, anxiety, relationship conflict, and loss of self-esteem. Innovations in cancer treatment such as robotic surgery or more targeted radiation therapy have not had the anticipated result of reducing sexual dysfunction. Some new and effective cancer treatments, including aromatase inhibitors for breast cancer or chemoradiation for anal cancer also have very severe sexual morbidity. Cancer-related infertility is an issue for younger patients, who comprise a much smaller percentage of total cancer survivors. However, the long-term emotional impact of being unable to have a child after cancer can be extremely distressing. Advances in knowledge about how cancer treatments may damage fertility, as well as newer techniques to preserve fertility, offer hope to patients who have not completed their childbearing at cancer diagnosis. Unfortunately, surveys in industrialised nations confirm that many cancer patients are still not informed about potential changes to their sexual function or fertility, and all modalities of fertility preservation remain underutilised. After cancer treatment, many patients continue to have unmet needs for information about restoring sexual function or becoming a parent. Although more research is needed on optimal clinical practice, current studies suggest a multidisciplinary approach, including both medical and psychosocial treatment options. PMID:26217165

Circulating microRNA-22-3p Predicts the Malignant Progression of Precancerous Gastric Lesions from Intestinal Metaplasia to Early Adenocarcinoma.

PubMed

Chen, Tsung-Hsing; Chiu, Cheng-Tang; Lee, Chieh; Chu, Yin-Yi; Cheng, Hao-Tsai; Hsu, Jun-Te; Wu, Ren-Chin; Yeh, Ta-Sen; Lin, Kwang-Huei

2018-05-07

Gastric cancer has a poor outcome and identifying useful biomarkers from peripheral blood or tissue could allow its early detection, or potentially precancerous changes, thus improving the curative rates. MicroRNAs (miRNAs) have been shown to offer great potential in cancer diagnosis and prediction. Here, we investigated the role of plasma miRNAs in the natural course of gastric cancer, from intestinal metaplasia to early cancer. The findings were used to understand whether patients at a high risk of malignancy could be given appropriate interventions in the early disease process, such as using endoscopic submucosal dissection to treat gastric dysplasia or early gastric cancer. Participants were divided into healthy control, intestinal metaplasia (IM), and dysplasia/early cancer (pT1a/b) groups. Microarray was used to select potential markers in tissue. Quantitative real-time polymerase chain reaction data showed circulating miRNA-22-3p had significantly different expression in patients with precancerous lesions or gastric adenocarcinoma. The areas under the curve of incomplete IM versus healthy control, low-grade/high-grade dysplasia, early gastric cancer, and GED were 0.8080, 0.8040, 0.8494, and 0.8095, respectively (all P values < 0.05). Circulating miRNA-22-3p could be a potential biomarker for gastric precancerous dysplasia and early cancer detection.

Chinese Anti-Cancer Association as a non-governmental organization undertakes systematic cancer prevention work in China.

PubMed

Xu, Tingting

2015-08-01

Cancer has become the first leading cause of death in the world, particularly in low- and middle-income countries. Facing the increasing trend of cancer incidence and mortality, China issued and implemented "three-early (early prevention, early diagnosis and early treatment)" national cancer prevention plan. As the main body and dependence of social governance, non-governmental organizations (NGOs) take over the role of government in the field of cancer prevention and treatment. American Cancer Society (ACS) made a research on cancer NGOs and civil society in cancer control and found that cancer NGOs in developing countries mobilize civil society to work together and advocate governments in their countries to develop policies to address the growing cancer burden. Union for International Cancer Control (UICC), Cancer Council Australia (CCA), and Malaysian cancer NGOs are the representatives of cancer NGOs in promoting cancer control. Selecting Chinese Anti-Cancer Association (CACA) as an example in China, this article is to investigate how NGOs undertake systematic cancer prevention work in China. By conducting real case study, we found that, as a NGO, CACA plays a significant role in intensifying the leading role of government in cancer control, optimizing cancer outcomes, decreasing cancer incidence and mortality rates and improving public health.

Chinese Anti-Cancer Association as a non-governmental organization undertakes systematic cancer prevention work in China

PubMed Central

2015-01-01

Cancer has become the first leading cause of death in the world, particularly in low- and middle-income countries. Facing the increasing trend of cancer incidence and mortality, China issued and implemented “three-early (early prevention, early diagnosis and early treatment)” national cancer prevention plan. As the main body and dependence of social governance, non-governmental organizations (NGOs) take over the role of government in the field of cancer prevention and treatment. American Cancer Society (ACS) made a research on cancer NGOs and civil society in cancer control and found that cancer NGOs in developing countries mobilize civil society to work together and advocate governments in their countries to develop policies to address the growing cancer burden. Union for International Cancer Control (UICC), Cancer Council Australia (CCA), and Malaysian cancer NGOs are the representatives of cancer NGOs in promoting cancer control. Selecting Chinese Anti-Cancer Association (CACA) as an example in China, this article is to investigate how NGOs undertake systematic cancer prevention work in China. By conducting real case study, we found that, as a NGO, CACA plays a significant role in intensifying the leading role of government in cancer control, optimizing cancer outcomes, decreasing cancer incidence and mortality rates and improving public health. PMID:26361412

Cancer risk elicitation and communication: lessons from the psychology of risk perception.

PubMed

Klein, William M P; Stefanek, Michael E

2007-01-01

Cancer risk perceptions are a key predictor of risk-reduction practices, health behaviors, and processing of cancer information. Nevertheless, patients and the general public (as well as health care providers) exhibit a number of errors and biases in the way they think about risk, such that their risk perceptions and decisions deviate greatly from those prescribed by normative decision models and by experts in risk assessment. For example, people are more likely to engage in screening behaviors such as mammography when faced with loss-based messages than gain-framed messages, and they often ignore the base rate of a given disease when assessing their own risk of obtaining this disease. In this article, we review many of the psychological processes that underlie risk perception and discuss how these processes lead to such deviations. Among these processes are difficulties with use of numerical information (innumeracy), cognitive processes (eg, use of time-saving heuristics), motivational factors (eg, loss and regret aversion), and emotion. We conclude with suggestions for future research in the area, as well as implications for improving the elicitation and communication of personal cancer risk.

The Mammary Stem Cell Hierarchy: A Looking Glass into Heterogeneous Breast Cancer Landscapes

PubMed Central

Sreekumar, Amulya; Roarty, Kevin; Rosen, Jeffrey M.

2015-01-01

The mammary gland is a dynamic organ that undergoes extensive morphogenesis during the different stages of embryonic development, puberty, estrus, pregnancy, lactation and involution. Systemic and local cues underlie this constant tissue remodeling and act by eliciting an intricate pattern of responses in the mammary epithelial and stromal cells. Decades of studies utilizing methods such as transplantation and lineage tracing have identified a complex hierarchy of mammary stem cells, progenitors and differentiated epithelial cells that fuel mammary epithelial development. Importantly, these studies have extended our understanding of the molecular crosstalk between cell types, and signaling pathways maintaining normal homeostasis that often are deregulated during tumorigenesis. While several questions remain, this research has many implications for breast cancer. Fundamental among these are the identification of the cells of origin for the multiple subtypes of breast cancer and the understanding of tumor heterogeneity. A deeper understanding of these critical questions will unveil novel breast cancer drug targets and treatment paradigms. In this review, we provide a current overview of normal mammary development and tumorigenesis from a stem cell perspective. PMID:26206777

Serum decoy receptor 3 level: a predictive marker for nodal metastasis and survival among oral cavity cancer patients.

PubMed

Tu, Hsi-Feng; Liu, Chung-Ji; Liu, Shyun-Yeu; Chen, Yu-Ping; Yu, En-Hao; Lin, Shu-Chun; Chang, Kuo-Wei

2011-03-01

Validating markers for prediction of nodal metastasis could be beneficial in treatment of oral cavity cancer. Decoy receptor 3 (DcR3), locus on 20q13, functions as a death decoy inhibiting apoptosis mediated by the tumor necrosis factor receptor (TNFR) family. This study analyzed the serum level of DcR3 in relationship to the clinical parameters of oral cavity cancer patients together with detection of DcR3 genomic copy number in primary and recurrent tumors. Elevated serum DcR3 was associated with nodal metastasis and worse prognosis. Gain of DcR3 copy number was detected in 17% of primary tumor tissue but not found in healthy areca chewers. Tissue from recurrent tumors showed more frequent DcR3 copy number alteration (48%) than the paired primary tumor tissue. Serum DcR3 level is a predictor for the nodal metastasis and survival among oral cavity cancer patients and the DcR3 copy number alteration could underlie oral carcinogenesis progression. Copyright © 2010 Wiley Periodicals, Inc.

Idiotypic Cascades in Cancer Patients Treated with Monoclonal Antibody CO17-1A

NASA Astrophysics Data System (ADS)

Wettendorff, Martine; Iliopoulos, Dimitrios; Tempero, Margaret; Kay, David; Defreitas, Elaine; Koprowski, Hilary; Herlyn, Dorothee

1989-05-01

We have previously shown that gastrointestinal cancer patients treated with monoclonal antibody CO17-1A (Ab1) developed anti-idiotypic antibodies (Ab2) to the Ab1. We now demonstrate that patients produce anti-anti-idiotypic antibodies (Ab3) to their autologous Ab2. Ab3 were demonstrated in culture supernatants of peripheral blood mononuclear cells from five Ab1-treated patients after stimulation of the cells with heterologous Ab2 that functionally mimicked the tumor antigen (Ag) defined by Ab1 and immunologically cross reacted with the patients' Ab2. Ab3 shared idiotopes with Ab1 and were Ab1-like in their binding specificities to tumor cells, Ag, and Ab2. Such antibodies were also elicited by stimulating cells with Ag. However, they were not produced by stimulating posttreatment mononuclear cells with control proteins or by stimulating pretreatment cells with either Ag or Ab2. Our results demonstrate idiotypic cascades in cancer patients treated with monoclonal antibody. Ag-specific Ab3 responses may underlie delayed clinical responses often observed in cancer patients treated with monoclonal antibodies of various specificities.

The impact of the metabotropic glutamate receptor and other gene family interaction networks on autism

PubMed Central

Hadley, Dexter; Wu, Zhi-liang; Kao, Charlly; Kini, Akshata; Mohamed-Hadley, Alisha; Thomas, Kelly; Vazquez, Lyam; Qiu, Haijun; Mentch, Frank; Pellegrino, Renata; Kim, Cecilia; Connolly, John; Pinto, Dalila; Merikangas, Alison; Klei, Lambertus; Vorstman, Jacob A.S.; Thompson, Ann; Regan, Regina; Pagnamenta, Alistair T.; Oliveira, Bárbara; Magalhaes, Tiago R.; Gilbert, John; Duketis, Eftichia; De Jonge, Maretha V.; Cuccaro, Michael; Correia, Catarina T.; Conroy, Judith; Conceição, Inês C.; Chiocchetti, Andreas G.; Casey, Jillian P.; Bolshakova, Nadia; Bacchelli, Elena; Anney, Richard; Zwaigenbaum, Lonnie; Wittemeyer, Kerstin; Wallace, Simon; Engeland, Herman van; Soorya, Latha; Rogé, Bernadette; Roberts, Wendy; Poustka, Fritz; Mouga, Susana; Minshew, Nancy; McGrew, Susan G.; Lord, Catherine; Leboyer, Marion; Le Couteur, Ann S.; Kolevzon, Alexander; Jacob, Suma; Guter, Stephen; Green, Jonathan; Green, Andrew; Gillberg, Christopher; Fernandez, Bridget A.; Duque, Frederico; Delorme, Richard; Dawson, Geraldine; Café, Cátia; Brennan, Sean; Bourgeron, Thomas; Bolton, Patrick F.; Bölte, Sven; Bernier, Raphael; Baird, Gillian; Bailey, Anthony J.; Anagnostou, Evdokia; Almeida, Joana; Wijsman, Ellen M.; Vieland, Veronica J.; Vicente, Astrid M.; Schellenberg, Gerard D.; Pericak-Vance, Margaret; Paterson, Andrew D.; Parr, Jeremy R.; Oliveira, Guiomar; Almeida, Joana; Café, Cátia; Mouga, Susana; Correia, Catarina; Nurnberger, John I.; Monaco, Anthony P.; Maestrini, Elena; Klauck, Sabine M.; Hakonarson, Hakon; Haines, Jonathan L.; Geschwind, Daniel H.; Freitag, Christine M.; Folstein, Susan E.; Ennis, Sean; Coon, Hilary; Battaglia, Agatino; Szatmari, Peter; Sutcliffe, James S.; Hallmayer, Joachim; Gill, Michael; Cook, Edwin H.; Buxbaum, Joseph D.; Devlin, Bernie; Gallagher, Louise; Betancur, Catalina; Scherer, Stephen W.; Glessner, Joseph; Hakonarson, Hakon

2014-01-01

Although multiple reports show that defective genetic networks underlie the aetiology of autism, few have translated into pharmacotherapeutic opportunities. Since drugs compete with endogenous small molecules for protein binding, many successful drugs target large gene families with multiple drug binding sites. Here we search for defective gene family interaction networks (GFINs) in 6,742 patients with the ASDs relative to 12,544 neurologically normal controls, to find potentially druggable genetic targets. We find significant enrichment of structural defects (P≤2.40E−09, 1.8-fold enrichment) in the metabotropic glutamate receptor (GRM) GFIN, previously observed to impact attention deficit hyperactivity disorder (ADHD) and schizophrenia. Also, the MXD-MYC-MAX network of genes, previously implicated in cancer, is significantly enriched (P≤3.83E−23, 2.5-fold enrichment), as is the calmodulin 1 (CALM1) gene interaction network (P≤4.16E−04, 14.4-fold enrichment), which regulates voltage-independent calcium-activated action potentials at the neuronal synapse. We find that multiple defective gene family interactions underlie autism, presenting new translational opportunities to explore for therapeutic interventions. PMID:24927284

Proteinase-Activated Receptor 2 May Drive Cancer Progression by Facilitating TGF-β Signaling.

PubMed

Ungefroren, Hendrik; Witte, David; Rauch, Bernhard H; Settmacher, Utz; Lehnert, Hendrik; Gieseler, Frank; Kaufmann, Roland

2017-11-22

The G protein-coupled receptor proteinase-activated receptor 2 (PAR2) has been implicated in various aspects of cellular physiology including inflammation, obesity and cancer. In cancer, it usually acts as a driver of cancer progression in various tumor types by promoting invasion and metastasis in response to activation by serine proteinases. Recently, we discovered another mode through which PAR2 may enhance tumorigenesis: crosstalk with transforming growth factor-β (TGF-β) signaling to promote TGF-β1-induced cell migration/invasion and invasion-associated gene expression in ductal pancreatic adenocarcinoma (PDAC) cells. In this chapter, we review what is known about the cellular TGF-β responses and signaling pathways affected by PAR2 expression, the signaling activities of PAR2 required for promoting TGF-β signaling, and the potential molecular mechanism(s) that underlie(s) the TGF-β signaling-promoting effect. Since PAR2 is activated through various serine proteinases and biased agonists, it may couple TGF-β signaling to a diverse range of other physiological processes that may or may not predispose cells to cancer development such as local inflammation, systemic coagulation and pathogen infection.

Proteinase-Activated Receptor 2 May Drive Cancer Progression by Facilitating TGF-β Signaling

PubMed Central

Ungefroren, Hendrik; Witte, David; Settmacher, Utz; Lehnert, Hendrik; Kaufmann, Roland

2017-01-01

The G protein-coupled receptor proteinase-activated receptor 2 (PAR2) has been implicated in various aspects of cellular physiology including inflammation, obesity and cancer. In cancer, it usually acts as a driver of cancer progression in various tumor types by promoting invasion and metastasis in response to activation by serine proteinases. Recently, we discovered another mode through which PAR2 may enhance tumorigenesis: crosstalk with transforming growth factor-β (TGF-β) signaling to promote TGF-β1-induced cell migration/invasion and invasion-associated gene expression in ductal pancreatic adenocarcinoma (PDAC) cells. In this chapter, we review what is known about the cellular TGF-β responses and signaling pathways affected by PAR2 expression, the signaling activities of PAR2 required for promoting TGF-β signaling, and the potential molecular mechanism(s) that underlie(s) the TGF-β signaling–promoting effect. Since PAR2 is activated through various serine proteinases and biased agonists, it may couple TGF-β signaling to a diverse range of other physiological processes that may or may not predispose cells to cancer development such as local inflammation, systemic coagulation and pathogen infection. PMID:29165389

NPM1 Silencing Reduces Tumour Growth and MAPK Signalling in Prostate Cancer Cells

PubMed Central

Loubeau, Gaëlle; Boudra, Rafik; Maquaire, Sabrina; Lours-Calet, Corinne; Beaudoin, Claude; Verrelle, Pierre; Morel, Laurent

2014-01-01

The chaperone nucleophosmin (NPM1) is over-expressed in the epithelial compartment of prostate tumours compared to adjacent healthy epithelium and may represent one of the key actors that support the neoplastic phenotype of prostate adenocarcinoma cells. Yet, the mechanisms that underlie NPM1 mediated phenotype remain elusive in the prostate. To better understand NPM1 functions in prostate cancer cells, we sought to characterize its impact on prostate cancer cells behaviour and decipher the mechanisms by which it may act. Here we show that NPM1 favors prostate tumour cell migration, invasion and colony forming. Furthermore, knockdown of NPM1 leads to a decrease in the growth of LNCaP-derived tumours grafted in Nude mice in vivo. Such oncogenic-like properties are found in conjunction with a positive regulation of NPM1 on the ERK1/2 (Extracellular signal-Regulated Kinases 1/2) kinase phosphorylation in response to EGF (Epidermal Growth Factor) stimulus, which is critical for prostate cancer progression following the setting of an autonomous production of the growth factor. NPM1 could then be a target to switch off specifically ERK1/2 pathway activation in order to decrease or inhibit cancer cell growth and migration. PMID:24796332

HGF-independent regulation of MET and GAB1 by nonreceptor tyrosine kinase FER potentiates metastasis in ovarian cancer

PubMed Central

Fan, Gaofeng; Zhang, Siwei; Gao, Yan; Greer, Peter A.; Tonks, Nicholas K.

2016-01-01

Ovarian cancer cells disseminate readily within the peritoneal cavity, which promotes metastasis, and are often resistant to chemotherapy. Ovarian cancer patients tend to present with advanced disease, which also limits treatment options; consequently, new therapies are required. The oncoprotein tyrosine kinase MET, which is the receptor for hepatocyte growth factor (HGF), has been implicated in ovarian tumorigenesis and has been the subject of extensive drug development efforts. Here, we report a novel ligand- and autophosphorylation-independent activation of MET through the nonreceptor tyrosine kinase feline sarcoma-related (FER). We demonstrated that the levels of FER were elevated in ovarian cancer cell lines relative to those in immortalized normal surface epithelial cells and that suppression of FER attenuated the motility and invasive properties of these cancer cells. Furthermore, loss of FER impaired the metastasis of ovarian cancer cells in vivo. Mechanistically, we demonstrated that FER phosphorylated a signaling site in MET: Tyr1349. This enhanced activation of RAC1/PAK1 and promoted a kinase-independent scaffolding function that led to recruitment and phosphorylation of GAB1 and the specific activation of the SHP2–ERK signaling pathway. Overall, this analysis provides new insights into signaling events that underlie metastasis in ovarian cancer cells, consistent with a prometastatic role of FER and highlighting its potential as a novel therapeutic target for metastatic ovarian cancer. PMID:27401557

DNMT3B -579 G>T Promoter Polymorphism and the Risk of Gastric Cancer in the West of Iran.

PubMed

Ahmadi, Kulsom; Soleimani, Azam; Irani, Shiva; Kiani, Aliasghar; Ghanadi, Kourosh; Noormohamadi, Zahra; Sakinejad, Foroozan

2018-06-01

Many studies have suggested that modulation of DNMT3B function caused by single nucleotide polymorphisms of the DNMT3B promoter region may underlie the susceptibility to various cancers such as tumors of the digestive system. The aim of this study was to investigate the effect of -579 G>T polymorphism in the promoter of the DNMT3B gene on risk of gastric cancer in a population from West Iran. We conducted a case-control study in 100 gastric cancer patients and 112 cancer-free controls to assess the correlation between DNMT3B -579 G>T (rs1569686) polymorphism and the risk of gastric cancer. Detection of genotypes of DNMT3B G39179T polymorphism was analyzed by PCR-RFLP. There was no significant difference in the distribution of DNMT3B -579 G>T genotypes between the cases and controls. However, in the stratified analysis by clinicopathological characteristic types, we found that statistically, the risk susceptibility to gastric cancer was significantly associated with tumor grade II and GT/TT genotype of patients, compared to patients having GG genotype, (OR = 5.4737, 95% CI = 1.4746. 20.3184, P = 0.01). Our study suggested that the -579 T allele may increase the relative risk for the progression of clinicopathological characteristic of tumor grade of gastric cancer patients.

Mapping MRI/MRS Parameters with Genetic Over-expression Profiles In Human Prostate Cancer: Demonstrating the Potential

PubMed Central

Lenkinski, Robert E.; Bloch, B. Nicholas; Liu, Fangbing; Frangioni, John V.; Perner, Sven; Rubin, Mark A.; Genega, Elizabeth; Rofsky, Neil M.; Gaston, Sandra M.

2009-01-01

Magnetic resonance imaging (MRI) and MR spectroscopy can probe a variety of physiological (e.g. blood vessel permeability) and metabolic characteristics of prostate cancer. However, little is known about the changes in gene expression that underlie the spectral and imaging features observed in prostate cancer. Tumor induced changes in vascular permeability and angiogenesis are thought to contribute to patterns of dynamic contrast enhanced (DCE) MRI images of prostate cancer even though the genetic basis of tumor vasculogenesis is complex and the specific mechanisms underlying these DCEMRI features have not yet been determined. In order to identify the changes in gene expression that correspond to MRS and DCEMRI patterns in human prostate cancers, we have utilized tissue print micropeel techniques to generate “whole mount” molecular maps of radical prostatectomy specimens that correspond to pre-surgical MRI/MRS studies. These molecular maps include RNA expression profiles from both Affymetrix GeneChip microarrays and quantitative reverse transcriptase PCR (qrt-PCR) analysis, as well as immunohistochemical studies. Using these methods on patients with prostate cancer, we found robust over-expression of choline kinase a in the majority of primary tumors. We also observed overexpression of neuropeptide Y (NPY), a newly identified angiogenic factor, in a subset of DCEMRI positive prostate cancers. These studies set the stage for establishing MRI/MRS parameters as validated biomarkers for human prostate cancer. PMID:18752015

The MLH1 c.-27C>A and c.85G>T variants are linked to dominantly inherited MLH1 epimutation and are borne on a European ancestral haplotype.

PubMed

Kwok, Chau-To; Vogelaar, Ingrid P; van Zelst-Stams, Wendy A; Mensenkamp, Arjen R; Ligtenberg, Marjolijn J; Rapkins, Robert W; Ward, Robyn L; Chun, Nicolette; Ford, James M; Ladabaum, Uri; McKinnon, Wendy C; Greenblatt, Marc S; Hitchins, Megan P

2014-05-01

Germline mutations of the DNA mismatch repair genes MLH1, MSH2, MSH6 or PMS2, and deletions affecting the EPCAM gene adjacent to MSH2, underlie Lynch syndrome by predisposing to early-onset colorectal, endometrial and other cancers. An alternative but rare cause of Lynch syndrome is constitutional epimutation of MLH1, whereby promoter methylation and transcriptional silencing of one allele occurs throughout normal tissues. A dominantly transmitted constitutional MLH1 epimutation has been linked to an MLH1 haplotype bearing two single-nucleotide variants, NM_000249.2: c.-27C>A and c.85G>T, in a Caucasian family with Lynch syndrome from Western Australia. Subsequently, a second seemingly unrelated Caucasian Australian case with the same MLH1 haplotype and concomitant epimutation was reported. We now describe three additional, ostensibly unrelated, cancer-affected families of European heritage with this MLH1 haplotype in association with constitutional epimutation, bringing the number of index cases reported to five. Array-based genotyping in four of these families revealed shared haplotypes between individual families that extended across ≤2.6-≤6.4 megabase regions of chromosome 3p, indicating common ancestry. A minimal ≤2.6 megabase founder haplotype common to all four families was identified, which encompassed MLH1 and additional flanking genes and segregated with the MLH1 epimutation in each family. Our findings indicate that the MLH1 c.-27C>A and c.85G>T variants are borne on a European ancestral haplotype and provide conclusive evidence for its pathogenicity via a mechanism of epigenetic silencing of MLH1 within normal tissues. Additional descendants bearing this founder haplotype may exist who are also at high risk of developing Lynch syndrome-related cancers.

Early Lung Cancer Diagnosis by Biosensors

PubMed Central

Zhang, Yuqian; Yang, Dongliang; Weng, Lixing; Wang, Lianhui

2013-01-01

Lung cancer causes an extreme threat to human health, and the mortality rate due to lung cancer has not decreased during the last decade. Prognosis or early diagnosis could help reduce the mortality rate. If microRNA and tumor-associated antigens (TAAs), as well as the corresponding autoantibodies, can be detected prior to clinical diagnosis, such high sensitivity of biosensors makes the early diagnosis and prognosis of cancer realizable. This review provides an overview of tumor-associated biomarker identifying methods and the biosensor technology available today. Laboratorial researches utilizing biosensors for early lung cancer diagnosis will be highlighted. PMID:23892596

Anti-early pregnancy by PDT

NASA Astrophysics Data System (ADS)

Ding, Ai-Hua; Chen, Hui-Ling

1993-03-01

The effect of laser on anti-early pregnancy in rabbits showed that laser in combination with HPD could induce necrosis of blastocysts and complete absorption. The anti-fertility efficiency of the combined treatment was more effective than that of the He-Ne laser or the HPD treatment alone. The fluorescence spectrum of HPD determined by PNQ3 showed that its affinity to embryonic tissue was about 4 times greater than that to uterine tissue. This may underlie the mechanisms of anti-early pregnancy of the laser. The operation of artificial abortion is a routine method to terminate early pregnancy. Though it is simple and easy, its syndrome and complications can not be absolutely avoided. Many antifertility drugs have been reported, however, they often bring in general reaction. Our present work is to explore a new way of anti-early pregnancy in rabbits by means of the light inhibitory and light sensitive effects of laser. It is a quite safe and painless treatment without expanding and scraping of the uterus.

TAILORx finds no chemotherapy benefit for most early breast cancers

Cancer.gov

Findings from the TAILORx clinical trial show chemotherapy does not benefit most women with early breast cancer. The new data, released at the 2018 ASCO annual meeting, will help inform treatment decisions for many women with early-stage breast cancer.

Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer

DTIC Science & Technology

2012-03-01

patients with early stage ErbB2-overexpressing biopsies and ER- atypia . 13 REFERENCES: 1. Jordan VC. Tamoxifen for breast cancer prevention. Proc Soc...Summary01-03-2012 Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer Shalini Jain University of Texas M.D. Anderson Cancer Center Houston...SUBTITLE “Src Kinase: A Novel Target of Early-Stage ER-Negative Breast Cancer” 5a. CONTRACT NUMBER W81XWH-11-1-0004 5b. GRANT NUMBER

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2017-11-01

SABR) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W Loo Jr, MD PhD CONTRACTING ORGANIZATION: The Leland Stanford Junior University...Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Billy W Loo Jr, MD...for early stage lung cancer in patients who are not candidates for surgery because of excessive surgical risk, and will be an important treatment option

DNA Copy Number Signature to Predict Recurrence in Early Stage Ovarian Cancer

DTIC Science & Technology

2016-08-01

AWARD NUMBER: W81XWH-14-1-0194 TITLE: DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer PRINCIPAL INVESTIGATOR...SUBTITLE 5a. CONTRACT NUMBER DNA Copy Number Signature to Predict Recurrence in Early-Stage Ovarian Cancer 5b. GRANT NUMBER W81XWH-14-1-0194 5c. PROGRAM...determine the copy number gain and loss for early stage high grade ovarian cancers through IlluminaHumanOmniExpress-FFPE BeadChip system • Subtask 1 DNA

Comment from the Editor to the Special Issue: “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis”

PubMed Central

Spaggiari, Lorenzo

2018-01-01

With this Editorial we want to present the Special Issue “Big Data and Precision Medicine Series I: Lung Cancer Early Diagnosis” to the scientific community, which aims to gather experts on the early detection of lung cancer in order to implement common efforts in the fight against cancer. PMID:29425180

A combination of circulating miRNAs for the early detection of ovarian cancer

PubMed Central

Yokoi, Akira; Yoshioka, Yusuke; Hirakawa, Akihiro; Yamamoto, Yusuke; Ishikawa, Mitsuya; Ikeda, Shun-ichi; Kato, Tomoyasu; Niimi, Kaoru; Kajiyama, Hiroaki; Kikkawa, Fumitaka; Ochiya, Takahiro

2017-01-01

Ovarian cancer is the leading cause of gynecologic cancer mortality, due to the difficulty of early detection. Current screening methods lack sufficient accuracy, and it is still challenging to propose a new early detection method that improves patient outcomes with less-invasiveness. Although many studies have suggested the utility of circulating microRNAs in cancer detection, their potential for early detection remains elusive. Here, we develop novel predictive models using a combination of 8 circulating serum miRNAs. This method was able to successfully distinguish ovarian cancer patients from healthy controls (area under the curve, 0.97; sensitivity, 0.92; and specificity, 0.91) and early-stage ovarian cancer from patients with benign tumors (0.91, 0.86 and 0.83, respectively). This method also enables subtype classification in 4 types of epithelial ovarian cancer. Furthermore, it is found that most of the 8 miRNAs were packaged in extracellular vesicles, including exosomes, derived from ovarian cancer cells, and they were circulating in murine blood stream. The circulating miRNAs described in this study may serve as biomarkers for ovarian cancer patients. Early detection and subtype determination prior to surgery are crucial for clinicians to design an effective treatment strategy for each patient, as is the goal of precision medicine. PMID:29163790

Liquid biopsy for early detection of lung cancer.

PubMed

Hofman, Paul

2017-01-01

The possibility of complete recovery for a lung cancer patient depends on very early diagnosis, as it allows total surgical resection. Screening for this cancer in a high-risk population can be performed using a radiological approach, but this holds a certain number of limitations. Liquid biopsy could become an alternative and complementary screening approach to chest imaging for early diagnosis of lung cancer. Several circulating biomarkers indicative of lung cancer can be investigated in blood, such as circulating tumor cells, circulating free nucleic acids (RNA and DNA) and proteins. However, none of these biomarkers have yet been adopted in routine clinical practice and studies are ongoing to confirm or not the usefulness and practical interest in routine early diagnosis and screening for lung cancers. Several potential circulating biomarkers for the early detection of lung cancer exist. When coupled to thoracic imaging, these biomarkers must give diagnosis of a totally resectable lung cancer and potentially provide new recommendations for surveillance by imagery of high-risk populations without a detectable nodule. Optimization of the specificity and sensitivity of the detection methods as well as standardization of the techniques is essential before considering for daily practice a liquid biopsy as an early diagnostic tool, or possibly as a predictive test, of lung cancer.

Strand exchange of telomeric DNA catalyzed by the Werner syndrome protein (WRN) is specifically stimulated by TRF2

PubMed Central

Edwards, Deanna N.; Orren, David K.; Machwe, Amrita

2014-01-01

Werner syndrome (WS), caused by loss of function of the RecQ helicase WRN, is a hereditary disease characterized by premature aging and elevated cancer incidence. WRN has DNA binding, exonuclease, ATPase, helicase and strand annealing activities, suggesting possible roles in recombination-related processes. Evidence indicates that WRN deficiency causes telomeric abnormalities that likely underlie early onset of aging phenotypes in WS. Furthermore, TRF2, a protein essential for telomere protection, interacts with WRN and influences its basic helicase and exonuclease activities. However, these studies provided little insight into WRN's specific function at telomeres. Here, we explored the possibility that WRN and TRF2 cooperate during telomeric recombination processes. Our results indicate that TRF2, through its interactions with both WRN and telomeric DNA, stimulates WRN-mediated strand exchange specifically between telomeric substrates; TRF2's basic domain is particularly important for this stimulation. Although TRF1 binds telomeric DNA with similar affinity, it has minimal effects on WRN-mediated strand exchange of telomeric DNA. Moreover, TRF2 is displaced from telomeric DNA by WRN, independent of its ATPase and helicase activities. Together, these results suggest that TRF2 and WRN act coordinately during telomeric recombination processes, consistent with certain telomeric abnormalities associated with alteration of WRN function. PMID:24880691

Chemoproteomics-Aided Medicinal Chemistry for the Discovery of EPHA2 Inhibitors.

PubMed

Heinzlmeir, Stephanie; Lohse, Jonas; Treiber, Tobias; Kudlinzki, Denis; Linhard, Verena; Gande, Santosh Lakshmi; Sreeramulu, Sridhar; Saxena, Krishna; Liu, Xiaofeng; Wilhelm, Mathias; Schwalbe, Harald; Kuster, Bernhard; Médard, Guillaume

2017-06-21

The receptor tyrosine kinase EPHA2 has gained attention as a therapeutic drug target for cancer and infectious diseases. However, EPHA2 research and EPHA2-based therapies have been hampered by the lack of selective small-molecule inhibitors. Herein we report the synthesis and evaluation of dedicated EPHA2 inhibitors based on the clinical BCR-ABL/SRC inhibitor dasatinib as a lead structure. We designed hybrid structures of dasatinib and the previously known EPHA2 binders CHEMBL249097, PD-173955, and a known EPHB4 inhibitor in order to exploit both the ATP pocket entrance as well as the ribose pocket as binding epitopes in the kinase EPHA2. Medicinal chemistry and inhibitor design were guided by a chemical proteomics approach, allowing early selectivity profiling of the newly synthesized inhibitor candidates. Concomitant protein crystallography of 17 inhibitor co-crystals delivered detailed insight into the atomic interactions that underlie the structure-affinity relationship. Finally, the anti-proliferative effect of the inhibitor candidates was confirmed in the glioblastoma cell line SF-268. In this work, we thus discovered a novel EPHA2 inhibitor candidate that features an improved selectivity profile while maintaining potency against EPHA2 and anticancer activity in SF-268 cells. © 2017 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim.

Analysis of the Cellular and Molecular Mechanisms Which Underlie Sensitivity to Bacterial Endotoxin and Early Tolerance

DTIC Science & Technology

1992-06-24

system, such as pneumococcal polysaccharide (Hiernaux et aI., 1989) or those that are presented by malignant tumors (O’Malley et ai., 1963). LPS...isolated the active ingredient, which they called ’’bacterial polysaccharide " (Shear and Andervont, 1936). The practice of inducing "therapeutic febrile...acylated, diphosphorylated, ~-1,6-linked D-glucosamine disaccharide (referred to as lipid A) which is attached covalently to a core polysaccharide that

Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management.

PubMed

Mulshine, James L; Avila, Rick; Yankelevitz, David; Baer, Thomas M; Estépar, Raul San Jose; Ambrose, Laurie Fenton; Aldigé, Carolyn R

2015-05-01

The Prevent Cancer Foundation Lung Cancer Workshop XI: Tobacco-Induced Disease: Advances in Policy, Early Detection and Management was held in New York, NY on May 16 and 17, 2014. The two goals of the Workshop were to define strategies to drive innovation in precompetitive quantitative research on the use of imaging to assess new therapies for management of early lung cancer and to discuss a process to implement a national program to provide high quality computed tomography imaging for lung cancer and other tobacco-induced disease. With the central importance of computed tomography imaging for both early detection and volumetric lung cancer assessment, strategic issues around the development of imaging and ensuring its quality are critical to ensure continued progress against this most lethal cancer.

Preference for language in early infancy: the human language bias is not speech specific.

PubMed

Krentz, Ursula C; Corina, David P

2008-01-01

Fundamental to infants' acquisition of their native language is an inherent interest in the language spoken around them over non-linguistic environmental sounds. The following studies explored whether the bias for linguistic signals in hearing infants is specific to speech, or reflects a general bias for all human language, spoken and signed. Results indicate that 6-month-old infants prefer an unfamiliar, visual-gestural language (American Sign Language) over non-linguistic pantomime, but 10-month-olds do not. These data provide evidence against a speech-specific bias in early infancy and provide insights into those properties of human languages that may underlie this language-general attentional bias.

T regulatory cells in childhood asthma.

PubMed

Strickland, Deborah H; Holt, Patrick G

2011-09-01

Asthma is a chronic disease of the airways, most commonly driven by immuno-inflammatory responses to ubiquitous airborne antigens. Epidemiological studies have shown that disease is initiated early in life when the immune and respiratory systems are functionally immature and less able to maintain homeostasis in the face of continuous antigen challenge. Here, we examine the cellular and molecular mechanisms that underlie initial aeroallergen sensitization and the ensuing regulation of secondary responses to inhaled allergens in the airway mucosa. In particular, we focus on how T-regulatory (Treg) cells influence early asthma initiation and the potential of Treg cells as therapeutic targets for drug development in asthma. Copyright © 2011 Elsevier Ltd. All rights reserved.

Increased global transcription activity as a mechanism of replication stress in cancer

PubMed Central

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M.; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-01-01

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRASV12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRASV12, elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer. PMID:27725641

Increased global transcription activity as a mechanism of replication stress in cancer.

PubMed

Kotsantis, Panagiotis; Silva, Lara Marques; Irmscher, Sarah; Jones, Rebecca M; Folkes, Lisa; Gromak, Natalia; Petermann, Eva

2016-10-11

Cancer is a disease associated with genomic instability that often results from oncogene activation. This in turn leads to hyperproliferation and replication stress. However, the molecular mechanisms that underlie oncogene-induced replication stress are still poorly understood. Oncogenes such as HRAS V12 promote proliferation by upregulating general transcription factors to stimulate RNA synthesis. Here we investigate whether this increase in transcription underlies oncogene-induced replication stress. We show that in cells overexpressing HRAS V12 , elevated expression of the general transcription factor TATA-box binding protein (TBP) leads to increased RNA synthesis, which together with R-loop accumulation results in replication fork slowing and DNA damage. Furthermore, overexpression of TBP alone causes the hallmarks of oncogene-induced replication stress, including replication fork slowing, DNA damage and senescence. Consequently, we reveal that increased transcription can be a mechanism of oncogene-induced DNA damage, providing a molecular link between upregulation of the transcription machinery and genomic instability in cancer.

Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks

PubMed Central

Albergante, Luca; Blow, J Julian; Newman, Timothy J

2014-01-01

The gene regulatory network (GRN) is the central decision‐making module of the cell. We have developed a theory called Buffered Qualitative Stability (BQS) based on the hypothesis that GRNs are organised so that they remain robust in the face of unpredictable environmental and evolutionary changes. BQS makes strong and diverse predictions about the network features that allow stable responses under arbitrary perturbations, including the random addition of new connections. We show that the GRNs of E. coli, M. tuberculosis, P. aeruginosa, yeast, mouse, and human all verify the predictions of BQS. BQS explains many of the small- and large‐scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response. BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation. DOI: http://dx.doi.org/10.7554/eLife.02863.001 PMID:25182846

Buffered Qualitative Stability explains the robustness and evolvability of transcriptional networks.

PubMed

Albergante, Luca; Blow, J Julian; Newman, Timothy J

2014-09-02

The gene regulatory network (GRN) is the central decision-making module of the cell. We have developed a theory called Buffered Qualitative Stability (BQS) based on the hypothesis that GRNs are organised so that they remain robust in the face of unpredictable environmental and evolutionary changes. BQS makes strong and diverse predictions about the network features that allow stable responses under arbitrary perturbations, including the random addition of new connections. We show that the GRNs of E. coli, M. tuberculosis, P. aeruginosa, yeast, mouse, and human all verify the predictions of BQS. BQS explains many of the small- and large-scale properties of GRNs, provides conditions for evolvable robustness, and highlights general features of transcriptional response. BQS is severely compromised in a human cancer cell line, suggesting that loss of BQS might underlie the phenotypic plasticity of cancer cells, and highlighting a possible sequence of GRN alterations concomitant with cancer initiation. Copyright © 2014, Albergante et al.

Prolactin Alters the Mammary Epithelial Hierarchy, Increasing Progenitors and Facilitating Ovarian Steroid Action.

PubMed

O'Leary, Kathleen A; Shea, Michael P; Salituro, Stephanie; Blohm, Courtney E; Schuler, Linda A

2017-10-10

Hormones drive mammary development and function and play critical roles in breast cancer. Epidemiologic studies link prolactin (PRL) to increased risk for aggressive cancers that express estrogen receptor α (ERα). However, in contrast to ovarian steroids, PRL actions on the mammary gland outside of pregnancy are poorly understood. We employed the transgenic NRL-PRL model to examine the effects of PRL alone and with defined estrogen/progesterone exposure on stem/progenitor activity and regulatory networks that drive epithelial differentiation. PRL increased progenitors and modulated transcriptional programs, even without ovarian steroids, and with steroids further raised stem cell activity associated with elevated canonical Wnt signaling. However, despite facilitating some steroid actions, PRL opposed steroid-driven luminal maturation and increased CD61 + luminal cells. Our findings demonstrate that PRL can powerfully influence the epithelial hierarchy alone and temper the actions of ovarian steroids, which may underlie its role in the development of breast cancer. Copyright © 2017 The Author(s). Published by Elsevier Inc. All rights reserved.

Glycoprofiling of Early Gastric Cancer Using Lectin Microarray Technology.

PubMed

Li, Taijie; Mo, Cuiju; Qin, Xue; Li, Shan; Liu, Yinkun; Liu, Zhiming

2018-01-01

Recently, studies have reported that protein glycosylation plays an important role in the occurrence and development of cancer. Gastric cancer is a common cancer with high morbidity and mortality owing to most gastric cancers are discovered only at an advanced stage. Here, we aim to discover novel specific serum glycanbased biomarkers for gastric cancer. A lectin microarray with 50 kinds of tumor-associated lectin was used to detect the glycan profiles of serum samples between early gastric cancer and healthy controls. Then lectin blot was performed to validate the differences. The result of the lectin microarray showed that the signal intensities of 13 lectins showed significant differences between the healthy controls and early gastric cancer. Compared to the healthy, the normalized fluorescent intensities of the lectins PWA, LEL, and STL were significantly increased, and it implied that their specifically recognized GlcNAc showed an especially elevated expression in early gastric cancer. Moreover, the binding affinity of the lectins EEL, RCA-II, RCA-I, VAL, DSA, PHA-L, UEA, and CAL were higher in the early gastric cancer than in healthy controls. These glycan structures containing GalNAc, terminal Galβ 1-4 GlcNAc, Tri/tetraantennary N-glycan, β-1, 6GlcNAc branching structure, α-linked fucose residues, and Tn antigen were elevated in gastric cancer. While the two lectins CFL GNL reduced their binding ability. In addition, their specifically recognized N-acetyl-D-galactosamine structure and (α-1,3) mannose residues were decreased in early gastric cancer. Furthermore, lectin blot results of LEL, STL, PHA-L, RCA-I were consistent with the results of the lectin microarray. The findings of our study clarify the specific alterations for glycosylation during the pathogenesis of gastric cancer. The specific high expression of GlcNAc structure may act as a potential early diagnostic marker for gastric cancer.

Colorectal Cancer: The Importance of Early Detection

MedlinePlus

... of this page please turn JavaScript on. Feature: Colorectal Cancer The Importance of Early Detection Past Issues / Summer ... Cancer of the colon or rectum is called colorectal cancer. The colon and the rectum are part of ...

Health Information in Bengali (Bangla / বাংলা)

MedlinePlus

... Society Guidelines for the Early Detection of Cancer - English PDF American Cancer Society Guidelines for the Early ... Screening It's a Simple Test - Cervical Cancer Screening - English PDF It's a Simple Test - Cervical Cancer Screening - ...

Perspectives and Open Problems in the Early Phases of Left-Right Patterning

PubMed Central

Vandenberg, Laura N.; Levin, Michael

2009-01-01

Summary Embryonic left-right (LR) patterning is a fascinating aspect of embryogenesis. The field currently faces important questions about the origin of LR asymmetry, the mechanisms by which consistent asymmetry is imposed on the scale of the whole embryo, and the degree of conservation of early phases of LR patterning among model systems. Recent progress on planar cell polarity and cellular asymmetry in a variety of tissues and species provides a new perspective on the early phases of LR patterning. Despite the huge diversity in body-plans over which consistent LR asymmetry is imposed, and the apparent divergence in molecular pathways that underlie laterality, the data reveal conservation of physiological modules among phyla and a basic scheme of cellular chirality amplified by a planar cell polarity-like pathway over large cell fields. PMID:19084609

Apoptosis and cell proliferation in the development of gastric carcinomas: associations with c-myc and p53 protein expression.

PubMed

Ishii, Hideaki H; Gobé, Glenda C; Pan, Wenshen; Yoneyama, Juichi; Ebihara, Yoshiro

2002-09-01

Patients with gastric carcinomas have a poor prognosis and low survival rates. The aim of the present paper was to characterize cellular and molecular properties to provide insight into aspects of tumor progression in early compared with advanced gastric cancers. One hundred and nine graded gastric carcinomas (early or advanced stage, undifferentiated or differentiated type) with paired non-cancer tissue were studied to define the correlation between apoptosis (morphology, terminal deoxyribonucleotidyl transferase-mediated dUTP-digoxigenin nick end-labeling), cell proliferation (Ki-67 expression, morphology) and expression and localization of two proteins frequently having altered expression in cancers, namely p53 and c-myc. Overall, apoptosis was lower in early stage, differentiated and undifferentiated gastric carcinomas compared with advanced-stage cancers. Cell proliferation was comparatively high in all stages. There was a high level of p53 positivity in all stages. Only the early- and advanced-stage undifferentiated cancers that were p53 positive had a significantly higher level of apoptosis (P < 0.05). Cell proliferation was significantly greater (P < 0.05) only in the early undifferentiated cancers that had either c-myc or p53-positivity. The results indicate that low apoptosis and high cell proliferation combine to drive gastric cancer development. The molecular controls for high cell proliferation of the early stage undifferentiated gastric cancers involve overexpression of both p53 and c-myc. Overexpression of p53 may also control cancer development in that its expression is associated with higher levels of apoptosis in early and late-stage undifferentiated, cancers. Copyright 2002 Blackwell Publishing Asia Pty Ltd

Barriers for Early Detection of Cancer Amongst Urban Indian Women: A Cross Sectional Study

PubMed Central

Kadam, Yugantara R.; Quraishi, Sanjay R.; Dhoble, Randheer V.; Sawant, Minaxi R.; Gore, Alka D.

2016-01-01

Background: Cancer is a leading cause of death globally. Every year, millions of cancer patients could be saved from premature death and and suffering if they had timely access to early detection and treatment. There are two main components of early detection: early diagnosis and screening. In India, cancers of cervix, breast, mouth/oropharynx are the most frequent cancers in women. These cancers are amenable to early detection. More than two third of the cancer patients are already in an advanced and incurable stage at the time of diagnosis. Objectives: This study was designed with the aim to know the reasons for non availment of cancer screening procedures and early diagnostic facilities. Materials and Methods: This cross-sectional study was planned in Sangli, Miraj and Kupwad Corporation area during October 2013 - March 2014 by a pretested questionnaire. Women of 25 years and above were study subjects selected randomly from a cluster sample of ward with estimated sample size of 559 women. Statistical analysis was done with the help of IBM SPSS 22. Results: Nearly 74% of women said that cancer is curable. For awareness about signs and symptoms, risk factors and screening test 82.3% women scored less than 50% of total score. Only 17.7% women had awareness score more than 50%. But their attitude score was > 50% in 85.2% of women. For practice score, 24.4% women scored > 50%. Significant association was found between awareness, attitude and practice scores and education, occupation and history of cancer in family, friends and neighborhood of respondents. Conclusions: Low awareness is the main barrier for undergoing cancer screening and early detection. There is a need of effective health education programme. PMID:27366310

Choroidal metastasis from early rectal cancer: Case report and literature review

PubMed Central

Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

2014-01-01

INTRODUCTION Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. PRESENTATION OF CASE A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. DISCUSSION Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. CONCLUSION This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. PMID:25460493

Choroidal metastasis from early rectal cancer: Case report and literature review.

PubMed

Tei, Mitsuyoshi; Wakasugi, Masaki; Akamatsu, Hiroki

2014-01-01

Choroidal metastasis from colorectal cancer is rare, and there have been no reported cases of such metastasis from early colorectal cancer. We report a case of choroidal metastasis from early rectal cancer. A 61 year-old-man experienced myodesopsia in the left eye 2 years and 6 months after primary rectal surgery for early cancer, and was diagnosed with left choroidal metastasis and multiple lung metastases. Radiotherapy was initiated for the left eye and systemic chemotherapy is initiated for the multiple lung metastases. The patient is living 2 years and 3 months after the diagnosis of choroidal metastasis without signs of recurrence in the left eye, and continues to receive systemic chemotherapy for multiple lung metastases. Current literatures have few recommendations regarding the appropriate treatment of choroidal metastasis from colorectal cancer, but an aggressive multi-disciplinary approach may be effective in local regression. This is the first report of choroidal metastasis from early rectal cancer. We consider it important to enforce systemic chemotherapy in addition to radiotherapy for choroidal metastasis from colorectal cancer. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

Early dissemination seeds metastasis in breast cancer

PubMed Central

Hosseini, Hedayatollah; Obradović, Milan M.S.; Hoffmann, Martin; Harper, Kathryn; Sosa, Maria Soledad; Werner-Klein, Melanie; Nanduri, Lahiri Kanth; Werno, Christian; Ehrl, Carolin; Maneck, Matthias; Patwary, Nina; Haunschild, Gundula; Gužvić, Miodrag; Reimelt, Christian; Grauvogl, Michael; Eichner, Norbert; Weber, Florian; Hartkopf, Andreas; Taran, Florin-Andrei; Brucker, Sara Y.; Fehm, Tanja; Rack, Brigitte; Buchholz, Stefan; Spang, Rainer; Meister, Gunter; Aguirre-Ghiso, Julio A.; Klein, Christoph A.

2016-01-01

Accumulating data suggest that metastatic dissemination often occurs early during tumour formation but the mechanisms of early metastatic spread have not yet been addressed. Here, we studied metastasis in a HER2-driven mouse breast cancer model and found that progesterone-induced signalling triggered migration of cancer cells from early lesions shortly after HER2 activation, but promoted proliferation in advanced primary tumour cells. The switch from migration to proliferation was regulated by elevated HER2 expression and increased tumour cell density involving miRNA-mediated progesterone receptor (PGR) down-regulation and was reversible. Cells from early, low-density lesions displayed more stemness features than cells from dense, advanced tumours, migrated more and founded more metastases. Strikingly, we found that at least 80% of metastases were derived from early disseminated cancer cells (DCC). Karyotypic and phenotypic analysis of human disseminated cancer cells and primary tumours corroborated the relevance of these findings for human metastatic dissemination. PMID:27974799

[Recurrent urological cancer--diagnose and treatment].

PubMed

Takeshima, H; Akaza, H

1998-02-01

Clinical efforts to spare bladder function even in the case of muscle invasive recurrent bladder cancer is taking. Early detection of recurrence is essential for bladder sparing, and both urinary NMP22 and BTA are thought to have potency to detect recurrence of bladder cancer earlier than urinary cytology. Intravesical administration of BCG for superficial bladder cancer and intraarterial injection of chemoagents (Methotrexate and Cisplatin) with radiation for muscle invasive bladder cancer are thought to play important roles in sparing the bladder. Early detection of recurrent prostate cancer is becoming easier by ultrasensitive PSA assay. Though the value of early detection of recurrence is not proven since the benefits of early hormonal treatment have not yet been established, that should be a good indicator to evaluate new and coming treatments and play a important role to develop an effective treatment for recurrent prostate cancer.

An early history of human breast cancer: West meets East.

PubMed

Yan, Shou-He

2013-09-01

Cancer has been increasingly recognized as a global issue. This is especially true in countries like China, where cancer incidence has increased likely because of changes in environment and lifestyle. However, cancer is not a modern disease; early cases have been recorded in ancient medical books in the West and in China. Here, we provide a brief history of cancer, focusing on cancer of the breast, and review the etymology of ai, the Chinese character for cancer. Notable findings from both Western and Chinese traditional medicine are presented to give an overview of the most important, early contributors to our evolving understanding of human breast cancer. We also discuss the earliest historical documents to record patients with breast cancer.

Promoting Cancer Control in Africa With "Ubuntu": A Report of the African Organization for Research and Training in Africa (AORTIC) 10th Conference, 2015 in Marrakech, Morocco.

PubMed

Simbiri, Kenneth O; Williams, Christopher K; Macaluso, Marcella; Giordano, Antonio

2017-09-01

The objectives of the African Organization for Research and Training in Cancer (AORTIC), includes bringing products of decades of advances in cancer research to African populations through local and international collaboration. The consistent and huge growth in participation in the conferences and the diversity of the nations is a witness to the success of the organization thus far. The theme for the Tenth AORTIC International Conference on Cancer in Africa in Morocco in 2015 was "Road map to Cancer Control in Africa" and topics of discussion of paramount importance for low- and middle-income African countries included childhood cancers such as BL, cancers of the cervix, breast, and prostate; cancers associated with HIV-infection such as cervical, vulvar, and anal; as well as cancer care challenges associated with palliative care. The role of environmental factors that underlie some epigenetic changes in some of the cancers was emphasized. Oral and poster presentations from various parts of the continent indicate the growth of basic and translational science of cancer in the region, with studies revealing regional diversity in the frequencies of the triple-negative breast cancer, cervical cancer, prostate cancer, HCC, and Burkitt's lymphoma. There was a sign that Africa is trying to keep pace with the paradigm shift and focusing on translational medicine. This was shown by suggestions for application of genome-wide association studies, new generation sequencing, as well as the evaluation of single nucleotide polymorphisms that may be responsible for variable susceptibility in some of the prevalent cancers in people of African descent. J. Cell. Physiol. 232: 2287-2295, 2017. © 2016 Wiley Periodicals, Inc. © 2016 Wiley Periodicals, Inc.

Comparison of gene-expression profiles between diffuse- and intestinal-type gastric cancers using a genome-wide cDNA microarray.

PubMed

Jinawath, Natini; Furukawa, Yoichi; Hasegawa, Suguru; Li, Meihua; Tsunoda, Tatsuhiko; Satoh, Seiji; Yamaguchi, Toshiharu; Imamura, Hiroshi; Inoue, Masatomo; Shiozaki, Hitoshi; Nakamura, Yusuke

2004-09-02

Gastric cancer is the fourth leading cause of cancer-related death in the world. Two histologically distinct types of gastric carcinoma, 'intestinal' and 'diffuse', have different epidemiological and pathophysiological features that suggest different mechanisms of carcinogenesis. A number of studies have investigated intestinal-type gastric cancers at the molecular level, but little is known about mechanisms involved in the diffuse type, which has a more invasive phenotype and poorer prognosis. To clarify the mechanisms that underlie its development and/or progression, we compared the expression profiles of 20 laser-microbeam-microdissected diffuse-type gastric-cancer tissues with corresponding noncancerous mucosae by means of a cDNA microarray containing 23,040 genes. We identified 153 genes that were commonly upregulated and more than 1500 that were commonly downregulated in the tumors. We also identified a number of genes related to tumor progression. Furthermore, comparison of the expression profiles of diffuse-type with those of intestinal-type gastric cancers identified 46 genes that may represent distinct molecular signatures of each histological type. The putative signature of diffuse-type cancer exhibited altered expression of genes related to cell-matrix interaction and extracellular-matrix (ECM) components, whereas that of intestinal-type cancer represented enhancement of cell growth. These data provide insight into different mechanisms underlying gastric carcinogenesis and may also serve as a starting point for identifying novel diagnostic markers and/or therapeutic targets for diffuse-type gastric cancers.

77 FR 51807 - Agency Forms Undergoing Paperwork Reduction Act Review

Federal Register 2010, 2011, 2012, 2013, 2014

2012-08-27

... Minimum Data Elements (MDEs) for the National Breast and Cervical Cancer Early Detection Program (NBCCEDP... screening and early detection tests for breast and cervical cancer. Mammography is extremely valuable as an early detection tool because it can detect breast cancer well before the woman can feel the lump, when...

Use of Autoantibodies to Detect the Onset of Breast Cancer

PubMed Central

Mangé, Alain; Solassol, Jérôme

2014-01-01

The widespread use of screening mammography has resulted in increased detection of early-stage breast disease, particularly for in situ carcinoma and early-stage breast cancer. However, the majority of women with abnormalities noted on screening mammograms are not diagnosed with cancer because of several factors, including radiologist assessment, patient age, breast density, malpractice concerns, and quality control procedures. Although magnetic resonance imaging is a highly sensitive detection tool that has become standard for women at very high risk of developing breast cancer, it lacks sufficient specificity and costeffectiveness for use as a general screening tool. Therefore, there is an important need to improve screening and diagnosis of early-invasive and noninvasive tumors, that is, in situ carcinoma. The great potential for molecular tools to improve breast cancer outcomes based on early diagnosis has driven the search for diagnostic biomarkers. Identification of tumor-specific markers capable of eliciting an immune response in the early stages of tumor development seems to provide an effective approach for early diagnosis. The aim of this review is to describe several autoantibodies identified during breast cancer diagnosis. We will focus on these molecules highlighted in the past two years and discuss the potential future use of autoantibodies as biomarkers of early-stage breast cancer. PMID:25143958

Blood-Based Biomarkers of Early-Onset Breast Cancer

DTIC Science & Technology

2015-10-01

n=51). The women with early-onset breast cancer were disease and treatment free for at least 6 months at time of blood donation . Cases and controls...were age matched to age at blood donation . 2. KEYWORDS: biomarkers, early-onset breast cancer, expression profiling, risk-assessment, breast cancer...matched controls. This prospectively collected cohort consists of blood donated to blood banks ~15 years ago and subsequently linked to the California

Synergistic Tailoring of Electrostatic and Hydrophobic Interactions for Rapid and Specific Recognition of Lysophosphatidic Acid, an Early-Stage Ovarian Cancer Biomarker.

PubMed

Wang, Ying; Pei, Hanwen; Jia, Yan; Liu, Jianhua; Li, Zelun; Ai, Kelong; Lu, Zhongyuan; Lu, Lehui

2017-08-23

Early detection of ovarian cancer, the most lethal type of gynecologic cancer, can dramatically improve the efficacy of available treatment strategies. However, few screening tools exist for rapidly and effectively diagnosing ovarian cancer in early stages. Here, we present a facile "lock-key" strategy, based on rapid, specific detection of plasma lysophosphatidic acid (LPA, an early stage biomarker) with polydiacetylenes (PDAs)-based probe, for the early diagnosis of ovarian cancer. This strategy relies on specifically inserting LPA "key" into the PDAs "lock" through the synergistic electrostatic and hydrophobic interactions between them, leading to conformation transition of the PDA backbone with a concomitant blue-to-red color change. The detailed mechanism underlying the high selectivity of PDAs toward LPA is revealed by comprehensive theoretical calculation and experiments. Moreover, the level of LPA can be quantified in plasma samples from both mouse xenograft tumor models and patients with ovarian cancer. Impressively, this approach can be introduced into a portable point-of-care device to successfully distinguish the blood samples of patients with ovarian cancer from those of healthy people, with 100% accuracy. This work provides a valuable portable tool for early diagnosis of ovarian cancer and thus holds a great promise to dramatically improve the overall survival.

Dynamic Patterns of Clonal Evolution in Tumor Vasculature Underlie Alterations in Lymphocyte-Endothelial Recognition to Foster Tumor Immune Escape.

PubMed

Corey, Daniel M; Rinkevich, Yuval; Weissman, Irving L

2016-03-15

Although tumor blood vessels have been a major therapeutic target for cancer chemotherapy, little is known regarding the stepwise development of the tumor microenvironment. Here, we use a multicolor Cre-dependent marker system to trace clonality within the tumor microenvironment to show that tumor blood vessels follow a pattern of dynamic clonal evolution. In an advanced melanoma tumor microenvironment, the vast majority of tumor vasculature clones are derived from a common precursor. Quantitative lineage analysis reveals founder clones diminish in frequency and are replaced by subclones as tumors evolve. These tumor-specific blood vessels are characterized by a developmental switch to a more invasive and immunologically silent phenotype. Gene expression profiling and pathway analysis reveals selection for traits promoting upregulation of alternative angiogenic programs such as unregulated HGF-MET signaling and enhanced autocrine signaling through VEGF and PDGF. Furthermore, we show a developmental switch in the expression of functionally significant primary lymphocyte adhesion molecules on tumor endothelium, such as the loss in expression of the mucosal addressin MAdCAM-1, whose counter receptor a4β7 on lymphocytes controls lymphocyte homing. Changes in adhesive properties on tumor endothelial subclones are accompanied by decreases in expression of lymphocyte chemokines CXCL16, CXCL13, CXCL12, CXCL9, CXCL10, and CCL19. These evolutionary patterns in the expressed genetic program within tumor endothelium will have both a quantitative and functional impact on lymphocyte distribution that may well influence tumor immune function and underlie escape mechanisms from current antiangiogenic pharmacotherapies. ©2015 American Association for Cancer Research.

SB225002 Induces Cell Death and Cell Cycle Arrest in Acute Lymphoblastic Leukemia Cells through the Activation of GLIPR1

PubMed Central

Leal, Paulo C.; Bhasin, Manoj K.; Zenatti, Priscila Pini; Nunes, Ricardo J.; Yunes, Rosendo A.; Nowill, Alexandre E.; Libermann, Towia A.; Zerbini, Luiz Fernando; Yunes, José Andrés

2015-01-01

Acute Lymphoblastic Leukemia (ALL) is the most frequent childhood malignancy. In the effort to find new anti-leukemic agents, we evaluated the small drug SB225002 (N-(2-hydroxy-4-nitrophenyl)-N’-(2-bromophenyl)urea). Although initially described as a selective antagonist of CXCR2, later studies have identified other cellular targets for SB225002, with potential medicinal use in cancer. We found that SB225002 has a significant pro-apoptotic effect against both B- and T-ALL cell lines. Cell cycle analysis demonstrated that treatment with SB225002 induces G2-M cell cycle arrest. Transcriptional profiling revealed that SB225002-mediated apoptosis triggered a transcriptional program typical of tubulin binding agents. Network analysis revealed the activation of genes linked to the JUN and p53 pathways and inhibition of genes linked to the TNF pathway. Early cellular effects activated by SB225002 included the up-regulation of GLIPR1, a p53-target gene shown to have pro-apoptotic activities in prostate and bladder cancer. Silencing of GLIPR1 in B- and T-ALL cell lines resulted in increased resistance to SB225002. Although SB225002 promoted ROS increase in ALL cells, antioxidant N-Acetyl Cysteine pre-treatment only modestly attenuated cell death, implying that the pro-apoptotic effects of SB225002 are not exclusively mediated by ROS. Moreover, GLIPR1 silencing resulted in increased ROS levels both in untreated and SB225002-treated cells. In conclusion, SB225002 induces cell cycle arrest and apoptosis in different B- and T-ALL cell lines. Inhibition of tubulin function with concurrent activation of the p53 pathway, in particular, its downstream target GLIPR1, seems to underlie the anti-leukemic effect of SB225002. PMID:26302043

Mixture models for undiagnosed prevalent disease and interval-censored incident disease: applications to a cohort assembled from electronic health records.

PubMed

Cheung, Li C; Pan, Qing; Hyun, Noorie; Schiffman, Mark; Fetterman, Barbara; Castle, Philip E; Lorey, Thomas; Katki, Hormuzd A

2017-09-30

For cost-effectiveness and efficiency, many large-scale general-purpose cohort studies are being assembled within large health-care providers who use electronic health records. Two key features of such data are that incident disease is interval-censored between irregular visits and there can be pre-existing (prevalent) disease. Because prevalent disease is not always immediately diagnosed, some disease diagnosed at later visits are actually undiagnosed prevalent disease. We consider prevalent disease as a point mass at time zero for clinical applications where there is no interest in time of prevalent disease onset. We demonstrate that the naive Kaplan-Meier cumulative risk estimator underestimates risks at early time points and overestimates later risks. We propose a general family of mixture models for undiagnosed prevalent disease and interval-censored incident disease that we call prevalence-incidence models. Parameters for parametric prevalence-incidence models, such as the logistic regression and Weibull survival (logistic-Weibull) model, are estimated by direct likelihood maximization or by EM algorithm. Non-parametric methods are proposed to calculate cumulative risks for cases without covariates. We compare naive Kaplan-Meier, logistic-Weibull, and non-parametric estimates of cumulative risk in the cervical cancer screening program at Kaiser Permanente Northern California. Kaplan-Meier provided poor estimates while the logistic-Weibull model was a close fit to the non-parametric. Our findings support our use of logistic-Weibull models to develop the risk estimates that underlie current US risk-based cervical cancer screening guidelines. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA. Published 2017. This article has been contributed to by US Government employees and their work is in the public domain in the USA.

Off to the Organelles - Killing Cancer Cells with Targeted Gold Nanoparticles

PubMed Central

Kodiha, Mohamed; Wang, Yi Meng; Hutter, Eliza; Maysinger, Dusica; Stochaj, Ursula

2015-01-01

Gold nanoparticles (AuNPs) are excellent tools for cancer cell imaging and basic research. However, they have yet to reach their full potential in the clinic. At present, we are only beginning to understand the molecular mechanisms that underlie the biological effects of AuNPs, including the structural and functional changes of cancer cells. This knowledge is critical for two aspects of nanomedicine. First, it will define the AuNP-induced events at the subcellular and molecular level, thereby possibly identifying new targets for cancer treatment. Second, it could provide new strategies to improve AuNP-dependent cancer diagnosis and treatment. Our review summarizes the impact of AuNPs on selected subcellular organelles that are relevant to cancer therapy. We focus on the nucleus, its subcompartments, and mitochondria, because they are intimately linked to cancer cell survival, growth, proliferation and death. While non-targeted AuNPs can damage tumor cells, concentrating AuNPs in particular subcellular locations will likely improve tumor cell killing. Thus, it will increase cancer cell damage by photothermal ablation, mechanical injury or localized drug delivery. This concept is promising, but AuNPs have to overcome multiple hurdles to perform these tasks. AuNP size, morphology and surface modification are critical parameters for their delivery to organelles. Recent strategies explored all of these variables, and surface functionalization has become crucial to concentrate AuNPs in subcellular compartments. Here, we highlight the use of AuNPs to damage cancer cells and their organelles. We discuss current limitations of AuNP-based cancer research and conclude with future directions for AuNP-dependent cancer treatment. PMID:25699096

Epigenetic susceptibility factors for prostate cancer with aging.

PubMed

Damaschke, N A; Yang, B; Bhusari, S; Svaren, J P; Jarrard, D F

2013-12-01

Increasing age is a significant risk factor for prostate cancer. The prostate is exposed to environmental and endogenous stress that may underlie this remarkable incidence. DNA methylation, genomic imprinting, and histone modifications are examples of epigenetic factors known to undergo change in the aging and cancerous prostate. In this review we examine the data linking epigenetic alterations in the prostate with aging to cancer development. An online search of current and past peer reviewed literature on epigenetic changes with cancer and aging was performed. Relevant articles were analyzed. Epigenetic changes are responsible for modifying expression of oncogenes and tumor suppressors. Several of these changes may represent a field defect that predisposes to cancer development. Focal hypermethylation occurs at CpG islands in the promoters of certain genes including GSTP1, RARβ2, and RASSF1A with both age and cancer, while global hypomethylation is seen in prostate cancer and known to occur in the colon and other organs. A loss of genomic imprinting is responsible for biallelic expression of the well-known Insulin-like Growth Factor 2 (IGF2) gene. Loss of imprinting (LOI) at IGF2 has been documented in cancer and is also known to occur in benign aging prostate tissue marking the presence of cancer. Histone modifications have the ability to dictate chromatin structure and direct gene expression. Epigenetic changes with aging represent molecular mechanisms to explain the increased susceptibly of the prostate to develop cancer in older men. These changes may provide an opportunity for diagnostic and chemopreventive strategies given the epigenome can be modified. © 2013 Wiley Periodicals, Inc.

Management of low-risk early-stage cervical cancer: Should conization, simple trachelectomy, or simple hysterectomy replace radical surgery as the new standard of care?

PubMed Central

Ramirez, Pedro T.; Pareja, Rene; Rendón, Gabriel J.; Millan, Carlos; Frumovitz, Michael; Schmeler, Kathleen M.

2014-01-01

The standard treatment for women with early-stage cervical cancer (IA2-IB1) remains radical hysterectomy with pelvic lymphadenectomy. In select patients interested in future fertility, the option of radical trachelectomy with pelvic lymphadenectomy is also considered a viable option. The possibility of less radical surgery may be appropriate not only for patients desiring to preserve fertility but also for all patients with low-risk early-stage cervical cancer. Recently, a number of studies have explored less radical surgical options for early-stage cervical cancer, including simple hysterectomy, simple trachelectomy, and cervical conization with or without sentinel lymph node biopsy and pelvic lymph node dissection. Such options may be available for patients with low-risk early-stage cervical cancer. Criteria that define this low-risk group include: squamous carcinoma, adenocarcinoma, or adenosquamous carcinoma, tumor size <2 cm, stromal invasion <10mm, and no lymph-vascular space invasion. In this report, we provide a review of the existing literature on the conservative management of cervical cancer and describe ongoing multi-institutional trials evaluating the role of conservative surgery in selected patients with early-stage cervical cancer. PMID:24041877

The African Organisation for Research and Training in Cancer and its conferences: a historical perspective and highlights of the Ninth International Conference, Durban, South Africa, 21–24 November 2013

PubMed Central

Williams, Christopher KO; Cristina Stefan, D; Rawlinson, Fiona; Simbiri, Kenneth; Mbulaiteye, Sam M

2014-01-01

The objectives of the African Organisation for Research and Training in Cancer (AORTIC), both at its inception in the early 1980s, and at its reactivation in 2000 following a decade of inactivity, included bringing the products of decades of advances in cancer research to African populations through international collaboration. The historical perspective provided in this report illustrates progress in achieving these objectives through successive continent-wide activities over a period of 30 years, culminating in the organisation’s most recent conference held in Durban, South Africa, 21–24 November 2013. The constant growth in the number of attendants and increasing diversity of the nations of their origin are consistent with advances, whereby the number of participants and the nations of their origin have grown from 24 in 1983 to almost 1000 in 2013, and from 14 to 70, respectively. While earlier AORTIC conferences used to assume the atmosphere of ‘jamborees’, more recent ones have morphed to problem-solving events, with the concerted collaboration of international organisations, including the World Health Organisation (WHO), International Union Against Cancer (UICC), the Africa Union (AU), the US National Cancer Institute (NCI), the International Psycho-Oncology Society (IPOS), and others. The topics of discussion at the Ninth AORTIC International Conference on Cancer in Africa in Durban were those of paramount importance for low- and middle-income countries: childhood cancers, cancers of the cervix, breast, and prostate, as well as cancer care challenges resulting from ignorance, neglect, and economic deprivation. The role of environmental factors that underlie Burkitt’s lymphoma was the subject of the Epidemiology of Burkitt Lymphoma in East-African Children and Minors Workshop, highlighting the NCI research programme in East Africa, while the Workshop on Cost Effectiveness of Treatment of Cancer in Africa surmised that treating childhood cancers is affordable in Africa in spite of widespread economic deprivation. WHO representatives emphasised the organisation’s commitment to the global control of non-communicable diseases (NCDs), including cancer, and promoted the new initiatives for the control of cervical cancer, one of the commonest and deadliest cancers in adult Africans. AU representative proffered the principles of ‘demographic dividends’ for Africa to be able to tackle its burden of NCDs. UICC, represented by its President, provided guidelines for cancer diagnosis and staging, and advised on its effort to improve global access to radiotherapy, especially in Africa, while IPOS led the discussions on mitigating the suffering that is associated with the late presentation of cancer in the region. Oral and poster presentations from various parts of the continent indicate the growth of basic science of cancer in the region, with studies revealing regional diversity in the frequencies of the triple-negative breast cancer. They also suggest a need for genome-wide association studies as well as the evaluation of single nucleotide polymorphisms that may be responsible for variable susceptibility in breast and prostate cancer in people of African descent. Finally, the AORTIC leadership announced its plan for the advancement of cancer control by intensifying cancer advocacy at all levels of governance in the region. PMID:24550997

Peak alpha frequency is a neural marker of cognitive function across the autism spectrum.

PubMed

Dickinson, Abigail; DiStefano, Charlotte; Senturk, Damla; Jeste, Shafali Spurling

2018-03-01

Cognitive function varies substantially and serves as a key predictor of outcome and response to intervention in autism spectrum disorder (ASD), yet we know little about the neurobiological mechanisms that underlie cognitive function in children with ASD. The dynamics of neuronal oscillations in the alpha range (6-12 Hz) are associated with cognition in typical development. Peak alpha frequency is also highly sensitive to developmental changes in neural networks, which underlie cognitive function, and therefore, it holds promise as a developmentally sensitive neural marker of cognitive function in ASD. Here, we measured peak alpha band frequency under a task-free condition in a heterogeneous sample of children with ASD (N = 59) and age-matched typically developing (TD) children (N = 38). At a group level, peak alpha frequency was decreased in ASD compared to TD children. Moreover, within the ASD group, peak alpha frequency correlated strongly with non-verbal cognition. As peak alpha frequency reflects the integrity of neural networks, our results suggest that deviations in network development may underlie cognitive function in individuals with ASD. By shedding light on the neurobiological correlates of cognitive function in ASD, our findings lay the groundwork for considering peak alpha frequency as a useful biomarker of cognitive function within this population which, in turn, will facilitate investigations of early markers of cognitive impairment and predictors of outcome in high risk infants. © 2017 Federation of European Neuroscience Societies and John Wiley & Sons Ltd.

Point/Counterpoint: early detection of prostate cancer: do the benefits outweigh the consequences?

PubMed

Carroll, Peter R; Vickers, Andrew J

2014-05-01

Few clinical issues have polarized the oncology community as much as screening for prostate cancer, with advocates of prostate-specific antigen (PSA) testing vocal on one side and skeptics just as vocal on the other. At the NCCN 19th Annual Conference, Dr. Peter R. Carroll and Dr. Andrew J. Vickers tackled the controversy surrounding early detection of prostate cancer, focusing attention on the randomized trial results at the heart of the matter; over-detection (the Achilles' heel of screening); and the rationale behind the new, streamlined 2014 NCCN Clinical Practice Guidelines in Oncology (NCCN Guidelines) for Prostate Cancer Early Detection, which emphasize selective early detection and treatment and are tightly aligned with the NCCN Guidelines for Prostate Cancer. Copyright © 2014 by the National Comprehensive Cancer Network.

Validating a mouse model of ovarian cancer for early detection through imaging | Division of Cancer Prevention

Cancer.gov

Despite advances in treatment strategies, ovarian cancer remains the deadliest gynecological malignancy and the 5th largest cancer killer in women. Located deep in the body, with few early symptoms and no effective screening technique, ovarian cancer has remained stubbornly difficult to understand, much less effectively combat. Ovarian cancer is almost always discovered at an

Location, location, location: does early cancer in Barrett's esophagus have a preference?

PubMed

Enestvedt, Brintha K; Lugo, Ricardo; Guarner-Argente, Carlos; Shah, Pari; Falk, Gary W; Furth, Emma; Ginsberg, Gregory G

2013-09-01

Early cancer (high-grade dysplasia [HGD] and intramucosal carcinoma [ImCa]) associated with Barrett's esophagus (BE) may have a circumferential spatial predilection. To describe the esophageal circumferential location of early cancer in BE. Retrospective study, single tertiary referral center. One hundred nineteen patients were referred for endoscopic eradication therapy for early cancer associated with BE. Endoscopic images and reports and pathology were reviewed. Circumferential location designation of early cancer in BE by using a clock-face orientation. One hundred nineteen of 131 patients referred for endoscopic eradication therapy had a location designation for their advanced histology (91.9%). There were a total of 57 patients (47.9%) with HGD and 62 patients (52.1%) with ImCa. There was a significantly higher rate of early cancer (HGD or ImCa) in the right hemisphere (12 to 6 o'clock location) compared with the left hemisphere (84.9% vs 15.1%, P < .0001). The highest percentage of early cancer was found in the 12 to 3 o'clock quadrant (64.7%); 71.9% of HGD and 58.1% of ImCa lesions were located in the 12 to 3 o'clock quadrant. Retrospective design, single center. Early cancer associated with BE is far more commonly found in the right hemisphere of the esophagus (12 to 6 o'clock) with the highest rate in the 12 to 3 o'clock quadrant. These findings support enhanced scrutiny of the right hemisphere of the esophagus during surveillance and endoscopic treatment of patients with BE. Copyright © 2013 American Society for Gastrointestinal Endoscopy. Published by Mosby, Inc. All rights reserved.

Redefining early gastric cancer.

PubMed

Barreto, Savio G; Windsor, John A

2016-01-01

The problem is that current definitions of early gastric cancer allow the inclusion of regional lymph node metastases. The increasing use of endoscopic submucosal dissection to treat early gastric cancer is a concern because regional lymph nodes are not addressed. The aim of the study was thus to critically evaluate current evidence with regard to tumour-specific factors associated with lymph node metastases in "early gastric cancer" to develop a more precise definition and improve clinical management. A systematic and comprehensive search of major reference databases (MEDLINE, EMBASE, PubMed and the Cochrane Library) was undertaken using a combination of text words "early gastric cancer", "lymph node metastasis", "factors", "endoscopy", "surgery", "lymphadenectomy" "mucosa", "submucosa", "lymphovascular invasion", "differentiated", "undifferentiated" and "ulcer". All available publications that described tumour-related factors associated with lymph node metastases in early gastric cancer were included. The initial search yielded 1494 studies, of which 42 studies were included in the final analysis. Over time, the definition of early gastric cancer has broadened and the indications for endoscopic treatment have widened. The mean frequency of lymph node metastases increased on the basis of depth of infiltration (mucosa 6% vs. submucosa 28%), presence of lymphovascular invasion (absence 9% vs. presence 53%), tumour differentiation (differentiated 13% vs. undifferentiated 34%) and macroscopic type (elevated 13% vs. flat 26%) and tumour diameter (≤2 cm 8% vs. >2 cm 25%). There is a need to re-examine the diagnosis and staging of early gastric cancer to ensure that patients with one or more identifiable risk factor for lymph node metastases are not denied appropriate chemotherapy and surgical resection.

Claire Zhu, PhD | Division of Cancer Prevention

Cancer.gov

Dr. Claire Zhu is a program director in the Early Detection Research Group of the Division of Cancer Prevention at the NCI, where she coordinates the Etiologic and Early Marker Studies Program (EEMS) in the Prostate, Lung, Colorectal and Ovarian Cancer Screening Trial (PLCO), as well as manages a grant portfolio in early detection research. |

Endoscopic mucosal resection for early gastric cancer. A case report.

PubMed

Gheorghe, Cristian; Sporea, Ioan; Becheanu, Gabriel; Gheorghe, Liana

2002-03-01

European experience in endoscopic mucosal resection (EMR) for early gastric cancer is still relatively low, since early stomach cancer is diagnosed at a much lower rate in Europe than in Japan and generally operable patients are referred to surgery for radical resection. Endoscopic mucosal resection or mucosectomy was developed as a promising technology to diagnose and treat mucosal lesions in the esophagus, stomach and colon. In contrast to surgical resection, EMR allows "early cancers" to be removed with a minimal cost, morbidity and mortality. We present the case of a patient with hepatic cirrhosis incidentally diagnosed with an elevated-type IIa early gastric cancer. Echoendoscopy was performed in order to assess the depth of invasion into the gastric wall confirming the only mucosal involvement. We performed an EMR using "cup and suction" method. After the procedure, the patient experienced an acute upper gastrointestinal bleeding from the ulcer bed requiring argon plasma coagulation. The histopathological examination confirmed an early cancer, without involvement of muscularis mucosae. The patient has had an uneventful evolution being well at six months after the procedure

Strategies for early detection of resectable pancreatic cancer

PubMed Central

Okano, Keiichi; Suzuki, Yasuyuki

2014-01-01

Pancreatic cancer is difficult to diagnose at an early stage and generally has a poor prognosis. Surgical resection is the only potentially curative treatment for pancreatic carcinoma. To improve the prognosis of this disease, it is essential to detect tumors at early stages, when they are resectable. The optimal approach to screening for early pancreatic neoplasia has not been established. The International Cancer of the Pancreas Screening Consortium has recently finalized several recommendations regarding the management of patients who are at an increased risk of familial pancreatic cancer. In addition, there have been notable advances in research on serum markers, tissue markers, gene signatures, and genomic targets of pancreatic cancer. To date, however, no biomarkers have been established in the clinical setting. Advancements in imaging modalities touch all aspects of the clinical management of pancreatic diseases, including the early detection of pancreatic masses, their characterization, and evaluations of tumor resectability. This article reviews strategies for screening high-risk groups, biomarkers, and current advances in imaging modalities for the early detection of resectable pancreatic cancer. PMID:25170207

Cancer as a Risk Factor for Cardiovascular Disease.

PubMed

Giza, Dana Elena; Iliescu, Gloria; Hassan, Saamir; Marmagkiolis, Konstantinos; Iliescu, Cezar

2017-06-01

Improvements in early diagnosis and cancer treatments have contributed to high survival rates for many cancer patients. However, these patients often die of cardiovascular disease rather than recurrence of their cancer. Heart disease manifesting after cancer may be due to several mechanisms: shared cardiovascular risks between cancer and cardiovascular disease, inflammatory states associated with malignancies, and/or cardiotoxic effects of cancer therapy. Cancer treatment increases the risk of cardiovascular diseases directly by damaging critical structures of the heart or indirectly by promoting accelerated atherosclerosis. Estimating cardiovascular risk by using advanced imaging and monitoring of the cardiac biomarkers can be used for early detection and treatment of subclinical cardiac injury. Better knowledge of these early and late cardiac effects in cancer patients will enable adoption of both primary and secondary prevention measures of long-term treatment complications in cancer survivors.

Cancer Detection and Diagnosis Methods - Annual Plan

Cancer.gov

Early cancer detection is a proven life-saving strategy. Learn about the research opportunities NCI supports, including liquid biopsies and other less-invasive methods, for detecting early cancers and precancerous growths.

Automated System for Early Breast Cancer Detection in Mammograms

NASA Technical Reports Server (NTRS)

Bankman, Isaac N.; Kim, Dong W.; Christens-Barry, William A.; Weinberg, Irving N.; Gatewood, Olga B.; Brody, William R.

1993-01-01

The increasing demand on mammographic screening for early breast cancer detection, and the subtlety of early breast cancer signs on mammograms, suggest an automated image processing system that can serve as a diagnostic aid in radiology clinics. We present a fully automated algorithm for detecting clusters of microcalcifications that are the most common signs of early, potentially curable breast cancer. By using the contour map of the mammogram, the algorithm circumvents some of the difficulties encountered with standard image processing methods. The clinical implementation of an automated instrument based on this algorithm is also discussed.

Is early-onset microsatellite and chromosomally stable colorectal cancer a hallmark of a genetic susceptibility syndrome?

PubMed

Kets, C M; van Krieken, J H J M; van Erp, P E J; Feuth, T; Jacobs, Y H A; Brunner, H G; Ligtenberg, M J L; Hoogerbrugge, N

2008-02-15

Most colorectal cancers show either microsatellite or chromosomal instability. A subset of colorectal cancers, especially those diagnosed at young age, is known to show neither of these forms of genetic instability and thus might have a distinct pathogenesis. Colorectal cancers diagnosed at young age are suggestive for hereditary predisposition. We investigate whether such early-onset microsatellite and chromosomally stable colorectal cancers are a hallmark of a genetic susceptibility syndrome. The ploidy status of microsatellite stable (familial) colorectal cancers of patients diagnosed before age 50 (n = 127) was analyzed in relation to the histopathological characteristics and family history. As a control the ploidy status of sporadic colorectal cancer, with normal staining of mismatch repair proteins, diagnosed at the age of 69 years or above (n = 70) was determined. A diploid DNA content was used as a marker for chromosomal stability. Within the group of patients with (familial) early onset microsatellite stable colorectal cancer the chromosomally stable tumors did not differ from chromosomally unstable tumors with respect to mean age at diagnosis, fulfillment of Amsterdam criteria or pathological characteristics. Segregation analysis did not reveal any family with microsatellite and chromosomally stable colorectal cancer in 2 relatives. The prevalence of microsatellite and chromosomally stable colorectal cancer was not significantly different for the early and late onset group (28 and 21%, respectively). We find no evidence that early-onset microsatellite and chromosomally stable colorectal cancer is a hallmark of a hereditary colorectal cancer syndrome. (c) 2007 Wiley-Liss, Inc.

[CT-Screening for Lung Cancer - what is the Evidence?

PubMed

Watermann, Iris; Reck, Martin

2018-04-01

In patients with lung cancer treatment opportunities and prognosis are correlated to the stage of disease with a chance for curative treatment in patients with early stage disease. Therefore, early detection of lung cancer is of paramount importance for improving the prognosis of lung cancer patients.The National Lung Screening Trial (NLST) has already shown that low-dose CT increases the number of identified early stage lung cancer patients and reduces lung cancer related mortality. Critically considered in terms of CT-screening are false-positive results, overdiagnosis and unessential invasive clarification. Preliminary results of relatively small European trials haven´t yet confirmed the results of the NLST-study.Until now Lung Cancer Screening by low dose CT-scan or other methods is neither approved nor available in Germany.To improve the efficacy of CT-Screening and to introduce early detection of lung cancer in standard practice, additional, complementing methods should be further evaluated. One option might be the supplementary analysis of biomarkers in liquid biopsies or exhaled breath condensates. In addition, defining the high-risk population is of great relevance to identify candidates who might benefit of early detection programs. © Georg Thieme Verlag KG Stuttgart · New York.

Nanotechnology-Based Detection of Novel microRNAs for Early Diagnosis of Prostate Cancer

DTIC Science & Technology

2017-08-01

AWARD NUMBER: W81XWH-15-1-0157 TITLE: Nanotechnology -Based Detection of Novel microRNAs for Early Diagnosis of Prostate Cancer PRINCIPAL...TITLE AND SUBTITLE Nanotechnology -Based Detection of Novel microRNAs for Early Diagnosis of Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER...identify novel differentially expressed miRNAs in the body fluids (blood, urine, etc.) for an early detection of PCa. Advances in nanotechnology and

Cardiac autonomic modulation impairments in advanced breast cancer patients.

PubMed

Arab, Claudia; Vanderlei, Luiz Carlos Marques; da Silva Paiva, Laércio; Fulghum, Kyle Levi; Fristachi, Carlos Elias; Nazario, Afonso Celso Pinto; Elias, Simone; Gebrim, Luiz Henrique; Ferreira Filho, Celso; Gidron, Yori; Ferreira, Celso

2018-05-02

To compare cardiac autonomic modulation in early- versus advanced-stage breast cancer patients before any type of cancer treatment and investigate associated factors. This cross-sectional study included women (30-69 years old) with primary diagnosis of breast cancer and women with benign breast tumors. We evaluated cardiac modulation by heart rate variability and assessed factors of anxiety, depression, physical activity, and other relevant medical variables. Patients were divided into three groups based on TNM staging of cancer severity: early-stage cancer (n = 42), advanced-stage cancer (n = 37), or benign breast tumors to serve as a control (n = 37). We analyzed heart rate variability in time and frequency domains. The advanced-stage cancer group had lower vagal modulation than early-stage and benign groups; also, the advance-stage group had lower overall heart rate variability when compared to benign conditions. Heart rate variability was influenced by age, menopausal status, and BMI. Heart rate variability seems to be a promising, non-invasive tool for early diagnosis of autonomic dysfunction in breast cancer and detection of cardiovascular impairments at cancer diagnosis. Cardiac autonomic modulation is inversely associated with breast cancer staging.

Phase 0/I/II Cancer Prevention Clinical Trials Program (Consortia) | Division of Cancer Prevention

Cancer.gov

Five cancer research centers lead multiple collaborative networks to assess potential cancer preventive agents and to conduct early clinical development of promising preventive agents. Also called the Consortia for Early Phase Prevention Trials, the studies require extensive biomarker analysis, investigation of the biologic effects of the cancer preventive agents on their

Arsenic and Immune Response to Infection During Pregnancy and Early Life

PubMed Central

Attreed, Sarah E.; Navas-Acien, Ana

2017-01-01

Purpose of Review Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity—including the specific mechanisms in humans—is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. Recent Findings The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Summary Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines. PMID:28488132

Arsenic and Immune Response to Infection During Pregnancy and Early Life.

PubMed

Attreed, Sarah E; Navas-Acien, Ana; Heaney, Christopher D

2017-06-01

Arsenic, a known carcinogen and developmental toxicant, is a major threat to global health. While the contribution of arsenic exposure to chronic diseases and adverse pregnancy and birth outcomes is recognized, its ability to impair critical functions of humoral and cell-mediated immunity-including the specific mechanisms in humans-is not well understood. Arsenic has been shown to increase risk of infectious diseases that have significant health implications during pregnancy and early life. Here, we review the latest research on the mechanisms of arsenic-related immune response alterations that could underlie arsenic-associated increased risk of infection during the vulnerable periods of pregnancy and early life. The latest evidence points to alteration of antibody production and transplacental transfer as well as failure of T helper cells to produce IL-2 and proliferate. Critical areas for future research include the effects of arsenic exposure during pregnancy and early life on immune responses to natural infection and the immunogenicity and efficacy of vaccines.

Early-Onset Severe Encephalopathy with Epilepsy: The BRAT1 Gene Should Be Added to the List of Causes.

PubMed

van de Pol, Laura A; Wolf, Nicole I; van Weissenbruch, Mirjam M; Stam, Cornelie J; Weiss, Janneke M; Waisfisz, Quinten; Kevelam, Sietske H; Bugiani, Mariana; van de Kamp, Jiddeke M; van der Knaap, Marjo S

2015-12-01

A variety of pathologies can underlie early-onset severe encephalopathy with epilepsy. To aid the diagnostic process in such patients we present an overview of causes, including the rapidly expanding list of genes involved. When no explanation is found, whole-exome sequencing (WES) can be used in an attempt to identify gene defects in patients suspected to suffer from a genetic form. We describe three siblings, born to consanguineous parents, with a lethal severe epileptic encephalopathy with early-infantile onset, including their magnetic resonance imaging, electroencephalography and, in one case, neuropathological findings. Using WES a homozygous frameshift mutation in the BRAT1 gene, c.638dup p.(Val214Glyfs*189), was identified. We present our cases in the context of all published cases with mutations in the BRAT1 gene and conclude that BRAT1 should be added to the growing list of genes related to early-onset severe encephalopathy with epilepsy. Georg Thieme Verlag KG Stuttgart · New York.

Mathematical models for the early detection and treatment of colorectal cancer.

PubMed

Harper, P R; Jones, S K

2005-05-01

Colorectal cancer is a major cause of death for men and women in the Western world. When the cancer is detected through an awareness of the symptoms by a patient, typically it is at an advanced stage. It is possible to detect cancer at an early stage through screening and the marked differences in survival for early and late stages provide the incentive for the primary prevention or early detection of colorectal cancer. This paper considers mathematical models for colorectal cancer screening together with models for the treatment of patients. Illustrative results demonstrate that detailed attention to the processes involved in diseases, interventions and treatment enable us to combine data and expert knowledge from various sources. Thus a detailed operational model is a very useful tool in helping to make decisions about screening at national and local levels.

Controlling fear: Jordanian women's perceptions of the diagnosis and surgical treatment of early-stage breast cancer.

PubMed

Obeidat, Rana F; Dickerson, Suzanne S; Homish, Gregory G; Alqaissi, Nesreen M; Lally, Robin M

2013-01-01

Despite the fact that breast cancer is the most prevalent cancer among Jordanian women, practically nothing is known about their perceptions of early-stage breast cancer and surgical treatment. The objective of this study was to gain understanding of the diagnosis and surgical treatment experience of Jordanian women with a diagnosis of early-stage breast cancer. An interpretive phenomenological approach was used for this study. A purposive sample of 28 Jordanian women who were surgically treated for early-stage breast cancer within 6 months of the interview was recruited. Data were collected using individual interviews and analyzed using Heideggerian hermeneutical methodology. Fear had a profound effect on Jordanian women's stories of diagnosis and surgical treatment of early-stage breast cancer. Women's experience with breast cancer and its treatment was shaped by their preexisting fear of breast cancer, the disparity in the quality of care at various healthcare institutions, and sociodemographic factors (eg, education, age). Early after the diagnosis, fear was very strong, and women lost perspective of the fact that this disease was treatable and potentially curable. To control their fears, women unconditionally trusted God, the healthcare system, surgeons, family, friends, and/or neighbors and often accepted treatment offered by their surgeons without questioning. Jordanian healthcare providers have a responsibility to listen to their patients, explore meanings they ascribe to their illness, and provide women with proper education and the support necessary to help them cope with their illness.

76 FR 55915 - Request for Nominations of Candidates to Serve on the Breast and Cervical Cancer Early Detection...

Federal Register 2010, 2011, 2012, 2013, 2014

2011-09-09

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Request for Nominations of Candidates to Serve on the Breast and Cervical Cancer Early Detection and Control Advisory... Secretary for Health, and the CDC on the early detection and control of breast and cervical cancer. The role...

Etiology and Early Marker Studies (EEMS) | Division of Cancer Prevention

Cancer.gov

The Etiology and Early Marker Studies (EEMS) is a component of the PLCO Trial. By collecting biologic materials and risk factor information from trial participants before the diagnosis of disease, PLCO EEMS adds substantial value to the trial, providing a resource for cancer research, focused, in particular, on cancer etiology and early markers. Etiologic studies investigate

Recursive SVM biomarker selection for early detection of breast cancer in peripheral blood.

PubMed

Zhang, Fan; Kaufman, Howard L; Deng, Youping; Drabier, Renee

2013-01-01

Breast cancer is worldwide the second most common type of cancer after lung cancer. Traditional mammography and Tissue Microarray has been studied for early cancer detection and cancer prediction. However, there is a need for more reliable diagnostic tools for early detection of breast cancer. This can be a challenge due to a number of factors and logistics. First, obtaining tissue biopsies can be difficult. Second, mammography may not detect small tumors, and is often unsatisfactory for younger women who typically have dense breast tissue. Lastly, breast cancer is not a single homogeneous disease but consists of multiple disease states, each arising from a distinct molecular mechanism and having a distinct clinical progression path which makes the disease difficult to detect and predict in early stages. In the paper, we present a Support Vector Machine based on Recursive Feature Elimination and Cross Validation (SVM-RFE-CV) algorithm for early detection of breast cancer in peripheral blood and show how to use SVM-RFE-CV to model the classification and prediction problem of early detection of breast cancer in peripheral blood.The training set which consists of 32 health and 33 cancer samples and the testing set consisting of 31 health and 34 cancer samples were randomly separated from a dataset of peripheral blood of breast cancer that is downloaded from Gene Express Omnibus. First, we identified the 42 differentially expressed biomarkers between "normal" and "cancer". Then, with the SVM-RFE-CV we extracted 15 biomarkers that yield zero cross validation score. Lastly, we compared the classification and prediction performance of SVM-RFE-CV with that of SVM and SVM Recursive Feature Elimination (SVM-RFE). We found that 1) the SVM-RFE-CV is suitable for analyzing noisy high-throughput microarray data, 2) it outperforms SVM-RFE in the robustness to noise and in the ability to recover informative features, and 3) it can improve the prediction performance (Area Under Curve) in the testing data set from 0.5826 to 0.7879. Further pathway analysis showed that the biomarkers are associated with Signaling, Hemostasis, Hormones, and Immune System, which are consistent with previous findings. Our prediction model can serve as a general model for biomarker discovery in early detection of other cancers. In the future, Polymerase Chain Reaction (PCR) is planned for validation of the ability of these potential biomarkers for early detection of breast cancer.

[Infections and epigenetic changes in cancer].

PubMed

Corvalán, Alejandro H; Maturana, María José

2016-01-01

The role of epigenetics and infectious diseases at early stages of life influence pre-malignant lesions of cancer, in particular, gastric cancer, one of the most frequent tumours in Chile, Latin America, and worldwide. This article examines the role of H.pylori and epigenetic alterations (i.e. DNA methylation) at early stages of gastric cancer and proposes, from the paediatric point of view, strategies for prevention and early detection. Copyright © 2016. Publicado por Elsevier España, S.L.U.

A Novel Apoptosis Pathway that is Defective in Early Breast Cancer

DTIC Science & Technology

2005-04-01

AD Award Number: DAMD17-02-1-0612 TITLE: A Novel Apoptosis Pathway that is Defective in Early Breast Cancer PRINCIPAL INVESTIGATOR: Scott Cramer...Defective in Early DAMD17-02-1-0612 Breast Cancer 6. AUTHOR(S) Scott Cramer, Ph.D. 7. PERFORMING ORGANIZATION NAME(S) AND ADDRESS(ES) 8. PERFORMING...These experiments were intended to determine why breast cancer cells are resistant to this apoptosis pathway BODY. As outlined in the previous

Find Cancer Early: Evaluation of a Community Education Campaign to Increase Awareness of Cancer Signs and Symptoms in People in Regional Western Australians.

PubMed

Croager, Emma Jane; Gray, Victoria; Pratt, Iain Stephen; Slevin, Terry; Pettigrew, Simone; Holman, C D'arcy; Bulsara, Max; Emery, Jon

2018-01-01

Cancer outcomes for people living in rural and remote areas are worse than for those living in urban areas. Although access to and quality of cancer treatment are important determinants of outcomes, delayed presentation has been observed in rural patients. Formative research with people from rural Western Australia (WA) led to the Find Cancer Early campaign. Find Cancer Early was delivered in three regions of WA, with two other regions acting as controls. Staff delivered the campaign using a community engagement approach, including promotion in local media. Television communications were not used to minimize contamination in the control regions. The campaign evaluation was undertaken at 20 months via a computer-assisted telephone interview (CATI) survey comparing campaign and control regions. The primary outcome variable was knowledge of cancer signs and symptoms. Recognition and recall of Find Cancer Early and symptom knowledge were higher in the campaign regions. More than a quarter of those who were aware of the campaign reported seeing the GP as a result of their exposure. Despite limited use of mass media, Find Cancer Early successfully improved knowledge of cancer symptoms and possibly led to changes in behavior. Social marketing campaigns using community development can raise awareness and knowledge of a health issue in the absence of television advertising.

Developing learning environments which support early algebraic reasoning: a case from a New Zealand primary classroom

NASA Astrophysics Data System (ADS)

Hunter, Jodie

2014-12-01

Current reforms in mathematics education advocate the development of mathematical learning communities in which students have opportunities to engage in mathematical discourse and classroom practices which underlie algebraic reasoning. This article specifically addresses the pedagogical actions teachers take which structure student engagement in dialogical discourse and activity which facilitates early algebraic reasoning. Using videotaped recordings of classroom observations, the teacher and researcher collaboratively examined the classroom practices and modified the participatory practices to develop a learning environment which supported early algebraic reasoning. Facilitating change in the classroom environment was a lengthy process which required consistent and ongoing attention initially to the social norms and then to the socio-mathematical norms. Specific pedagogical actions such as the use of specifically designed tasks, materials and representations and a constant press for justification and generalisation were required to support students to link their numerical understandings to algebraic reasoning.

Cancer prevention trial of a synergistic mixture of green tea concentrate plus Capsicum (CAPSOL-T) in a random population of subjects ages 40-84

PubMed Central

2014-01-01

Background Experts agree that one of the more promising strategies in cancer management is early detection coupled with early intervention. In this study, we evaluated an early cancer detection strategy of cancer presence based on serum levels of the cancer-specific transcript variants of ENOX2 in serum coupled with an ENOX2-targeted nutraceutical preparation of green tea concentrate plus Capsicum (Capsol-T®) as a strategy of Curative Prevention® involving early detection coupled with early intervention in early stage cancer when in its most susceptible and manageable stages. Experimental design One hundred ten (110) subjects were tested for cancer presence using the ONCOblot® Tissue of Origin 2-D gel/western blot protocol for detection of serum presence of transcript variants of the ENOX2 protein. Subjects testing positive for ENOX2 received 350 mg of Capsol-T® in capsule form every 4 h including during the night for periods of at least 3 to 6 months or longer after which they were again tested for ENOX2 presence using the ONCOblot® Tissue of Origin Cancer Test protocol. Results Of the 110 subjects, both male and female, ages 40 to 84, with no evidence of clinical symptoms of cancer, 40% were positive for ENOX2 presence in the ONCOblot® Tissue of Origin Cancer Test. After completion of 3 to 17 months of Capsol-T® use, 94% of subjects subsequently tested negative for ENOX2 presence. Conclusions Oral Capsol-T® is well tolerated and, for ENOX2 presence in serum in the absence of clinical cancer symptoms, is consistently effective in reducing the serum ENOX2 levels to below detectable limits. PMID:24393573

Long noncoding RNAs(lncRNAs) and the molecular hallmarks of aging.

PubMed

Grammatikakis, Ioannis; Panda, Amaresh C; Abdelmohsen, Kotb; Gorospe, Myriam

2014-12-01

During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits.

The driver landscape of sporadic chordoma

DOE PAGES

Tarpey, Patrick S.; Behjati, Sam; Young, Matthew D.; ...

2017-10-12

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.

The driver landscape of sporadic chordoma

DOE Office of Scientific and Technical Information (OSTI.GOV)

Tarpey, Patrick S.; Behjati, Sam; Young, Matthew D.

Chordoma is a malignant, often incurable bone tumour showing notochordal differentiation. Here, we defined the somatic driver landscape of 104 cases of sporadic chordoma. We reveal somatic duplications of the notochordal transcription factor brachyury (T) in up to 27% of cases. These variants recapitulate the rearrangement architecture of the pathogenic germline duplications of T that underlie familial chordoma. In addition, we find potentially clinically actionable PI3K signalling mutations in 16% of cases. Intriguingly, one of the most frequently altered genes, mutated exclusively by inactivating mutation, was LYST (10%), which may represent a novel cancer gene in chordoma.

Long noncoding RNAs (lncRNAs) and the molecular hallmarks of aging

PubMed Central

Abdelmohsen, Kotb; Gorospe, Myriam

2014-01-01

During aging, progressive deleterious changes increase the risk of disease and death. Prominent molecular hallmarks of aging are genomic instability, telomere attrition, epigenetic alterations, loss of proteostasis, cellular senescence, stem cell exhaustion, and altered intercellular communication. Long noncoding RNAs (lncRNAs) play important roles in a wide range of biological processes, including age-related diseases like cancer, cardiovascular pathologies, and neurodegenerative disorders. Evidence is emerging that lncRNAs influence the molecular processes that underlie age-associated phenotypes. Here, we review our current understanding of lncRNAs that control the development of aging traits. PMID:25543668

Can you un-ring the bell? A qualitative study of how affect influences cancer screening decisions.

PubMed

Driedger, S Michelle; Annable, Gary; Brouwers, Melissa; Turner, Donna; Maier, Ryan

2017-09-13

The belief that early detection is the best protection against cancer underlies cancer screening. Emerging research now suggests harms associated with early detection may sometimes outweigh the benefits. Governments, cancer agencies, and organizations that publish screening guidelines have found it is difficult to "un-ring the bell" on the message that "early detection is your best protection" because of its widespread communication and enduring resonance. This study explores affective factors-and their interplay with relevant analytical factors-in public/laypersons' decision making about cancer screening. A total of 93 people (47 men, 46 women) attended focus groups about, respectively, prostate cancer screening and breast cancer screening in two Canadian cities. Affective factors were a major influence on many focus group participants' decision making about cancer screening, including fear of cancer and a generalized enthusiasm for prevention/screening, and they were often inspired by anecdotes about the cancer experiences of family and friends. Affect also existed alongside more analytical factors including assessments of reduced risk in the management of any cancer diagnosis if caught early, and, for men, the belief that an unreliable test is "better than nothing," and that men deserve prostate cancer screening because women have breast and cervical cancer screening. Affective factors were particularly noticeable in the sub-groups most supportive of screening and the "early detection" message: older women who felt that mammogram screening should begin at age 40 rather than 50, and older men who felt that prostate cancer screening should be expanded beyond its current unorganized, opportunistic usage. In contrast, younger participants displayed less affective attachments to "early detection" messages and had greater concerns about harms of screening and were more receptive to nuanced messages informed by evidence. Policymakers attempting to communicate more nuanced versions of the "early detection" message need to understand the role of affect alongside other judgments brought into laypersons' decision making processes and anticipate how affective responses to their messages will be shaped, transformed, and potentially subverted by external forces beyond their control. Particularly overt external factors are campaigns by cancer advocacy organizations actively promoting breast and prostate cancer awareness and screening to younger women and men using affectively-charged messages.

Early Detection of Lung Cancer Using Nano-Nose - A Review

PubMed Central

Fernandes, M. P.; Venkatesh, S; Sudarshan, B. G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer. PMID:26628933

Early Detection of Lung Cancer Using Nano-Nose - A Review.

PubMed

Fernandes, M P; Venkatesh, S; Sudarshan, B G

2015-01-01

Lung cancer is one of the malignancies causing deaths worldwide. The yet to be developed non-invasive diagnostic techniques, are a challenge for early detection of cancer before it progresses to its later stages. The currently available diagnostic methods are expensive or invasive, and are not fit for general screening purposes. Early identification not only helps in detecting primary cancer, but also in treating its secondaries; which creates a need for easily applicable tests to screen individuals at risk. A detailed review of the various screening methods, including the latest trend of breath analysis using gold nanoparticles, to identify cancer at its early stage, are studied here. The VOC based breath biomarkers are used to analyze the exhaled breath of the patients. These biomarkers are utilized by Chemiresistors coated with gold nanoparticles, which are found to be the most suited technique for early detection of lung cancer. This technique is highly accurate and is relatively easy to operate and was tested on smokers and non-smokers. This review also gives as an outline of the fabrication and working of the device Na-Nose. The Chemiresistors coated with Gold nanoparticles, show a great potential in being an non-invasive and cost-effective diagnostic technique for early detection of lung cancer.

CHEK2*1100delC heterozygosity in women with breast cancer associated with early death, breast cancer-specific death, and increased risk of a second breast cancer.

PubMed

Weischer, Maren; Nordestgaard, Børge G; Pharoah, Paul; Bolla, Manjeet K; Nevanlinna, Heli; Van't Veer, Laura J; Garcia-Closas, Montserrat; Hopper, John L; Hall, Per; Andrulis, Irene L; Devilee, Peter; Fasching, Peter A; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M; Wang, Qin; Muranen, Taru A; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C; Czene, Kamila; Knight, Julia A; Tollenaar, Rob A E M; Beckmann, Matthias W; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W R; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E; Kosma, Veli-Matti; Kristensen, Vessela N; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B; Leunen, Karin; Kriege, Mieke; Cross, Simon S; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F; Schmidt, Marjanka K; Bojesen, Stig E

2012-12-10

We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer-specific death, and risk of a second breast cancer in women with a first breast cancer. From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer-specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor-positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer-specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor-positive first breast cancer only. Among women with estrogen receptor-positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer-specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer.

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2014-09-01

Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W...CONTRACT NUMBER Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer 5b. GRANT NUMBER W81XWH-12-1-0236 5c...NOTES 14. ABSTRACT Purpose and scope: Stereotactic ablative radiotherapy ( SABR ) has become a new standard of care for early stage lung

Long Non-Coding RNA Emergence During Renal Cell Carcinoma Tumorigenesis.

PubMed

Liu, Xiaobing; Hao, Yaxing; Yu, Wei; Yang, Xia; Luo, Xing; Zhao, Jiang; Li, Jia; Hu, Xiaoyan; Li, Longkun

2018-05-22

Renal cell carcinoma (RCC) is the most common kidney cancer diagnosed across the globe and has steadily increased in incidence in recent decades. Techniques for diagnosing or treating RCC are limited, and confined mostly to later stages of the disease. Almost all RCC pathological types are resistant to chemotherapeutics and radiation therapy. To this effect, new markers for diagnosis and target therapy are urgently needed. Advanced genome sequencing technologies have revealed long non-coding RNAs (lncRNAs) as a novel marker, transcribed throughout the human genome. The emergence of lncRNAs is an aberrant expression and is involved in the tumorigenesis of RCC. LncRNAs drive cancer phenotypes through their interaction with other cellular macromolecules including DNA, protein, and RNA. Recent research on lncRNA molecular mechanisms has revealed new markers to functionally annotate these cancers' associated transcripts, making them targets for effective diagnosis and therapeutic intervention in the fight against cancer. In this review, we first highlight the common mechanisms that underlie aberrant lncRNA expression in RCC. We go on to discuss the potential translational application of lncRNA research in the diagnosis, prognosis, and treatment of RCC. © 2018 The Author(s). Published by S. Karger AG, Basel.

Ovarian cancer stem cells: still an elusive entity?

PubMed

Lupia, Michela; Cavallaro, Ugo

2017-03-20

The cancer stem cell (CSC) model proposes that tumor development and progression are fueled and sustained by undifferentiated cancer cells, endowed with self-renewal and tumor-initiating capacity. Ovarian carcinoma, based on its biological features and clinical evolution, appears as a prototypical example of CSC-driven disease. Indeed, ovarian cancer stem cells (OCSC) would account not only for the primary tumor growth, the peritoneal spread and the relapse, but also for the development of chemoresistance, thus having profound implication for the treatment of this deadly disease. In the last decade, an increasing body of experimental evidence has supported the existence of OCSC and their pathogenic role in the disease. Nevertheless, the identification of OCSC and the definition of their phenotypical and functional traits have proven quite challenging, mainly because of the heterogeneity of the disease and of the difficulties in establishing reliable biological models. A deeper understanding of OCSC pathobiology will shed light on the mechanisms that underlie the clinical behaviour of OC. In addition, it will favour the design of innovative treatment regimens that, on one hand, would counteract the resistance to conventional chemotherapy, and, on the other, would aim at the eradication of OC through the elimination of its CSC component.

Structure and function of Helicobacter pylori CagA, the first-identified bacterial protein involved in human cancer

PubMed Central

HATAKEYAMA, Masanori

2017-01-01

Chronic infection with Helicobacter pylori cagA-positive strains is the strongest risk factor of gastric cancer. The cagA gene-encoded CagA protein is delivered into gastric epithelial cells via bacterial type IV secretion, where it undergoes tyrosine phosphorylation at the Glu-Pro-Ile-Tyr-Ala (EPIYA) motifs. Delivered CagA then acts as a non-physiological scaffold/hub protein by interacting with multiple host signaling molecules, most notably the pro-oncogenic phosphatase SHP2 and the polarity-regulating kinase PAR1/MARK, in both tyrosine phosphorylation-dependent and -independent manners. CagA-mediated manipulation of intracellular signaling promotes neoplastic transformation of gastric epithelial cells. Transgenic expression of CagA in experimental animals has confirmed the oncogenic potential of the bacterial protein. Structural polymorphism of CagA influences its scaffold function, which may underlie the geographic difference in the incidence of gastric cancer. Since CagA is no longer required for the maintenance of established gastric cancer cells, studying the role of CagA during neoplastic transformation will provide an excellent opportunity to understand molecular processes underlying “Hit-and-Run” carcinogenesis. PMID:28413197

Identification of conserved pathways of DNA-damage response and radiation protection by genome-wide RNAi.

PubMed

van Haaften, Gijs; Romeijn, Ron; Pothof, Joris; Koole, Wouter; Mullenders, Leon H F; Pastink, Albert; Plasterk, Ronald H A; Tijsterman, Marcel

2006-07-11

Ionizing radiation is extremely harmful for human cells, and DNA double-strand breaks (DSBs) are considered to be the main cytotoxic lesions induced. Improper processing of DSBs contributes to tumorigenesis, and mutations in DSB response genes underlie several inherited disorders characterized by cancer predisposition. Here, we performed a comprehensive screen for genes that protect animal cells against ionizing radiation. A total of 45 C. elegans genes were identified in a genome-wide RNA interference screen for increased sensitivity to ionizing radiation in germ cells. These genes include orthologs of well-known human cancer predisposition genes as well as novel genes, including human disease genes not previously linked to defective DNA-damage responses. Knockdown of eleven genes also impaired radiation-induced cell-cycle arrest, and seven genes were essential for apoptosis upon exposure to irradiation. The gene set was further clustered on the basis of increased sensitivity to DNA-damaging cancer drugs cisplatin and camptothecin. Almost all genes are conserved across animal phylogeny, and their relevance for humans was directly demonstrated by showing that their knockdown in human cells results in radiation sensitivity, indicating that this set of genes is important for future cancer profiling and drug development.

Risk of Breast Cancer among Young Women and Importance of Early Screening.

PubMed

Memon, Zahid Ali; Kanwal, Noureen; Sami, Munam; Larik, Parsa Azam; Farooq, Mohammad Zain

2015-01-01

Breast cancer is the most common type of cancer in women throughout the world. However, in comparison with Western women, it presents relatively early in women of Asian ethnicity. Early menarche, late menopause, use of OCP's, family history of benign or malignant breast disease, exposure to radiation and BMI in the under-weight range are well known risk factors for the development of breast cancer in premenopausal women. Early detection with the use of breast self-examination (BSE) and breast cancer screening programs can lead to a reduction in the mortality rates due to breast cancer. The aim of our study was to assess the risk factors for breast cancer among young women and to emphasize the importance of early screening among them. We conducted a cross-sectional study among women aged 18 to 25 using a self- administered questionnaire. Data was collected over a period of 6 months from June to December, 2014. A total of 300 young women selected randomly from Dow Medical College and various departments of Karachi University successfully completed the survey. Respondents were 18-25 years of age (mean age=21.5). Out of the 300 young females, 90 (30%) had at least one risk factor, 90 (30%) had two, 40 (13%) had three, 8 (2.7%) had four, 2 (0.7%) had five while one female was found to have six positive risk factors for breast cancer. Some 66 women (22%) experienced symptoms of breast cancer such as non-cyclical pain and lumps. While 222 women (74%) had never performed breast self-examination, 22 (7.3%) had had a breast examination done by a health professional while 32 (10.7%) had participated in breast screening programs. A total of 223 (74.3%) women considered breast cancer screening important for young women. The percentage of young women with risk factors for breast cancer was found to be alarmingly high. Therefore, screening for breast cancer should start at an early age especially in high risk groups. Awareness about breast self-examination should be emphasized. Moreover, screening programs should be started to ensure early detection and reduction of mortality rates caused by breast cancer also in young Pakistani females.

Audit of the autoantibody test, EarlyCDT®-lung, in 1600 patients: an evaluation of its performance in routine clinical practice.

PubMed

Jett, James R; Peek, Laura J; Fredericks, Lynn; Jewell, William; Pingleton, William W; Robertson, John F R

2014-01-01

EarlyCDT(®)-Lung may enhance detection of early stage lung cancer by aiding physicians in assessing high-risk patients through measurement of biological markers (i.e., autoantibodies). The test's performance characteristics in routine clinical practice were evaluated by auditing clinical outcomes of 1613 US patients deemed at high risk for lung cancer by their physician, who ordered the EarlyCDT-Lung test for their patient. Clinical outcomes for all 1613 patients who provided HIPAA authorization are reported. Clinical data were collected from each patient's treating physician. Pathology reports when available were reviewed for diagnostic classification. Staging was assessed on histology, otherwise on imaging. Six month follow-up for the positives/negatives was 99%/93%. Sixty-one patients (4%) were identified with lung cancer, 25 of whom tested positive by EarlyCDT-Lung (sensitivity=41%). A positive EarlyCDT-Lung test on the current panel was associated with a 5.4-fold increase in lung cancer incidence versus a negative. Importantly, 57% (8/14) of non-small cell lung cancers detected as positive (where stage was known) were stage I or II. EarlyCDT-Lung has been extensively tested and validated in case-control settings and has now been shown in this audit to perform in routine clinical practice as predicted. EarlyCDT-Lung may be a complementary tool to CT for detection of early lung cancer. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

[Individual susceptibility to occupational carcinogens: the evidence from biomonitoring and molecular epidemiology studies].

PubMed

Pavanello, S; Clonfero, E

2004-01-01

This paper reviews the literature on the influence of metabolic and DNA repair polymorphisms of biological indicators of genotoxic risk commonly used in biomonitoring occupational exposure to carcinogens. Genetic polymorphisms which influence biomarkers (urinary metabolites, protein and DNA adducts), include P450 cytochromes (CYPs) and glutathione S-transferases (GSTs) in exposure to polycyclic aromatic hydrocarbons (PAHs), and acetyltransferases (NATs) in exposure to aromatic amines (AAs). As regards exposure to benzene, also relevant is the influence of epoxydohydrolase (EPHX) and NAD(P)H quinone oxidoreductase (NQO1) on the urinary excretion of t,t-muconic and phenylmercapturic acids. With respect to occupational exposure to styrene, EPHX significantly influences the levels of Chromosome Aberrations (CAs), strongly predictive genotoxic biomarkers of cancer risk. Some recent studies examine the role of polymorphisms linked to DNA repair genes in the modulation of genotoxic risk associated with PAH exposure, both for life-style (dietary and smoking behaviour) and for occupational reasons. In addition, molecular epidemiology studies (case/control studies) of lung cancer in smokers published since 2000 may also be viewed as representing models of effects due to exposure to carcinogenic mixtures, some of which are present in the working environment (e.g., BaP, benzene, AAs). Almost all studies show the clearcut influence (i.e., increased lung cancer risk with OR > or = 2) of genetic polymorphisms linked to PAH metabolism (in particular, CYPIA1, GSTM1 and P1). Among the risk factors are the different mutagen sensitivity towards, for instance, bleomycin and BaP (tested in vitro), the reduced repair capacity to DNA damage induced by BaP, and increases in some biomarkers of early biological effect (DNA adducts and stable CAs). Other risk factors, such as heredity (siblings of cancer patients have a risk factor > or = 3 with respect to the general population), ethnicity (Chileans > Caucasians; Japanese > Americans) and gender (women > men), have still not been clearly characterized and these are also reported in this paper. It is clear from the above that genetic differences underlie individual susceptibility to lung cancer, whether caused by exposure to tobacco smoke or to occupational carcinogens like PAHs. Some of these indicators of exposure/individual susceptibility can be evaluated in groups at high risk of occupational lung cancer, such as coke-oven and aluminium workers and those exposed to coal tar fumes and soot, etc., with the aim of identifying subjects who are susceptible due to the high concentrations of carcinogens found in their working environment.

[Geomagnetic field variation in early ontogenesis as a risk factor for oncopathology].

PubMed

Iamshanov, V A

2003-01-01

The data on 534 cancer patients with tumors of 15 different sites were evaluated to elucidate the influence of geomagnetic field (GMF) in certain months of the pre- and early postnatal periods on future incidence of cancer. We identified neoplasms of the breast, lung, urinary bladder, hypophysis, ovary, prostate, liver, Hodgkin's disease, lymphoma and, possibly, gastric cancer as GMF-dependent. This relationship appeared to be idiosyncratic with every cancer variety. It was negligible in cases of esophagus, thyroid, uterine cervix and colorectal cancer. GMF variations as a carcinogenic factor in early ontogenesis can be assessed quantitatively.

Fluorodeoxyglucose positron emission tomography–computed tomography in evaluation of pelvic and para-aortic nodal involvement in early stage and operable cervical cancer: Comparison with surgicopathological findings

PubMed Central

Bansal, Vandana; Damania, Kaizad; Sharma, Anshu Rajnish

2011-01-01

Introduction: Nodal metastases in cervical cancer have prognostic implications. Imaging is used as an adjunct to clinical staging for evaluation of nodal metastases. Fluorodeoxyglucose (FDG) positron emission tomography/computed tomography (PET/CT) has an advantage of superior resolution of its CT component and detecting nodal disease based on increased glycolytic activity rather than node size. But there are limited studies describing its limitations in early stage cervical cancers. Objective: We have done meta-analysis with an objective to evaluate the efficacy of FDG PET/CT and its current clinical role in early stage and operable cervical cancer. Materials and Methods: Studies in which FDG PET/CT was performed before surgery in patients with early stage cervical cancers were included for analysis. PET findings were confirmed with histopathological diagnosis rather than clinical follow-up. FDG PET/CT showed lower sensitivity and clinically unacceptable negative predictive value in detecting nodal metastases in early stage cervical cancer and therefore, can not replace surgicopathological staging. False negative results in presence of microscopic disease and sub-centimeter diseased nodes are still the area of concern for metabolic imaging. However, these studies are single institutional and performed in a small group of patients. There is enough available evidence of clinical utility of FDG PET/CT in locally advanced cervical cancer. But these results can not be extrapolated for early stage disease. Conclusion: The current data suggest that FDG PET/CT is suboptimal in nodal staging in early stage cervical cancer. PMID:23559711

Mechanisms of Cables 1 gene inactivation in human ovarian cancer development.

PubMed

Sakamoto, Hideo; Friel, Anne M; Wood, Antony W; Guo, Lankai; Ilic, Ana; Seiden, Michael V; Chung, Daniel C; Lynch, Maureen P; Serikawa, Takehiro; Munro, Elizabeth; Oliva, Esther; Orsulic, Sandra; Kirley, Sandra D; Foster, Rosemary; Zukerberg, Lawrence R; Rueda, Bo R

2008-02-01

Cables 1, a cyclin-dependent kinase binding protein, is primarily involved in cell cycle regulation. Loss of nuclear Cables 1 expression is observed in human colon, lung and endometrial cancers. We previously reported that loss of nuclear Cables 1 expression was also observed with high frequency in a limited sample set of human ovarian carcinomas, although the mechanisms underlying loss of nuclear Cables 1 expression remained unknown. Our present objective was to examine Cables 1 expression in ovarian cancer in greater detail, and determine the predominant mechanisms of Cables 1 loss. We assessed potential genetic and epigenetic modifications of the Cables 1 locus through analyses of mutation, polymorphisms, loss of heterozygosity and DNA methylation. We observed a marked loss of nuclear Cables 1 expression in serous and endometrioid ovarian carcinomas that correlated with decreased Cables 1 mRNA levels. Although we detected no Cables 1 mutations, there was evidence of LOH at the Cables 1 locus and epigenetic modification of the Cables 1 promoter region in a subset of ovarian carcinomas and established cancer cell lines. From a functional perspective, over-expression of Cables 1 induced apoptosis, whereas, knockdown of Cables 1 negated this effect. Together these findings suggest that multiple mechanisms underlie the loss of Cables 1 expression in ovarian cancer cells, supporting the hypothesis that Cables 1 is a tumor suppressor in human ovarian cancer.

Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway Regulated-Circulating microRNA

DTIC Science & Technology

2016-05-01

Award Number: W81XWH-11-1-0715 TITLE: Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway-Regulated Circulating microRNA PRINCIPAL...TITLE AND SUBTITLE Sa. CONTRACT NUMBER Early Diagnosis of Clear Cell Kidney Cancer via VHL/HIF Pathway- Regulated Circulating microRNA Sb. GRANT NUMBER...panel of diagnostic miRNAs that are measurable in serum and will be able to identify kidney cancer in its earliest stages. We hypothesized that serum

77 FR 60703 - Breast and Cervical Cancer Early Detection and Control Advisory Committee: Notice of Charter Renewal

Federal Register 2010, 2011, 2012, 2013, 2014

2012-10-04

... DEPARTMENT OF HEALTH AND HUMAN SERVICES Centers for Disease Control and Prevention Breast and Cervical Cancer Early Detection and Control Advisory Committee: Notice of Charter Renewal This gives notice under the Federal Advisory Committee Act (Pub. L. 92-463) of October 6, 1972, that the Breast and Cervical Cancer Early Detection and Control...

SEOM clinical guidelines in early-stage breast cancer 2015.

PubMed

Garcia-Saenz, J A; Bermejo, B; Estevez, L G; Palomo, A G; Gonzalez-Farre, X; Margeli, M; Pernas, S; Servitja, S; Rodriguez, C A; Ciruelos, E

2015-12-01

Breast cancer is a major public health problem. Despite remarkable advances in early diagnosis and treatment, one in three women may have metastases since diagnosis. Better understanding of prognostic and predictive factors allows us to select the most appropriate adjuvant therapy in each patient. In these guidelines, we summarize current evidence for the medical management of early-stage breast cancer.

Communication by Mothers with Breast Cancer or Melanoma with Their Children

PubMed Central

Gaber, Rikki; Desai, Sapna; Smith, Maureen; Eilers, Steve; Blatt, Hanz; Guevara, Yanina; Robinson, June K.

2013-01-01

Communication of familial risk of breast cancer and melanoma has the potential to educate relatives about their risk, and may also motivate them to engage in prevention and early detection practices. With the Health Insurance Portability and Accountability Act (HIPAA) privacy laws, the patient often becomes the sole communicator of such risks to family members. This study surveys mothers diagnosed with either breast cancer or melanoma and their adult children about their family communication style, knowledge of increased risk, and early detection practices. In both cancer groups, most mothers alerted their children of the risk and need for early detection practices. Breast cancer mothers communicated risk and secondary prevention with early detection by breast self-examination and mammograms whereas the melanoma mothers communicated risk and primary prevention strategies like applying sunscreen and avoiding deliberate tanning. Open communication about health matters significantly increased the likelihood that children engaged in early detection and/or primary prevention behaviors. Examining the information conveyed to at-risk family members, and whether such information motivated them to engage in early detection/prevention behaviors, is key to guiding better cancer prevention communication between doctors and patients. PMID:23965923

Communication by mothers with breast cancer or melanoma with their children.

PubMed

Gaber, Rikki; Desai, Sapna; Smith, Maureen; Eilers, Steve; Blatt, Hanz; Guevara, Yanina; Robinson, June K

2013-08-08

Communication of familial risk of breast cancer and melanoma has the potential to educate relatives about their risk, and may also motivate them to engage in prevention and early detection practices. With the Health Insurance Portability and Accountability Act (HIPAA) privacy laws, the patient often becomes the sole communicator of such risks to family members. This study surveys mothers diagnosed with either breast cancer or melanoma and their adult children about their family communication style, knowledge of increased risk, and early detection practices. In both cancer groups, most mothers alerted their children of the risk and need for early detection practices. Breast cancer mothers communicated risk and secondary prevention with early detection by breast self-examination and mammograms whereas the melanoma mothers communicated risk and primary prevention strategies like applying sunscreen and avoiding deliberate tanning. Open communication about health matters significantly increased the likelihood that children engaged in early detection and/or primary prevention behaviors. Examining the information conveyed to at-risk family members, and whether such information motivated them to engage in early detection/prevention behaviors, is key to guiding better cancer prevention communication between doctors and patients.

Differential effects of early palliative care based on the age and sex of patients with advanced cancer from a randomized controlled trial.

PubMed

Nipp, Ryan D; El-Jawahri, Areej; Traeger, Lara; Jacobs, Jamie M; Gallagher, Emily R; Park, Elyse R; Jackson, Vicki A; Pirl, William F; Temel, Jennifer S; Greer, Joseph A

2018-04-01

Early palliative care interventions enhance patient outcomes, including quality of life, mood, and coping, but it remains unclear whether certain subgroups of patients are more likely to benefit from early palliative care. We explored whether age and sex moderate the improved outcomes seen with early palliative care. We performed a secondary analysis of data from a randomized trial of 350 patients with advanced lung and non-colorectal gastrointestinal cancer. Patients received an early palliative care intervention integrated with oncology care or usual oncology care alone. We used linear regression to determine if age (older or younger than 65) and sex moderated the effects of the intervention on quality of life (Functional Assessment of Cancer Therapy-General (FACT-G)), depression symptoms (Patient Health Questionnaire 9 (PHQ-9)), and coping (Brief COPE) within lung and gastrointestinal subgroups. At 24 weeks, younger patients with lung cancer receiving early palliative care reported increased use of active coping ( B = 1.74; p = 0.02) and decreased use of avoidant coping ( B = -0.97; p = 0.02), but the effects of early palliative care on these outcomes were not significant for older patients. Male patients with lung cancer assigned to early palliative care reported better quality of life (FACT-G: B = 9.31; p = 0.01) and lower depression scores (PHQ-9: B = -2.82; p = 0.02), but the effects of early palliative care on these outcomes were not significant for female patients. At 24 weeks, we found no age or sex moderation effects within the gastrointestinal cancer subgroup. Age and sex moderate the effects of early palliative care for patients with advanced lung cancer. Early palliative care may need to be tailored to individuals' unique sociodemographic and clinical characteristics.

Effectiveness of peer education for breast cancer screening and health beliefs in eastern Turkey.

PubMed

Gözüm, Sebahat; Karayurt, Ozgul; Kav, Sultan; Platin, Nurgun

2010-01-01

The primary site of cancer in Turkish women is breast cancer. The incidence of breast cancer is increasing in Turkey. The aim of the research was to educate women 40 years and older to increase their awareness on early detection and diagnosis, to facilitate the use of the early diagnosis methods, to improve the women's beliefs in relation breast cancer, and to increase the use of Cancer Early Diagnosis and Screening Centers available in the city. The target population of the research was 5000 women. Forty selected women were educated as peer educators. Twenty-five of them were selected as principal peer educator. Each peer educator was expected to educate 200 women. Peer trainers educated their peer and also arranged for the mammography appointment of the women who decided to have theirs taken. Data were obtained before and after the training by Champion's Health Belief Model Scale, questionnaire forms, and Cancer Early Diagnosis and Screening Centers data for mammography practice. Breast cancer was detected in 8 women. Statistical analyses showed positive changes in women's health beliefs and breast self-examination knowledge. There were 20.4% of women (n = 1040) who did get mammograms, and 8% (n = 8) of women were found to have cancer in all of those screened. Peer education was found to be effective for increasing the knowledge, beliefs, and practice of women related to breast cancer. Peers can reinforce learning through ongoing contact. Peer education can be used to improve early diagnosis of breast cancer and breast cancer awareness in asymptomatic women.

Endometrial Cancer Treatment (PDQ®)—Health Professional Version

Cancer.gov

Endometrial cancer is usually diagnosed at an early stage and can be treated with surgery. Learn about the symptoms, diagnosis, prognosis, staging, and treatment for early- and advanced-stage endometrial cancer in this expert-reviewed summary.

Prognostic and predictive biomarkers post curative intent therapy

PubMed Central

Feldman, Rebecca

2017-01-01

Large-scale screening trials have demonstrated that early diagnosis of lung cancer results in a significant reduction in lung cancer mortality. Despite improvements in detecting more lung cancers at early stages, the 5-year survival rates of lung cancers diagnosed before widespread disease is only 30–50%. High rates of recurrence, despite early diagnosis, suggest the need to improve treatment strategies based on the likelihood of recurrence in patient subsets, as well as explore the role of predictive markers for therapy selection in the adjuvant setting. In the era of personalized medicine, there have been a wide array of molecular alterations and signatures studied for their potential prognostic and predictive utility, however most have failed to translate into clinical tools. This review will discuss progress made in clinical management of lung cancer, and recent progress in the development of patient selection tools for the refinement of early stage lung cancers. PMID:29057234

Phase II Validation of a New Panel of Biomarkers for Early Detection of Ovarian Cancer — EDRN Public Portal

Cancer.gov

While all cancer patients could potentially benefit from earlier detection and prevention, the development of new screening technologies and chemoprevention for epithelial ovarian cancer (EOC) is unique in this regard. EOC is characterized by few early symptoms, presentation at an advanced stage, and poor survival. Presently there is no commercially available test that is diagnostic for either early or advanced stage epithelial ovarian cancer. The most commonly used marker, CA125, identifies a group of cell surface glycoproteins, which have uncertain biological behavior and very limited clinical utility for the detection of early stage disease. In recent years, several approaches have been used in order to develop a test for early detection, including the analysis of serum samples by SELDI-TOF and MALDI-TOF to find proteins or protein fragments of unknown identity that detect the presence/absence of cancer. Unfortunately, at the present time, none of these techniques have been shown to be adequate. Therefore, the development of a test that can detect early stages of the disease could dramatically improve treatment success and long-term survival. We have developed a new blood test based on a different approach: 1) we used known proteins related to cancer biology, 2) we characterized these proteins with several different screening steps using samples obtained from both healthy and cancer patient populations, and 3) validated the results with different techniques. Using split point analysis with four markers, 96 out of 100 EOC patients (96%) were correctly diagnosed with ovarian cancer (including 23 of 24 patients with Stage I/II EOC). In the healthy group, 6 out of 106 individuals were diagnosed incorrectly (5.6%). Working in collaboration with the Early Detection Network (EDRN/NCI/NIH), we performed Phase I discovery study confirming the potential application of this test for early detection of ovarian cancer (Preliminary results). The main objective of this pr

Liquid biopsy for early stage lung cancer.

PubMed

Liang, Wenhua; Zhao, Yi; Huang, Weizhe; Liang, Hengrui; Zeng, Haikang; He, Jianxing

2018-04-01

Liquid biopsy, which analyzes biological fluids especially blood specimen to detect and quantify circulating cancer biomarkers, have been rapidly introduced and represents a promising potency in clinical practice of lung cancer diagnosis and prognosis. Unlike conventional tissue biopsy, liquid biopsy is non-invasive, safe, simple in procedure, and is not influenced by manipulators' skills. Notably, some circulating cancer biomarkers are already detectable in disease with low-burden, making liquid biopsy feasible in detecting early stage lung cancer. In this review, we described a landscape of different liquid biopsy methods by highlighting the rationale and advantages, accessing the value of various circulating biomarkers and discussing their possible future development in the detection of early lung cancer.

[A Case of Early Gastric Cancer with Nodular Tumor-like Scalp Metastasis].

PubMed

Song, Young Wook; Kim, Woo Sub; Yun, Gee Young; Park, Sun Wook; Kang, Sun Hyung; Moon, Hee Seok; Sung, Jae Kyu; Jeong, Hyun Yong

2016-07-25

Many neoplasms, including lung cancer, breast cancer, melanoma, and gastrointestinal tract malignancy, possess potential for skin metastasis. Skin metastases can represent the first presentation of such malignancies and may be observed incidentally during routine exam. Skin metastases from gastric adenocarcinoma are uncommon, with a prevalence rate of 0.04-0.8%. Cutaneous metastases from gastric cancer are generally observed as the initial symptom of advanced gastric cancer. Early detection and treatment can increase patient survival. A 42-year-old woman visited our department with nodule about 1 cm in size on the right frontal scalp noticed incidentally after laparoscopy-assisted distal gastrectomy and adjuvant systemic chemo-therapy for early gastric cancer about 16 months prior. The patient was diagnosed with skin metastasis from gastric adenocarcinoma. Complete excision of the skin lesion and additional chemotherapy were performed. Herein, we report a case of nodular tumor-like scalp metastasis from early gastric cancer with a brief review of the literature.

Perigastric lymph node metastasis from papillary thyroid carcinoma in a patient with early gastric cancer: the first case report.

PubMed

Jeong, Gui-Ae; Kim, Hyung-Chul; Kim, Hee-Kyung; Cho, Gyu-Seok

2014-09-01

Distant metastasis from papillary thyroid carcinoma (PTC), particularly from papillary thyroid microcarcinoma, is rare. We present a case of perigastric lymph node metastasis from PTC in a patient with early gastric cancer and breast cancer. During post-surgical follow-up for breast cancer, a 56-year-old woman was diagnosed incidentally with early gastric cancer and synchronous left thyroid cancer. Therefore, laparoscopic distal gastrectomy with lymph node dissection and left thyroidectomy were performed. On the basis of the pathologic findings of the surgical specimens, the patient was diagnosed to have papillary thyroid microcarcinoma with perigastric lymph node metastasis and early gastric cancer with mucosal invasion. Finally, on the basis of immunohistochemical staining with galectin-3, the diagnosis of perigastric lymph node metastasis from PTC was made. When a patient has multiple primary malignancies with lymph node metastasis, careful pathologic examination of the surgical specimen is necessary; immunohistochemical staining may be helpful in determining the primary origin of lymph node metastasis.

Ex vivo generation of a functional and regenerative wound epithelium from axolotl (Ambystoma mexicanum) skin.

PubMed

Ferris, Donald R; Satoh, Akira; Mandefro, Berhan; Cummings, Gillian M; Gardiner, David M; Rugg, Elizabeth L

2010-10-01

Urodele amphibians (salamanders) are unique among adult vertebrates in their ability to regenerate structurally complete and fully functional limbs. Regeneration is a stepwise process that requires interactions between keratinocytes, nerves and fibroblasts. The formation of a wound epithelium covering the amputation site is an early and necessary event in the process but the molecular mechanisms that underlie the role of the wound epithelium in regeneration remain unclear. We have developed an ex vivo model that recapitulates many features of in vivo wound healing. The model comprises a circular explant of axolotl (Ambystoma mexicanum) limb skin with a central circular, full thickness wound. Re-epithelialization of the wound area is rapid (typically <11 h) and is dependent on metalloproteinase activity. The ex vivo wound epithelium is viable, responds to neuronal signals and is able to participate in ectopic blastema formation and limb regeneration. This ex vivo model provides a reproducible and tractable system in which to study the cellular and molecular events that underlie wound healing and regeneration. © 2010 The Authors. Journal compilation © 2010 Japanese Society of Developmental Biologists.

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2015-09-01

SABR ) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W. Loo, Jr., M.D., Ph.D CONTRACTING ORGANIZATION: Stanford University Stanford, CA...CONTRACT NUMBER W81XWH-12-1-0236 Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer 5b. GRANT NUMBER 5c. PROGRAM...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Purpose and scope: Stereotactic ablative radiotherapy ( SABR ) has become a new standard of care for early

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer and optimal selection of traditional Chinese medicine target.

PubMed

Tian, Tongde; Chen, Chuanliang; Yang, Feng; Tang, Jingwen; Pei, Junwen; Shi, Bian; Zhang, Ning; Zhang, Jianhua

2017-03-01

The paper aimed to screen out genetic markers applicable to early diagnosis for colorectal cancer and establish apoptotic regulatory network model for colorectal cancer, and to analyze the current situation of traditional Chinese medicine (TCM) target, thereby providing theoretical evidence for early diagnosis and targeted therapy of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers that are applied to early diagnosis of colorectal cancer were searched and performed comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. KEGG analysis was employed to establish apoptotic regulatory network model based on screened genetic markers, and optimization was conducted on TCM targets. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, P53, APC, DCC and PTEN, among which DCC has the highest diagnostic efficiency. Apoptotic regulatory network was built by KEGG analysis. Currently, it was reported that TCM has regulatory function on gene locus in apoptotic regulatory network. The apoptotic regulatory model of colorectal cancer established in this study provides theoretical evidence for early diagnosis and TCM targeted therapy of colorectal cancer in clinic.

Applying NGS Data to Find Evolutionary Network Biomarkers from the Early and Late Stages of Hepatocellular Carcinoma

PubMed Central

Wu, Chia-Chou; Lin, Chih-Lung; Chen, Ting-Shou

2015-01-01

Hepatocellular carcinoma (HCC) is a major liver tumor (~80%), besides hepatoblastomas, angiosarcomas, and cholangiocarcinomas. In this study, we used a systems biology approach to construct protein-protein interaction networks (PPINs) for early-stage and late-stage liver cancer. By comparing the networks of these two stages, we found that the two networks showed some common mechanisms and some significantly different mechanisms. To obtain differential network structures between cancer and noncancer PPINs, we constructed cancer PPIN and noncancer PPIN network structures for the two stages of liver cancer by systems biology method using NGS data from cancer cells and adjacent noncancer cells. Using carcinogenesis relevance values (CRVs), we identified 43 and 80 significant proteins and their PPINs (network markers) for early-stage and late-stage liver cancer. To investigate the evolution of network biomarkers in the carcinogenesis process, a primary pathway analysis showed that common pathways of the early and late stages were those related to ordinary cancer mechanisms. A pathway specific to the early stage was the mismatch repair pathway, while pathways specific to the late stage were the spliceosome pathway, lysine degradation pathway, and progesterone-mediated oocyte maturation pathway. This study provides a new direction for cancer-targeted therapies at different stages. PMID:26366411

Early Detection of Pancreatic Cancer: The Role of Industry in the Development of Biomarkers.

PubMed

Kenner, Barbara J; Go, Vay Liang W; Chari, Suresh T; Goldberg, Ann E; Rothschild, Laura J

A diagnosis of pancreatic cancer is devastating owing to its poor prognosis, with a 5-year survival rate of only 9%. Currently, most individuals are diagnosed at a late stage when treatment options are limited. Early detection of pancreatic cancer provides the greatest hope for making substantial improvements in survival. The Kenner Family Research Fund in partnership with the American Pancreatic Association has sponsored a series of fora to stimulate discussion and collaboration on early detection of pancreatic cancer. At the first forum in 2014, "Early Detection of Sporadic Pancreatic Cancer Summit Conference," a strategic plan was set forth by an international group of interdisciplinary scientific representatives and subsequently The Strategic Map for Innovation was generated. The current conference report is the third forum in the series, "Early Detection of Pancreatic Cancer: The Role of Industry in the Development of Biomarkers," which was held in Boston, Massachusetts, on October 27, 2016. This report provides an overview of examples of innovative initiatives by industry and confirms the critical need for collaboration among industry, government, research institutions, and advocacy groups in order to make pancreatic cancer more easily detectable in its earlier stages, when it is more treatable.

Establishment of apoptotic regulatory network for genetic markers of colorectal cancer.

PubMed

Hao, Yibin; Shan, Guoyong; Nan, Kejun

2017-03-01

Our purpose is to screen out genetic markers applicable to early diagnosis for colorectal cancer and to establish apoptotic regulatory network model for colorectal cancer, thereby providing theoretical evidence and targeted therapy for early diagnosis of colorectal cancer. Taking databases including CNKI, VIP, Wanfang data, Pub Med, and MEDLINE as main sources of literature retrieval, literatures associated with genetic markers applied to early diagnosis of colorectal cancer were searched to perform comprehensive and quantitative analysis by Meta analysis, hence screening genetic markers used in early diagnosis of colorectal cancer. Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were employed to establish apoptotic regulatory network model based on screened genetic markers, and then verification experiment was conducted. Through Meta analysis, seven genetic markers were screened out, including WWOX, K-ras, COX-2, p53, APC, DCC and PTEN, among which DCC shows highest diagnostic efficiency. GO analysis of genetic markers found that six genetic markers played role in biological process, molecular function and cellular component. It was indicated in apoptotic regulatory network built by KEGG analysis and verification experiment that WWOX could promote tumor cell apoptotic in colorectal cancer and elevate expression level of p53. The apoptotic regulatory model of colorectal cancer established in this study provides clinically theoretical evidence and targeted therapy for early diagnosis of colorectal cancer.

More than the genes, the tumor microenvironment in neuroblastoma

PubMed Central

Borriello, Lucia; Seeger, Robert C.; Asgharzadeh, Shahab; DeClerck, Yves A.

2017-01-01

Neuroblastoma is the second most common solid tumor in children. Since the seminal discovery of the role of amplification of the MYCN oncogene in the pathogenesis of neuroblastoma in the 1980s, much focus has been on the contribution of genetic alterations in the progression of this cancer. However it is now clear that not only genetic events play a role but that the tumor microenvironment (TME) substantially contributes to the biology of neuroblastoma. In this article, we present a comprehensive review of the literature on the contribution of the TME to the ten hallmarks of cancer in neuroblastoma and discuss the mechanisms of communication between neuroblastoma cells and the TME that underlie the influence of the TME on neuroblastoma progression. We end our review by discussing how the knowledge acquired over the last two decades in this field is now leading to new clinical trials targeting the TME. PMID:26597947

More than the genes, the tumor microenvironment in neuroblastoma.

PubMed

Borriello, Lucia; Seeger, Robert C; Asgharzadeh, Shahab; DeClerck, Yves A

2016-09-28

Neuroblastoma is the second most common solid tumor in children. Since the seminal discovery of the role of amplification of the MYCN oncogene in the pathogenesis of neuroblastoma in the 1980s, much focus has been on the contribution of genetic alterations in the progression of this cancer. However it is now clear that not only genetic events play a role but that the tumor microenvironment (TME) substantially contributes to the biology of neuroblastoma. In this article, we present a comprehensive review of the literature on the contribution of the TME to the ten hallmarks of cancer in neuroblastoma and discuss the mechanisms of communication between neuroblastoma cells and the TME that underlie the influence of the TME on neuroblastoma progression. We end our review by discussing how the knowledge acquired over the last two decades in this field is now leading to new clinical trials targeting the TME. Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

[The touched masculinity: a discussion about the digital rectal exam for prostate cancer prevention].

PubMed

Gomes, Romeu; do Nascimento, Elaine Ferreira; Rebello, Lúcia Emília Figueiredo de Sousa; de Araújo, Fábio Carvalho

2008-01-01

The present study aims at analyzing the meanings attributed to the digital rectal exam, seeking to problematize questions underlying the masculine discourse on the basis of aspects of the hegemonic masculinity model. Semi-structured interviews were held with 28 men in the city of Rio de Janeiro, in 2004. Among the main results is the idea that the digital rectal exam is something that violates an interdicted space, something that compromises the current understanding of masculinity, shall say, the digital rectal exam does not only affect the prostate, it also affects the masculinity, puts it to shame. We conclude that for understanding and problematizing the questions related to the prostate cancer prevention in special, and to the question of taking care of oneself from the masculine perspective in general, we need to consider the structural and symbolic aspects that underlie these questions.

A central role for vesicle trafficking in epithelial neoplasia: Intracellular highways to carcinogenesis

PubMed Central

Goldenring, James R.

2014-01-01

Epithelial cell carcinogenesis involves the loss of polarity, alteration of polarized protein presentation, dynamic cell morphology changes, increased proliferation and increased cell motility and invasion. Elements of membrane vesicle trafficking underlie all of these processes. Specific membrane trafficking regulators, including Rab small GTPases, through the coordinated dynamics of intracellular trafficking along cytoskeletal pathways, determine cell surface presentation of proteins and overall function of both differentiated and neoplastic cells. While mutations in vesicle trafficking proteins may not be direct drivers of transformation, elements of the machinery of vesicle movement play critical roles in the phenotypes of neoplastic cells. Therefore, the regulators of membrane vesicle trafficking decisions are critical mediators of the full spectrum of cell physiologies driving cancer cell biology, including initial loss of polarity, invasion and metastasis. Targeting of these fundamental intracellular processes may provide important points for manipulation of cancer cell behaviour. PMID:24108097

NCCN Guidelines Insights: Central Nervous System Cancers, Version 1.2017.

PubMed

Nabors, Louis Burt; Portnow, Jana; Ammirati, Mario; Baehring, Joachim; Brem, Henry; Butowski, Nicholas; Fenstermaker, Robert A; Forsyth, Peter; Hattangadi-Gluth, Jona; Holdhoff, Matthias; Howard, Steven; Junck, Larry; Kaley, Thomas; Kumthekar, Priya; Loeffler, Jay S; Moots, Paul L; Mrugala, Maciej M; Nagpal, Seema; Pandey, Manjari; Parney, Ian; Peters, Katherine; Puduvalli, Vinay K; Ragsdale, John; Rockhill, Jason; Rogers, Lisa; Rusthoven, Chad; Shonka, Nicole; Shrieve, Dennis C; Sills, Allen K; Swinnen, Lode J; Tsien, Christina; Weiss, Stephanie; Wen, Patrick Yung; Willmarth, Nicole; Bergman, Mary Anne; Engh, Anita

2017-11-01

For many years, the diagnosis and classification of gliomas have been based on histology. Although studies including large populations of patients demonstrated the prognostic value of histologic phenotype, variability in outcomes within histologic groups limited the utility of this system. Nonetheless, histology was the only proven and widely accessible tool available at the time, thus it was used for clinical trial entry criteria, and therefore determined the recommended treatment options. Research to identify molecular changes that underlie glioma progression has led to the discovery of molecular features that have greater diagnostic and prognostic value than histology. Analyses of these molecular markers across populations from randomized clinical trials have shown that some of these markers are also predictive of response to specific types of treatment, which has prompted significant changes to the recommended treatment options for grade III (anaplastic) gliomas. Copyright © 2017 by the National Comprehensive Cancer Network.

Couples' Support-Related Communication, Psychological Distress, and Relationship Satisfaction among Women with Early Stage Breast Cancer

ERIC Educational Resources Information Center

Manne, Sharon; Sherman, Marne; Ross, Stephanie; Ostroff, Jamie; Heyman, Richard E.; Fox, Kevin

2004-01-01

This study examined associations between couple communication about cancer and psychological distress and relationship satisfaction of women diagnosed with early stage breast cancer. One hundred forty-eight couples completed a videotaped discussion of a cancer-related issue and a general issue. Patients completed measures of psychological distress…

Computer-aided detection of early cancer in the esophagus using HD endoscopy images

NASA Astrophysics Data System (ADS)

van der Sommen, Fons; Zinger, Svitlana; Schoon, Erik J.; de With, Peter H. N.

2013-02-01

Esophageal cancer is the fastest rising type of cancer in the Western world. The recent development of High-Definition (HD) endoscopy has enabled the specialist physician to identify cancer at an early stage. Nevertheless, it still requires considerable effort and training to be able to recognize these irregularities associated with early cancer. As a first step towards a Computer-Aided Detection (CAD) system that supports the physician in finding these early stages of cancer, we propose an algorithm that is able to identify irregularities in the esophagus automatically, based on HD endoscopic images. The concept employs tile-based processing, so our system is not only able to identify that an endoscopic image contains early cancer, but it can also locate it. The identification is based on the following steps: (1) preprocessing, (2) feature extraction with dimensionality reduction, (3) classification. We evaluate the detection performance in RGB, HSI and YCbCr color space using the Color Histogram (CH) and Gabor features and we compare with other well-known features to describe texture. For classification, we employ a Support Vector Machine (SVM) and evaluate its performance using different parameters and kernel functions. In experiments, our system achieves a classification accuracy of 95.9% on 50×50 pixel tiles of tumorous and normal tissue and reaches an Area Under the Curve (AUC) of 0.990. In 22 clinical examples our algorithm was able to identify all (pre-)cancerous regions and annotate those regions reasonably well. The experimental and clinical validation are considered promising for a CAD system that supports the physician in finding early stage cancer.

Five common tumor biomarkers and CEA for diagnosing early gastric cancer: A protocol for a network meta-analysis of diagnostic test accuracy.

PubMed

Shen, Minghui; Wang, Hui; Wei, Kongyuan; Zhang, Jianling; You, Chongge

2018-05-01

Although surgical resection is the recommended treatment for the patients with gastric cancer, lots of patients show advanced or metastatic gastric cancer at the time of diagnosis. Detection of gastric cancer at early stages is a huge challenge because of lack of appropriate detection tests. Unfortunately, existing clinical guidelines focusing on early diagnosis of gastric cancer do not provide consistent and prudent evidence. Serum carcinoembryonic antigen was considered as a complementary test, although it is not good enough to diagnose early gastric cancer. There are no other tumor markers recommended for diagnosing early gastric cancer. This study aims to evaluate and compare the diagnostic accuracy of 5 common tumor biomarkers (CA19-9, CA125, PG, IncRNA, and DNA methylation) and CEA and their combinations for diagnosing gastric cancer through network meta-analysis method, and to rank these tests using a superiority index. PubMed, EMBASE.com, and the Cochrane Central Register of Controlled Trials (CENTRAL) will be searched from their inception to March 2018. We will include diagnostic tests which assessed the accuracy of the above-mentioned tumor biomarkers and CEA for diagnosing gastric cancer. The risk of bias for each study will be independently assessed as low, moderate, or high using criteria adapted from Quality Assessment of Diagnostic Accuracy Studies 2 (QUADAS-2). Network meta-analysis will be performed using STATA 12.0 and R 3.4.1 software. The competing diagnostic tests will be ranked by a superiority index. This study is ongoing and will be submitted to a peer-reviewed journal for publication. This study will provide systematically suggestions to select different tumor biomarkers for detecting the early gastric cancer.

Detection of oral early cancerous lesion by using polarization-sensitive optical coherence tomography: mice model

NASA Astrophysics Data System (ADS)

Lee, Hong-Yi; Chen, Ping-Hsien; Lee, Tzu-Han; Chang, Kuo-Wei; Kuo, Wen-Chuan

2018-02-01

Oral cancer is the 11th most common cancer worldwide, especially in a male adult. The median age of death in oral cancer was 55 years, 10-20 years earlier than other cancers. Presently, oral cancer is often found in late stage, because the lesion is often flat in early stage and is difficult to diagnose under traditional white light imaging. The only definitive method for determining cancer is an invasive biopsy and then using histology examination. How to detect precancerous lesions or early malignant lesions is an important issue for improving prognosis of oral cancer. Optical coherence tomography (OCT) is a new optical tool for diagnosing early malignant lesions in the skin or gastrointestinal tract recently. Here we report a new method for detecting precancerous or early malignant oral lesions by using swept source polarization-sensitive optical coherence tomography (PS-OCT) with center-wavelength 1310 nm, bandwidth 110 nm and 100 kHz swept rate. We used all single-mode fiber design to detect the change of birefringence information in the epithelium structure. This system has an advantage that enables measurement of backscattered intensity and birefringence simultaneously with only one A-scan per transverse location. In preliminary result, we computed the slope of the every A-scan signal in tissue part using a linear-curve fitting in backscattered intensity and birefringence on the enface. In this research, we used an oral cancer mice model for observing the change of structure and birefringence properties in different stages of oral cancer mice. We presented the parametric enface imaging that can detect the early oral malignant lesions.

A Prospective Evaluation of Early Detection Biomarkers for Ovarian Cancer in the European EPIC Cohort.

PubMed

Terry, Kathryn L; Schock, Helena; Fortner, Renée T; Hüsing, Anika; Fichorova, Raina N; Yamamoto, Hidemi S; Vitonis, Allison F; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H Bas; Onland-Moret, N Charlotte; Peeters, Petra H; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C; Gunter, Marc J; Merritt, Melissa A; Riboli, Elio; Cramer, Daniel W; Kaaks, Rudolf

2016-09-15

About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. We measured CA125, HE4, CA72.4, and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as area under the receiver operator curve (C-statistic) for each marker individually and in combination. In addition, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. We observed the best discrimination between cases and controls within 6 months of diagnosis for CA125 (C-statistic = 0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early-stage cases. Clin Cancer Res; 22(18); 4664-75. ©2016 AACRSee related commentary by Skates, p. 4542. ©2016 American Association for Cancer Research.

BRCA1 and BRCA2 mutation analysis of early-onset and familial breast cancer cases in Mexico.

PubMed

Ruiz-Flores, Pablo; Sinilnikova, Olga M; Badzioch, Michael; Calderon-Garcidueñas, A L; Chopin, Sandrine; Fabrice, Odefrey; González-Guerrero, J F; Szabo, Csilla; Lenoir, Gilbert; Goldgar, David E; Barrera-Saldaña, Hugo A

2002-12-01

The entire coding regions of BRCA1 and BRCA2 were screened for mutations by heteroduplex analysis in 51 Mexican breast cancer patients. One BRCA1 and one BRCA2 truncating mutation each was identified in the group of 32 (6%) early-onset breast cancer patients (< or =35 years). Besides these two likely deleterious mutations, eight rare variants of unknown significance, mostly in the BRCA2 gene, were detected in six of 32 (19%) early-onset breast cancer cases and in three of 17 (18%) site-specific breast cancer families, one containing a male breast cancer case. No mutations or rare sequence variants have been identified in two additional families including each an early-onset breast cancer case and an ovarian cancer patient. The two truncating mutations (BRCA1 3857delT; BRCA2 2663-2664insA) and six of the rare variants have never been reported before and may be of country-specific origin. The majority of the alterations appeared to be distinct, with only one of them being observed in more than one family. Copyright 2002 Wiley-Liss, Inc.

Adjuvant therapy for resected colon cancer 2017, including the IDEA analysis.

PubMed

Tang, Monica; Price, Timothy Jay; Shapiro, Jeremy; Gibbs, Peter; Haller, Daniel G; Arnold, Dirk; Peeters, Marc; Segelov, Eva; Roy, Amitesh; Tebbutt, Niall; Pavlakis, Nick; Karapetis, Chris; Burge, Matthew

2018-04-01

Oxaliplatin-based adjuvant chemotherapy has been the standard of care for resected early colon cancer for over a decade. Recent results from the IDEA meta-analysis attempt to address the question of whether 3 or 6 months of adjuvant chemotherapy is preferable in Stage III colon cancer. Areas covered: A review of the literature and recent conference presentations was undertaken on the topic of adjuvant therapy for resected early colon cancers. This article reviews the current evidence for adjuvant treatment of Stage II and III colon cancer, as well as up-to-date data regarding optimal duration of therapy. This article reviews the evidence for lifestyle modifications in the management of early colorectal cancer and other future directions for research in early colon cancer. Expert commentary: In recent years, there have been no advances in the development of novel agents for adjuvant therapy in colorectal cancer. Although the IDEA meta-analysis was negative for its primary non-inferiority endpoint, the detailed results provide valuable information that allows personalisation of treatment regimen and duration.

Selenium- or vitamin E-related gene variants, interaction with supplementation, and risk of high-grade prostate cancer in SELECT

PubMed Central

Chan, June M.; Darke, Amy K.; Penney, Kathryn L.; Tangen, Catherine M.; Goodman, Phyllis J.; Lee, Gwo-Shu Mary; Sun, Tong; Peisch, Sam; Tinianow, Alex M.; Rae, James M.; Klein, Eric A.; Thompson, Ian M.

2016-01-01

Background Epidemiological studies and secondary analyses of randomized trials supported the hypothesis that selenium and vitamin E lower prostate cancer risk. However, the Selenium and Vitamin E Cancer Prevention Trial (SELECT) showed no benefit of either supplement. Genetic variants involved in selenium or vitamin E metabolism or transport may underlie the complex associations of selenium and vitamin E. Methods We undertook a case-cohort study of SELECT participants randomized to placebo, selenium or vitamin E. The subcohort included 1,434 men; our primary outcome was high-grade prostate cancer (N=278 cases, Gleason 7 or higher cancer). We used weighted Cox regression to examine the association between SNPs and high-grade prostate cancer risk. To assess effect modification, we created interaction terms between randomization arm and genotype and calculated log likelihood statistics. Results We noted statistically significant (p<0.05) interactions between selenium assignment, SNPs in CAT, SOD2, PRDX6, SOD3, and TXNRD2 and high-grade prostate cancer risk. Statistically significant SNPs that modified the association of vitamin E assignment and high-grade prostate cancer included SEC14L2, SOD1, and TTPA. In the placebo arm, several SNPs, hypothesized to interact with supplement assignment and risk of high-grade prostate cancer, were also directly associated with outcome. Conclusion Variants in selenium and vitamin E metabolism/transport genes may influence risk of overall and high-grade prostate cancer, and may modify an individual man’s response to vitamin E or selenium supplementation with regards to these risks. Impact The effect of selenium or vitamin E supplementation on high-grade prostate cancer risk may vary by genotype. PMID:27197287

New Round of Studies Begin in Phase 0/I/II Cancer Prevention Clinical Trials Program | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention’s Phase 0/I/II Cancer Prevention Clinical Trials Program, also known as the Consortia for Early Phase Prevention Trials, is beginning a new round of studies in the effort toward systematic early clinical development of promising preventive agents for people at increased risk of developing cancer. |

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed Central

Ried, Karin; Eng, Peter; Sali, Avni

2017-01-01

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 out-of 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with higher risk of malignancy. CTC monitoring over time indicated treatment effectiveness. Nutrients with anti-carcinogenic properties could reduce CTC count, and included curcumin, garlic, green tea, grape seed, modified citrus pectin, and medicinal mushroom extract. PMID:28843267

Screening for Circulating Tumour Cells Allows Early Detection of Cancer and Monitoring of Treatment Effectiveness: An Observational Study

PubMed

Ried, Karin; Eng, Peter; Sali, Avni

2017-08-27

Background: Circulating-Tumour-Cells (CTC) provide a blood biomarker for early carcinogenesis, cancer progression and treatment effectiveness. An increase in CTCs is associated with cancer progression, a CTC decrease with cancer containment or remission. Several technologies have been developed to identify CTC, including the validated Isolation-by-Size-of-Epithelial-Tumour (ISET, Rarecells) technology, combining blood filtration and microscopy using standard histo-pathological criteria. Methods: This observational study compared CTC count to cancer status and cancer risk, by monitoring treatment effectiveness in cancer patients and by screening for CTC in asymptomatic patients with risk factors, including family history of cancer. Results: Between Sept-2014 and Dec-2016 we undertook 600 CTC tests (542 patients), including 50% screening requests of patients without cancer diagnosis but with risk factors. CTC were detected in all cancer patients (n=277, 100%), and in half of the asymptomatic patients screened (50%, 132 out-of 265 patients). Follow-up tests including scans, scheduled within 1-10 months of positive CTC tests, found early cancerous lesions in 20% of screened patients. In 50% of male patients with CTC and normal PSA (prostate-specific-antigen) levels, PSMA-PET scans revealed increased uptake in the prostate, indicative of early prostate cancer. Other types of cancers detected by CTC screening and subsequent scans included early breast, ovarian, lung, or renal cancer. Patients with CTC were advised on integrative approaches including immune-stimulating and anti-carcinogenic nutritional therapies. CTC repeat tests were available in 10% of patients with detected CTC (40 outof 409 patients, n=98 CTC tests) to assess treatment effectiveness, suggesting nutritional therapies to be beneficial in reducing CTC count. Conclusions: CTC screening provided a highly sensitive biomarker for the early detection of cancer, with higher CTC counts being associated with higher risk of malignancy. CTC monitoring over time indicated treatment effectiveness. Nutrients with anti-carcinogenic properties could reduce CTC count, and included curcumin, garlic, green tea, grape seed, modified citrus pectin, and medicinal mushroom extract. Creative Commons Attribution License

Identification of early cancerous lesion of esophagus with endoscopic images by hyperspectral image technique (Conference Presentation)

NASA Astrophysics Data System (ADS)

Huang, Shih-Wei; Chen, Shih-Hua; Chen, Weichung; Wu, I.-Chen; Wu, Ming Tsang; Kuo, Chie-Tong; Wang, Hsiang-Chen

2016-03-01

This study presents a method to identify early esophageal cancer within endoscope using hyperspectral imaging technology. The research samples are three kinds of endoscopic images including white light endoscopic, chromoendoscopic, and narrow-band endoscopic images with different stages of pathological changes (normal, dysplasia, dysplasia - esophageal cancer, and esophageal cancer). Research is divided into two parts: first, we analysis the reflectance spectra of endoscopic images with different stages to know the spectral responses by pathological changes. Second, we identified early cancerous lesion of esophagus by principal component analysis (PCA) of the reflectance spectra of endoscopic images. The results of this study show that the identification of early cancerous lesion is possible achieve from three kinds of images. In which the spectral characteristics of NBI endoscopy images of a gray area than those without the existence of the problem the first two, and the trend is very clear. Therefore, if simply to reflect differences in the degree of spectral identification, chromoendoscopic images are suitable samples. The best identification of early esophageal cancer is using the NBI endoscopic images. Based on the results, the use of hyperspectral imaging technology in the early endoscopic esophageal cancer lesion image recognition helps clinicians quickly diagnose. We hope for the future to have a relatively large amount of endoscopic image by establishing a hyperspectral imaging database system developed in this study, so the clinician can take this repository more efficiently preliminary diagnosis.

Vulvar Cancer

MedlinePlus

... sex painful and difficult. If found early, vulvar cancer has a high cure rate and the treatment options involve less surgery. ... people may also need radiation therapy. When vulvar cancer is found and treated early, the cure rate is over 90%. The key to a ...

Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production

PubMed Central

Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

2015-01-01

S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis. PMID:26315114

Elevated S100A9 expression in tumor stroma functions as an early recurrence marker for early-stage oral cancer patients through increased tumor cell invasion, angiogenesis, macrophage recruitment and interleukin-6 production.

PubMed

Fang, Wei-Yu; Chen, Yi-Wen; Hsiao, Jenn-Ren; Liu, Chiang-Shin; Kuo, Yi-Zih; Wang, Yi-Ching; Chang, Kung-Chao; Tsai, Sen-Tien; Chang, Mei-Zhu; Lin, Siao-Han; Wu, Li-Wha

2015-09-29

S100A9 is a calcium-binding protein with two EF-hands and frequently deregulated in several cancer types, however, with no clear role in oral cancer. In this report, the expression of S100A9 in cancer and adjacent tissues from 79 early-stage oral cancer patients was detected by immunohistochemical staining. Although S100A9 protein was present in both tumor and stromal cells, only the early-stage oral cancer patients with high stromal expression had reduced recurrence-free survival. High stromal S100A9 expression was also significantly associated with non-well differentiation and recurrence. In addition to increasing cell migration and invasion, ectopic S100A9 expression in tumor cells promoted xenograft tumorigenesis as well as the dominant expression of myeloid cell markers and pro-inflammatory IL-6. The expression of S100A9 in one stromal component, monocytes, stimulated the aggressiveness of co-cultured oral cancer cells. We also detected the elevation of serum S100A9 levels in early-stage oral cancer patients of a separate cohort of 73 oral cancer patients. The release of S100A9 protein into extracellular milieu enhanced tumor cell invasion, transendothelial monocyte migration and angiogenic activity. S100A9-mediated release of IL-6 requires the crosstalk of tumor cells with monocytes through the activation of NF-κB and STAT-3. Early-stage oral cancer patients with both high S100A9 expression and high CD68+ immune infiltrates in stroma had shortest recurrence-free survival, suggesting the use of both S100A9 and CD68 as poor prognostic markers for oral cancer. Together, both intracellular and extracellular S100A9 exerts a tumor-promoting action through the activation of oral cancer cells and their associated stroma in oral carcinogenesis.

[Sea urchin embryo, DNA-damaged cell cycle checkpoint and the mechanisms initiating cancer development].

PubMed

Bellé, Robert; Le Bouffant, Ronan; Morales, Julia; Cosson, Bertrand; Cormier, Patrick; Mulner-Lorillon, Odile

2007-01-01

Cell division is an essential process for heredity, maintenance and evolution of the whole living kingdom. Sea urchin early development represents an excellent experimental model for the analysis of cell cycle checkpoint mechanisms since embryonic cells contain a functional DNA-damage checkpoint and since the whole sea urchin genome is sequenced. The DNA-damaged checkpoint is responsible for an arrest in the cell cycle when DNA is damaged or incorrectly replicated, for activation of the DNA repair mechanism, and for commitment to cell death by apoptosis in the case of failure to repair. New insights in cancer biology lead to two fundamental concepts about the very first origin of cancerogenesis. Cancers result from dysfunction of DNA-damaged checkpoints and cancers appear as a result of normal stem cell (NCS) transformation into a cancer stem cell (CSC). The second aspect suggests a new definition of "cancer", since CSC can be detected well before any clinical evidence. Since early development starts from the zygote, which is a primary stem cell, sea urchin early development allows analysis of the early steps of the cancerization process. Although sea urchins do not develop cancers, the model is alternative and complementary to stem cells which are not easy to isolate, do not divide in a short time and do not divide synchronously. In the field of toxicology and incidence on human health, the sea urchin experimental model allows assessment of cancer risk from single or combined molecules long before any epidemiologic evidence is available. Sea urchin embryos were used to test the worldwide used pesticide Roundup that contains glyphosate as the active herbicide agent; it was shown to activate the DNA-damage checkpoint of the first cell cycle of development. The model therefore allows considerable increase in risk evaluation of new products in the field of cancer and offers a tool for the discovery of molecular markers for early diagnostic in cancer biology. Prevention and early diagnosis are two decisive elements of human cancer therapy.

Knowledge and Practices Related to Screening for Breast Cancer among Women in Delhi, India

PubMed

Dahiya, Neha; Basu, Saurav; Singh, Megha Chandra; Garg, Suneela; Kumar, Rajesh; Kohli, Charu

2018-01-27

Background: Breast cancer is a major public health problem globally. The ongoing epidemiological, socio-cultural and demographic transition by accentuating the associated risk factors has disproportionately increased the incidence of breast cancer cases and resulting mortality in developing countries like India. Early diagnosis with rapid initiation of treatment reduces breast cancer mortality. Therefore awareness of breast cancer risk and a willingness to undergo screening are essential. The objective of the present study was to assess the knowledge and practices relating to screening for breast cancer among women in Delhi. Methods: Data were obtained from 222 adult women using a pretested selfadministered questionnaire. Results: Rates for knowledge of known risk factors of breast cancer were: family history of breast cancer, 59.5%; smoking, 57.7%; old age, 56.3%; lack of physical exercise, 51.9%; lack of breastfeeding, 48.2%; late menopause, 37.4%; and early menarche, 34.7%. Women who were aged < 30 and those who were unmarried registered significantly higher knowledge scores (p ≤ 0.01). Breast self-examination (BSE) was regularly practiced at-least once a month by 41.4% of the participants. Some 48% knew mammography has a role in the early detection of breast cancer. Since almost three-fourths of the participants believed BSE could help in early diagnosis of breast cancer, which is not supported by evidence, future studies should explore the consequences of promoting BSE at the potential expense of screening mammography. Conclusion: Our findings highlight the need for awareness generation among adult women regarding risk factors and methods for early detection of breast cancer. Creative Commons Attribution License

Knowledge and Practices Related to Screening for Breast Cancer among Women in Delhi, India

PubMed Central

Dahiya, Neha; Basu, Saurav; Singh, Megha Chandra; Garg, Suneela; Kumar, Rajesh; Kohli, Charu

2018-01-01

Background: Breast cancer is a major public health problem globally. The ongoing epidemiological, socio-cultural and demographic transition by accentuating the associated risk factors has disproportionately increased the incidence of breast cancer cases and resulting mortality in developing countries like India. Early diagnosis with rapid initiation of treatment reduces breast cancer mortality. Therefore awareness of breast cancer risk and a willingness to undergo screening are essential. The objective of the present study was to assess the knowledge and practices relating to screening for breast cancer among women in Delhi. Methods: Data were obtained from 222 adult women using a pretested self-administered questionnaire. Results: Rates for knowledge of known risk factors of breast cancer were: family history of breast cancer, 59.5%; smoking, 57.7%; old age, 56.3%; lack of physical exercise, 51.9%; lack of breastfeeding, 48.2%; late menopause, 37.4%; and early menarche, 34.7%. Women who were aged < 30 and those who were unmarried registered significantly higher knowledge scores (p ≤ 0.01). Breast self-examination (BSE) was regularly practiced at-least once a month by 41.4% of the participants. Some 48% knew mammography has a role in the early detection of breast cancer. Since almost three-fourths of the participants believed BSE could help in early diagnosis of breast cancer, which is not supported by evidence, future studies should explore the consequences of promoting BSE at the potential expense of screening mammography. Conclusion: Our findings highlight the need for awareness generation among adult women regarding risk factors and methods for early detection of breast cancer. PMID:29373907

Predictors of early retirement after cancer rehabilitation-a longitudinal study.

PubMed

Mehnert, A; Barth, J; Gaspar, M; Leibbrand, B; Kegel, C-D; Bootsveld, W; Friedrich, M; Hartung, T J; Berger, D; Koch, U

2017-09-01

This longitudinal study was designed to assess patients' desire for early retirement and investigate which cancer-related and psychosocial characteristics are associated with early retirement. We assessed 750 cancer patients at the beginning (t 0 ) and end (t 1 ) of, and 12 months after (t 2 ) inpatient cancer rehabilitation. At t 0 , 22% had a desire to retire early. These patients reported significantly longer sick leave periods, less favourable workplace environments, lower work ability, higher psychological distress and lower quality of life than other patients. At t 2 , 12.5% of patients received temporary or permanent early retirement pensions. Of all patients with a desire for early retirement at t 0 , 43% had returned to work at t 2 . This subgroup had a significantly lower physical quality of life than other patients returning to work. The most influential predictors of early retirement were being on sick leave (OR = 6.50, 95% CI = 1.97-21.47) and a desire for early retirement (OR = 5.61, 95% CI = 2.73-11.52). Inverse predictors of early retirement were cancer remission (OR = 0.23, 95% CI = 0.10-0.53), perceived productivity (OR = 0.38, 95% CI = 0.18-0.83), work satisfaction (OR = 0.36, 95% CI = 0.17-0.77) and mental quality of life (OR = 0.94, 95% CI = 0.91-0.98). This underlines the need for cancer-specific multi-professional rehabilitation and occupational therapy programmes. © 2016 John Wiley & Sons Ltd.

Sarsaparilla (Smilax Glabra Rhizome) Extract Activates Redox-Dependent ATM/ATR Pathway to Inhibit Cancer Cell Growth by S Phase Arrest, Apoptosis, and Autophagy.

PubMed

She, Tiantian; Feng, Junnan; Lian, Shenyi; Li, Ruobing; Zhao, Chuanke; Song, Guoliang; Luo, Jie; Dawuti, Rouxianguli; Cai, Shaoqing; Qu, Like; Shou, Chengchao

2017-01-01

Sarsaparilla (Smilax Glabra Rhizome) exerts growth inhibitory effect on multiple cancer cells in vitro and in vivo, and redox-dependent persistent activation of ERK1/2 has been reported to underlie this effect. Here, we report an activation of ATM/ATR-dependent signaling pathway also as a mechanism for the cancer cell growth inhibition induced by the supernatant fraction of the water-soluble extract from sarsaparilla (SW). SW treatment (3.5 μg/μL) promoted the phosphorylations of ATM, ATR, and CHK1 in AGS and HT-29 cells. The ATM kinase inhibitor, KU55933, could reverse SW-induced ERK phosphorylation but not the reduced glutathione/oxidized glutathione (GSH/GSSG) imbalance in AGS cells. However, both the redox inhibitor glutathione (GSH) and ERK inhibitor U0126 antagonized SW-induced phosphorylations of ATM, ATR, and CHK1 in AGS cells. We further found KU55933 significantly antagonized SW-induced S phase arrest, apoptosis, autophagy and the resultant cell growth inhibition. Our results provide another molecular basis for the anticancer action of sarsaparilla.

Impact of culture on health outcomes.

PubMed

Kagawa-Singer, Marjorie

2011-10-01

The diagnosis of cancer creates anticipatory grief and fear for the patient and the family, and the x cancer care experience is fraught with physical, emotional and spiritual challenges. The palliative care literature in Europe and North American is rapidly growing, but such literature is sparse in other parts of the world. Translating the findings from the West however, may be problematic in non-Western, and particularly, non-Christian cultures, for many of the assumptions that underlie the approach to suffering and death in the West are culturally based in the values and beliefs of western European society. Therefore this paper provides a means to explore how such translation across cultures might occur by: (1) providing a definition of culture so that the context for the subsequent discussion is framed, (2) describing how culture impacts the cancer experience, (3) how culture affects communication to relieve suffering and improve quality of life for patients and families. The paper closes with 8 recommended steps to improve communication cross-culturally to provide effective quality palliative care for patients and families from diverse backgrounds.

Understanding resistance to EGFR inhibitors—impact on future treatment strategies

PubMed Central

Wheeler, Deric L.; Dunn, Emily F.; Harari, Paul M.

2010-01-01

EGFR is a tyrosine kinase that participates in the regulation of cellular homeostasis. Following ligand binding, EGFR stimulates downstream cell signaling cascades that influence cell proliferation, apoptosis, migration, survival and complex processes, including angiogenesis and tumorigenesis. EGFR has been strongly implicated in the biology of human epithelial malignancies, with therapeutic applications in cancers of the colon, head and neck, lung, and pancreas. Accordingly, targeting EGFR has been intensely pursued, with the development of a series of promising molecular inhibitors for use in clinical oncology. As is common in cancer therapy, challenges with respect to treatment resistance emerge over time. This situation is certainly true of EGFR inhibitor therapies, where intrinsic and acquired resistance is now well recognized. In this Review, we provide a brief overview regarding the biology of EGFR biology, preclinical and clinical development of EGFR inhibitors, and molecular mechanisms that underlie the development of treatment resistance. A greater understanding of the mechanisms that lead to EGFR resistance may provide valuable insights to help design new strategies that will enhance the impact of this promising class of inhibitors for the treatment of cancer. PMID:20551942

Maximizing the Therapeutic Potential of Hsp90 Inhibitors

PubMed Central

Butler, Lisa M.; Ferraldeschi, Roberta; Armstrong, Heather K.; Centenera, Margaret M.; Workman, Paul

2015-01-01

Hsp90 is required for maintaining the stability and activity of a diverse group of client proteins, including protein kinases, transcription factors and steroid hormone receptors involved in cell signaling, proliferation, survival, oncogenesis and cancer progression. Inhibition of Hsp90 alters the Hsp90-client protein complex, leading to reduced activity, misfolding, ubiquitination and, ultimately, proteasomal degradation of client proteins. Hsp90 inhibitors have demonstrated significant antitumor activity in a wide variety of preclinical models with evidence of selectivity for cancer versus normal cells. In the clinic however, the efficacy of this class of therapeutic agents has been relatively limited to date, with promising responses mainly observed in breast and lung cancer, but no major activity seen in other tumor types. In addition, adverse events and some significant toxicities have been documented. Key to improving these clinical outcomes is a better understanding of the cellular consequences of inhibiting Hsp90 that may underlie treatment response or resistance. This review considers the recent progress that has been made in the study of Hsp90 and its inhibitors, and highlights new opportunities to maximize their therapeutic potential. PMID:26219697

ATF1 and RAS in exosomes are potential clinical diagnostic markers for cervical cancer.

PubMed

Shi, Yanhua; Wang, Wei; Yang, Baozhi; Tian, Hongge

2017-10-01

Cervical cancer is one of the most common cancers among women worldwide. It is highly lethal yet can be treated when found in early stage. Thus, early detection is of significant important for early diagnosis of cervical cancer. Exosomes have been used as biomarkers in clinical diagnosis. It is unknown that whether blood exosomes associated with cervical cancer can be detected and if these exosomes can accurately represent the developmental stage of cervical cancer. Mouse models were made out of a relapsed cervical cancer patient's tumour sample for original and recurrent cervical cancer, and gene analysis in both tumours and exosomes in these mouse models were performed. We found that activating transcription factor 1 (ATF1) and RAS genes were significantly up-regulated in tumours of both primary and recurrent cervical cancer mouse model, and they can also be detected in the blood exosomes of the mouse model. Our results indicated that ATF1 and RAS could be potential candidate biomarkers for cervical cancer in early diagnosis. ATF1 and RAS genes were found significantly elevated in tumours of primary and recurrent cervical cancer mouse model, and they were also detected in the blood exosomes. Therefore, ATF1 and RAS could be used as a diagnostic marker for cervical cancer in the future. Copyright © 2017 John Wiley & Sons, Ltd.

Palliative care content on cancer center websites.

PubMed

Vater, Laura B; Rebesco, Gina; Schenker, Yael; Torke, Alexia M; Gramelspacher, Gregory

2018-03-01

Professional guidelines recommend that palliative care begin early in advanced cancer management, yet integration of palliative and cancer care remains suboptimal. Cancer centers may miss opportunities to provide palliative care information online. In this study, we described the palliative care content on cancer center websites. We conducted a systematic content analysis of 62 National Cancer Institute- (NCI) designated cancer center websites. We assessed the content of center homepages and analyzed search results using the terms palliative care, supportive care, and hospice. For palliative and supportive care webpages, we assessed services offered and language used to describe care. Two researchers analyzed all websites using a standardized coding manual. Kappa values ranged from 0.78 to 1. NCI-designated cancer center homepages presented information about cancer-directed therapy (61%) more frequently than palliative care (5%). Ten percent of cancer centers had no webpage with palliative care information for patients. Among centers with information for patients, the majority (96%) defined palliative or supportive care, but 30% did not discuss delivery of palliative care alongside curative treatment, and 14% did not mention provision of care early in the disease process. Cancer center homepages rarely mention palliative care services. While the majority of centers have webpages with palliative care content, they sometimes omit information about early use of care. Improving accessibility of palliative care information and increasing emphasis on early provision of services may improve integration of palliative and cancer care.

A multi-wavelength (u.v. to visible) laser system for early detection of oral cancer

NASA Astrophysics Data System (ADS)

Najda, S. P.; Perlin, P.; Leszczyński, M.; Slight, T. J.; Meredith, W.; Schemmann, M.; Moseley, H.; Woods, J. A.; Valentine, R.; Kalra, S.; Mossey, P.; Theaker, E.; Macluskey, M.; Mimnagh, G.; Mimnagh, W.

2015-03-01

A multi-wavelength (360nm - 440nm), real-time Photonic Cancer Detector (PCD) optical system based on GaN semiconductor laser technology is outlined. A proof of concept using blue laser technology for early detection of cancer has already been tested and proven for esophageal cancer. This concept is expanded to consider a wider range of wavelengths and the PCD will initially be used for early diagnosis of oral cancers. The PCD creates an image of the oral cavity (broad field white light detection) and maps within the oral cavity any suspicious lesions with high sensitivity using a narrow field tunable detector.

Assessment of a lecture on cancer prevention and the early detection of cancer.

PubMed

Banner, William P; Booroojian, Stefani; Hernandez, Lori; Lopez, Brad; Pinzon-Perez, Helda

2002-01-01

Cancer prevention and the early detection can affect morbidity and mortality. Through educational programs, recommendations for beneficial lifestyle changes and cancer screening may be introduced to the public. The purpose of this study was to determine whether a videotaped lecture concerning cancer prevention and early detection is of educational value. College students in a health science class participated in the study. The students' comprehension of the subject matter was assessed immediately before and a week after they viewed the lecture. The students' scores on the second test were significantly better as measured by a paired-difference experiment. This videotaped lecture has merit as an educational program.

Factors Influencing Early Detection of Oral Cancer by Primary Health-Care Professionals.

PubMed

Hassona, Y; Scully, C; Shahin, A; Maayta, W; Sawair, F

2016-06-01

The purposes of this study are to determine early detection practices performed by primary healthcare professionals, to compare medical and dental sub-groups, and to identify factors that influence the ability of medical and dental practitioners to recognize precancerous changes and clinical signs of oral cancer. A 28-item survey instrument was used to interview a total of 330 Jordanian primary health-care professionals (165 dental and 165 medical). An oral cancer knowledge scale (0 to 31) was generated from correct responses on oral cancer general knowledge. An early detection practice scale (0 to 24) was generated from the reported usage and frequency of procedures in oral cancer examination. Also, a diagnostic ability scale (0 to 100) was generated from correct selections of suspicious oral lesions. Only 17.8 % of the participants reported that they routinely performed oral cancer screening in practices. Their oral cancer knowledge scores ranged from 3 to 31 with a mean of 15.6. The early detection practice scores ranged from 2 to 21 with a mean of 11.6. A significant positive correlation was found between knowledge scores and early detection practice scores (r = 0.22; p < 0.001). The diagnostic ability scores ranged from 11.5 to 96 with a mean of 43.6. The diagnostic ability score was significantly correlated with knowledge scores (r = 0.39; p < 0.001), but not with early detection practice scores (r = 0.01; p = 0.92). Few significant differences were found between medical and dental primary care professionals. Continuous education courses on early diagnosis of oral cancer and oral mucosal lesions are needed for primary health-care professionals.

Prevention and Early Detection of Prostate Cancer

PubMed Central

Cuzick, Jack; Thorat, Mangesh A.; Andriole, Gerald; Brawley, Otis W.; Brown, Powel H.; Culig, Zoran; Eeles, Rosalind A.; Ford, Leslie G.; Hamdy, Freddie C.; Holmberg, Lars; Ilic, Dragan; Key, Timothy J.; La Vecchia, Carlo; Lilja, Hans; Marberger, Michael; Meyskens, Frank L.; Minasian, Lori M.; Parker, Chris; Parnes, Howard L.; Perner, Sven; Rittenhouse, Harry; Schalken, Jack; Schmid, Hans-Peter; Schmitz-Dräger, Bernd J.; Schröder, Fritz H.; Stenzl, Arnulf; Tombal, Bertrand; Wilt, Timothy J.; Wolk, Alicja

2014-01-01

Prostate cancer is one of the most common cancers in men and the global burden of this disease is rising. Lifestyle modifications like smoking cessation, exercise and weight control offer opportunities to decrease the risk of developing prostate cancer. Early detection of prostate cancer by PSA screening remains controversial; yet, changes in PSA threshold, frequency of screening, and addition of other biomarkers have potential to minimise overdiagnosis associated with PSA screening. Several new biomarkers appear promising in individuals with elevated PSA levels or those diagnosed with prostate cancer, these are likely to guide in separating individuals who can be spared of aggressive treatment from those who need it. Several pharmacological agents like 5α-reductase inhibitors, aspirin etc. have a potential to prevent development of prostate cancer. In this review, we discuss the current evidence and research questions regarding prevention, early detection of prostate cancer and management of men either at high risk of prostate cancer or diagnosed with low-grade prostate cancer. PMID:25281467

Consortium for Imaging and Biomarkers (CIB) Created: Eight Grants Awarded | Division of Cancer Prevention

Cancer.gov

The NCI Division of Cancer Prevention awarded eight grants to create the Consortium for Imaging and Biomarkers (CIB) on August 3, 2015. | 8 lead investigators combining imaging methods for the visualization of lesions with biomarkers to improve the accuracy of screening, early cancer detection, and the diagnosis of early stage cancers.

The Costs of Waiting: Implications of the Timing of Palliative Care Consultation among a Cohort of Decedents at a Comprehensive Cancer Center.

PubMed

Scibetta, Colin; Kerr, Kathleen; Mcguire, Joseph; Rabow, Michael W

2016-01-01

Palliative care is recommended along with oncologic care for patients with advanced cancer. However, there are limited data about how the timing of palliative care affects quality and costs. Comparison of health care utilization and care quality for patients with cancer who died having received early versus late palliative care. Analysis of cancer registry, administrative, and billing databases. Patients with cancer who died having received specialty palliative care consultation. Comparing early (more than 90 days prior to death) versus late (less than 90 days prior to death) palliative care, outcome measures included rates of health care utilization and health care costs. Among 922 decedents, 297 (32.2%) had palliative care referrals, with 93 (10.1%) receiving early referrals and 204 (22.1%) late referrals. Compared to patients receiving late palliative care, early palliative care patients had lower rates of inpatient (33% versus 66%, p < 0.01), ICU (5% versus 20%, p < 0.01), and ED utilization (34% versus 54%, p = 0.04) in the last month of life. Direct costs of inpatient care in the last 6 months of life for patients with early palliative care were lower compared to late palliative care ($19,067 versus $25,754, p < 0.01), while direct outpatient costs were similar ($13,040 versus $11,549, p = 0.85). Early palliative care was predominantly delivered in the outpatient setting (84%) while late palliative care was mostly delivered in the hospital (82%). Early palliative care is associated with less intensive medical care, improved quality outcomes, and cost savings at the end of life for patients with cancer. Despite recommendations that early palliative care be offered to all patients with metastatic cancer, palliative care services remain underutilized.

The predictive factors for lymph node metastasis in early gastric cancer: A clinical study.

PubMed

Wang, Yinzhong

2015-01-01

To detect the clinicopathological factors associated with lymph node metastases in early gastric cancer. We retrospectively evaluated the distribution of metastatic nodes in 198 patients with early gastric cancer treated in our hospital between May 2008 and January 2015, the clinicopathological factors including age, gender, tumor location, tumor size, macroscopic type, depth of invasion, histological type and venous invasion were studied, and the relationship between various parameters and lymph node metastases was analyzed. In this study, one hundred and ninety-eight patients with early gastric cancer were included, and lymph node metastasis was detected in 28 patients. Univariate analysis revealed a close relationship between tumor size, depth of invasion, histological type, venous invasion, local ulceration and lymph node metastases. Multivariate analysis revealed that the five factors were independent risk factors for lymph node metastases. The clinicopathological parameters including tumor size, depth of invasion, local ulceration, histological type and venous invasion are closely correlated with lymph node metastases, should be paid high attention in early gastric cancer patients.

Detection of early primary colorectal cancer with upconversion luminescent NP-based molecular probes

NASA Astrophysics Data System (ADS)

Liu, Chunyan; Qi, Yifei; Qiao, Ruirui; Hou, Yi; Chan, Kaying; Li, Ziqian; Huang, Jiayi; Jing, Lihong; Du, Jun; Gao, Mingyuan

2016-06-01

Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation.Early detection and diagnosis of cancers is extremely beneficial for improving the survival rate of cancer patients and molecular imaging techniques are believed to be relevant for offering clinical solutions. Towards early cancer detection, we developed a primary animal colorectal cancer model and constructed a tumor-specific imaging probe by using biocompatible NaGdF4:Yb,Er@NaGdF4 upconversion luminescent NPs for establishing a sensitive early tumor imaging method. The primary animal tumor model, which can better mimic the human colorectal cancer, was built upon continual administration of 1,2-dimethylhydrazine in Kunming mice and the tumor development was carefully monitored through histopathological and immunohistochemical analyses to reveal the pathophysiological processes and molecular features of the cancer microenvironment. The upconversion imaging probe was constructed through covalent coupling of PEGylated core-shell NPs with folic acid whose receptor is highly expressed in the primary tumors. Upon 980 nm laser excitation, the primary colorectal tumors in the complex abdominal environment were sensitively imaged owing to the ultralow background of the upconversion luminescence and the high tumor-targeting specificity of the nanoprobe. We believe that the current studies provide a highly effective and potential approach for early colorectal cancer diagnosis and tumor surgical navigation. Electronic supplementary information (ESI) available: (1) Molecular structure of Jeffamine-modified FA; (2) immunohistochemical analysis of FR expression in the colorectal tissue derived from mice treated with NaCl at different weeks; (3) biodistributions of probes of NP-FA and NP-IgG in the main organs of mice. See DOI: 10.1039/c5nr07858j

Family history of skin cancer is associated with early-onset basal cell carcinoma independent of MC1R genotype.

PubMed

Berlin, Nicholas L; Cartmel, Brenda; Leffell, David J; Bale, Allen E; Mayne, Susan T; Ferrucci, Leah M

2015-12-01

As a marker of genetic susceptibility and shared lifestyle characteristics, family history of cancer is often used to evaluate an individual's risk for developing a particular malignancy. With comprehensive data on pigment characteristics, lifestyle factors, and melanocortin 1 receptor (MC1R) gene sequence, we sought to clarify the role of family history of skin cancer in early-onset basal cell carcinoma (BCC). Early onset BCC cases (n=376) and controls with benign skin conditions (n=383) under age 40 were identified through Yale dermatopathology. Self-report data on family history of skin cancer (melanoma and non-melanoma skin cancer), including age of onset in relatives, was available from a structured interview. Participants also provided saliva samples for sequencing of MC1R. A family history of skin cancer was associated with an increased risk of early-onset BCC (OR 2.49, 95% CI 1.80-3.45). In multivariate models, family history remained a strong risk factor for early-onset BCC after adjustment for pigment characteristics, UV exposure, and MC1R genotype (OR 2.41, 95% CI 1.74-3.35). Risk for BCC varied based upon the type and age of onset of skin cancer among affected relatives; individuals with a first-degree relative diagnosed with skin cancer prior to age 50 were at highest risk for BCC (OR 4.79, 95% CI 2.90-7.90). Even after taking into account potential confounding effects of MC1R genotype and various lifestyle factors that close relatives may share, family history of skin cancer remained strongly associated with early-onset BCC. Copyright © 2015. Published by Elsevier Ltd.

Decreased early mortality associated with the treatment of acute myeloid leukemia at National Cancer Institute-designated cancer centers in California.

PubMed

Ho, Gwendolyn; Wun, Ted; Muffly, Lori; Li, Qian; Brunson, Ann; Rosenberg, Aaron S; Jonas, Brian A; Keegan, Theresa H M

2018-05-01

To the authors' knowledge, few population-based studies to date have evaluated the association between location of care, complications with induction therapy, and early mortality in patients with acute myeloid leukemia (AML). Using linked data from the California Cancer Registry and Patient Discharge Dataset (1999-2014), the authors identified adult (aged ≥18 years) patients with AML who received inpatient treatment within 30 days of diagnosis. A propensity score was created for treatment at a National Cancer Institute-designated cancer center (NCI-CC). Inverse probability-weighted, multivariable logistic regression models were used to determine associations between location of care, complications, and early mortality (death ≤60 days from diagnosis). Of the 7007 patients with AML, 1762 (25%) were treated at an NCI-CC. Patients with AML who were treated at NCI-CCs were more likely to be aged ≤65 years, live in higher socioeconomic status neighborhoods, have fewer comorbidities, and have public health insurance. Patients treated at NCI-CCs had higher rates of renal failure (23% vs 20%; P = .010) and lower rates of respiratory failure (11% vs 14%; P = .003) and cardiac arrest (1% vs 2%; P = .014). After adjustment for baseline characteristics, treatment at an NCI-CC was associated with lower early mortality (odds ratio, 0.46; 95% confidence interval, 0.38-0.57). The impact of complications on early mortality did not differ by location of care except for higher early mortality noted among patients with respiratory failure treated at non-NCI-CCs. The initial treatment of adult patients with AML at NCI-CCs is associated with a 53% reduction in the odds of early mortality compared with treatment at non-NCI-CCs. Lower early mortality may result from differences in hospital or provider experience and supportive care. Cancer 2018;124:1938-45. © 2018 American Cancer Society. © 2018 American Cancer Society.

The right brain is dominant in psychotherapy.

PubMed

Schore, Allan N

2014-09-01

This article discusses how recent studies of the right brain, which is dominant for the implicit, nonverbal, intuitive, holistic processing of emotional information and social interactions, can elucidate the neurobiological mechanisms that underlie the relational foundations of psychotherapy. Utilizing the interpersonal neurobiological perspective of regulation theory, I describe the fundamental role of the early developing right brain in relational processes, throughout the life span. I present interdisciplinary evidence documenting right brain functions in early attachment processes, in emotional communications within the therapeutic alliance, in mutual therapeutic enactments, and in therapeutic change processes. This work highlights the fact that the current emphasis on relational processes is shared by, cross-fertilizing, and indeed transforming both psychology and neuroscience, with important consequences for clinical psychological models of psychotherapeutic change. PsycINFO Database Record (c) 2014 APA, all rights reserved.

Early transcriptional and epigenetic regulation of CD8+ T cell differentiation revealed by single-cell RNA-seq

PubMed Central

Kakaradov, Boyko; Arsenio, Janilyn; Widjaja, Christella E.; He, Zhaoren; Aigner, Stefan; Metz, Patrick J.; Yu, Bingfei; Wehrens, Ellen J.; Lopez, Justine; Kim, Stephanie H.; Zuniga, Elina I.; Goldrath, Ananda W.; Chang, John T.; Yeo, Gene W.

2017-01-01

SUMMARY During microbial infection, responding CD8+ T lymphocytes differentiate into heterogeneous subsets that together provide immediate and durable protection. To elucidate the dynamic transcriptional changes that underlie this process, we applied a single-cell RNA sequencing approach and analyzed individual CD8+ T lymphocytes sequentially throughout the course of a viral infection in vivo. Our analyses revealed a striking transcriptional divergence among cells that had undergone their first division and identified previously unknown molecular determinants controlling CD8+ T lymphocyte fate specification. These findings suggest a model of terminal effector cell differentiation initiated by an early burst of transcriptional activity and subsequently refined by epigenetic silencing of transcripts associated with memory lymphocytes, highlighting the power and necessity of single-cell approaches. PMID:28218746

Diagnostic value of selected markers and apoptotic pathways for pancreatic cancer

PubMed Central

Słotwińska, Sylwia Małgorzata

2017-01-01

Pancreatic cancer occupies the fourth place as a cause of death from cancer, and the mortality rate is similar to the number of newly detected cases. Due to the late diagnosis, only 5-6% of patients with pancreatic cancer survive for five years. Given that early diagnosis is critical for improving patients’ survival rates, there is an urgent need for the discovery and validation of new biomarkers with sufficient sensitivity and specificity to help diagnose pancreatic cancer early. Detection of serum tumor markers (CA19-9, CEA, CA125 and CA242) is conducive to the early diagnosis of pancreatic cancer. The combination of miR-16, miR-196a and CA19-9 plasma level was more effective, especially in early tumor screening. Furthermore, recent studies reported that mainly miR-21, miR-155 and miR-196 were dysregulated in IPMN (intraductal papillary mucinous neoplasms) and PanIN (pancreatic intraepithelial neoplasia) lesions, suggesting their usefulness as early biomarkers of these diseases. The reduced rate of apoptosis plays a crucial role in carcinogenesis, and it is one of the most important characteristics acquired by pancreatic cancer cells, which protects them from attack by the immune system and reduces the effectiveness of pharmacological treatment. This review summarizes the data concerning the clinical utility of selected biomarkers in pancreatic cancer patients. The review mainly focuses on the genetic aspects of signaling pathway disorders associated with apoptosis in the pathogenesis and diagnosis of pancreatic cancer. PMID:28450803

MRI surveillance of cancer cell fate in a brain metastasis model after early radiotherapy.

PubMed

Murrell, Donna H; Zarghami, Niloufar; Jensen, Michael D; Dickson, Fiona; Chambers, Ann F; Wong, Eugene; Foster, Paula J

2017-10-01

Incidence of brain metastasis attributed to breast cancer is increasing and prognosis is poor. It is thought that disseminated dormant cancer cells persist in metastatic organs and may evade treatments, thereby facilitating a mechanism for recurrence. Radiotherapy is used to treat brain metastases clinically, but assessment has been limited to macroscopic tumor volumes detectable by clinical imaging. Here, we use cellular MRI to understand the concurrent responses of metastases and nonproliferative or slowly cycling cancer cells to radiotherapy. MRI cell tracking was used to investigate the impact of early cranial irradiation on the fate of individual iron-labeled cancer cells and outgrowth of breast cancer brain metastases in the human MDA-MB-231-BR-HER2 cell model. Early whole-brain radiotherapy significantly reduced the outgrowth of metastases from individual disseminated cancer cells in treated animals compared to controls. However, the numbers of nonproliferative iron-retaining cancer cells in the brain were not significantly different. Radiotherapy, when given early in cancer progression, is effective in preventing the outgrowth of solitary cancer cells to brain metastases. Future studies of the nonproliferative cancer cells' clonogenic potentials are warranted, given that their persistent presence suggests that they may have evaded treatment. Magn Reson Med 78:1506-1512, 2017. © 2016 International Society for Magnetic Resonance in Medicine. © 2016 International Society for Magnetic Resonance in Medicine.

Increased lung and bladder cancer incidence in adults after in utero and early-life arsenic exposure.

PubMed

Steinmaus, Craig; Ferreccio, Catterina; Acevedo, Johanna; Yuan, Yan; Liaw, Jane; Durán, Viviana; Cuevas, Susana; García, José; Meza, Rodrigo; Valdés, Rodrigo; Valdés, Gustavo; Benítez, Hugo; VanderLinde, Vania; Villagra, Vania; Cantor, Kenneth P; Moore, Lee E; Perez, Saida G; Steinmaus, Scott; Smith, Allan H

2014-08-01

From 1958 to 1970, >100,000 people in northern Chile were exposed to a well-documented, distinct period of high drinking water arsenic concentrations. We previously reported ecological evidence suggesting that early-life exposure in this population resulted in increased mortality in adults from several outcomes, including lung and bladder cancer. We have now completed the first study ever assessing incident cancer cases after early-life arsenic exposure, and the first study on this topic with individual participant exposure and confounding factor data. Subjects included 221 lung and 160 bladder cancer cases diagnosed in northern Chile from 2007 to 2010, and 508 age and gender-matched controls. ORs adjusted for age, sex, and smoking in those only exposed in early life to arsenic water concentrations of ≤110, 110 to 800, and >800 μg/L were 1.00, 1.88 [95% confidence interval (CI), 0.96-3.71], and 5.24 (3.05-9.00; P(trend) < 0.001) for lung cancer, and 1.00, 2.94 (1.29-6.70), and 8.11 (4.31-15.25; P(trend) < 0.001) for bladder cancer. ORs were lower in those not exposed until adulthood. The highest category (>800 μg/L) involved exposures that started 49 to 52 years before, and ended 37 to 40 years before the cancer cases were diagnosed. Lung and bladder cancer incidence in adults was markedly increased following exposure to arsenic in early life, even up to 40 years after high exposures ceased. Such findings have not been identified before for any environmental exposure, and suggest that humans are extraordinarily susceptible to early-life arsenic exposure. Policies aimed at reducing early-life exposure may help reduce the long-term risks of arsenic-related disease. ©2014 American Association for Cancer Research.

Risk of early-onset prostate cancer associated with occupation in the Nordic countries.

PubMed

Barry, Kathryn Hughes; Martinsen, Jan Ivar; Alavanja, Michael C R; Andreotti, Gabriella; Blair, Aaron; Hansen, Johnni; Kjærheim, Kristina; Koutros, Stella; Lynge, Elsebeth; Sparèn, Pär; Tryggvadottir, Laufey; Weiderpass, Elisabete; Berndt, Sonja I; Pukkala, Eero

2017-12-01

Early-onset prostate cancer is often more aggressive and may have a different aetiology than later-onset prostate cancer, but has been relatively little studied to date. We evaluated occupation in relation to early- and later-onset prostate cancer in a large pooled study. We used occupational information from census data in five Nordic countries from 1960 to 1990. We identified prostate cancer cases diagnosed from 1961 to 2005 by linkage of census information to national cancer registries and calculated standardised incidence ratios (SIRs) separately for men aged 30-49 and those aged 50 or older. We also conducted separate analyses by period of follow-up, 1961-1985 and 1986-2005, corresponding to pre- and post-prostate-specific antigen (PSA) screening. For early-onset prostate cancer (n = 1521), we observed the highest SIRs for public safety workers (e.g. firefighters) (SIR = 1.71, 95% confidence interval [CI]: 1.23-2.31) and military personnel (SIR = 1.97, 95% CI: 1.31-2.85). These SIRs were significantly higher than the SIRs for later-onset disease (for public safety workers, SIR = 1.10, 95% CI: 1.07-1.14 and for military personnel, SIR = 1.09, 95% CI: 1.05-1.13; p heterogeneity  = 0.005 and 0.002, respectively). Administrators and technical workers also demonstrated significantly increased risks for early-onset prostate cancer, but the SIRs did not differ from those of later-onset disease (p heterogeneity >0.05). While our early-onset finding for public safety workers was restricted to the post-PSA period, that for military personnel was restricted to the pre-PSA period. Our results suggest that occupational exposures, particularly for military personnel, may be associated with early-onset prostate cancer. Further evaluation is needed to explain these findings. Copyright © 2017 Elsevier Ltd. All rights reserved.

Developing a "toolkit" to measure implementation of concurrent palliative care in rural community cancer centers.

PubMed

Zubkoff, Lisa; Dionne-Odom, J Nicholas; Pisu, Maria; Babu, Dilip; Akyar, Imatullah; Smith, Tasha; Mancarella, Gisella A; Gansauer, Lucy; Sullivan, Margaret Murray; Swetz, Keith M; Azuero, Andres; Bakitas, Marie A

2018-02-01

Despite national guidelines recommending early concurrent palliative care for individuals newly diagnosed with metastatic cancer, few community cancer centers, especially those in underserved rural areas do so. We are implementing an early concurrent palliative care model, ENABLE (Educate, Nurture, Advise, Before Life Ends) in four, rural-serving community cancer centers. Our objective was to develop a "toolkit" to assist community cancer centers that wish to integrate early palliative care for patients with newly diagnosed advanced cancer and their family caregivers. Guided by the RE-AIM (Reach, Effectiveness-Adoption, Implementation, Maintenance) framework, we undertook an instrument-development process based on the literature, expert and site stakeholder review and feedback, and pilot testing during site visits. We developed four instruments to measure ENABLE implementation: (1) the ENABLE RE-AIM Self-Assessment Tool to assess reach, adoption, implementation, and maintenance; (2) the ENABLE General Organizational Index to assess institutional implementation; (3) an Implementation Costs Tool; and (4) an Oncology Clinicians' Perceptions of Early Concurrent Oncology Palliative Care survey. We developed four measures to determine early palliative care implementation. These measures have been pilot-tested, and will be integrated into a comprehensive "toolkit" to assist community cancer centers to measure implementation outcomes. We describe the lessons learned and recommend strategies for promoting long-term program sustainability.

Women with breast cancer: self-reported distress in early survivorship.

PubMed

Lester, Joanne; Crosthwaite, Kara; Stout, Robin; Jones, Rachel N; Holloman, Christopher; Shapiro, Charles; Andersen, Barbara L

2015-01-01

To identify and compare levels of distress and sources of problems among patients with breast cancer in early survivorship. Descriptive, cross-sectional. A National Cancer Institute-designated comprehensive cancer center. 100 breast cancer survivors were selected to represent four time points in the cancer trajectory. Distress was self-reported using the Distress Thermometer and its 38-item problem list. Analysis of variance and chi-square analyses were performed as appropriate. Distress scores, problem reports, and time groups. Participants scored in range of the cutoff of more than 4 (range = 4.1-5.1) from treatment through three months post-treatment. At six months post-treatment, distress levels were significantly lower. Significant differences were found between groups on the total problem list score (p = 0.007) and emotional (p = 0.01) and physical subscale scores (p = 0.003). Comparison of groups at different points in the cancer trajectory found similar elevated levels from diagnosis through three months. Distress remained elevated in early survivorship but significantly decreased at six months post-treatment. Interventions to reduce or prevent distress may improve outcomes in early survivorship.

Breast cancer risk accumulation starts early – Prevention must also

PubMed Central

Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S.

2014-01-01

Purpose Nearly 1 in 4 breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. Methods Literature review Results Exposures during childhood and adolescence affect a woman’s long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors are related to breast cancer risk and risk of premalignant proliferative benign lesions. Conclusion Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention. PMID:24820413

Breast cancer risk accumulation starts early: prevention must also.

PubMed

Colditz, Graham A; Bohlke, Kari; Berkey, Catherine S

2014-06-01

Nearly one in four breast cancers is diagnosed before the age of 50, and many early-stage premalignant lesions are present but not yet diagnosed. Therefore, we review evidence to support the strategy that breast cancer prevention efforts must begin early in life. This study follows the literature review methods and format. Exposures during childhood and adolescence affect a woman's long-term risk of breast cancer, but have received far less research attention than exposures that occur later in life. Breast tissue undergoes rapid cellular proliferation between menarche and first full-term pregnancy, and risk accumulates rapidly until the terminal differentiation that accompanies first pregnancy. Evidence on childhood diet and growth in height, and adolescent alcohol intake, among other adolescent factors is related to breast cancer risk and risk of premalignant proliferative benign lesions. Breast cancer prevention efforts will have the greatest effect when initiated at an early age and continued over a lifetime. Gaps in knowledge are identified and deserve increase attention to inform prevention.

Early diagnosis of pancreatic cancer: neutrophil gelatinase-associated lipocalin as a marker of pancreatic intraepithelial neoplasia

PubMed Central

Moniaux, N; Chakraborty, S; Yalniz, M; Gonzalez, J; Shostrom, V K; Standop, J; Lele, S M; Ouellette, M; Pour, P M; Sasson, A R; Brand, R E; Hollingsworth, M A; Jain, M; Batra, S K

2008-01-01

Pancreatic cancer is a highly lethal malignancy with a dismal 5-year survival of less than 5%. The scarcity of early biomarkers has considerably hindered our ability to launch preventive measures for this malignancy in a timely manner. Neutrophil gelatinase-associated lipocalin (NGAL), a 24-kDa glycoprotein, was reported to be upregulated nearly 27-fold in pancreatic cancer cells compared to normal ductal cells in a microarray analysis. Given the need for biomarkers in the early diagnosis of pancreatic cancer, we investigated the expression of NGAL in tissues with the objective of examining if NGAL immunostaining could be used to identify foci of pancreatic intraepithelial neoplasia, premalignant lesions preceding invasive cancer. To examine a possible correlation between NGAL expression and the degree of differentiation, we also analysed NGAL levels in pancreatic cancer cell lines with varying grades of differentiation. Although NGAL expression was strongly upregulated in pancreatic cancer, and moderately in pancreatitis, only a weak expression could be detected in the healthy pancreas. The average composite score for adenocarcinoma (4.26±2.44) was significantly higher than that for the normal pancreas (1.0) or pancreatitis (1.0) (P<0.0001). Further, although both well- and moderately differentiated pancreatic cancer were positive for NGAL, poorly differentiated adenocarcinoma was uniformly negative. Importantly, NGAL expression was detected as early as the PanIN-1 stage, suggesting that it could be a marker of the earliest premalignant changes in the pancreas. Further, we examined NGAL levels in serum samples. Serum NGAL levels were above the cutoff for healthy individuals in 94% of pancreatic cancer and 62.5% each of acute and chronic pancreatitis samples. However, the difference between NGAL levels in pancreatitis and pancreatic cancer was not significant. A ROC curve analysis revealed that ELISA for NGAL is fairly accurate in distinguishing pancreatic cancer from non-cancer cases (area under curve=0.75). In conclusion, NGAL is highly expressed in early dysplastic lesions in the pancreas, suggesting a possible role as an early diagnostic marker for pancreatic cancer. Further, serum NGAL measurement could be investigated as a possible biomarker in pancreatitis and pancreatic adenocarcinoma. PMID:18392050

CHEK2*1100delC Heterozygosity in Women With Breast Cancer Associated With Early Death, Breast Cancer–Specific Death, and Increased Risk of a Second Breast Cancer

PubMed Central

Weischer, Maren; Nordestgaard, Børge G.; Pharoah, Paul; Bolla, Manjeet K.; Nevanlinna, Heli; van't Veer, Laura J.; Garcia-Closas, Montserrat; Hopper, John L.; Hall, Per; Andrulis, Irene L.; Devilee, Peter; Fasching, Peter A.; Anton-Culver, Hoda; Lambrechts, Diether; Hooning, Maartje; Cox, Angela; Giles, Graham G.; Burwinkel, Barbara; Lindblom, Annika; Couch, Fergus J.; Mannermaa, Arto; Grenaker Alnæs, Grethe; John, Esther M.; Dörk, Thilo; Flyger, Henrik; Dunning, Alison M.; Wang, Qin; Muranen, Taru A.; van Hien, Richard; Figueroa, Jonine; Southey, Melissa C.; Czene, Kamila; Knight, Julia A.; Tollenaar, Rob A.E.M.; Beckmann, Matthias W.; Ziogas, Argyrios; Christiaens, Marie-Rose; Collée, Johanna Margriet; Reed, Malcolm W.R.; Severi, Gianluca; Marme, Frederik; Margolin, Sara; Olson, Janet E.; Kosma, Veli-Matti; Kristensen, Vessela N.; Miron, Alexander; Bogdanova, Natalia; Shah, Mitul; Blomqvist, Carl; Broeks, Annegien; Sherman, Mark; Phillips, Kelly-Anne; Li, Jingmei; Liu, Jianjun; Glendon, Gord; Seynaeve, Caroline; Ekici, Arif B.; Leunen, Karin; Kriege, Mieke; Cross, Simon S.; Baglietto, Laura; Sohn, Christof; Wang, Xianshu; Kataja, Vesa; Børresen-Dale, Anne-Lise; Meyer, Andreas; Easton, Douglas F.; Schmidt, Marjanka K.; Bojesen, Stig E.

2012-01-01

Purpose We tested the hypotheses that CHEK2*1100delC heterozygosity is associated with increased risk of early death, breast cancer–specific death, and risk of a second breast cancer in women with a first breast cancer. Patients and Methods From 22 studies participating in the Breast Cancer Association Consortium, 25,571 white women with invasive breast cancer were genotyped for CHEK2*1100delC and observed for up to 20 years (median, 6.6 years). We examined risk of early death and breast cancer–specific death by estrogen receptor status and risk of a second breast cancer after a first breast cancer in prospective studies. Results CHEK2*1100delC heterozygosity was found in 459 patients (1.8%). In women with estrogen receptor–positive breast cancer, multifactorially adjusted hazard ratios for heterozygotes versus noncarriers were 1.43 (95% CI, 1.12 to 1.82; log-rank P = .004) for early death and 1.63 (95% CI, 1.24 to 2.15; log-rank P < .001) for breast cancer–specific death. In all women, hazard ratio for a second breast cancer was 2.77 (95% CI, 2.00 to 3.83; log-rank P < .001) increasing to 3.52 (95% CI, 2.35 to 5.27; log-rank P < .001) in women with estrogen receptor–positive first breast cancer only. Conclusion Among women with estrogen receptor–positive breast cancer, CHEK2*1100delC heterozygosity was associated with a 1.4-fold risk of early death, a 1.6-fold risk of breast cancer–specific death, and a 3.5-fold risk of a second breast cancer. This is one of the few examples of a genetic factor that influences long-term prognosis being documented in an extensive series of women with breast cancer. PMID:23109706

Chest wall leiomyosarcoma after breast-conservative therapy for early-stage breast cancer in a young woman with Li-Fraumeni syndrome.

PubMed

Henry, Eve; Villalobos, Victor; Million, Lynn; Jensen, Kristin C; West, Robert; Ganjoo, Kristen; Lebensohn, Alexandra; Ford, James M; Telli, Melinda L

2012-08-01

Li-Fraumeni syndrome (LFS) is one of the most penetrant forms of familial cancer susceptibility syndromes, characterized by early age at tumor onset and a wide spectrum of malignant tumors. Identifying LFS in patients with cancer is clinically imperative because they have an increased sensitivity to ionizing radiation and are more likely to develop radiation-induced secondary malignancies. This case report describes a young woman whose initial presentation of LFS was early-onset breast cancer and whose treatment of this primary malignancy with breast conservation likely resulted in a secondary malignancy arising in her radiation field. As seen in this case, most breast cancers in patients with LFS exhibit a triple-positive phenotype (estrogen receptor-positive/progesterone receptor-positive/HER2-positive). Although this patient met classic LFS criteria based on age and personal and family history of cancer, the NCCN Clinical Practice Guidelines in Oncology for Genetic/Familial High-Risk Assessment: Breast and Ovarian Cancer endorse genetic screening for TP53 mutations in a subset of patients with early-onset breast cancer, even in the absence of a suggestive family history, because of the potential for de novo TP53 mutations.

Dietary aspirin decreases the stage of ovarian cancer in the hen.

PubMed

Urick, M E; Giles, J R; Johnson, P A

2009-01-01

We aimed to determine the effects of dietary aspirin treatment on ovarian cancer incidence and progression in the hen as a model for the human disease. Hens were fed a standard layer diet (control) or the same diet containing 0.1% aspirin for 1 year. Liver prostaglandin E(2) (PGE(2)) was measured using an enzyme immunoassay. Incidence and stage of ovarian cancer were determined through necropsy and immunohistochemical analysis of ovarian sections for each hen. Aspirin treatment decreased liver PGE(2) in treated hens as compared to control hens. Treatment with aspirin did not decrease ovarian cancer incidence. Significantly more control hens developed late stage ovarian cancer than early stage, while the same was not true for aspirin-treated hens. Hens that developed ovarian cancer, even early ovarian cancer, produced significantly fewer eggs in the year prior to diagnosis than hens without ovarian cancer. Aspirin treatment may inhibit the progression of ovarian cancer in the hen and egg production may be used to identify hens with early stages of the disease.

About the Early Detection Research Group | Division of Cancer Prevention

Cancer.gov

The Early Detection Research Group supports research that seeks to determine the effectiveness, operating characteristics and clinical impact (harms as well as benefits) of cancer early detection technologies and practices, such as imaging and molecular biomarker approaches.   The group ran two large-scale early detection trials for which data and biospecimens are available

Oral cancer. Practical prevention and early detection for the dental team.

PubMed

Kerr, A Ross; Cruz, Gustavo D

2002-01-01

Approximately 2,000 patients a year are diagnosed with oral cancer in New York State. In an effort to control this deadly disease, Governor George Pataki has taken a leadership role in the United States by mandating and funding training for dentists in the prevention and early detection of oral cancer. The purpose of this article is to highlight the epidemiology of oral cancer, to show how the dental profession can contribute to the health of the citizens of New York State, and to provide practical guidelines for both tobacco cessation intervention and utilization of existing technology for the early detection of oral cancer and precancerous conditions in the general dental practice setting.

[Application of Mass Spectrometry to the Diagnosis of Cancer--Chairman's Introductory Remarks].

PubMed

Yatomi, Yutaka

2015-09-01

In this symposium, the latest application of mass spectrometry to laboratory medicine, i.e., to the early diagnosis of cancer, was introduced. Dr. Masaru YOSHIDA, who has been using metabolome analysis to discover biomarker candidates for gastroenterological diseases, presented an automated early diagnosis system for early stages of colon cancer based on metabolome analysis and using a minute amount of blood. On the other hand, Dr. Sen TAKEDA, who has developed a new approach by employing both mass spectrometry and machine-learning for cancer diagnosis, presented a device for the clinical diagnosis of cancer using probe electrospray ionization (PESI) and machine-learning called the dual penalized logistic regression machine (dPLRM).

Letrozole: a review of its use in the treatment of postmenopausal women with hormone-responsive early breast cancer.

PubMed

Keating, Gillian M

2009-08-20

Letrozole (Femara) is a third-generation, nonsteroidal aromatase inhibitor. Adjuvant therapy with letrozole is more effective than tamoxifen in postmenopausal women with hormone-responsive early breast cancer, and extended adjuvant therapy with letrozole after the completion of adjuvant tamoxifen therapy is more effective than placebo in this patient population; letrozole is generally well tolerated. Ongoing trials will help answer outstanding questions regarding the optimal duration of letrozole therapy in early breast cancer and its efficacy compared with other third-generation aromatase inhibitors such as anastrozole. In the meantime, letrozole should be considered a valuable option in the treatment of postmenopausal women with hormone-responsive early breast cancer, both as adjuvant and extended adjuvant therapy.

Risk Factors and Control Strategies for the Rapidly Rising Rate of Breast Cancer in Korea

PubMed Central

Park, Sue K.; Kim, Yeonju; Kang, Daehee; Jung, En-Joo

2011-01-01

Due to the aging population and tremendous changes in life style over the past decades, cancer has been the leading cause of death in Korea. The incidence rate of breast cancer is the second highest in Korea, and it has shown an annual increase of 6.8% for the past 6 years. The major risk factors of breast cancer in Korean women are as follows: Early menarche, late menopause, late full-term pregnancy (FTP), and low numbers of FTP. Height and body mass index increased the risk of breast cancer in postmenopausal women only. There are ethnic variations in breast cancer due to the differences in genetic susceptibility or exposure to etiologic agent. With the epidemiological evidences on the possibility of further increase of breast cancer in Korea, the Korean Government began implementing the National Cancer Screening Program against breast cancer in 2002. Five-year survival rates for female breast cancer have improved significantly from 78.0% in early 1993-1995 to 90.0% in 2004-2008. This data indicate that improvement of the survival rate may be partially due to the early diagnosis of breast cancer as well as the increased public awareness about the significance of early detection and organized cancer screening program. The current primary prevention programs are geared towards strengthening national prevention campaigns. In accordance with the improvement in 5-year survival rate, the overall cancer mortality has started to decrease. However, breast cancer death rate and incidence rates are still increasing, which need further organized effort by the Korean Government. PMID:21847401

Economic savings and costs of periodic mammographic screening in the workplace.

PubMed

Griffiths, R I; McGrath, M M; Vogel, V G

1996-03-01

This article discusses the costs and benefits of mammographic screening in the workplace. The cost of mammography itself and of diagnostic work-up are two of the largest costs involved. Therefore, the most efficient approach to providing mammography depends on the number of employees receiving mammography; and the diagnostic accuracy of mammography and underlying incidence of breast cancer in the screened population strongly influence the number of suspicious mammograms that are not associated with breast cancer. The health benefit of mammographic screening is due to reduced mortality and morbidity through early detection and more effective treatment, which may also result in economic savings if early-stage cancer is less expensive to treat. However, the total lifetime cost of treating early-stage cancer may be greater than treating late-stage cancer because of improved survival of early-stage patients. Thus, although periodic mammographic screening is not likely to result in overall economic savings, in many populations of working-age women, especially those with identifiable risk factors, screening is cost-effective because the expenditure required to save a year of life through early detection of breast cancer is low compared to other types of health services for which employers commonly pay.

Advances in pancreatic cancer research: moving towards early detection.

PubMed

He, Xiang-Yi; Yuan, Yao-Zong

2014-08-28

Pancreatic ductal adenocarcinoma (PDAC) is one of the most lethal forms of cancer. Substantial progress has been made in the understanding of the biology of pancreatic cancer, and advances in patient management have been significant. However, most patients (nearly 80%) who present with locally advanced or metastatic disease have an extremely poor prognosis. Survival is better for those with malignant disease localized to the pancreas, because surgical resection at present offers the only chance of cure. Therefore, the early detection of pancreatic cancer may benefit patients with PDAC. However, its low rate of incidence and the limitations of current screening strategies make early detection difficult. Recent advances in the understanding of the pathogenesis of PDAC suggest that it is possible to detect PDAC in early stages and even identify precursor lesions. The presence of new-onset diabetes mellitus in the early phase of pancreatic cancer may provide clues for its early diagnosis. Advances in the identification of novel circulating biomarkers including serological signatures, autoantibodies, epigenetic markers, circulating tumor cells and microRNAs suggest that they can be used as potential tools for the screening of precursors and early stage PDAC in the future. However, proper screening strategies based on effective screening methodologies need to be tested for clinical application.

Experimental Lung Cancer Drug Shows Early Promise | Frederick National Laboratory for Cancer Research

Cancer.gov

A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and

CCR study: evidence for benefit of TARP vaccine for men with early stage prostate cancer | Center for Cancer Research

Cancer.gov

Results from a pilot clinical trial found that TARP, or T-cell receptor gamma chain alternate reading frame protein, vaccination slowed prostate-specific antigen (PSA) rise in the majority of patients with early stage prostate cancer.

Consortium for Imaging and Biomarkers (CIB) | Division of Cancer Prevention

Cancer.gov

Overdiagnosis and false positives present significant clinical problems in the prevention, detection and treatment of | 8 lead investigators combining imaging methods for the visualization of lesions with biomarkers to improve the accuracy of screening, early cancer detection, and the diagnosis of early stage cancers.

Role of non-Invasive Tests for the Early Detection of Cancer | Division of Cancer Prevention

Cancer.gov

Speaker | Dr. Nickolas Papadopoulos will present "Role of non-Invasive Tests for the Early Detection of Cancers". Date: June 5, 2018; Time: 11:00am - 12:00pm; Location: NCI Shady Grove, Conference Room: Seminar 110 Terrace Level East

Stress exposure in early post-natal life reduces telomere length: an experimental demonstration in a long-lived seabird

PubMed Central

Herborn, Katherine A.; Heidinger, Britt J.; Boner, Winnie; Noguera, Jose C.; Adam, Aileen; Daunt, Francis; Monaghan, Pat

2014-01-01

Exposure to stressors early in life is associated with faster ageing and reduced longevity. One important mechanism that could underlie these late life effects is increased telomere loss. Telomere length in early post-natal life is an important predictor of subsequent lifespan, but the factors underpinning its variability are poorly understood. Recent human studies have linked stress exposure to increased telomere loss. These studies have of necessity been non-experimental and are consequently subjected to several confounding factors; also, being based on leucocyte populations, where cell composition is variable and some telomere restoration can occur, the extent to which these effects extend beyond the immune system has been questioned. In this study, we experimentally manipulated stress exposure early in post-natal life in nestling European shags (Phalacrocorax aristotelis) in the wild and examined the effect on telomere length in erythrocytes. Our results show that greater stress exposure during early post-natal life increases telomere loss at this life-history stage, and that such an effect is not confined to immune cells. The delayed effects of increased telomere attrition in early life could therefore give rise to a ‘time bomb’ that reduces longevity in the absence of any obvious phenotypic consequences early in life. PMID:24648221

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer.

PubMed

Kellas-Ślęczka, Sylwia; Wojcieszek, Piotr; Białas, Brygida

2012-12-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years.

Gender differences in pulmonary disease.

PubMed

Caracta, Cynthia F

2003-09-01

Epidemiologic evidence points to gender-based differences in incidence, risk, histology, and pathogenesis of certain lung diseases in women as compared with men. Gender influences not only physiological differences, but also the social, economic, and cultural context in which men and women coexist. Central to these differences is the role of sex hormones, which may contribute to the pathogenesis of disease or serve as protective factors. This paper seeks to review the role of gender in major areas of pulmonary disease and explore the mechanisms that may underlie gender differences in asthma, chronic obstructive pulmonary disease and mycobacterial disease (tuberculosis and Mycobacterium avium intracellulare infection), on lung cancer.

Mechanisms governing the health and performance benefits of exercise

PubMed Central

Bishop-Bailey, D

2013-01-01

Humans are considered among the greatest if not the greatest endurance land animals. Over the last 50 years, as the population has become more sedentary, rates of cardiovascular disease and its associated risk factors such as obesity, type 2 diabetes and hypertension have all increased. Aerobic fitness is considered protective for all-cause mortality, cardiovascular disease, a variety of cancers, joint disease and depression. Here, I will review the emerging mechanisms that underlie the response to exercise, focusing on the major target organ the skeletal muscle system. Understanding the mechanisms of action of exercise will allow us to develop new therapies that mimic the protective actions of exercise. PMID:24033098

Brachytherapy in early prostate cancer--early experience.

PubMed

Jose, B O; Bailen, J L; Albrink, F H; Steinbock, G S; Cornett, M S; Benson, D C; Schmied, W K; Medley, R N; Spanos, W J; Paris, K J; Koerner, P D; Gatenby, R A; Wilson, D L; Meyer, R

1999-01-01

Use of brachytherapy with radioactive seeds in the management of early prostate cancer is commonly used in the United States. The early experience has been reported from the prostate treatment centers in Seattle for the last 10 years. In this manuscript we are reporting our early experience of 150 radioactive seed implantations in early stage prostate cancer using either Iodine 125 or Palladium 103 seeds. The average age of the patient is 66 years and the median Gleason score is 5.4 with a median PSA of 6. A brief description of the evolution of the treatment of prostate cancer as well as the preparation for the seed implantation using the volume study with ultrasound of the prostate, pubic arch study using CT scan of the pelvis and the complete planning using the treatment planning computers are discussed. We also have described the current technique which is used in our experience based on the Seattle guidelines. We plan a follow-up report with the results of the studies with longer follow-up.

Geographic remoteness, area-level socioeconomic disadvantage and inequalities in colorectal cancer survival in Queensland: a multilevel analysis

PubMed Central

2013-01-01

Background To explore the impact of geographical remoteness and area-level socioeconomic disadvantage on colorectal cancer (CRC) survival. Methods Multilevel logistic regression and Markov chain Monte Carlo simulations were used to analyze geographical variations in five-year all-cause and CRC-specific survival across 478 regions in Queensland Australia for 22,727 CRC cases aged 20–84 years diagnosed from 1997–2007. Results Area-level disadvantage and geographic remoteness were independently associated with CRC survival. After full multivariate adjustment (both levels), patients from remote (odds Ratio [OR]: 1.24, 95%CrI: 1.07-1.42) and more disadvantaged quintiles (OR = 1.12, 1.15, 1.20, 1.23 for Quintiles 4, 3, 2 and 1 respectively) had lower CRC-specific survival than major cities and least disadvantaged areas. Similar associations were found for all-cause survival. Area disadvantage accounted for a substantial amount of the all-cause variation between areas. Conclusions We have demonstrated that the area-level inequalities in survival of colorectal cancer patients cannot be explained by the measured individual-level characteristics of the patients or their cancer and remain after adjusting for cancer stage. Further research is urgently needed to clarify the factors that underlie the survival differences, including the importance of geographical differences in clinical management of CRC. PMID:24152961

The Slow Cycling Phenotype: A Growing Problem for Treatment Resistance in Melanoma.

PubMed

Ahn, Antonio; Chatterjee, Aniruddha; Eccles, Michael R

2017-06-01

Treatment resistance in metastatic melanoma is a longstanding issue. Current targeted therapy regimes in melanoma largely target the proliferating cancer population, leaving slow-cycling cancer cells undamaged. Consequently, slow-cycling cells are enriched upon drug therapy and can remain in the body for years until acquiring proliferative potential that triggers cancer relapse. Here we overview the molecular mechanisms of slow-cycling cells that underlie treatment resistance in melanoma. Three main areas of molecular reprogramming are discussed that mediate slow cycling and treatment resistance. First, a low microphthalmia-associated transcription factor (MITF) dedifferentiated state activates various signaling pathways. This includes WNT5A, EGFR, as well as other signaling activators, such as AXL and NF-κB. Second, the chromatin-remodeling factor Jumonji/ARID domain-containing protein 1B (JARID1B, KDM5B ) orchestrates and maintains slow cycling and treatment resistance in a small subpopulation of melanoma cells. Finally, a shift in metabolic state toward oxidative phosphorylation has been demonstrated to regulate treatment resistance in slow-cycling cells. Elucidation of the underlying processes of slow cycling and its utilization by melanoma cells may reveal new vulnerable characteristics as therapeutic targets. Moreover, combining current therapies with targeting slow-cycling subpopulations of melanoma cells may allow for more durable and greater treatment responses. Mol Cancer Ther; 16(6); 1002-9. ©2017 AACR . ©2017 American Association for Cancer Research.

BMI1 and H-RAS Cooperate to Drive Breast Cancer Metastasis | Center for Cancer Research

Cancer.gov

There have been significant improvements in the diagnosis of breast cancer at early stages of the disease. However, even when patients are identified early, there is a 30 percent chance of recurrence after apparently successful treatment of the initial tumor. The major cause of death for breast cancer patients is metastasis of the tumor to other organs but, unfortunately, the mechanisms of metastatic progression and cancer recurrence are poorly understood.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery

PubMed Central

Klimberg, V. Suzanne; Allasia, Arianna; Deutz, Nicolaas EP

2017-01-01

Abstract Background Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. Methods In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post‐absorptive state and net protein anabolic response to a meal. Results Major surgery resulted in an up‐regulation of post‐absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2 = 0.85, P < 0.001) was independent of the presence of non‐cachectic early stage breast cancer or surgery. Conclusions The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after major surgery in patients with non‐cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non‐cachectic early stage breast cancer after major surgery. PMID:28093897

Whole-genome sequencing of asian lung cancers: second-hand smoke unlikely to be responsible for higher incidence of lung cancer among Asian never-smokers.

PubMed

Krishnan, Vidhya G; Ebert, Philip J; Ting, Jason C; Lim, Elaine; Wong, Swee-Seong; Teo, Audrey S M; Yue, Yong G; Chua, Hui-Hoon; Ma, Xiwen; Loh, Gary S L; Lin, Yuhao; Tan, Joanna H J; Yu, Kun; Zhang, Shenli; Reinhard, Christoph; Tan, Daniel S W; Peters, Brock A; Lincoln, Stephen E; Ballinger, Dennis G; Laramie, Jason M; Nilsen, Geoffrey B; Barber, Thomas D; Tan, Patrick; Hillmer, Axel M; Ng, Pauline C

2014-11-01

Asian nonsmoking populations have a higher incidence of lung cancer compared with their European counterparts. There is a long-standing hypothesis that the increase of lung cancer in Asian never-smokers is due to environmental factors such as second-hand smoke. We analyzed whole-genome sequencing of 30 Asian lung cancers. Unsupervised clustering of mutational signatures separated the patients into two categories of either all the never-smokers or all the smokers or ex-smokers. In addition, nearly one third of the ex-smokers and smokers classified with the never-smoker-like cluster. The somatic variant profiles of Asian lung cancers were similar to that of European origin with G.C>T.A being predominant in smokers. We found EGFR and TP53 to be the most frequently mutated genes with mutations in 50% and 27% of individuals, respectively. Among the 16 never-smokers, 69% had an EGFR mutation compared with 29% of 14 smokers/ex-smokers. Asian never-smokers had lung cancer signatures distinct from the smoker signature and their mutation profiles were similar to European never-smokers. The profiles of Asian and European smokers are also similar. Taken together, these results suggested that the same mutational mechanisms underlie the etiology for both ethnic groups. Thus, the high incidence of lung cancer in Asian never-smokers seems unlikely to be due to second-hand smoke or other carcinogens that cause oxidative DNA damage, implying that routine EGFR testing is warranted in the Asian population regardless of smoking status. ©2014 American Association for Cancer Research.

Challenges of Early Detection of Oral Cancer: Raising Awareness as a First Step to Successful Campaigning

ERIC Educational Resources Information Center

Baumann, Eva; Koller, Michael; Wiltfang, Jörg; Wenz, Hans-Jürgen; Möller, Björn; Hertrampf, Katrin

2016-01-01

In Germany, ~13 000 people are found to have oral and pharyngeal cancer every year. Awareness and knowledge about this cancer remain insufficient, particularly amongst elderly people. A campaign for early detection was launched in Northern Germany in April 2012. The first step of the campaign was to increase awareness about oral cancer. Prior to a…

BMI1 and H-RAS Cooperate to Drive Breast Cancer Metastasis | Center for Cancer Research

Cancer.gov

There have been significant improvements in the diagnosis of breast cancer at early stages of the disease. However, even when patients are identified early, there is a 30 percent chance of recurrence after apparently successful treatment of the initial tumor. The major cause of death for breast cancer patients is metastasis of the tumor to other organs but, unfortunately, the

Treatment of early-stage prostate cancer among rural and urban patients.

PubMed

Baldwin, Laura-Mae; Andrilla, C Holly A; Porter, Michael P; Rosenblatt, Roger A; Patel, Shilpen; Doescher, Mark P

2013-08-15

Geographic barriers and limited availability of cancer specialists may influence early prostate cancer treatment options for rural men. This study compares receipt of different early prostate cancer treatments between rural and urban patients. Using 2004-2006 SEER Limited-Use Data, 51,982 early prostate cancer patients were identified (T1c, T2a, T2b, T2c, T2NOS; no metastases) who were most likely to benefit from definitive treatment (< 75 years old, Gleason score < 8, PSA ≤ 20). Definitive treatment included radical prostatectomy, daily external beam radiation for 5 to 8 weeks, brachytherapy, or combination external beam radiation/brachytherapy. Adjusted definitive treatment rates were calculated by rural-urban residence overall, and for different sociodemographic and cancer characteristics, and different states based on logistic regression analyses, using general estimating equation methods to account for clustering by county. Adjusted definitive treatment rates were lower for rural (83.7%) than urban (87.1%) patients with early-stage prostate cancer (P ≤ .01). Rural men were more likely than urban men to receive non-definitive surgical treatment and no initial treatment. The lowest definitive treatment rates were among rural subgroups: 70 to 74 years (73.9%), African Americans (75.6%), American Indians/Alaska Natives (77.8%), single/separated/divorced (76.8%), living in New Mexico (69.3%), and living in counties with persistent poverty (79.6%). Between 2004 and 2006, this adjusted analysis found that men who were living in rural areas were less likely to receive definitive treatment for their early-stage prostate cancer than those living in urban areas. Certain rural patient groups with prostate cancer need particular attention to ensure their access to appropriate treatment. Rural providers, rural health care systems, and cancer advocacy and support organizations should ensure resources are in place so that the most vulnerable rural groups (men between 60 and 74 years of age; African American men; men who are single, separated, or divorced; and men living in rural New Mexico) can make informed prostate cancer treatment choices based on their preferences. Copyright © 2013 American Cancer Society.

Development of a multiplex methylation specific PCR suitable for (early) detection of non-small cell lung cancer

PubMed Central

Nawaz, Imran; Qiu, Xiaoming; Wu, Heng; Li, Yang; Fan, Yaguang; Hu, Li-Fu; Zhou, Qinghua; Ernberg, Ingemar

2014-01-01

Lung cancer is a worldwide health problem and a leading cause of cancer-related deaths. Silencing of potential tumor suppressor genes (TSGs) by aberrant promoter methylation is an early event in the initiation and development of cancer. Thus, methylated cancer type-specific TSGs in DNA can serve as useful biomarkers for early cancer detection. We have now developed a “Multiplex Methylation Specific PCR” (MMSP) assay for analysis of the methylation status of multiple potential TSGs by a single PCR reaction. This method will be useful for early diagnosis and treatment outcome studies of non-small cell lung cancer (NSCLC). Genome-wide CpG methylation and expression microarrays were performed on lung cancer tissues and matched distant non-cancerous tissues from three NSCLC patients from China. Thirty-eight potential TSGs were selected and analyzed by methylation PCR on bisulfite treated DNA. On the basis of sensitivity and specificity, six marker genes, HOXA9, TBX5, PITX2, CALCA, RASSF1A, and DLEC1, were selected to establish the MMSP assay. This assay was then used to analyze lung cancer tissues and matched distant non-cancerous tissues from 70 patients with NSCLC, as well as 24 patients with benign pulmonary lesion as controls. The sensitivity of the assay was 99% (69/70). HOXA9 and TBX5 were the 2 most sensitive marker genes: 87% (61/70) and 84% (59/70), respectively. RASSF1A and DLEC1 showed the highest specificity at 99% (69/70). Using the criterion of identifying at least any two methylated marker genes, 61/70 cancer samples were positive, corresponding to a sensitivity of 87% and a specificity of 94%. Early stage I or II NSCLC could even be detected with a 100% specificity and 86% sensitivity. In conclusion, MMSP has the potential to be developed into a population-based screening tool and can be useful for early diagnosis of NSCLC. It might also be suitable for monitoring treatment outcome and recurrence. PMID:24937636

Colon cancer

MedlinePlus

Colorectal cancer; Cancer - colon; Rectal cancer; Cancer - rectum; Adenocarcinoma - colon; Colon - adenocarcinoma; Colon carcinoma ... In the United States, colorectal cancer is one of the leading ... to cancer. Early diagnosis can often lead to a complete cure. ...

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors.

PubMed

Trigos, Anna S; Pearson, Richard B; Papenfuss, Anthony T; Goode, David L

2017-06-13

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer.

Altered interactions between unicellular and multicellular genes drive hallmarks of transformation in a diverse range of solid tumors

PubMed Central

Trigos, Anna S.; Pearson, Richard B.; Papenfuss, Anthony T.; Goode, David L.

2017-01-01

Tumors of distinct tissues of origin and genetic makeup display common hallmark cellular phenotypes, including sustained proliferation, suppression of cell death, and altered metabolism. These phenotypic commonalities have been proposed to stem from disruption of conserved regulatory mechanisms evolved during the transition to multicellularity to control fundamental cellular processes such as growth and replication. Dating the evolutionary emergence of human genes through phylostratigraphy uncovered close association between gene age and expression level in RNA sequencing data from The Cancer Genome Atlas for seven solid cancers. Genes conserved with unicellular organisms were strongly up-regulated, whereas genes of metazoan origin were primarily inactivated. These patterns were most consistent for processes known to be important in cancer, implicating both selection and active regulation during malignant transformation. The coordinated expression of strongly interacting multicellularity and unicellularity processes was lost in tumors. This separation of unicellular and multicellular functions appeared to be mediated by 12 highly connected genes, marking them as important general drivers of tumorigenesis. Our findings suggest common principles closely tied to the evolutionary history of genes underlie convergent changes at the cellular process level across a range of solid cancers. We propose altered activity of genes at the interfaces between multicellular and unicellular regions of human gene regulatory networks activate primitive transcriptional programs, driving common hallmark features of cancer. Manipulation of cross-talk between biological processes of different evolutionary origins may thus present powerful and broadly applicable treatment strategies for cancer. PMID:28484005

The Role of Adiponectin in Cancer: A Review of Current Evidence

PubMed Central

Dalamaga, Maria; Diakopoulos, Kalliope N.

2012-01-01

Excess body weight is associated not only with an increased risk of type 2 diabetes and cardiovascular disease (CVD) but also with various types of malignancies. Adiponectin, the most abundant protein secreted by adipose tissue, exhibits insulin-sensitizing, antiinflammatory, antiatherogenic, proapoptotic, and antiproliferative properties. Circulating adiponectin levels, which are determined predominantly by genetic factors, diet, physical activity, and abdominal adiposity, are decreased in patients with diabetes, CVD, and several obesity-associated cancers. Also, adiponectin levels are inversely associated with the risk of developing diabetes, CVD, and several malignancies later in life. Many cancer cell lines express adiponectin receptors, and adiponectin in vitro limits cell proliferation and induces apoptosis. Recent in vitro studies demonstrate the antiangiogenic and tumor growth-limiting properties of adiponectin. Studies in both animals and humans have investigated adiponectin and adiponectin receptor regulation and expression in several cancers. Current evidence supports a role of adiponectin as a novel risk factor and potential diagnostic and prognostic biomarker in cancer. In addition, either adiponectin per se or medications that increase adiponectin levels or up-regulate signaling pathways downstream of adiponectin may prove to be useful anticancer agents. This review presents the role of adiponectin in carcinogenesis and cancer progression and examines the pathophysiological mechanisms that underlie the association between adiponectin and malignancy in the context of a dysfunctional adipose tissue in obesity. Understanding of these mechanisms may be important for the development of preventive and therapeutic strategies against obesity-associated malignancies. PMID:22547160

Does educating patients about the Early Palliative Care Study increase preferences for outpatient palliative cancer care? Findings from Project EMPOWER.

PubMed

Hoerger, Michael; Perry, Laura M; Gramling, Robert; Epstein, Ronald M; Duberstein, Paul R

2017-06-01

Randomized controlled trials, especially the Early Palliative Care Study (Temel et al., 2010), have shown that early outpatient palliative cancer care can improve quality of life for patients with advanced cancer or serious symptoms. However, fear and misconceptions drive avoidance of palliative care. Drawing from an empowerment perspective, we examined whether educating patients about evidence from the Early Palliative Care Study would increase preferences for palliative care. A sample of 598 patients with prostate, breast, lung, colon/rectal, skin, and other cancer diagnoses completed an Internet-mediated experiment using a between-group prepost design. Intervention participants received a summary of the Early Palliative Care Study; controls received no intervention. Participants completed baseline and posttest assessments of preferences of palliative care. Analyses controlled for age, gender, education, cancer type, presence of metastases, time since diagnosis, and baseline preferences. As hypothesized, the intervention had a favorable impact on participants' preferences for outpatient palliative cancer care relative to controls (d = 1.01, p < .001), while controlling for covariates. Intervention participants came to view palliative care as more efficacious (d = 0.79, p < .001) and less scary (d = 0.60, p < .001) and exhibited stronger behavioral intentions to utilize outpatient palliative care if referred (d = 0.60, p < .001). Findings were comparable in patients with metastatic disease, those with less education, and those experiencing financial strain. Educating patients about the Early Palliative Care Study increases preferences for early outpatient palliative care. This research has implications for future studies aimed at improving quality of life in cancer by increasing palliative care utilization. (PsycINFO Database Record (c) 2017 APA, all rights reserved).

Cancer in relation to socioeconomic status: stage at diagnosis in Texas, 2004-2008.

PubMed

Risser, David R; Miller, Eric A

2012-10-01

To determine whether stage of cancer diagnosis was associated with the socioeconomic status (SES) of the census tract where the patient resides, and to assess whether this is modified by race, ethnicity, or urban/rural residence, other factors known to affect cancer diagnosis stage. Using 2004-2008 data from the Texas Cancer Registry, we examined the distribution of stage at diagnosis in Texas residents for 15 cancer sites by the SES of the census tract of residence. Stage at diagnosis was categorized into the summary stage categories of early (in situ [preinvasive disease] and localized) and late stage (regional and distant spread). Age-adjusted odds ratios for late-stage versus early-stage cancer diagnosis in low versus high SES census tracts were evaluated by cancer site, race, ethnicity, and urban versus rural residence. For most cancer sites, late-stage cancer diagnosis increased with decreasing SES. These findings were consistent by cancer site, race, ethnicity, and in urban and rural areas of the state. For most cancer sites, particularly those likely to have patients diagnosed early by screening, late-stage cancer diagnosis is increased in Texas populations residing in lower SES census tracts compared with higher SES census tracts.

Evolution of early embryogenesis in rhabditid nematodes

PubMed Central

Brauchle, Michael; Kiontke, Karin; MacMenamin, Philip; Fitch, David H. A.; Piano, Fabio

2009-01-01

The cell biological events that guide early embryonic development occur with great precision within species but can be quite diverse across species. How these cellular processes evolve and which molecular components underlie evolutionary changes is poorly understood. To begin to address these questions, we systematically investigated early embryogenesis, from the one- to the four-cell embryo, in 34 nematode species related to C. elegans. We found 40 cell-biological characters that captured the phenotypic differences between these species. By tracing the evolutionary changes on a molecular phylogeny, we found that these characters evolved multiple times and independently of one another. Strikingly, all these phenotypes are mimicked by single-gene RNAi experiments in C. elegans. We use these comparisons to hypothesize the molecular mechanisms underlying the evolutionary changes. For example, we predict that a cell polarity module was altered during the evolution of the Protorhabditis group and show that PAR-1, a kinase localized asymmetrically in C. elegans early embryos, is symmetrically localized in the one-cell stage of Protorhabditis group species. Our genome-wide approach identifies candidate molecules—and thereby modules—associated with evolutionary changes in cell-biological phenotypes. PMID:19643102

In Vivo Photoacoustic Imaging of Prostate Cancer Using Targeted Contrast Agent

DTIC Science & Technology

2015-09-01

detection of early stage prostate cancer, development of near infrared dyes - labeled RNA aptamer that recognizes the prostate specific cell surface protein...the application of PAI for the detection of early stage prostate cancer, development of a NIR dye - labeled RNA aptamer that recognizes the prostate...proposed to enhance the application of PAI for the detection of early stage PrCa: 1. Use of a NIR dye labeled RNA aptamer that recognizes the prostate

A Cell-Based Approach to Early Pancreatic Cancer Detection

DTIC Science & Technology

2016-10-01

Award Number: W81XWH-15-1-0457 TITLE: A Cell -Based Approach to Early Pancreatic Cancer Detection PRINCIPAL INVESTIGATOR: Dr. Ben Stanger...SUBTITLE 5a. CONTRACT NUMBER A Cell -Based Approach to Early Pancreatic Cancer Detection 5b. GRANT NUMBER W81XWH-15-1-0457 5c. PROGRAM ELEMENT NUMBER 6...tumor cells from mouse blood by depleting the sample of white blood cells (WBCs). Furthermore, the RNA profile of these cells can be assessed by

EF5 PET of Tumor Hypoxia: A Predictive Imaging Biomarker of Response to Stereotactic Ablative Radiotherapy (SABR) for Early Lung Cancer

DTIC Science & Technology

2016-09-01

Radiotherapy ( SABR ) for Early Lung Cancer PRINCIPAL INVESTIGATOR: Billy W. Loo, Jr., M.D., Ph.D CONTRACTING ORGANIZATION: Leland Stanford Junior University...CONTRACT NUMBER W81XWH-12-1-0236 Response to Stereotactic Ablative Radiotherapy ( SABR ) for Early Lung Cancer 5b. GRANT NUMBER 5c. PROGRAM...Distribution Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Purpose and scope: Stereotactic ablative radiotherapy ( SABR ) has become a new standard

Determinants of Access to Fertility Preservation in Women with Breast Cancer

PubMed Central

Lee, Sanghoon; Heytens, Elke; Moy, Fred; Ozkavukcu, Sinan; Oktay, Kutluk

2012-01-01

OBJECTIVE Evaluation of socio-economic, demographic, and medical factors that influence the referral pattern either before cancer treatment to fertility preservation (FP, early referral) or post-chemotherapy to assisted reproduction (PCART, delayed referral). DESIGN Secondary analysis. SETTING Academic medical centers. PATIENT(S) Three hundred fourteen patients with breast cancer who were counseled for FP (n=218) or PCART (n=96) from June 1999 to July 2009. INTERVENTION(S) None MAIN OUTCOME MEASURE(S) Factors favoring early referrals RESULT(S) Mean age at diagnosis was higher in FP vs PCART (35.3±4.5 vs 33.9±4.7, p<0.01). Ninety percent presented with cancer stage 1 or 2. From 2000 to 2009 the proportion of referrals for FP increased continually. In 2009, nearly all (95.5%) were for FP. The majority (63.8%) was referred from an academic center. Patients with a family history of breast cancer were more likely to consult for FP (75.2% vs 64.3% without, p=0.04). There was no association with occupation, income, race, ethnicity, obstetrical history, and prior infertility treatment. Only 22.9% of those counseled in PCART compared to 45.0% in the FP group proceeded with a procedure (p<0.001). CONCLUSION(S) There has been an increasing trend within the last 10 years for early referral of breast cancer patients to FP. Factors favoring early referrals are older age, early stage cancer, family history of breast cancer, and an academic center involvement. Those seen before cancer treatment are more likely to receive an intervention. PMID:21371704

Cancer in patients with schizophrenia: What is the next step?

PubMed

Chou, Frank H-C; Tsai, Kuan-Yi; Wu, Hung-Chi; Shen, Shih-Pei

2016-11-01

People with schizophrenia, who constitute approximately 0.3-1% of the general population, have a nearly 20% shorter life expectancy than the general population. The incidence of varied types of cancers in patients with schizophrenia is controversial. The majority of previous research has demonstrated that patients who have schizophrenia and cancer have early mortality compared to the general population with cancer. The causes of early mortality in patients with schizophrenia and cancer might be attributed to a lower cancer screening rate and lack of effective treatment, including: (i) patient factors, such as poor lifestyle, passive attitude toward treatment, or comorbidity; (ii) physician factors, such as physician bias, which may decrease the delivery of care for individuals with mental disorders; and (iii) hospital administration factors, such as stigma and discrimination. Additional studies on patients with schizophrenia and cancer are warranted and should include the following: a comprehensive review of previous studies; a focus on differentiating the specific types of cancer; and methods for improvement. To decrease the early mortality of patients with schizophrenia, the following measures are proposed: (i) enhance early detection and early treatment, such as increasing the cancer screening rate for patients with schizophrenia; (ii) provide effective, timely treatment and rehabilitation; (iii) improve patients' psychiatric symptoms and cognitive impairment; (iv) promote healthy behavior in the general population and emphasize healthy lifestyles in vulnerable populations; and (v) remove the stigma of schizophrenia. To reduce disparities in physical health, public health strategies and welfare policies must continue to focus on this group of patients. © 2016 The Authors. Psychiatry and Clinical Neurosciences © 2016 Japanese Society of Psychiatry and Neurology.

Developing a discrete choice experiment in Malawi: eliciting preferences for breast cancer early detection services.

PubMed

Kohler, Racquel E; Lee, Clara N; Gopal, Satish; Reeve, Bryce B; Weiner, Bryan J; Wheeler, Stephanie B

2015-01-01

In Malawi, routine breast cancer screening is not available and little is known about women's preferences regarding early detection services. Discrete choice experiments are increasingly used to reveal preferences about new health services; however, selecting appropriate attributes that describe a new health service is imperative to ensure validity of the choice experiment. To identify important factors that are relevant to Malawian women's preferences for breast cancer detection services and to select attributes and levels for a discrete choice experiment in a setting where both breast cancer early detection and choice experiments are rare. We reviewed the literature to establish an initial list of potential attributes and levels for a discrete choice experiment and conducted qualitative interviews with health workers and community women to explore relevant local factors affecting decisions to use cancer detection services. We tested the design through cognitive interviews and refined the levels, descriptions, and designs. Themes that emerged from interviews provided critical information about breast cancer detection services, specifically, that breast cancer interventions should be integrated into other health services because asymptomatic screening may not be practical as an individual service. Based on participants' responses, the final attributes of the choice experiment included travel time, health encounter, health worker type and sex, and breast cancer early detection strategy. Cognitive testing confirmed the acceptability of the final attributes, comprehension of choice tasks, and women's abilities to make trade-offs. Applying a discrete choice experiment for breast cancer early detection was feasible with appropriate tailoring for a low-income, low-literacy African setting.

Protein Kinase Cα Modulates Estrogen-Receptor-Dependent Transcription and Proliferation in Endometrial Cancer Cells

PubMed Central

Thorne, Alicia M.; Jackson, Twila A.; Willis, Van C.; Bradford, Andrew P.

2013-01-01

Endometrial cancer is the most common invasive gynecologic malignancy in developed countries. The most prevalent endometrioid tumors are linked to excessive estrogen exposure and hyperplasia. However, molecular mechanisms and signaling pathways underlying their etiology and pathophysiology remain poorly understood. We have shown that protein kinase Cα (PKCα) is aberrantly expressed in endometrioid tumors and is an important mediator of endometrial cancer cell survival, proliferation, and invasion. In this study, we demonstrate that expression of active, myristoylated PKCα conferred ligand-independent activation of estrogen-receptor- (ER-) dependent promoters and enhanced responses to estrogen. Conversely, knockdown of PKCα reduced ER-dependent gene expression and inhibited estrogen-induced proliferation of endometrial cancer cells. The ability of PKCα to potentiate estrogen activation of ER-dependent transcription was attenuated by inhibitors of phosphoinositide 3-kinase (PI3K) and Akt. Evidence suggests that PKCα and estrogen signal transduction pathways functionally interact, to modulate ER-dependent growth and transcription. Thus, PKCα signaling, via PI3K/Akt, may be a critical element of the hyperestrogenic environment and activation of ER that is thought to underlie the development of estrogen-dependent endometrial hyperplasia and malignancy. PKCα-dependent pathways may provide much needed prognostic markers of aggressive disease and novel therapeutic targets in ER positive tumors. PMID:23843797

Cells Comprising the Prostate Cancer Microenvironment Lack Recurrent Clonal Somatic Genomic Aberrations

PubMed Central

Bianchi-Frias, Daniella; Basom, Ryan; Delrow, Jeffrey J; Coleman, Ilsa M; Dakhova, Olga; Qu, Xiaoyu; Fang, Min; Franco, Omar E.; Ericson, Nolan G.; Bielas, Jason H.; Hayward, Simon W.; True, Lawrence; Morrissey, Colm; Brown, Lisha; Bhowmick, Neil A.; Rowley, David; Ittmann, Michael; Nelson, Peter S.

2017-01-01

Prostate cancer-associated stroma (CAS) plays an active role in malignant transformation, tumor progression, and metastasis. Molecular analyses of CAS have demonstrated significant changes in gene expression; however, conflicting evidence exists on whether genomic alterations in benign cells comprising the tumor microenvironment (TME) underlie gene expression changes and oncogenic phenotypes. This study evaluates the nuclear and mitochondrial DNA integrity of prostate carcinoma cells, CAS, matched benign epithelium and benign epithelium-associated stroma by whole genome copy number analyses, targeted sequencing of TP53, and fluorescence in situ hybridization. Comparative genomic hybridization (aCGH) of CAS revealed a copy-neutral diploid genome with only rare and small somatic copy number aberrations (SCNAs). In contrast, several expected recurrent SCNAs were evident in the adjacent prostate carcinoma cells, including gains at 3q, 7p, and 8q, and losses at 8p and 10q. No somatic TP53 mutations were observed in CAS. Mitochondrial DNA (mtDNA) extracted from carcinoma cells and stroma identified 23 somatic mtDNA mutations in neoplastic epithelial cells but only one mutation in stroma. Finally, genomic analyses identified no SCNAs, no loss of heterozygosity (LOH) or copy-neutral LOH in cultured cancer-associated fibroblasts (CAFs), which are known to promote prostate cancer progression in vivo. PMID:26753621

The multikinase inhibitor Sorafenib enhances glycolysis and synergizes with glycolysis blockade for cancer cell killing.

PubMed

Tesori, Valentina; Piscaglia, Anna Chiara; Samengo, Daniela; Barba, Marta; Bernardini, Camilla; Scatena, Roberto; Pontoglio, Alessandro; Castellini, Laura; Spelbrink, Johannes N; Maulucci, Giuseppe; Puglisi, Maria Ausiliatrice; Pani, Giovambattista; Gasbarrini, Antonio

2015-03-17

Although the only effective drug against primary hepatocarcinoma, the multikinase inhibitor Sorafenib (SFB) usually fails to eradicate liver cancer. Since SFB targets mitochondria, cell metabolic reprogramming may underlie intrinsic tumor resistance. To characterize cancer cell metabolic response to SFB, we measured oxygen consumption, generation of reactive oxygen species (ROS) and ATP content in rat LCSC (Liver Cancer Stem Cells) -2 cells exposed to the drug. Genome wide analysis of gene expression was performed by Affymetrix technology. SFB cytotoxicity was evaluated by multiple assays in the presence or absence of metabolic inhibitors, or in cells genetically depleted of mitochondria. We found that low concentrations (2.5-5 μM) of SFB had a relatively modest effect on LCSC-2 or 293 T cell growth, but damaged mitochondria and increased intracellular ROS. Gene expression profiling of SFB-treated cells was consistent with a shift toward aerobic glycolysis and, accordingly, SFB cytotoxicity was dramatically increased by glucose withdrawal or the glycolytic inhibitor 2-DG. Under metabolic stress, activation of the AMP dependent Protein Kinase (AMPK), but not ROS blockade, protected cells from death. We conclude that mitochondrial damage and ROS drive cell killing by SFB, while glycolytic cell reprogramming may represent a resistance strategy potentially targetable by combination therapies.

Amplification and protein overexpression of cyclin D1: Predictor of occult nodal metastasis in early oral cancer.

PubMed

Noorlag, Rob; Boeve, Koos; Witjes, Max J H; Koole, Ronald; Peeters, Ton L M; Schuuring, Ed; Willems, Stefan M; van Es, Robert J J

2017-02-01

Accurate nodal staging is pivotal for treatment planning in early (stage I-II) oral cancer. Unfortunately, current imaging modalities lack sensitivity to detect occult nodal metastases. Chromosomal region 11q13, including genes CCND1, Fas-associated death domain (FADD), and CTTN, is often amplified in oral cancer with nodal metastases. However, evidence in predicting occult nodal metastases is limited. In 158 patients with early tongue and floor of mouth (FOM) squamous cell carcinomas, both CCND1 amplification and cyclin D1, FADD, and cortactin protein expression were correlated with occult nodal metastases. CCND1 amplification and cyclin D1 expression correlated with occult nodal metastases. Cyclin D1 expression was validated in an independent multicenter cohort, confirming the correlation with occult nodal metastases in early FOM cancers. Cyclin D1 is a predictive biomarker for occult nodal metastases in early FOM cancers. Prospective research on biopsy material should confirm these results before implementing its use in routine clinical practice. © 2016 Wiley Periodicals, Inc. Head Neck 39: 326-333, 2017. © 2016 Wiley Periodicals, Inc.

Inequalities in adoption of cancer screening from a diffusion of innovation perspective: identification of late adopters.

PubMed

Hahm, Myung-Il; Park, Eun-Cheol; Choi, Kui Son; Lee, Hoo-Yeon; Park, Jae-Hyun; Park, Sohee

2011-02-01

Although national-level organized cancer screening programs have reduced barriers to screening for people of low socioeconomic status, barriers to early screening remain. Our aim was to determine the diffusion pattern and identify the factors associated with early participation in stomach and breast cancer screening programs. The study population was derived from the Korean National Cancer Screening Survey, conducted in 2007. A stratified random sample of people aged 40 years and older from a nationwide population-based database was gathered in Korea (n=1,517) in 2007. Time of participation in early screening was defined as the number of years that had elapsed between the participant's 30th birthday and the age at first screening. Significant differences were observed in the probability of adopting stomach and breast cancer screening in relation to education, household income, and job level. Results from Cox's proportional hazard model indicated that higher household income was significantly associated with an increased probability of adopting stomach cancer screening earlier (p<0.05), and people with high household incomes were more likely to adopt breast cancer screening earlier than were those with incomes under US$1,500 per month (p<0.01). When considered at a significance level of 0.1, we found that the most highly educated women were more likely than the least educated to be screened early. Despite organized governmental screening programs, there are still inequalities in the early adoption of cancer screening. The results of this study also suggest that inequalities in early adoption may affect participation in regular screening. Copyright © 2010 Elsevier Ltd. All rights reserved.

Assessment of the quality of medical care among patients with early stage prostate cancer undergoing expectant management in the United States.

PubMed

Ritchey, Jamie; Gay, E Greer; Spencer, Benjamin A; Miller, David C; Wallner, Lauren P; Stewart, Andrew K; Dunn, Rodney L; Litwin, Mark S; Wei, John T

2012-09-01

Given the increased attention to the quality and cost of medical care, the Institute of Medicine and Centers for Medicare and Medicaid Services have called for performance measurement and reporting. The clinical management of prostate cancer has been outlined, yet is not intended to describe quality prostate cancer care. Therefore, RAND researchers developed quality indicators for early stage prostate cancer. The ACoS (American College of Surgeons) used these indicators to perform the first national assessment to our knowledge of the quality of care among men with early stage prostate cancer undergoing expectant management. Information from medical records was abstracted for evidence of compliance with the RAND indicators (structure and process). Weighted and stratified proportions were calculated to assess indicator compliance. Logistic regression models were fit and evaluated by hospital type and patient factors. A weighted and stratified total of 13,876 early stage prostate cancer cases on expectant management in 2000 to 2001 were investigated. Compliance with structural indicators was high (greater than 80%) and compliance with process indicators varied (19% to 87%). Differences in process indicators were observed from models by hospital type and comorbid conditions, but not for age, race or insurance status. Using the RAND quality indicators this study revealed several process areas for quality improvement among men with early stage prostate cancer on expectant management in the United States. Efforts to improve the quality of early stage prostate cancer care need to move beyond the paradigm of age, race and insurance status. Copyright © 2012 American Urological Association Education and Research, Inc. Published by Elsevier Inc. All rights reserved.

A prospective evaluation of early detection biomarkers for ovarian cancer in the European EPIC cohort

PubMed Central

Terry, Kathryn L.; Schock, Helena; Fortner, Renée T.; Hüsing, Anika; Fichorova, Raina N.; Yamamoto, Hidemi S.; Vitonis, Allison F.; Johnson, Theron; Overvad, Kim; Tjønneland, Anne; Boutron-Ruault, Marie-Christine; Mesrine, Sylvie; Severi, Gianluca; Dossus, Laure; Rinaldi, Sabina; Boeing, Heiner; Benetou, Vassiliki; Lagiou, Pagona; Trichopoulou, Antonia; Krogh, Vittorio; Kuhn, Elisabetta; Panico, Salvatore; Bueno-de-Mesquita, H. Bas; Onland-Moret, N. Charlotte; Peeters, Petra H.; Gram, Inger Torhild; Weiderpass, Elisabete; Duell, Eric J.; Sanchez, Maria-Jose; Ardanaz, Eva; Etxezarreta, Nerea; Navarro, Carmen; Idahl, Annika; Lundin, Eva; Jirström, Karin; Manjer, Jonas; Wareham, Nicholas J.; Khaw, Kay-Tee; Byrne, Karl Smith; Travis, Ruth C.; Gunter, Marc J.; Merritt, Melissa A.; Riboli, Elio; Cramer, Daniel W.; Kaaks, Rudolf

2016-01-01

Purpose About 60% of ovarian cancers are diagnosed at late stage, when 5-year survival is less than 30% in contrast to 90% for local disease. This has prompted search for early detection biomarkers. For initial testing, specimens taken months or years before ovarian cancer diagnosis are the best source of information to evaluate early detection biomarkers. Here we evaluate the most promising ovarian cancer screening biomarkers in prospectively collected samples from the European Prospective Investigation into Cancer and Nutrition study. Experimental Design We measured CA125, HE4, CA72.4 and CA15.3 in 810 invasive epithelial ovarian cancer cases and 1,939 controls. We calculated the sensitivity at 95% and 98% specificity as well as Area under the Receiver Operator Curve (C-statistic) for each marker individually and in combination. Additionally, we evaluated marker performance by stage at diagnosis and time between blood draw and diagnosis. Results We observed the best discrimination between cases and controls within six months of diagnosis for CA125 (C-statistic=0.92), then HE4 (0.84), CA72.4 (0.77), and CA15.3 (0.73). Marker performance declined with longer time between blood draw and diagnosis and for earlier staged disease. However, assessment of discriminatory ability at early stage was limited by small numbers. Combinations of markers performed modestly, but significantly better than any single marker. Conclusions CA125 remains the single best marker for the early detection of invasive epithelial ovarian cancer, but can be slightly improved by combining with other markers. Identifying novel markers for ovarian cancer will require studies including larger numbers of early stage cases. PMID:27060155

A computer system to be used with laser-based endoscopy for quantitative diagnosis of early gastric cancer.

PubMed

Miyaki, Rie; Yoshida, Shigeto; Tanaka, Shinji; Kominami, Yoko; Sanomura, Yoji; Matsuo, Taiji; Oka, Shiro; Raytchev, Bisser; Tamaki, Toru; Koide, Tetsushi; Kaneda, Kazufumi; Yoshihara, Masaharu; Chayama, Kazuaki

2015-02-01

To evaluate the usefulness of a newly devised computer system for use with laser-based endoscopy in differentiating between early gastric cancer, reddened lesions, and surrounding tissue. Narrow-band imaging based on laser light illumination has come into recent use. We devised a support vector machine (SVM)-based analysis system to be used with the newly devised endoscopy system to quantitatively identify gastric cancer on images obtained by magnifying endoscopy with blue-laser imaging (BLI). We evaluated the usefulness of the computer system in combination with the new endoscopy system. We evaluated the system as applied to 100 consecutive early gastric cancers in 95 patients examined by BLI magnification at Hiroshima University Hospital. We produced a set of images from the 100 early gastric cancers; 40 flat or slightly depressed, small, reddened lesions; and surrounding tissues, and we attempted to identify gastric cancer, reddened lesions, and surrounding tissue quantitatively. The average SVM output value was 0.846 ± 0.220 for cancerous lesions, 0.381 ± 0.349 for reddened lesions, and 0.219 ± 0.277 for surrounding tissue, with the SVM output value for cancerous lesions being significantly greater than that for reddened lesions or surrounding tissue. The average SVM output value for differentiated-type cancer was 0.840 ± 0.207 and for undifferentiated-type cancer was 0.865 ± 0.259. Although further development is needed, we conclude that our computer-based analysis system used with BLI will identify gastric cancers quantitatively.

Imaging in the evaluation and follow-up of early and advanced breast cancer: When, why, and how often?

PubMed

Bychkovsky, Brittany L; Lin, Nancy U

2017-02-01

Imaging in the evaluation and follow-up of patients with early or advanced breast cancer is an important aspect of cancer care. The role of imaging in breast cancer depends on the goal and should only be performed to guide clinical decisions. Imaging is valuable if a finding will change the course of treatment and improve outcomes, whether this is disease-free survival, overall survival or quality-of-life. In the last decade, imaging is often overused in oncology and contributes to rising healthcare costs. In this context, we review the data that supports the appropriate use of imaging for breast cancer patients. We will discuss: 1) the optimal use of staging imaging in both early (Stage 0-II) and locally advanced (Stage III) breast cancer, 2) the role of surveillance imaging to detect recurrent disease in Stage 0-III breast cancer and 3) how patients with metastatic breast cancer should be followed with advanced imaging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Breast cancer statistics and prediction methodology: a systematic review and analysis.

PubMed

Dubey, Ashutosh Kumar; Gupta, Umesh; Jain, Sonal

2015-01-01

Breast cancer is a menacing cancer, primarily affecting women. Continuous research is going on for detecting breast cancer in the early stage as the possibility of cure in early stages is bright. There are two main objectives of this current study, first establish statistics for breast cancer and second to find methodologies which can be helpful in the early stage detection of the breast cancer based on previous studies. The breast cancer statistics for incidence and mortality of the UK, US, India and Egypt were considered for this study. The finding of this study proved that the overall mortality rates of the UK and US have been improved because of awareness, improved medical technology and screening, but in case of India and Egypt the condition is less positive because of lack of awareness. The methodological findings of this study suggest a combined framework based on data mining and evolutionary algorithms. It provides a strong bridge in improving the classification and detection accuracy of breast cancer data.

Retrospective cohort study of cancer incidence and mortality by HIV status in a Georgia, USA, prisoner cohort during the HAART era.

PubMed

Zlotorzynska, Maria; Spaulding, Anne C; Messina, Lauren C; Coker, Daniella; Ward, Kevin; Easley, Kirk; Baillargeon, Jacques; Mink, Pamela J; Simard, Edgar P

2016-04-11

Non-AIDS-defining cancers (NADCs) have emerged as significant contributors to cancer mortality and morbidity among persons living with HIV (PLWH). Because NADCs are also associated with many social and behavioural risk factors that underlie HIV, determining the extent to which each of these factors contributes to NADC risk is difficult. We examined cancer incidence and mortality among persons with a history of incarceration, because distributions of other cancer risk factors are likely similar between prisoners living with HIV and non-infected prisoners. Registry-based retrospective cohort study. Cohort of 22,422 persons incarcerated in Georgia, USA, prisons on 30 June 1991, and still alive in 1998. Cancer incidence and mortality were assessed between 1998 and 2009, using cancer and death registry data matched to prison administrative records. Age, race and sex-adjusted standardised mortality and incidence ratios, relative to the general population, were calculated for AIDS-defining cancers, viral-associated NADCs and non-infection-associated NADCs, stratified by HIV status. There were no significant differences in cancer mortality relative to the general population in the cohort, regardless of HIV status. In contrast, cancer incidence was elevated among the PLWH. Furthermore, incidence of viral-associated NADCs was significantly higher among PLWH versus those without HIV infection (standardised incidence ratio=6.1, 95% CI 3.0 to 11.7, p<0.001). Among PLWH with a history of incarceration, cancer incidence was elevated relative to the general population, likely related to increased prevalence of oncogenic viral co-infections. Cancer prevention and screening programmes within prisons may help to reduce the cancer burden in this high-risk population. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/

Physician-Initiated Stop-Smoking Program for Patients Receiving Treatment for Early-Stage Cancer

ClinicalTrials.gov

2015-10-06

Bladder Cancer; Breast Cancer; Colorectal Cancer; Head and Neck Cancer; Lung Cancer; Lymphoma; Prostate Cancer; Testicular Germ Cell Tumor; Tobacco Use Disorder; Unspecified Adult Solid Tumor, Protocol Specific

Big data analytics for early detection of breast cancer based on machine learning

NASA Astrophysics Data System (ADS)

Ivanova, Desislava

2017-12-01

This paper presents the concept and the modern advances in personalized medicine that rely on technology and review the existing tools for early detection of breast cancer. The breast cancer types and distribution worldwide is discussed. It is spent time to explain the importance of identifying the normality and to specify the main classes in breast cancer, benign or malignant. The main purpose of the paper is to propose a conceptual model for early detection of breast cancer based on machine learning for processing and analysis of medical big dataand further knowledge discovery for personalized treatment. The proposed conceptual model is realized by using Naive Bayes classifier. The software is written in python programming language and for the experiments the Wisconsin breast cancer database is used. Finally, the experimental results are presented and discussed.

Enhancing early bladder cancer detection with fluorescence-guided endoscopic optical coherence tomography

NASA Astrophysics Data System (ADS)

Pan, Y. T.; Xie, T. Q.; Du, C. W.; Bastacky, S.; Meyers, S.; Zeidel, M. L.

2003-12-01

We report an experimental study of the possibility of enhancing early bladder cancer diagnosis with fluorescence-image-guided endoscopic optical coherence tomography (OCT). After the intravesical instillation of a 10% solution of 5-aminolevulinic acid, simultaneous fluorescence imaging (excitation of 380-420 nm, emission of 620-700 nm) and OCT are performed on rat bladders to identify the photochemical and morphological changes associated with uroepithelial tumorigenesis. The preliminary results of our ex vivo study reveal that both fluorescence and OCT can identify early uroepithelial cancers, and OCT can detect precancerous lesions (e.g., hyperplasia) that fluorescence may miss. This suggests that a cystoscope combining 5-aminolevulinic acid fluorescence and OCT imaging has the potential to enhance the efficiency and sensitivity of early bladder cancer diagnosis.

DOE Office of Scientific and Technical Information (OSTI.GOV)

McDermott, I.

Modern therapeutic modalities and emphasis on early detection have made oral cancer a treatable, and in many cases, a curable disease. The role of the dentist in cancer patient management is two-fold. Early detection of oral lesions during routine dental examination has been shown to be a significant factor in cancer diagnosis. The dentist's other role comes after cancer treatment, specifically therapeutic radiation. Ionizing radiation can have permanent effects on both hard and soft tissues. Prescription and use of fluoride gel in topical applicators can aid in assuring oral health for post-cancer patients.

The role of social media use in improving cancer survivors' emotional well-being: a moderated mediation study.

PubMed

Jiang, Shaohai

2017-06-01

In the USA, levels of emotional well-being among cancer survivors remain low. Social media is recognized as important to improve their emotional well-being. However, little is known about social mechanisms that underlie the impact of health-related social media in cancer care. This study proposed a moderated mediation model to signify a pathway linking social media use to emotional well-being. Four-hundred and fifty-nine cancer survivors identified through the 2013 US-based Health Information National Trends Survey were included for data analysis. First, structural equation modeling was conducted to examine the path from social media use to emotional well-being, mediated by patient activation. Second, hierarchical regression was performed to test the moderation effect of emotion management. Last, a normal theory-based approach was used to explore the final moderated mediation model. The effect of health-related social media use on emotional well-being was completely mediated by patient activation. Also, emotion management positively moderated the effect of patient activation on emotional well-being. Last, emotion management positively moderated the mediation pathway from health-related social media use to patient activation, and finally, to emotional well-being. Health-related social media, by itself, is not sufficient to bring about improvement in cancer survivors' emotional well-being. Patient activation and emotion management play a significant role. In future interventions designed to improve cancer survivors' emotional health, health practitioners should not only encourage cancer survivors to use social media for health purposes, but also activate them in the course of care, and improve their emotion self-management skills.

[Factors associated with advanced thyroid cancer in pediatric patients in a high specialty medical unit in Northeast Mexico].

PubMed

García-Castillo, Lizbeth Ariana; Bahena-García, Ana Laura; Sánchez-Sánchez, Luz María; del Carmen Palacios-Saucedo, Gerardo

2015-01-01

Thyroid cancer represents 2% of all childhood malignances. Its incidence rises 1.1% per year. In comparison with adults, childhood thyroid cancer is detected in a more advanced stage, but with a survival rate above 95%. The objective of this study was to evaluate whether there are factors associated with advanced stages of thyroid cancer in pediatric patients. Nineteen patients were included, 13 (68.4%) were female and six male, all between 7-15 years, with a median of 11 years. Fifteen in advanced and four in early stage. The median age of patients in advanced stage at time of diagnosis was 10.6 years (7-15) and 13.2 (12-14) were in early stage (p=0.075). There was a delay of nine months to get a diagnosis in advanced stage, and 7.2 in early stage (p=0.931). Three of the patients with advanced stage and two with early stage were from Nuevo León (Mexico) and the rest were foreign (p=0.567). In the group with advanced stage, two had thyroid cancer familiar history, and none in the early stage group (p=0.452). Nine patients in advanced stage and three in early stage presented thyroid nodule as the first sign of illness. Six patients in advanced stage and one in early stage presented goiter (p=0.590). None of the studied patients had radiation history. Six patients in advanced stage and one in early stage suffered from Hashimoto's Thyroiditis (p=0.590). Eleven in advanced stage and one in early stage had papillary histologic variety. Four in advanced stage and three in early stage had papillary histologic variety with a follicular patter (p=0.083). Eight patients presented lung metastasis at time of diagnosis (p=0.061). There are no factors associated with advanced stage thyroid cancer in pediatric populations. Although half of studied patients presented lung metastasis, treatment response and survival is satisfactory.

[Early diagnosis and early treatment for liver cancer in Qidong: survival of patients and effectiveness of screening].

PubMed

Chen, J G; Zhang, Y H; Zhu, J; Lu, J H; Wang, J B; Sun, Y; Xue, X F; Lu, L L; Chen, Y S; Wu, Y; Jiang, X P; Ding, L L; Zhang, Q N; Zhu, Y R

2017-12-23

Objective: To evaluate the patients' survival and effectiveness of the live cancer screening for population at high risk for liver cancer in Qidong. Methods: According to the Expert Scheme proposed the Expert Committee of Early Detection and Early Treatment, China Cancer Foundation, diagnostical screening by using combined methods of alpha-fetoprotein and B ultrasound monitoring were carried out biannually in individuals with positive HBsAg who were screened from Qidong area. The evaluation indices of the effectiveness are task completion rate of screening, detection rate of liver cancer, early diagnosis rate, and treatment rate. The deadline of the follow-up for the surviving outcome was March 31, 2016. The life-table method was used to calculate the observed survival, and to make comparison and significant tests between survival rates in Group A (those found via repeated periodic screening) and Group B (those diagnosed without periodic screening). Results: Since 2007, 38 016 target population have been screened, and 3 703(9.74%) individuals with positive HBsAg were found. Except for 29 patients with liver cancer at the initial screening, 3 674 persons in the cohort were followed up; 268 patients with liver cancer were detected from the 33 199 person-times screening, with an annual detection rate of 1.61%. Of them, 186 patients were found in Group A(1.12%), in which 149 patients were the early cases, with an early detection rate of 80.11%; 167 out of 186(89.78%) patients received treatment after diagnosis. The incidence of liver cancer in this HBsAg (+ ) cohort of 25 452 person-years was 1 052.96 per 100 000 annually, 187 cases in males(1 488.45/100 000)and 81 cases in females(628.46/100 000). The 1-, 3-, 5-, and 8-year survival of all patients with liver cancer were 64.55%, 40.50%, 32.54%, and 19.65%, respectively. The 1-, 3-, 5-, and 8-year survival rates were 77.16%, 49.04%, 38.53%, and 24.25% in Group A, and were 36.25%, 21.21%, 21.21%, and 0% in Group B, respectively, with significant differences between two groups ( P <0.05). Conclusion: The findings show that screening of individuals at high-risk of development of liver cancer, with semiannual AFP and B ultrasound, according to the Expert Scheme, is effective not only in increasing detection rate but also in detecting liver cancer at early stage, and in improving patients' survival as well.

Indicators of distress in newly diagnosed breast cancer patients

PubMed Central

Lucidi, Fabio; Mallia, Luca; D’Aiuto, Massimiliano; Merluzzi, Thomas V.

2015-01-01

Background. The diagnosis, treatment, and long-term management of cancer can present individuals with a multitude of stressors at various points in that trajectory. Psychosocial distress may appear early in the diagnostic process and have negative effects on compliance with treatment and subsequent quality of life. Purpose. The aim of the study was to determine early-phase predictors of distress before any medical treatment. Method. Consistent with the goals of the study, 123 newly diagnosed breast cancer patients (20 to 74 years old) completed multiple indicators of knowledge about breast cancer management and treatment, attitudes toward cancer, social support, coping efficacy, and distress. Results. SEM analysis confirmed the hypothesized model. Age was negatively associated with the patient’s knowledge (β = − 0.22), which, in turn, was positively associated with both attitudes toward breast cancer (β = 0.39) and coping self-efficacy (β = 0.36). Self-efficacy was then directly related to psychological distress (β = − 0.68). Conclusions. These findings establish indicators of distress in patients early in the cancer trajectory. From a practical perspective, our results have implications for screening for distress and for the development of early interventions that may be followed by healthcare professionals to reduce psychological distress. PMID:26244115

Women With Breast Cancer: Self-Reported Distress in Early Survivorship

PubMed Central

Lester, Joanne; Crosthwaite, Kara; Stout, Robin; Jones, Rachel N.; Holloman, Christopher; Shapiro, Charles; Andersen, Barbara L.

2015-01-01

Purpose/Objectives To identify and compare levels of distress and sources of problems among patients with breast cancer in early survivorship. Design Descriptive, cross-sectional. Setting A National Cancer Institute–designated comprehensive cancer center. Sample 100 breast cancer survivors were selected to represent four time points in the cancer trajectory. Methods Distress was self-reported using the Distress Thermometer and its 38-item problem list. Analysis of variance and chi-square analyses were performed as appropriate. Main Research Variables Distress scores, problem reports, and time groups. Findings Participants scored in range of the cutoff of more than 4 (range = 4.1–5.1) from treatment through three months post-treatment. At six months post-treatment, distress levels were significantly lower. Significant differences were found between groups on the total problem list score (p = 0.007) and emotional (p = 0.01) and physical subscale scores (p = 0.003). Conclusions Comparison of groups at different points in the cancer trajectory found similar elevated levels from diagnosis through three months. Distress remained elevated in early survivorship but significantly decreased at six months post-treatment. Implications for Nursing Interventions to reduce or prevent distress may improve outcomes in early survivorship. PMID:25542330

Early increased density of cyclooxygenase-2 (COX-2) immunoreactive neurons in Down syndrome.

PubMed

Mulet, Maria; Blasco-Ibáńez, José Miguel; Crespo, Carlos; Nácher, Juan; Varea, Emilio

2017-01-01

Neuroinflammation is one of the hallmarks of Alzheimer's disease. One of the enzymes involved in neuroinflammation, even in early stages of the disease, is COX-2, an inducible cyclooxygenase responsible for the generation of eicosanoids and for the generation of free radicals. Individuals with Down syndrome develop Alzheimer's disease early in life. Previous studies pointed to the possible overexpression of COX-2 and correlated it to brain regions affected by the disease. We analysed the COX-2 expression levels in individuals with Down syndrome and in young, adult and old mice of the Ts65Dn mouse model for Down syndrome. We have observed an overexpression of COX-2 in both, Down syndrome individuals and mice. Importantly, mice already presented an overexpression of COX-2 at postnatal day 30, before neurodegeneration begins; which suggests that neuroinflammation may underlie the posterior neurodegeneration observed in individuals with Down syndrome and in Ts65Dn mice and could be a factor for the premature appearance of Alzheimer's disease..

Health effects models for nuclear power plant accident consequence analysis: Low LET radiation

DOE Office of Scientific and Technical Information (OSTI.GOV)

Evans, J.S.

1990-01-01

This report describes dose-response models intended to be used in estimating the radiological health effects of nuclear power plant accidents. Models of early and continuing effects, cancers and thyroid nodules, and genetic effects are provided. Weibull dose-response functions are recommended for evaluating the risks of early and continuing health effects. Three potentially lethal early effects -- the hematopoietic, pulmonary, and gastrointestinal syndromes -- are considered. In addition, models are included for assessing the risks of several nonlethal early and continuing effects -- including prodromal vomiting and diarrhea, hypothyroidism and radiation thyroiditis, skin burns, reproductive effects, and pregnancy losses. Linear andmore » linear-quadratic models are recommended for estimating cancer risks. Parameters are given for analyzing the risks of seven types of cancer in adults -- leukemia, bone, lung, breast, gastrointestinal, thyroid, and other.'' The category, other'' cancers, is intended to reflect the combined risks of multiple myeloma, lymphoma, and cancers of the bladder, kidney, brain, ovary, uterus and cervix. Models of childhood cancers due to in utero exposure are also developed. For most cancers, both incidence and mortality are addressed. The models of cancer risk are derived largely from information summarized in BEIR III -- with some adjustment to reflect more recent studies. 64 refs., 18 figs., 46 tabs.« less

What characteristics of primary care and patients are associated with early death in patients with lung cancer in the UK?

PubMed

O'Dowd, Emma L; McKeever, Tricia M; Baldwin, David R; Anwar, Sadia; Powell, Helen A; Gibson, Jack E; Iyen-Omofoman, Barbara; Hubbard, Richard B

2015-02-01

The UK has poor lung cancer survival rates and high early mortality, compared to other countries. We aimed to identify factors associated with early death, and features of primary care that might contribute to late diagnosis. All cases of lung cancer diagnosed between 2000 and 2013 were extracted from The Health Improvement Network database. Patients who died within 90 days of diagnosis were compared with those who survived longer. Standardised chest X-ray (CXR) and lung cancer rates were calculated for each practice. Of 20,142 people with lung cancer, those who died early consulted with primary care more frequently prediagnosis. Individual factors associated with early death were male sex (OR 1.17; 95% CI 1.10 to 1.24), current smoking (OR 1.43; 95% CI 1.28 to 1.61), increasing age (OR 1.80; 95% CI 1.62 to 1.99 for age ≥80 years compared to 65-69 years), social deprivation (OR 1.16; 95% CI 1.04 to 1.30 for Townsend quintile 5 vs 1) and rural versus urban residence (OR 1.22; 95% CI 1.06 to 1.41). CXR rates varied widely, and the odds of early death were highest in the practices which requested more CXRs. Lung cancer incidence at practice level did not affect early deaths. Patients who die early from lung cancer are interacting with primary care prediagnosis, suggesting potentially missed opportunities to identify them earlier. A general increase in CXR requests may not improve survival; rather, a more timely and appropriate targeting of this investigation using risk assessment tools needs further assessment. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Fertility conserving management of early cervical cancer: our experience of LLETZ and pelvic lymph node dissection.

PubMed

Lindsay, Rhona; Burton, Kevin; Shanbhag, Smruta; Tolhurst, Jenny; Millan, David; Siddiqui, Nadeem

2014-01-01

Presently, for those diagnosed with early cervical cancer who wish to conserve their fertility, there is the option of radical trachelectomy. Although successful, this procedure is associated with significant obstetric morbidity. The recurrence risk of early cervical cancer is low and in tumors measuring less than 2 cm; if the lymphatics are negative, the likelihood of parametrial involvement is less than 1%. Therefore, pelvic lymph nodes are a surrogate marker of parametrial involvement and radical excision of the parametrium can be omitted if they are negative. The aim of this study was to report our experience of the fertility conserving management of early cervical cancer with repeat large loop excision of the transformation zone and laparoscopic pelvic lymph node dissection. Between 2004 and 2011, a retrospective review of cases of early cervical cancer who had fertility conserving management within Glasgow Royal Infirmary was done. Forty-three patients underwent fertility conserving management of early cervical cancer. Forty were screen-detected cancers; 2 were stage IA1, 4 were stage IA2, and 37 were stage IB1. There were 2 central recurrences during the follow-up period. There have been 15 live children to 12 women and there are 4 ongoing pregnancies. To our knowledge, this is the largest case series described and confirms the low morbidity and mortality of this procedure. However, even within our highly select group, there have been 2 cases of central recurrent disease. We, therefore, are urging caution in the global adoption of this technique and would welcome a multicenter multinational randomized controlled trial.

Prognostic model for survival in patients with early stage cervical cancer.

PubMed

Biewenga, Petra; van der Velden, Jacobus; Mol, Ben Willem J; Stalpers, Lukas J A; Schilthuis, Marten S; van der Steeg, Jan Willem; Burger, Matthé P M; Buist, Marrije R

2011-02-15

In the management of early stage cervical cancer, knowledge about the prognosis is critical. Although many factors have an impact on survival, their relative importance remains controversial. This study aims to develop a prognostic model for survival in early stage cervical cancer patients and to reconsider grounds for adjuvant treatment. A multivariate Cox regression model was used to identify the prognostic weight of clinical and histological factors for disease-specific survival (DSS) in 710 consecutive patients who had surgery for early stage cervical cancer (FIGO [International Federation of Gynecology and Obstetrics] stage IA2-IIA). Prognostic scores were derived by converting the regression coefficients for each prognostic marker and used in a score chart. The discriminative capacity was expressed as the area under the curve (AUC) of the receiver operating characteristic. The 5-year DSS was 92%. Tumor diameter, histological type, lymph node metastasis, depth of stromal invasion, lymph vascular space invasion, and parametrial extension were independently associated with DSS and were included in a Cox regression model. This prognostic model, corrected for the 9% overfit shown by internal validation, showed a fair discriminative capacity (AUC, 0.73). The derived score chart predicting 5-year DSS showed a good discriminative capacity (AUC, 0.85). In patients with early stage cervical cancer, DSS can be predicted with a statistical model. Models, such as that presented here, should be used in clinical trials on the effects of adjuvant treatments in high-risk early cervical cancer patients, both to stratify and to include patients. Copyright © 2010 American Cancer Society.

Selecting postoperative adjuvant systemic therapy for early stage breast cancer: A critical assessment of commercially available gene expression assays

PubMed Central

Schuur, Eric; Angel Aristizabal, Javier; Bargallo Rocha, Juan Enrique; Cabello, Cesar; Elizalde, Roberto; García‐Estévez, Laura; Gomez, Henry L.; Katz, Artur; Nuñez De Pierro, Aníbal

2017-01-01

Risk stratification of patients with early stage breast cancer may support adjuvant chemotherapy decision‐making. This review details the development and validation of six multi‐gene classifiers, each of which claims to provide useful prognostic and possibly predictive information for early stage breast cancer patients. A careful assessment is presented of each test's analytical validity, clinical validity, and clinical utility, as well as the quality of evidence supporting its use. PMID:28211064

Manganese Superoxide Dismutase in Cancer Prevention

PubMed Central

Robbins, Delira

2014-01-01

Abstract Significance: Cancer is the second leading cause of death in the United States. Considering the quality of life and treatment cost, the best way to fight against cancer is to prevent or suppress cancer development. Cancer is preventable as indicated by human papilloma virus (HPV) vaccination and tamoxifen/raloxifen treatment in breast cancer prevention. The activities of superoxide dismutases (SODs) are often lowered during early cancer development, making it a rational candidate for cancer prevention. Recent Advances: SOD liposome and mimetics have been shown to be effective in cancer prevention animal models. They've also passed safety tests during early phase clinical trials. Dietary supplement-based SOD cancer prevention provides another opportunity for antioxidant-based cancer prevention. New mechanistic studies have revealed that SOD inhibits not only oncogenic activity, but also subsequent metabolic shifts during early tumorigenesis. Critical Issues: Lack of sufficient animal model studies targeting specific cancers; and lack of clinical trials and support from pharmaceutical industries also hamper efforts in further advancing SOD-based cancer prevention. Future Directions: To educate and obtain support from our society that cancer is preventable. To combine SOD-based therapeutics with other cancer preventive agents to obtain synergistic effects. To formulate a dietary supplementation-based antioxidant approach for cancer prevention. Lastly, targeting specific populations who are prone to carcinogens, which can trigger oxidative stress as the mechanism of carcinogenesis. Antioxid. Redox Signal. 20, 1628–1645. PMID:23706068

Breast cancer screening

MedlinePlus

Mammogram - breast cancer screening; Breast exam - breast cancer screening; MRI - breast cancer screening ... performed to screen women to detect early breast cancer when it is more likely to be cured. ...

Health economics evaluation of a gastric cancer early detection and treatment program in China.

PubMed

Li, Dan; Yuan, Yuan; Sun, Li-Ping; Fang, Xue; Zhou, Bao-Sen

2014-01-01

To use health economics methodology to assess the screening program on gastric cancer in Zhuanghe, China, so as to provide the basis for health decision on expanding the program of early detection and treatment. The expense of an early detection and treatment program for gastric cancer in patients found by screening, and also costs of traditional treatment in a hospital of Zhuanghe were assessed. Three major techniques of medical economics, namely cost-effective analysis (CEA), cost-benefit analysis (CBA) and cost-utility analysis (CUA), were used to assess the screening program. RESULTS from CEA showed that investing every 25, 235 Yuan on screening program in Zhuanghe area, one gastric cancer patient could be saved. Data from CUA showed that it was cost 1, 370 Yuan per QALY saved. RESULTS from CBA showed that: the total cost was 1,945,206 Yuan with a benefit as 8,669,709 Yuan and an CBR of 4.46. The early detection and treatment program of gastric cancer appears economic and society-beneficial. We suggest that it should be carry out in more high risk areas for gastric cancer.

Adjuvant vaginal brachytherapy as a part of management in early endometrial cancer

PubMed Central

Wojcieszek, Piotr; Białas, Brygida

2012-01-01

Endometrial cancer is the most frequent cancer of female genital tract. Metro- and menorrhagia or postmenopausal bleeding results in its early presentation. It allows radical treatment. However, controversies remain on surgery coverage or adjuvant therapies in early endometrial women cancer. Optimal management should minimize intervention instead of aggressive approach, as showed by recent studies. There is a role for brachytherapy as an adjuvant irradiation. Crucial publications including PORTEC-1, GOG 99, MRC ASTEC, ASTEC/EN.5, PORTEC-2 or Italian lymphadenectomy trial are discussed. Moreover, there is attention paid on adjuvant vaginal brachytherapy analyses for the past fifteen years. PMID:23378855

Oral Cancer Knowledge and Awareness in Patients Visiting Kantipur Dental College.

PubMed

Bajracharya, Dipshikha; Gupta, Sujaya; Sapkota, Manish; Bhatta, Shishir

2018-01-01

Lack of knowledge and awareness about oral cancer, its risk factors and negligence of the early warning signs play crucial role in raising the incidence of the disease. The present study was carried out to evaluate the awareness of oral cancer among patients visiting Kantipur Dental College, Kathmandu, Nepal. The cross-sectional study was done in 471 patients from 15-85 years. Self administered questionnaire was prepared which comprised of knowledge of oral cancer, source of information, its early signs and symptoms along with the awareness of its risk factors. Most of the participants (41.80%) had not heard of oral cancer. 31.60% recognized tobacco smoking and tobacco chewing as the chief risk factor with 15.50% and 10.80% of participants who identified white patch and red patch as early sign of oral cancer respectively. Pearson's chi square test was used which showed statistically significant association of total mean knowledge score and awareness score with age, education level and occupation (p<0.05). This study done in dental patients showed lack of knowledge and awareness in general public about oral cancer. There seem to be a need for more planned awareness programs through newspapers, radio, television and health campaigns regarding the association of habits in the development of oral cancer and benefits of detecting oral cancer at early stage for better prognosis.

Multiple biomarkers in molecular oncology. II. Molecular diagnostics applications in breast cancer management.

PubMed

Malinowski, Douglas P

2007-05-01

In recent years, the application of genomic and proteomic technologies to the problem of breast cancer prognosis and the prediction of therapy response have begun to yield encouraging results. Independent studies employing transcriptional profiling of primary breast cancer specimens using DNA microarrays have identified gene expression profiles that correlate with clinical outcome in primary breast biopsy specimens. Recent advances in microarray technology have demonstrated reproducibility, making clinical applications more achievable. In this regard, one such DNA microarray device based upon a 70-gene expression signature was recently cleared by the US FDA for application to breast cancer prognosis. These DNA microarrays often employ at least 70 gene targets for transcriptional profiling and prognostic assessment in breast cancer. The use of PCR-based methods utilizing a small subset of genes has recently demonstrated the ability to predict the clinical outcome in early-stage breast cancer. Furthermore, protein-based immunohistochemistry methods have progressed from using gene clusters and gene expression profiling to smaller subsets of expressed proteins to predict prognosis in early-stage breast cancer. Beyond prognostic applications, DNA microarray-based transcriptional profiling has demonstrated the ability to predict response to chemotherapy in early-stage breast cancer patients. In this review, recent advances in the use of multiple markers for prognosis of disease recurrence in early-stage breast cancer and the prediction of therapy response will be discussed.

A Systematic Literature Review and Meta-Regression Analysis on Early-Life Energy Restriction and Cancer Risk in Humans.

PubMed

Elands, Rachel J J; Simons, Colinda C J M; Dongen, Martien van; Schouten, Leo J; Verhage, Bas A J; van den Brandt, Piet A; Weijenberg, Matty P

2016-01-01

In animal models, long-term moderate energy restriction (ER) is reported to decelerate carcinogenesis, whereas the effect of severe ER is inconsistent. The impact of early-life ER on cancer risk has never been reviewed systematically and quantitatively based on observational studies in humans. We conducted a systematic review of observational studies and a meta-(regression) analysis on cohort studies to clarify the association between early-life ER and organ site-specific cancer risk. PubMed and EMBASE (1982 -August 2015) were searched for observational studies. Summary relative risks (RRs) were estimated using a random effects model when available ≥3 studies. Twenty-four studies were included. Eleven publications, emanating from seven prospective cohort studies and some reporting on multiple cancer endpoints, met the inclusion criteria for quantitative analysis. Women exposed to early-life ER (ranging from 220-1660 kcal/day) had a higher breast cancer risk than those not exposed (RRRE all ages = 1.28, 95% CI: 1.05-1.56; RRRE for 10-20 years of age = 1.21, 95% CI: 1.09-1.34). Men exposed to early-life ER (ranging from 220-800kcal/day) had a higher prostate cancer risk than those not exposed (RRRE = 1.16, 95% CI: 1.03-1.30). Summary relative risks were not computed for colorectal cancer, because of heterogeneity, and for stomach-, pancreas-, ovarian-, and respiratory cancer because there were <3 available studies. Longer duration of exposure to ER, after adjustment for severity, was positively associated with overall cancer risk in women (p = 0.02). Ecological studies suggest that less severe ER is generally associated with a reduced risk of cancer. Early-life transient severe ER seems to be associated with increased cancer risk in the breast (particularly ER exposure at adolescent age) and prostate. The duration, rather than severity of exposure to ER, seems to positively influence relative risk estimates. This result should be interpreted with caution due to the limited number of studies and difficulty in disentangling duration, severity, and geographical setting of exposure.

A Systematic Literature Review and Meta-Regression Analysis on Early-Life Energy Restriction and Cancer Risk in Humans

PubMed Central

Elands, Rachel J. J.; Simons, Colinda C. J. M.; van Dongen, Martien; Schouten, Leo J.; Verhage, Bas A. J.; van den Brandt, Piet A.; Weijenberg, Matty P.

2016-01-01

Background In animal models, long-term moderate energy restriction (ER) is reported to decelerate carcinogenesis, whereas the effect of severe ER is inconsistent. The impact of early-life ER on cancer risk has never been reviewed systematically and quantitatively based on observational studies in humans. Objective We conducted a systematic review of observational studies and a meta-(regression) analysis on cohort studies to clarify the association between early-life ER and organ site-specific cancer risk. Methods PubMed and EMBASE (1982 –August 2015) were searched for observational studies. Summary relative risks (RRs) were estimated using a random effects model when available ≥3 studies. Results Twenty-four studies were included. Eleven publications, emanating from seven prospective cohort studies and some reporting on multiple cancer endpoints, met the inclusion criteria for quantitative analysis. Women exposed to early-life ER (ranging from 220–1660 kcal/day) had a higher breast cancer risk than those not exposed (RRRE all ages = 1.28, 95% CI: 1.05–1.56; RRRE for 10–20 years of age = 1.21, 95% CI: 1.09–1.34). Men exposed to early-life ER (ranging from 220–800kcal/day) had a higher prostate cancer risk than those not exposed (RRRE = 1.16, 95% CI: 1.03–1.30). Summary relative risks were not computed for colorectal cancer, because of heterogeneity, and for stomach-, pancreas-, ovarian-, and respiratory cancer because there were <3 available studies. Longer duration of exposure to ER, after adjustment for severity, was positively associated with overall cancer risk in women (p = 0.02). Ecological studies suggest that less severe ER is generally associated with a reduced risk of cancer. Conclusions Early-life transient severe ER seems to be associated with increased cancer risk in the breast (particularly ER exposure at adolescent age) and prostate. The duration, rather than severity of exposure to ER, seems to positively influence relative risk estimates. This result should be interpreted with caution due to the limited number of studies and difficulty in disentangling duration, severity, and geographical setting of exposure. PMID:27643873

Anal cancer and intraepithelial neoplasia screening: A review

PubMed Central

Leeds, Ira L; Fang, Sandy H

2016-01-01

This review focuses on the early diagnosis of anal cancer and its precursor lesions through routine screening. A number of risk-stratification strategies as well as screening techniques have been suggested, and currently little consensus exists among national societies. Much of the current clinical rationale for the prevention of anal cancer derives from the similar tumor biology of cervical cancer and the successful use of routine screening to identify cervical cancer and its precursors early in the disease process. It is thought that such a strategy of identifying early anal intraepithelial neoplasia will reduce the incidence of invasive anal cancer. The low prevalence of anal cancer in the general population prevents the use of routine screening. However, routine screening of selected populations has been shown to be a more promising strategy. Potential screening modalities include digital anorectal exam, anal Papanicolaou testing, human papilloma virus co-testing, and high-resolution anoscopy. Additional research associating high-grade dysplasia treatment with anal cancer prevention as well as direct comparisons of screening regimens is necessary to develop further anal cancer screening recommendations. PMID:26843912

Perceived social isolation moderates the relationship between early childhood trauma and pulse pressure in older adults.

PubMed

Norman, Greg J; Hawkley, Louise; Ball, Aaron; Berntson, Gary G; Cacioppo, John T

2013-06-01

Over a million children are subjected to some form of trauma in the United States every year. Early trauma has been shown to have deleterious effects on cardiovascular health in adulthood. However, the presence of strong social relationships as an adult can buffer an individual against many of the harmful effects of early trauma. Furthermore, the perception of social isolation has been shown to be a significant risk factor for the development of cardiovascular disease and is a strong predictor of all cause mortality. One likely mechanism thought to underlie the influence of perceived isolation on health is changes in arterial stiffness. One of the more widely used measures of arterial stiffness in older individuals is pulse pressure. The goal of the present study was to determine whether early childhood trauma is associated with elevations on pulse pressure. Furthermore, this study sought to determine whether perceived social isolation moderates the relationship between early trauma and pulse pressure. Results revealed that individuals with low perceived social isolation displayed no significant relationship between early trauma and pulse pressure. However, individuals who reported higher levels of perceived isolation showed a significant positive association between early trauma and pulse pressure. Therefore, the detrimental effects of early trauma may be partially dependent upon the quality of social relationships as an adult. Copyright © 2012 Elsevier B.V. All rights reserved.

Molecular evolutionary analysis of vertebrate transducins: a role for amino acid variation in photoreceptor deactivation.

PubMed

Lin, Yi G; Weadick, Cameron J; Santini, Francesco; Chang, Belinda S W

2013-12-01

Transducin is a heterotrimeric G protein that plays a critical role in phototransduction in the rod and cone photoreceptor cells of the vertebrate retina. Rods, highly sensitive cells that recover from photoactivation slowly, underlie dim-light vision, whereas cones are less sensitive, recover more quickly, and underlie bright-light vision. Transducin deactivation is a critical step in photoreceptor recovery and may underlie the functional distinction between rods and cones. Rods and cones possess distinct transducin α subunits, yet they share a common deactivation mechanism, the GTPase activating protein (GAP) complex. Here, we used codon models to examine patterns of sequence evolution in rod (GNAT1) and cone (GNAT2) α subunits. Our results indicate that purifying selection is the dominant force shaping GNAT1 and GNAT2 evolution, but that GNAT2 has additionally been subject to positive selection operating at multiple phylogenetic scales; phylogeny-wide analysis identified several sites in the GNAT2 helical domain as having substantially elevated dN/dS estimates, and branch-site analysis identified several nearby sites as targets of strong positive selection during early vertebrate history. Examination of aligned GNAT and GAP complex crystal structures revealed steric clashes between several positively selected sites and the deactivating GAP complex. This suggests that GNAT2 sequence variation could play an important role in adaptive evolution of the vertebrate visual system via effects on photoreceptor deactivation kinetics and provides an alternative perspective to previous work that focused instead on the effect of GAP complex concentration. Our findings thus further the understanding of the molecular biology, physiology, and evolution of vertebrate visual systems.

Can responses to basic non-numerical visual features explain neural numerosity responses?

PubMed

Harvey, Ben M; Dumoulin, Serge O

2017-04-01

Humans and many animals can distinguish between stimuli that differ in numerosity, the number of objects in a set. Human and macaque parietal lobes contain neurons that respond to changes in stimulus numerosity. However, basic non-numerical visual features can affect neural responses to and perception of numerosity, and visual features often co-vary with numerosity. Therefore, it is debated whether numerosity or co-varying low-level visual features underlie neural and behavioral responses to numerosity. To test the hypothesis that non-numerical visual features underlie neural numerosity responses in a human parietal numerosity map, we analyze responses to a group of numerosity stimulus configurations that have the same numerosity progression but vary considerably in their non-numerical visual features. Using ultra-high-field (7T) fMRI, we measure responses to these stimulus configurations in an area of posterior parietal cortex whose responses are believed to reflect numerosity-selective activity. We describe an fMRI analysis method to distinguish between alternative models of neural response functions, following a population receptive field (pRF) modeling approach. For each stimulus configuration, we first quantify the relationships between numerosity and several non-numerical visual features that have been proposed to underlie performance in numerosity discrimination tasks. We then determine how well responses to these non-numerical visual features predict the observed fMRI responses, and compare this to the predictions of responses to numerosity. We demonstrate that a numerosity response model predicts observed responses more accurately than models of responses to simple non-numerical visual features. As such, neural responses in cognitive processing need not reflect simpler properties of early sensory inputs. Copyright © 2017 Elsevier Inc. All rights reserved.

Neratinib for the treatment of HER2-positive early stage breast cancer.

PubMed

Echavarria, Isabel; López-Tarruella, Sara; Márquez-Rodas, Iván; Jerez, Yolanda; Martin, Miguel

2017-08-01

Despite the advances in the treatment of HER2-positive breast cancer, resistance to actual chemotherapeutic regimens eventually occurs. Neratinib, an orally available pan-inhibitor of the ERBB family, represents an interesting new option for early-stage HER2-positive breast cancer. Areas covered: In this article, the development of neratinib, with a special focus on its potential value in the treatment of early-stage HER2-positive breast cancer, has been reviewed. For this purpose, a literature search was conducted, including preclinical studies, early-phase trials in advanced cancer with neratinib in monotherapy and in combination, and phase II and large phase III trials in the early setting. Management of neratinib-induced toxicity, future perspectives for the drug, and ongoing trials are also discussed in this review. Expert commentary: Neratinib is emerging as a promising oral drug for the treatment of HER2-positive breast cancer. Although FDA and EMA approval is derived from the extended adjuvant treatment, this setting may not be the ideal scenario to obtain the beneficial effects of neratinib. Confirmatory data in the neoadjuvant setting and subgroup analysis from the ExTENET trial might bring some light into the best setting for neratinib therapy. Data from confirmatory trials in the metastatic setting are also required.

A Mass Spectrometric Analysis Method Based on PPCA and SVM for Early Detection of Ovarian Cancer.

PubMed

Wu, Jiang; Ji, Yanju; Zhao, Ling; Ji, Mengying; Ye, Zhuang; Li, Suyi

2016-01-01

Background. Surfaced-enhanced laser desorption-ionization-time of flight mass spectrometry (SELDI-TOF-MS) technology plays an important role in the early diagnosis of ovarian cancer. However, the raw MS data is highly dimensional and redundant. Therefore, it is necessary to study rapid and accurate detection methods from the massive MS data. Methods. The clinical data set used in the experiments for early cancer detection consisted of 216 SELDI-TOF-MS samples. An MS analysis method based on probabilistic principal components analysis (PPCA) and support vector machine (SVM) was proposed and applied to the ovarian cancer early classification in the data set. Additionally, by the same data set, we also established a traditional PCA-SVM model. Finally we compared the two models in detection accuracy, specificity, and sensitivity. Results. Using independent training and testing experiments 10 times to evaluate the ovarian cancer detection models, the average prediction accuracy, sensitivity, and specificity of the PCA-SVM model were 83.34%, 82.70%, and 83.88%, respectively. In contrast, those of the PPCA-SVM model were 90.80%, 92.98%, and 88.97%, respectively. Conclusions. The PPCA-SVM model had better detection performance. And the model combined with the SELDI-TOF-MS technology had a prospect in early clinical detection and diagnosis of ovarian cancer.

Autoantibodies to aberrantly glycosylated MUC1 in early stage breast cancer are associated with a better prognosis

PubMed Central

2011-01-01

Introduction Detection of serum biomarkers for early diagnosis of breast cancer remains an important goal. Changes in the structure of O-linked glycans occur in all breast cancers resulting in the expression of glycoproteins that are antigenically distinct. Indeed, the serum assay widely used for monitoring disease progression in breast cancer (CA15.3), detects a glycoprotein (MUC1), but elevated levels of the antigen cannot be detected in early stage patients. However, since the immune system acts to amplify the antigenic signal, antibodies can be detected in sera long before the antigen. We have exploited the change in O-glycosylation to measure autoantibody responses to cancer-associated glycoforms of MUC1 in sera from early stage breast cancer patients. Methods We used a microarray platform of 60mer MUC1 glycopeptides, to confirm the presence of autoantibodies to cancer associated glycoforms of MUC1 in a proportion of early breast cancer patients (54/198). Five positive sera were selected for detailed definition of the reactive epitopes using on chip glycosylation technology and a panel of glycopeptides based on a single MUC1 tandem repeat carrying specific glycans at specific sites. Based on these results, larger amounts of an extended repertoire of defined MUC1 glycopeptides were synthesised, printed on microarrays, and screened with sera from a large cohort of breast cancer patients (n = 395), patients with benign breast disease (n = 108) and healthy controls (n = 99). All sera were collected in the 1970s and 1980s and complete clinical follow-up of breast cancer patients is available. Results The presence and level of autoantibodies was significantly higher in the sera from cancer patients compared with the controls, and a highly significant correlation with age was observed. High levels of a subset of autoantibodies to the core3MUC1 (GlcNAcβ1-3GalNAc-MUC1) and STnMUC1 (NeuAcα2,6GalNAc-MUC1) glycoforms were significantly associated with reduced incidence and increased time to metastasis. Conclusions Autoantibodies to specific cancer associated glycoforms of MUC1 are found more frequently and at higher levels in early stage breast cancer patients than in women with benign breast disease or healthy women. Association of strong antibody response with reduced rate and delay in metastases suggests that autoantibodies can affect disease progression. PMID:21385452

Exploring barriers to the delivery of cervical cancer screening and early treatment services in Malawi: some views from service providers

PubMed Central

Munthali, Alister C; Ngwira, Bagrey M; Taulo, Frank

2015-01-01

Background Cervical cancer is the most common reproductive health cancer in Malawi. In most cases, women report to health facilities when the disease is in its advanced stage. In this study, we investigate service providers’ perceptions about barriers for women to access cervical cancer screening and early treatment services in Malawi. Methods We conducted in-depth interviews with 13 district coordinators and 40 service providers of cervical cancer screening and early treatment services in 13 districts in Malawi. The study was conducted in 2012. The district coordinators helped the research team identify the health facilities which were providing cervical cancer screening and early treatment services. Results Almost all informants reported that cervical cancer was a major public health problem in their districts and that prevention efforts for this disease were being implemented. They were aware of the test and treat approach using visual inspection with acetic acid (VIA). They, however, said that the delivery of cervical cancer screening and early treatment services was compromised because of factors such as gross shortage of staff, lack of equipment and supplies, the lack of supportive supervision, and the use of male service providers. Informants added that the lack of awareness about the disease among community members, long distances to health facilities, the lack of involvement of husbands, and prevailing misperceptions about the disease (eg, that it is caused by the exposure to the VIA process) affect the uptake of these services. Conclusion While progress has been made in the provision of cervical cancer screening and early treatment services in Malawi, a number of factors affect service delivery and uptake. There is a need to continue creating awareness among community members including husbands and also addressing identified barriers such as shortage of staff and supplies in order to improve uptake of services. PMID:25848229

Intrauterine Growth Restriction Is a Direct Consequence of Localized Maternal Uropathogenic Escherichia coli Cystitis

PubMed Central

Bolton, Michael; Horvath, Dennis J.; Li, Birong; Cortado, Hanna; Newsom, David; White, Peter; Partida-Sanchez, Santiago; Justice, Sheryl S.

2012-01-01

Despite the continually increasing rates of adverse perinatal outcomes across the globe, the molecular mechanisms that underlie adverse perinatal outcomes are not completely understood. Clinical studies report that 10% of pregnant women will experience a urinary tract infection (UTI) and there is an association of UTIs with adverse perinatal outcomes. We introduced bacterial cystitis into successfully outbred female mice at gestational day 14 to follow pregnancy outcomes and immunological responses to determine the mechanisms that underlie UTI-mediated adverse outcomes. Outbred fetuses from mothers experiencing localized cystitis displayed intrauterine growth restriction (20–80%) as early as 48 hours post-infection and throughout the remainder of normal gestation. Robust infiltration of cellular innate immune effectors was observed in the uteroplacental tissue following introduction of UTI despite absence of viable bacteria. The magnitude of serum proinflammatory cytokines is elevated in the maternal serum during UTI. This study demonstrates that a localized infection can dramatically impact the immunological status as well as the function of non-infected distal organs and tissues. This model can be used as a platform to determine the mechanism(s) by which proinflammatory changes occur between non-contiguous genitourinary organs PMID:22470490

[The progress and prospect of application of genetic testing technology-based gene detection technology in the diagnosis and treatment of hereditary cancer].

PubMed

He, J X; Jiang, Y F

2017-08-06

Hereditary cancer is caused by specific pathogenic gene mutations. Early detection and early intervention are the most effective ways to prevent and control hereditary cancer. High-throughput sequencing based genetic testing technology (NGS) breaks through the restrictions of pedigree analysis, provide a convenient and efficient method to detect and diagnose hereditary cancer. Here, we introduce the mechanism of hereditary cancer, summarize, discuss and prospect the application of NGS and other genetic tests in the diagnosis of hereditary retinoblastoma, hereditary breast and ovarian cancer syndrome, hereditary colorectal cancer and other complex and rare hereditary tumors.

Cancer screening and early detection in the 21st century

PubMed Central

Murphy, Jeanne

2017-01-01

Objective To review the trends in and principles of cancer screening and early detection. Data Sources Journal articles, United States Preventive Services Task Force (U SPSTF) publications, professional organization position statements, evidence-based summaries Conclusion Cancer screening has contributed to decreasing the morbidity and mortality of cancer. Efforts to improve the selection of candidates for cancer screening, to understand the biological basis of carcinogenesis, and the development of new technologies for cancer screening will allow for improvements in the cancer screening over time. Implications for Nursing Practice Nurses are well-positioned to lead the implementation of cancer screening recommendations in the 21st Century through their practice, research, educational efforts and advocacy. PMID:28343835

Health system costs of skin cancer and cost-effectiveness of skin cancer prevention and screening: a systematic review.

PubMed

Gordon, Louisa G; Rowell, David

2015-03-01

The objective of this study was to review the literature for malignant melanoma, basal and squamous cell carcinomas to understand: (a) national estimates of the direct health system costs of skin cancer and (b) the cost-effectiveness of interventions for skin cancer prevention or early detection. A systematic review was performed using Medline, Cochrane Library and the National Health Service Economic Evaluation Databases as well as a manual search of reference lists to identify relevant studies up to 31 August 2013. A narrative synthesis approach was used to summarize the data. National cost estimates were adjusted for country-specific inflation and presented in 2013 euros. The CHEERS statement was used to assess the quality of the economic evaluation studies. Sixteen studies reporting national estimates of skin cancer costs and 11 cost-effectiveness studies on skin cancer prevention or early detection were identified. Relative to the size of their respective populations, the annual direct health system costs for skin cancer were highest for Australia, New Zealand, Sweden and Denmark (2013 euros). Skin cancer prevention initiatives are highly cost-effective and may also be cost-saving. Melanoma early detection programmes aimed at high-risk individuals may also be cost-effective; however, updated analyses are needed. There is a significant cost burden of skin cancer for many countries and health expenditure for this disease will grow as incidence increases. Public investment in skin cancer prevention and early detection programmes show strong potential for health and economic benefits.

Roadmap to eliminate gastric cancer with Helicobacter pylori eradication and consecutive surveillance in Japan.

PubMed

Asaka, Masahiro; Kato, Mototsugu; Sakamoto, Naoya

2014-01-01

In Japan, the annual number of deaths from gastric cancer is approximately 50,000 and there has been no change over the last 50 years. So far, all efforts have been directed toward improving the detection of early gastric cancer by barium X-ray and endoscopy, since early cancer has a good prognosis, resulting in Japan having the best diagnostic capability for early gastric cancer worldwide. The 5-year survival rate of gastric cancer patients exceeds 60 % in Japan and is much higher than that in Europe and the US (20 %) because of this superior diagnosis of early gastric cancer. In February 2013, national health insurance coverage for Helicobacter pylori eradication therapy to treat H. pylori-associated chronic gastritis became available in Japan. H. pylori-associated gastritis leads to development of gastric and duodenal ulcers and gastric polyps. Therefore, providing treatment for gastritis is likely to substantially decrease the prevalence of both gastric and duodenal ulcers and polyps. Because treatment for H. pylori-associated gastritis, which leads to atrophic gastritis and gastric cancer, is now covered by health insurance in Japan, a strategy to eliminate gastric cancer-related deaths by taking advantage of this innovation was planned. According to this strategy, patients with gastritis will be investigated for H. pylori infection and those who are positive will receive eradication therapy followed by periodic surveillance. If this strategy is implemented, deaths from gastric cancer in Japan will decrease dramatically after 10-20 years.

Latent Tricuspid Valve Rupture after Motor Vehicle Accident and Routine Echocardiography in All Chest-Wall Traumas

PubMed Central

Khurana, Suchi; Puri, Rishi; Wong, Dennis; Dundon, Benjamin K.; Brown, Michael A.; Worthley, Matthew I.; Worthley, Stephen G.

2009-01-01

Blunt chest-wall trauma is common; however, resultant tricuspid valve rupture is rare and can be subtle in its presentation. Transthoracic echocardiography plays a key role in diagnosis. Herein, we report the case of a 42-year-old woman who sustained substantial chest-wall trauma in a high-speed motor vehicle accident. She presented a week later with symptoms of right-heart failure, secondary to flail tricuspid valve leaflets and torrential tricuspid regurgitation. The case of this patient highlights the importance of early diagnosis and elicits discussion of the mechanisms that can underlie delayed tricuspid valve rupture. Because the clinical diagnosis of tricuspid valve rupture can be difficult, we believe that echocardiography should be used early and, if necessary, repeatedly in all patients who sustain blunt chest-wall trauma. PMID:20069094

Early Onset Malignancies - Genomic Study of Cancer Disparities

Cancer.gov

The Early Onset Malignancies Initiative studies the genomic basis of six cancers that develop at an earlier age, occur in higher rates, and are typically more aggressive in certain minority populations.

Application of biomarkers in cancer risk management: evaluation from stochastic clonal evolutionary and dynamic system optimization points of view.

PubMed

Li, Xiaohong; Blount, Patricia L; Vaughan, Thomas L; Reid, Brian J

2011-02-01

Aside from primary prevention, early detection remains the most effective way to decrease mortality associated with the majority of solid cancers. Previous cancer screening models are largely based on classification of at-risk populations into three conceptually defined groups (normal, cancer without symptoms, and cancer with symptoms). Unfortunately, this approach has achieved limited successes in reducing cancer mortality. With advances in molecular biology and genomic technologies, many candidate somatic genetic and epigenetic "biomarkers" have been identified as potential predictors of cancer risk. However, none have yet been validated as robust predictors of progression to cancer or shown to reduce cancer mortality. In this Perspective, we first define the necessary and sufficient conditions for precise prediction of future cancer development and early cancer detection within a simple physical model framework. We then evaluate cancer risk prediction and early detection from a dynamic clonal evolution point of view, examining the implications of dynamic clonal evolution of biomarkers and the application of clonal evolution for cancer risk management in clinical practice. Finally, we propose a framework to guide future collaborative research between mathematical modelers and biomarker researchers to design studies to investigate and model dynamic clonal evolution. This approach will allow optimization of available resources for cancer control and intervention timing based on molecular biomarkers in predicting cancer among various risk subsets that dynamically evolve over time.

Meat consumption, heterocyclic amines and colorectal cancer risk: the Multiethnic Cohort Study.

PubMed

Ollberding, Nicholas J; Wilkens, Lynne R; Henderson, Brian E; Kolonel, Laurence N; Le Marchand, Loïc

2012-10-01

Greater consumption of red and processed meat has been associated with an increased risk of colorectal cancer in several recent meta-analyses. Heterocyclic amines (HCAs) have been hypothesized to underlie this association. In this prospective analysis conducted within the Multiethnic Cohort Study, we examined whether greater consumption of total, red or processed meat was associated with the risk of colorectal cancer among 165,717 participants who completed a detailed food frequency questionnaire at baseline. In addition, we examined whether greater estimated intake of HCAs was associated with the risk of colorectal cancer among 131,763 participants who completed a follow-up questionnaire that included a meat-cooking module. A total of 3,404 and 1,757 invasive colorectal cancers were identified from baseline to the end of follow-up and from the date of administration of the meat-cooking module to the end of follow-up, respectively. Proportional hazard models were used to estimate basic and multivariable-adjusted relative risks (RRs) and 95% confidence intervals for colorectal cancer associated with dietary exposures. In multivariable models, no association with the risk of colorectal cancer was detected for density-adjusted total meat (RR(Q5 vs. Q1) = 0.93 [0.83-1.05]), red meat (RR = 1.02 [0.91-1.16]) or processed meat intake (RR = 1.06 [0.94-1.19]) or for total (RR = 0.90 [0.76-1.05]) or specific HCA intake whether comparing quintiles of dietary exposure or using continuous variables. Although our results do not support a role for meat or for HCAs from meat in the etiology of colorectal cancer, we cannot rule out the possibility of a modest effect. Copyright © 2012 UICC.

Meat Consumption, Heterocyclic Amines, and Colorectal Cancer Risk: The Multiethnic Cohort Study

PubMed Central

Ollberding, Nicholas J.; Wilkens, Lynne R.; Henderson, Brian E.; Kolonel, Laurence N.; Le Marchand, Loïc

2012-01-01

Greater consumption of red and processed meat has been associated with an increased risk of colorectal cancer in several recent meta-analyses. Heterocyclic amines (HCAs) have been hypothesized to underlie this association. In this prospective analysis conducted within the Multiethnic Cohort Study, we examined whether greater consumption of total, red, or processed meat was associated with the risk of colorectal cancer among 165,717 participants who completed a detailed food frequency questionnaire at baseline. In addition, we examined whether greater estimated intake of HCAs was associated with the risk of colorectal cancer among 131,763 participants who completed a follow-up questionnaire that included a meat-cooking module. A total of 3,404 and 1,757 invasive colorectal cancers were identified from baseline to the end of follow-up, and from the date of administration of the meat-cooking module to the end of follow-up, respectively. Proportional hazards models were used to estimate basic and multivariable-adjusted relative risks (RRs) and 95% confidence intervals (CIs) for colorectal cancer associated with dietary exposures. In multivariable models, no association with the risk of colorectal cancer was detected for density-adjusted total meat (RRQ5 vs Q1=0.93 [0.83–1.05]), red meat (RR =1.02 [0.91–1.16]), or processed meat intake (RR =1.06 [0.94–1.19]), or for total (RR =0.90 [0.76–1.05]) or specific HCA intake whether comparing quintiles of dietary exposure or using continuous variables. Although our results do not support a role for meat or for HCAs from meat in the etiology of colorectal cancer, we cannot rule out the possibility of a modest effect. PMID:22438055

Family history of cancer and head and neck cancer survival.

PubMed

Getz, Kayla R; Rozek, Laura S; Peterson, Lisa A; Bellile, Emily L; Taylor, Jeremy M G; Wolf, Gregory T; Mondul, Alison M

2017-08-01

Patients with a family history of cancer may be genetically predisposed to carcinogenesis. This could affect risk of recurrence, second primary tumors, and overall outcomes after treatment of a primary cancer. We evaluated the association between family history of cancer and disease-specific survival in a cohort of patients with primary head and neck squamous carcinoma (HNSCC). Six hundred and forty-three incident HNSCC patients recruited through the University of Michigan Specialized Program of Research Excellence were followed for up to 5 years for survival. Participants were interviewed about personal and family cancer history, demographic information, and behavioral habits. Cox proportional hazards models were used to estimate the association between family history of cancer in a first-degree relative and disease-specific survival. After multivariable adjustment, we found a nonsignificant inverse association between family history and HNSCC mortality (hazard ratio [HR] = 0.88, 95% confidence interval [CI] 0.57-1.35). This association was stronger and statistically significant among patients who currently both drank alcohol and smoked cigarettes at diagnosis (HR = 0.46, 95% CI = 0.22-0.97); no association was observed among participants who did not both drink and smoke at the time of diagnosis (HR = 1.14, 95% CI = 0.68-1.91; p-interaction = 0.046). Results from this study suggest that having a family history of cancer may be associated with improved disease-specific survival in patients who use tobacco and alcohol. Additional large studies, particularly in populations including nonwhites and women, are needed to confirm or refute the association and to elucidate the genetic factors that may underlie this potential association. 2b. Laryngoscope, 127:1816-1820, 2017. © 2017 The American Laryngological, Rhinological and Otological Society, Inc.

Does the Breast Cancer Age at Diagnosis Differ by Ethnicity? A Study on Immigrants to Sweden

PubMed Central

Hemminki, Kari; Sundquist, Jan; Brandt, Andreas

2011-01-01

Background. Age-specific incidence rates for breast cancer in low-risk and high-risk ethnic populations differ by age at which the incidence maximum is reached: around 50 years in low-risk populations and over 60 years in high-risk populations. The interpretation of these differences remains unsettled, one line primarily referring to biological differences, the second one to cohort effects of rapidly increasing rates in young populations, and the third one to incomplete registration of cancer in the elderly. Methods. The nationwide Family-Cancer Database was used to analyze standardized incidence ratios (SIRs) and age at diagnosis of breast cancer in female immigrants to Sweden by their region of origin compared with women native to Sweden matched on birth year and other relevant factors. Results. We showed first that the SIRs for breast cancer were lower in many immigrant groups compared with natives of Sweden; women from Turkey had the lowest SIR of 0.45, followed by those from Chile (0.54) and Southeast Asia (0.57). Women from nine regions showed an earlier mean age at diagnosis than their matched Swedish controls, the largest differences being 5.5 years for women from Turkey, 5.1 years for those from Asian Arab and “Other African” countries, 4.3 years for those from Iran, and 4.0 years for those from Iraq. Conclusions. The results show that in many immigrant groups, the diagnostic age is earlier (<50 years) than in natives of Sweden (>50 years), suggesting that true biological factors underlie the differences. These factors may explain much of the international variation in breast cancer incidence. Identifying these factors should advance understanding of breast cancer etiology and prevention. PMID:21266400

Does the breast cancer age at diagnosis differ by ethnicity? A study on immigrants to Sweden.

PubMed

Hemminki, Kari; Mousavi, Seyed Mohsen; Sundquist, Jan; Brandt, Andreas

2011-01-01

Age-specific incidence rates for breast cancer in low-risk and high-risk ethnic populations differ by age at which the incidence maximum is reached: around 50 years in low-risk populations and over 60 years in high-risk populations. The interpretation of these differences remains unsettled, one line primarily referring to biological differences, the second one to cohort effects of rapidly increasing rates in young populations, and the third one to incomplete registration of cancer in the elderly. The nationwide Family-Cancer Database was used to analyze standardized incidence ratios (SIRs) and age at diagnosis of breast cancer in female immigrants to Sweden by their region of origin compared with women native to Sweden matched on birth year and other relevant factors. We showed first that the SIRs for breast cancer were lower in many immigrant groups compared with natives of Sweden; women from Turkey had the lowest SIR of 0.45, followed by those from Chile (0.54) and Southeast Asia (0.57). Women from nine regions showed an earlier mean age at diagnosis than their matched Swedish controls, the largest differences being 5.5 years for women from Turkey, 5.1 years for those from Asian Arab and "Other African" countries, 4.3 years for those from Iran, and 4.0 years for those from Iraq. The results show that in many immigrant groups, the diagnostic age is earlier (<50 years) than in natives of Sweden (>50 years), suggesting that true biological factors underlie the differences. These factors may explain much of the international variation in breast cancer incidence. Identifying these factors should advance understanding of breast cancer etiology and prevention.

Exercise-Induced Dose-Response Alterations in Adiponectin and Leptin Levels Are Dependent on Body Fat Changes in Women at Risk for Breast Cancer.

PubMed

Sturgeon, Kathleen; Digiovanni, Laura; Good, Jerene; Salvatore, Domenick; Fenderson, Desiré; Domchek, Susan; Stopfer, Jill; Galantino, Mary Lou; Bryan, Cathy; Hwang, Wei-Ting; Schmitz, Kathryn

2016-08-01

Dysregulation of adipokines, such as adiponectin and leptin, is associated with a variety of chronic diseases, including cancer. Physical activity protects against breast cancer and one of the mechanisms which may underlie this association is exercise-induced changes in adipokine levels. The WISER Sister Trial was a three-armed randomized controlled trial in premenopausal women (n = 137) with an elevated risk for breast cancer. A 5-menstrual-cycle-long dosed aerobic exercise intervention compared low-dose exercise (150 min/wk; n = 44) or high-dose exercise (300 min/wk; n = 48) with a control group asked to maintain usual activity levels (n = 45). Exercise intensity progressed to and was maintained at 70% to 80% of age predicted heart rate max. Body composition and adipokine levels were measured at baseline and follow-up. We observed significant linear trends for increased fitness capacity (Δ%: -2.0% control, 10.1% low dose, 13.1% high dose), decreased fat tissue-to-total tissue mass (Δ%: 0.7% control, -2.9% low dose, -3.7% high dose), increased body fat adjusted adiponectin (Δ%: -0.6% control, 0.6% low dose, 0.9% high dose), and decreased body fat adjusted leptin (Δ%: 0.7% control, -8.2% low dose, -10.2% high dose). In this randomized clinical trial of premenopausal women at risk for breast cancer, we demonstrate a dose-response effect of exercise on adiponectin and leptin and that dose response is dependent on changes in body fat. Improved adipokine levels, achieved by aerobic exercise training-induced decreases in body fat, may decrease breast cancer risk for high-risk premenopausal women. Cancer Epidemiol Biomarkers Prev; 25(8); 1195-200. ©2016 AACR. ©2016 American Association for Cancer Research.

Potential usefulness of apolipoprotein A2 isoforms for screening and risk stratification of pancreatic cancer

PubMed Central

Honda, Kazufumi; Srivastava, Sudhir

2016-01-01

Given the low incidence of pancreatic cancer in the general population, screening of pancreatic cancer in the general population using invasive modalities is not feasible. Combination of invasive screening with noninvasive biomarkers for pancreatic cancer and its precancerous lesions has the potential to reduce mortality due to pancreatic cancer. In this review, we focus on biomarkers found in the blood that can indicate early-stage pancreatic cancer, and we discuss current strategies for screening for pancreatic cancer. We recently identified a unique alteration in apolipoprotein A2 isoforms in pancreatic cancer and its precancerous lesions, and we describe its clinical usefulness as a potential biomarker for the early detection and risk stratification of pancreatic cancer. PMID:27673558

[Clinical Advanced in Early-stage ALK-positive Non-small Cell Lung Cancer Patients].

PubMed

Gao, Qiongqiong; Jiang, Xiangli; Huang, Chun

2017-02-20

Lung cancer is the leading cause of cancer death in China. Non-small cell lung cancer (NSCLC) accounts for 85% of lung cancer cases, with the majority of the cases diagnosed at the advanced stage. Molecular targeted therapy is becoming the focus attention for advanced NSCLC. Echinoderm microtubule-associated protein-like 4 gene and the anaplastic lymphoma kinase gene (EML4-ALK) is among the most common molecular targets of NSCLC; its specific small-molecule tyrosine kinase inhibitors (TKIs) are approved for use in advanced NSCLC cases of ALK-positive. However, the influence of EML4-ALK fusion gene on the outcome of early-stage NSCLC cases and the necessity of application of TKIs for early-stage ALK-positive NSCLC patients are still uncertain. In this paper, we summarized the progression of testing methods for ALK-positive NSCLC patients as well as clinicopathological implication, outcome, and necessity of application of TKIs for early-stage ALK-positive NSCLC patients.

Large early gastric cancers treated by endoscopic submucosal dissection with an insulation-tipped diathermic knife.

PubMed

Chang, Chun-Chao; Tiong, Cheng; Fang, Chia-Lang; Pan, Shiann; Liu, Jean-Dean; Lou, Horng-Yuan; Hsieh, Ching-Ruey; Chen, Sheng-Hsuan

2007-03-01

It is difficult to remove a large early gastric cancer (> or = 3 cm) in one-piece resection using conventional endoscopic mucosal resection. We tried to use an insulation-tipped (IT) diathermic knife to dissect these lesions. IT-endoscopic submucosal dissection (ESD) was performed in four aging patients with gastric malignancy. All lesions could be removed in one-piece resection by IT-ESD, although three of them exhibited remarkable fibrosis and ulceration. Three cases experienced curative treatment with IT-ESD after the pathologic evaluation, but it was not curative in one case because the pathology showed angiolymphatic invasion. This patient refused additional surgery in consideration of existing major systemic diseases. At 3 months to 1 year of follow-up, endoscopy showed no evidence of residual cancer. IT-ESD is effective in the treatment of large early gastric cancer and is an alternative treatment for early gastric cancer patients who are at risk for major operation.

Early detection of sporadic pancreatic cancer: summative review.

PubMed

Chari, Suresh T; Kelly, Kimberly; Hollingsworth, Michael A; Thayer, Sarah P; Ahlquist, David A; Andersen, Dana K; Batra, Surinder K; Brentnall, Teresa A; Canto, Marcia; Cleeter, Deborah F; Firpo, Matthew A; Gambhir, Sanjiv Sam; Go, Vay Liang W; Hines, O Joe; Kenner, Barbara J; Klimstra, David S; Lerch, Markus M; Levy, Michael J; Maitra, Anirban; Mulvihill, Sean J; Petersen, Gloria M; Rhim, Andrew D; Simeone, Diane M; Srivastava, Sudhir; Tanaka, Masao; Vinik, Aaron I; Wong, David

2015-07-01

Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC.

Early Detection of Sporadic Pancreatic Cancer

PubMed Central

Chari, Suresh T.; Kelly, Kimberly; Hollingsworth, Michael A.; Thayer, Sarah P.; Ahlquist, David A.; Andersen, Dana K.; Batra, Surinder K.; Brentnall, Teresa A.; Canto, Marcia; Cleeter, Deborah F.; Firpo, Matthew A.; Gambhir, Sanjiv Sam; Go, Vay Liang W.; Hines, O. Joe; Kenner, Barbara J.; Klimstra, David S.; Lerch, Markus M.; Levy, Michael J.; Maitra, Anirban; Mulvihill, Sean J.; Petersen, Gloria M.; Rhim, Andrew D.; Simeone, Diane M.; Srivastava, Sudhir; Tanaka, Masao; Vinik, Aaron I.; Wong, David

2015-01-01

Abstract Pancreatic cancer (PC) is estimated to become the second leading cause of cancer death in the United States by 2020. Early detection is the key to improving survival in PC. Addressing this urgent need, the Kenner Family Research Fund conducted the inaugural Early Detection of Sporadic Pancreatic Cancer Summit Conference in 2014 in conjunction with the 45th Anniversary Meeting of the American Pancreatic Association and Japan Pancreas Society. This seminal convening of international representatives from science, practice, and clinical research was designed to facilitate challenging interdisciplinary conversations to generate innovative ideas leading to the creation of a defined collaborative strategic pathway for the future of the field. An in-depth summary of current efforts in the field, analysis of gaps in specific areas of expertise, and challenges that exist in early detection is presented within distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. In addition, an overview of efforts in familial PC is presented in an addendum to this article. It is clear from the summit deliberations that only strategically designed collaboration among investigators, institutions, and funders will lead to significant progress in early detection of sporadic PC. PMID:25931254

Oral cancer prevention and early detection knowledge and practices of Illinois dentists--a brief communication.

PubMed

Lehew, Charles W; Kaste, Linda M

2007-01-01

The purpose of the study was to assess Illinois dentists' self-reported knowledge and practices concerning oral cancer prevention, early detection, and management as a baseline prior to conducting interventions designed to increase dentists' capacity to detect and manage oral cancers and counsel their patients about risk reduction. A weighted sample to represent licensed dentists in 19 counties yielded 518 dentists who responded to a 38-item mailed survey in 2004. Over 92 percent of the dentists reported providing oral cancer exams. However, many are not doing them properly or at frequent intervals. Over two-thirds had oral cancer continuing education, but 40 percent had it more than 2 years prior to the survey. Training in risk counseling was rare. Interventions are needed to assure appropriate skill and knowledge levels for oral cancer early detection, management, and risk counseling by Illinois dentists.

Breast cancer early detection via tracking of skin back-scattered secondary speckle patterns

NASA Astrophysics Data System (ADS)

Bennett, Aviya; Sirkis, Talia; Beiderman, Yevgeny; Agdarov, Sergey; Beiderman, Yafim; Zalevsky, Zeev

2018-02-01

Breast cancer has become a major cause of death among women. The lifetime risk of a woman developing this disease has been established as one in eight. The most useful way to reduce breast cancer death is to treat the disease as early as possible. The existing methods of early diagnostics of breast cancer are mainly based on screening mammography or Magnetic Resonance Imaging (MRI) periodically conducted at medical facilities. In this paper the authors proposing a new approach for simple breast cancer detection. It is based on skin stimulation by sound waves, illuminating it by laser beam and tracking the reflected secondary speckle patterns. As first approach, plastic balls of different sizes were placed under the skin of chicken breast and detected by the proposed method.

Hybrid light transport model based bioluminescence tomography reconstruction for early gastric cancer detection

NASA Astrophysics Data System (ADS)

Chen, Xueli; Liang, Jimin; Hu, Hao; Qu, Xiaochao; Yang, Defu; Chen, Duofang; Zhu, Shouping; Tian, Jie

2012-03-01

Gastric cancer is the second cause of cancer-related death in the world, and it remains difficult to cure because it has been in late-stage once that is found. Early gastric cancer detection becomes an effective approach to decrease the gastric cancer mortality. Bioluminescence tomography (BLT) has been applied to detect early liver cancer and prostate cancer metastasis. However, the gastric cancer commonly originates from the gastric mucosa and grows outwards. The bioluminescent light will pass through a non-scattering region constructed by gastric pouch when it transports in tissues. Thus, the current BLT reconstruction algorithms based on the approximation model of radiative transfer equation are not optimal to handle this problem. To address the gastric cancer specific problem, this paper presents a novel reconstruction algorithm that uses a hybrid light transport model to describe the bioluminescent light propagation in tissues. The radiosity theory integrated with the diffusion equation to form the hybrid light transport model is utilized to describe light propagation in the non-scattering region. After the finite element discretization, the hybrid light transport model is converted into a minimization problem which fuses an l1 norm based regularization term to reveal the sparsity of bioluminescent source distribution. The performance of the reconstruction algorithm is first demonstrated with a digital mouse based simulation with the reconstruction error less than 1mm. An in situ gastric cancer-bearing nude mouse based experiment is then conducted. The primary result reveals the ability of the novel BLT reconstruction algorithm in early gastric cancer detection.

Does breast screening offer a survival benefit? A retrospective comparative study of oncological outcomes of screen-detected and symptomatic early stage breast cancer cases.

PubMed

Újhelyi, M; Pukancsik, D; Kelemen, P; Kovács, E; Kenessey, I; Udvarhelyi, N; Bak, M; Kovács, T; Mátrai, Z

2016-12-01

Mammography screening reduces breast cancer mortality by up to 32%. However, some recent studies have questioned the impact of non-palpable breast cancer detection on mortality reduction. The aim of this study was to analyse the clinicopathological and long-term follow-up data of early stage screened and symptomatic breast cancer patients. The institutional prospectively led database was systematically analysed for breast cancer cases diagnosed via the mammography screening program from 2002 to 2009. As a control group, symptomatic early stage breast cancer patients were collected randomly from the same database and matched for age and follow-up period. All medical records were reviewed retrospectively. Data from 298 breast cancer patients were collected from 47,718 mammography screenings. In addition, 331 symptomatic breast cancer patients were randomly selected. The screened group presented a significantly lower median tumour size (P < 0.00001). The incidence of negative regional lymph nodes was significantly higher in the screened group (P < 0.0006). The incidence of chemotherapy was 17% higher in the symptomatic group (P = 4*10 -5 ). At the median follow-up of 65 and 80 months, the screened group did not exhibit better overall (P = 0.717) or disease-free survival (P = 0.081) compared to the symptomatic group. Our results do not suggest that mammography screening does not reduce breast cancer mortality but the mammography screening did not bring any significant improvement in patient overall or disease-free survival for the early stage breast cancer patients compared to the symptomatic group. The drawback of symptomatic early stage tumours compared to non-palpable tumours could be equalized by modern multimodality oncology treatments. Copyright © 2016 Elsevier Ltd, BASO ~ the Association for Cancer Surgery, and the European Society of Surgical Oncology. All rights reserved.

Is breast compression associated with breast cancer detection and other early performance measures in a population-based breast cancer screening program?

PubMed

Moshina, Nataliia; Sebuødegård, Sofie; Hofvind, Solveig

2017-06-01

We aimed to investigate early performance measures in a population-based breast cancer screening program stratified by compression force and pressure at the time of mammographic screening examination. Early performance measures included recall rate, rates of screen-detected and interval breast cancers, positive predictive value of recall (PPV), sensitivity, specificity, and histopathologic characteristics of screen-detected and interval breast cancers. Information on 261,641 mammographic examinations from 93,444 subsequently screened women was used for analyses. The study period was 2007-2015. Compression force and pressure were categorized using tertiles as low, medium, or high. χ 2 test, t tests, and test for trend were used to examine differences between early performance measures across categories of compression force and pressure. We applied generalized estimating equations to identify the odds ratios (OR) of screen-detected or interval breast cancer associated with compression force and pressure, adjusting for fibroglandular and/or breast volume and age. The recall rate decreased, while PPV and specificity increased with increasing compression force (p for trend <0.05 for all). The recall rate increased, while rate of screen-detected cancer, PPV, sensitivity, and specificity decreased with increasing compression pressure (p for trend <0.05 for all). High compression pressure was associated with higher odds of interval breast cancer compared with low compression pressure (1.89; 95% CI 1.43-2.48). High compression force and low compression pressure were associated with more favorable early performance measures in the screening program.

Early retirement and non-employment after breast cancer.

PubMed

Lindbohm, M-L; Kuosma, E; Taskila, T; Hietanen, P; Carlsen, K; Gudbergsson, S; Gunnarsdottir, H

2014-06-01

This study examined whether workplace support, sociodemographic factors and co-morbidity are associated with early retirement or non-employment due to other reasons among breast cancer survivors. We also compared quality of life and chronic symptoms (pain, fatigue, anxiety and depression) among employed, retired and other non-employed breast cancer survivors. We identified breast cancer survivors diagnosed between 1997 and 2002 from either a hospital or a cancer registry in Denmark, Finland, Iceland and Norway (NOCWO study). All patients had been treated with curative intent. Information on employment, co-morbidity and support was collected via a questionnaire. The sample included 1111 working-aged cancer-free survivors who had been employed at the time of diagnosis. We used multinomial logistic regression models to analyse the association of various determinants with early retirement and other non-employment (due to unemployment, subsidized employment or being a homemaker). Low education, low physical quality of life, co-morbidity and pain were associated with both early retirement and other non-employment after cancer. Other non-employed survivors also rated their mental quality of life as lower and experienced anxiety and fatigue more often than all the other survivors. Moreover, they reported a lower level of supervisor support after their diagnosis than the employed survivors. Retired survivors more often reported weak support from colleagues. Differences in ill health and functional status between various groups of non-employed cancer survivors need to be considered when planning policy measures for improving the labour market participation of this population and preventing their early withdrawal from working life. Copyright © 2013 John Wiley & Sons, Ltd.

Cancer early detection program based on awareness and clinical breast examination: Interim results from an urban community in Mumbai, India.

PubMed

Gadgil, Anita; Sauvaget, Catherine; Roy, Nobhojit; Muwonge, Richard; Kantharia, Surita; Chakrabarty, Anuradha; Bantwal, Kanchan; Haldar, Indrani; Sankaranarayanan, Rengaswamy

2017-02-01

Indian women with breast cancer are usually diagnosed in advanced stages leading to poor survival. Improving breast awareness and increasing access to early diagnosis and adequate treatment has been advocated for breast cancer control. We implemented a program to increase awareness on breast cancer and access to its early detection in an occupational health care scheme in Mumbai, India. Breast awareness brochures were mailed annually between June 2013 and June 2016 to a cohort of 22,500 eligible women aged 30-69 years old receiving universal health care from an occupational health care scheme comprising of primary health centres and a referral secondary care hospital in Mumbai. Women with suspected breast cancers were provided with diagnostic investigations and treatment. Socio-demographic information and tumour characteristics were compared between the breast awareness pre-intervention period (Jan 2005-May 2013) and the breast awareness intervention period after four rounds of mailers (June 2013-June 2016). The proportion of women with early tumours and axillary lymph node negative cancers increased from 74% to 81% and 46% to 53% respectively, between the two periods. While the proportion of patients receiving breast conserving surgery increased from 39% to 51%, the proportion receiving chemotherapy decreased from 84% to 56%. Interim results following efforts to improve breast awareness and access to care in a cohort of women in an occupational health care scheme indicate early detection and more conservative treatment of breast cancers. Creating awareness and improving access to care may result in cancer down-staging. Copyright © 2016 Elsevier Ltd. All rights reserved.

Inflammatory metastatic breast cancer with gallbladder metastasis: an incidental finding.

PubMed

Ebrahim, Hassan; Graham, David; Rice, David; Ribadeneyra, Michael; Thorner, Kim; Shipley, William; Wehmueller, Michael

2015-07-01

Breast cancer is the most frequently diagnosed cancer in women, with an estimated 231,840 new cases representing 14.0% of all new cancer cases in the United States in 2015. Early screening and modern techniques of imaging and diagnosis have led to a significant improvement in detecting early-stage breast cancers and to a decrease in the incidence of metastatic breast cancer (MBC). About 20%-30% of patients who are initially diagnosed with an early-stage, nonmetastatic breast cancer will subsequently develop a distant metastatic disease. Between 6%-10% of the new breast cancer cases present initially as stage IV, referred to as de novo MBC. The most common sites of breast cancer metastases are lymph nodes, chest wall, skeleton, lung, skin, and the central nervous system (CNS). Lobular carcinoma, in particular, may metastasize to the gastrointestinal tract, peritoneum, and retroperitoneum. Gallbladder metastasis from breast cancer is very rare, and only 15-20 cases have been reported in the literature. Most of those cases have been associated particularly with a lobular histology. We report an additional rare case of MBC to the gallbladder, but with a ductal histology. ©2015 Frontline Medical Communications.

Early Phase Endotoxin Tolerance: A Study of the Cellular Mechanisms which Underlie a State of Acquired Refractoriness to Endotoxin-induced Toxic Manifestations

DTIC Science & Technology

1985-12-13

Her leadership , help, and understanding at crltlcal times will always be remembered. Thank you for help ing me attain this great goal and captu~e a...by Braude §1 ~!- (1955) and Cremer and Watson (1957 ) to be the primary site of endotoxin localization following i.v. injection] were st imulated by...A-specif ic tr iggeri ng r eceptor on murine B lymp hocytes. Eur. J. Immunol. 8:63 . Cremer , N. and D.W. Watson. 1957. Inf luence of s tress on

Phylogenetic ctDNA analysis depicts early stage lung cancer evolution

PubMed Central

Abbosh, Christopher; Birkbak, Nicolai J.; Wilson, Gareth A.; Jamal-Hanjani, Mariam; Constantin, Tudor; Salari, Raheleh; Le Quesne, John; Moore, David A; Veeriah, Selvaraju; Rosenthal, Rachel; Marafioti, Teresa; Kirkizlar, Eser; Watkins, Thomas B K; McGranahan, Nicholas; Ward, Sophia; Martinson, Luke; Riley, Joan; Fraioli, Francesco; Al Bakir, Maise; Grönroos, Eva; Zambrana, Francisco; Endozo, Raymondo; Bi, Wenya Linda; Fennessy, Fiona M.; Sponer, Nicole; Johnson, Diana; Laycock, Joanne; Shafi, Seema; Czyzewska-Khan, Justyna; Rowan, Andrew; Chambers, Tim; Matthews, Nik; Turajlic, Samra; Hiley, Crispin; Lee, Siow Ming; Forster, Martin D.; Ahmad, Tanya; Falzon, Mary; Borg, Elaine; Lawrence, David; Hayward, Martin; Kolvekar, Shyam; Panagiotopoulos, Nikolaos; Janes, Sam M; Thakrar, Ricky; Ahmed, Asia; Blackhall, Fiona; Summers, Yvonne; Hafez, Dina; Naik, Ashwini; Ganguly, Apratim; Kareht, Stephanie; Shah, Rajesh; Joseph, Leena; Quinn, Anne Marie; Crosbie, Phil; Naidu, Babu; Middleton, Gary; Langman, Gerald; Trotter, Simon; Nicolson, Marianne; Remmen, Hardy; Kerr, Keith; Chetty, Mahendran; Gomersall, Lesley; Fennell, Dean; Nakas, Apostolos; Rathinam, Sridhar; Anand, Girija; Khan, Sajid; Russell, Peter; Ezhil, Veni; Ismail, Babikir; Irvin-sellers, Melanie; Prakash, Vineet; Lester, Jason; Kornaszewska, Malgorzata; Attanoos, Richard; Adams, Haydn; Davies, Helen; Oukrif, Dahmane; Akarca, Ayse U; Hartley, John A; Lowe, Helen L; Lock, Sara; Iles, Natasha; Bell, Harriet; Ngai, Yenting; Elgar, Greg; Szallasi, Zoltan; Schwarz, Roland F; Herrero, Javier; Stewart, Aengus; Quezada, Sergio A; Peggs, Karl S.; Van Loo, Peter; Dive, Caroline; Lin, Jimmy; Rabinowitz, Matthew; Aerts, Hugo JWL; Hackshaw, Allan; Shaw, Jacqui A; Zimmermann, Bernhard G.; Swanton, Charles

2017-01-01

Summary The early detection of relapse following primary surgery for non-small cell lung cancer and the characterization of emerging subclones seeding metastatic sites might offer new therapeutic approaches to limit tumor recurrence. The potential to non-invasively track tumor evolutionary dynamics in ctDNA of early-stage lung cancer is not established. Here we conduct a tumour-specific phylogenetic approach to ctDNA profiling in the first 100 TRACERx (TRAcking non-small cell lung Cancer Evolution through therapy (Rx)) study participants, including one patient co-recruited to the PEACE (Posthumous Evaluation of Advanced Cancer Environment) post-mortem study. We identify independent predictors of ctDNA release and perform tumor volume limit of detection analyses. Through blinded profiling of post-operative plasma, we observe evidence of adjuvant chemotherapy resistance and identify patients destined to experience recurrence of their lung cancer. Finally, we show that phylogenetic ctDNA profiling tracks the subclonal nature of lung cancer relapse and metastases, providing a new approach for ctDNA driven therapeutic studies PMID:28445469

Smartphone Mobile Applications to Enhance Diagnosis of Skin Cancer: A Guide for the Rural Practitioner.

PubMed

Cook, Shane E; Palmer, Louis C; Shuler, Franklin D

2015-01-01

Primary care physicians occupy a vital position to impact many devastating conditions, especially those dependent upon early diagnosis, such as skin cancer. Skin cancer is the most common cancer in the United States and despite improvements in skin cancer therapy, patients with a delay in diagnosis and advanced disease continue to have a grave prognosis. Due to a variety of barriers, advanced stages of skin cancer are more prominent in rural populations. In order to improve early diagnosis four things are paramount: increased patient participation in prevention methods, establishment of screening guidelines, increased diagnostic accuracy of malignant lesions, and easier access to dermatologists. Recent expansion in smartphone mobile application technology offers simple ways for rural practitioners to address these problems. More than 100,000 health related applications are currently available, with over 200 covering dermatology. This review will evaluate the newest and most useful of those applications offered to enhance the prevention and early diagnosis of skin cancer, particularly in the rural population.

Early detection of sporadic pancreatic cancer: strategic map for innovation--a white paper.

PubMed

Kenner, Barbara J; Chari, Suresh T; Cleeter, Deborah F; Go, Vay Liang W

2015-07-01

Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer.

Early Detection of Sporadic Pancreatic Cancer

PubMed Central

Kenner, Barbara J.; Chari, Suresh T.; Cleeter, Deborah F.; Go, Vay Liang W.

2015-01-01

Abstract Innovation leading to significant advances in research and subsequent translation to clinical practice is urgently necessary in early detection of sporadic pancreatic cancer. Addressing this need, the Early Detection of Sporadic Pancreatic Cancer Summit Conference was conducted by Kenner Family Research Fund in conjunction with the 2014 American Pancreatic Association and Japan Pancreas Society Meeting. International interdisciplinary scientific representatives engaged in strategic facilitated conversations based on distinct areas of inquiry: Case for Early Detection: Definitions, Detection, Survival, and Challenges; Biomarkers for Early Detection; Imaging; and Collaborative Studies. Ideas generated from the summit have led to the development of a Strategic Map for Innovation built upon 3 components: formation of an international collaborative effort, design of an actionable strategic plan, and implementation of operational standards, research priorities, and first-phase initiatives. Through invested and committed efforts of leading researchers and institutions, philanthropic partners, government agencies, and supportive business entities, this endeavor will change the future of the field and consequently the survival rate of those diagnosed with pancreatic cancer. PMID:25938853

Constrictive Pericarditis 5 Months after Radiation Therapy in a 62-Year-Old Woman with Esophageal Cancer.

PubMed

Yeneneh, Beeletsega T; Allen, Sorcha; Panse, Prasad; Mookadam, Farouk; Rule, William

2017-12-01

Most pericardial changes appear within a few weeks in patients who have undergone radiation therapy for thoracic neoplasms. Chronic pericardial constriction typically occurs decades later, consequent to fibrosis. Early constrictive pericarditis after chest irradiation is quite rare. We report the case of a 62-year-old woman who underwent radiation therapy for esophageal cancer and presented with constrictive pericarditis 5 months later. We searched the English-language medical literature from January 1986 through December 2015 for reports of early constrictive pericarditis after irradiation for thoracic malignancies. We defined "early" as a diagnosis within one year after radiation therapy. Five cases fit our criteria, and we summarize the findings here. To our knowledge, ours is the first definitive report of a patient with esophageal cancer to present with early radiation-induced constrictive pericarditis. We conclude that constrictive pericarditis can occur early after radiation for thoracic malignancies, albeit rarely. When planning care for cancer patients, awareness of this sequela is helpful.

Baby Boomers and Birth Certificates: Early-Life Socioeconomic Status and Cancer Risk in Adulthood.

PubMed

Stroup, Antoinette M; Herget, Kimberly A; Hanson, Heidi A; Reed, Diana Lane; Butler, Jared T; Henry, Kevin A; Harrell, C Janna; Sweeney, Carol; Smith, Ken R

2017-01-01

Early-life socioeconomic status (SES) may play a role in cancer risk in adulthood. However, measuring SES retrospectively presents challenges. Parental occupation on the birth certificate is a novel method of ascertaining early-life SES that has not been applied in cancer epidemiology. For a Baby-Boom cohort born from 1945-1959 in two Utah counties, individual-level Nam-Powers SES (Np-SES) was derived from parental industry/occupation reported on birth certificates. Neighborhood SES was estimated from average household income of census tract at birth. Cancer incidence was determined by linkage to Utah Cancer Registry records through the Utah Population Database. Hazard ratios (HR) for cancer risk by SES quartile were estimated using Cox proportional hazards regression. Females with low Np-SES at birth had lower risk of breast cancer compared with those in the highest Np-SES group [HR Q1/Q4 = 0.83; 95% confidence interval (CI), 0.72-0.97; HR Q2/Q4 = 0.81; 95% CI, 0.69-0.96]. Np-SES was inversely associated with melanoma (HR Q1/Q4 = 0.81; 95% CI, 0.67-0.98) and prostate cancer (HR Q1/Q4 = 0.70; 95% CI, 0.56-0.88). Women born into lower SES neighborhoods had significantly increased risk for invasive cervical cancer (HR Q1/Q4 = 1.44; 95% CI, 1.12-1.85; HR Q2/Q4 = 1.33; 95% CI, 1.04-1.72). Neighborhood SES had similar effects for melanoma and prostate cancers, but was not associated with female breast cancer. We found no association with SES for pancreas, lung, and colon and rectal cancers. Individual SES derived from parental occupation at birth was associated with altered risk for several cancer sites. This novel methodology can contribute to improved understanding of the role of early-life SES on cancer risk. Cancer Epidemiol Biomarkers Prev; 26(1); 75-84. ©2016 AACR. ©2016 American Association for Cancer Research.

Surgery versus radical endotherapies for early cancer and high-grade dysplasia in Barrett's oesophagus.

PubMed

Bennett, Cathy; Green, Susi; Decaestecker, John; Almond, Max; Barr, Hugh; Bhandari, Pradeep; Ragunath, Krish; Singh, Rajvinder; Jankowski, Janusz

2012-11-14

Barrett's oesophagus is one of the most common pre-malignant lesions in the world. Currently the mainstay of therapy is surgical management of advanced cancer but this has improved the five-year survival very little since the 1980s. As a consequence, improved survival relies on early detection through endoscopic surveillance programmes. Success of this strategy relies on the fact that late-stage pre-malignant lesions or very early cancers can be cured by intervention. Currently there is considerable controversy over which method is best: that is conventional open surgery or endotherapy (techniques involving endoscopy). We used data from randomised controlled trials (RCTs) to examine the effectiveness of endotherapies compared with surgery in people with Barrett's oesophagus, those with early neoplasias (defined as high-grade dysplasia (HGD) and those with early cancer (defined as carcinoma in-situ, superficially invasive, early cancer or superficial cancer T-1m (T1-a) and T-1sm (T1-b)). We used the Cochrane highly sensitive search strategy to identify RCTs in MEDLINE, EMBASE, the Cochrane Central Register of Controlled Trials (CENTRAL), ISI Web of Science, EBMR, Controlled Trials mRCT and ISRCTN, and LILACS, in July and August 2008. The searches were updated in 2009 and again in April 2012. Types of studies: RCTs comparing endotherapies with surgery in the treatment of or early cancer. All cellular types of cancer were included (i.e. adenocarcinomas, squamous cell carcinomas and more unusual types) but will be discussed separately. patients of any age and either gender with a histologically confirmed diagnosis of early neoplasia (HGD and early cancer) in Barrett's or squamous lined oesophagus.Types of interventions; endotherapies (the intervention) compared with surgery (the control), all with curative intent. Reports of studies that meet the inclusion criteria for this review would have been analysed using the methods detailed in Appendix 9. We did not identify any studies that met the inclusion criteria. In total we excluded 13 studies that were not RCTs but that compared surgery and endotherapies. This Cochrane review has indicated that there are no RCTs to compare management options in this vital area, therefore trials should be undertaken as a matter of urgency. The problems with such randomised methods are standardising surgery and endotherapies in all sites, standardising histopathology in all centres, assessing which patients are fit or unfit for surgery and making sure there are relevant outcomes for the study (i.e. long-term survival (over five or more years)) and no progression of HGD.

Death Within 1 Month of Diagnosis in Childhood Cancer: An Analysis of Risk Factors and Scope of the Problem.

PubMed

Green, Adam L; Furutani, Elissa; Ribeiro, Karina Braga; Rodriguez Galindo, Carlos

2017-04-20

Purpose Despite advances in childhood cancer care, some patients die soon after diagnosis. This population is not well described and may be under-reported. Better understanding of risk factors for early death and scope of the problem could lead to prevention of these occurrences and thus better survival rates in childhood cancer. Methods We retrieved data from SEER 13 registries on 36,337 patients age 0 to 19 years diagnosed with cancer between 1992 and 2011. Early death was defined as death within 1 month of diagnosis. Socioeconomic status data for each individual's county of residence were derived from Census 2000. Crude and adjusted odds ratios and corresponding 95% CIs were estimated for the association between early death and demographic, clinical, and socioeconomic factors. Results Percentage of early death in the period was 1.5% (n = 555). Children with acute myeloid leukemia, infant acute lymphoblastic leukemia, hepatoblastoma, and malignant brain tumors had the highest risk of early death. On multivariable analysis, an age younger than 1 year was a strong predictor of early death in all disease groups examined. Black race and Hispanic ethnicity were both risk factors for early death in multiple disease groups. Residence in counties with lower than median average income was associated with a higher risk of early death in hematologic malignancies. Percentages of early death decreased significantly over time, especially in hematologic malignancies. Conclusion Risk factors for early death in childhood cancer include an age younger than 1 year, specific diagnoses, minority race and ethnicity, and disadvantaged socioeconomic status. The population-based disease-specific percentages of early death were uniformly higher than those reported in cooperative clinical trials, suggesting that early death is under-reported in the medical literature. Initiatives to identify those at risk and develop preventive interventions should be prioritized.

Jung-Min Lee, M.D. | Center for Cancer Research

Cancer.gov

Conducts early clinical trials targeting BRCA mutation-associated breast or ovarian cancer, epithelial ovarian cancer, and triple negative breast cancer at the National Cancer Institute, NIH Clinical Center.

Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study.

PubMed

Farvid, Maryam S; Chen, Wendy Y; Michels, Karin B; Cho, Eunyoung; Willett, Walter C; Eliassen, A Heather

2016-05-11

To evaluate the association between fruit and vegetable intake during adolescence and early adulthood and risk of breast cancer. Prospective cohort study. Health professionals in the United States. 90 476 premenopausal women aged 27-44 from the Nurses' Health Study II who completed a questionnaire on diet in 1991 as well as 44 223 of those women who completed a questionnaire about their diet during adolescence in 1998. Incident cases of invasive breast cancer, identified through self report and confirmed by pathology report. There were 3235 cases of invasive breast cancer during follow-up to 2013. Of these, 1347 cases were among women who completed a questionnaire about their diet during adolescence (ages 13-18). Total fruit consumption during adolescence was associated with a lower risk of breast cancer. The hazard ratio was 0.75 (95% confidence interval 0.62 to 0.90; P=0.01 for trend) for the highest (median intake 2.9 servings/day) versus the lowest (median intake 0.5 serving/day) fifth of intake. The association for fruit intake during adolescence was independent of adult fruit intake. There was no association between risk and total fruit intake in early adulthood and total vegetable intake in either adolescence or early adulthood. Higher early adulthood intake of fruits and vegetables rich in α carotene was associated with lower risk of premenopausal breast cancer. The hazard ratio was 0.82 (0.70 to 0.96) for the highest fifth (median intake 0.5 serving/day) versus the lowest fifth (median intake 0.03 serving/day) intake. The association with adolescent fruit intake was stronger for both estrogen and progesterone receptor negative cancers than estrogen and progesterone receptor positive cancers (P=0.02 for heterogeneity). For individual fruits and vegetables, greater consumption of apple, banana, and grapes during adolescence and oranges and kale during early adulthood was significantly associated with a reduced risk of breast cancer. Fruit juice intake in adolescence or early adulthood was not associated with risk. There is an association between higher fruit intake and lower risk of breast cancer. Food choices during adolescence might be particularly important. Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://group.bmj.com/group/rights-licensing/permissions.

Presence of early stage cancer does not impair the early protein metabolic response to major surgery.

PubMed

Engelen, Mariëlle P K J; Klimberg, V Suzanne; Allasia, Arianna; Deutz, Nicolaas Ep

2017-06-01

Combined bilateral mastectomy and reconstruction is a common major surgical procedure in women with breast cancer and in those with a family history of breast cancer. As this large surgical procedure induces muscle protein loss, a preserved anabolic response to nutrition is warranted for optimal recovery. It is unclear whether the presence of early stage cancer negatively affects the protein metabolic response to major surgery as this would mandate perioperative nutritional support. In nine women with early stage (Stage II) breast malignancy and nine healthy women with a genetic predisposition to breast cancer undergoing the same large surgical procedure, we examined whether surgery influences the catabolic response to overnight fasting and the anabolic response to nutrition differently. Prior to and within 24 h after combined bilateral mastectomy and reconstruction surgery, whole body protein synthesis and breakdown rates were assessed after overnight fasting and after meal intake by stable isotope methodology to enable the calculation of net protein catabolism in the post-absorptive state and net protein anabolic response to a meal. Major surgery resulted in an up-regulation of post-absorptive protein synthesis and breakdown rates (P < 0.001) and lower net protein catabolism (P < 0.05) and was associated with insulin resistance and increased systemic inflammation (P < 0.01). Net anabolic response to the meal was reduced after surgery (P < 0.05) but higher in cancer (P < 0.05) indicative of a more preserved meal efficiency. The significant relationship between net protein anabolism and the amount of amino acids available in the circulation (R 2  = 0.85, P < 0.001) was independent of the presence of non-cachectic early stage breast cancer or surgery. The presence of early stage breast cancer does not enhance the normal catabolic response to major surgery or further attenuates the anabolic response to meal intake within 24 h after major surgery in patients with non-cachectic breast cancer. This indicates that the acute anabolic potential to conventional feeding is maintained in non-cachectic early stage breast cancer after major surgery. © 2017 The Authors. Journal of Cachexia, Sarcopenia and Muscle published by John Wiley & Sons Ltd on behalf of the Society on Sarcopenia, Cachexia and Wasting Disorders.

Fruit and vegetable consumption in adolescence and early adulthood and risk of breast cancer: population based cohort study

PubMed Central

Chen, Wendy Y; Michels, Karin B; Cho, Eunyoung; Willett, Walter C; Eliassen, A Heather

2016-01-01

Objective To evaluate the association between fruit and vegetable intake during adolescence and early adulthood and risk of breast cancer. Design Prospective cohort study. Setting Health professionals in the United States. Participants 90 476 premenopausal women aged 27-44 from the Nurses’ Health Study II who completed a questionnaire on diet in 1991 as well as 44 223 of those women who completed a questionnaire about their diet during adolescence in 1998. Main outcome measure Incident cases of invasive breast cancer, identified through self report and confirmed by pathology report. Results There were 3235 cases of invasive breast cancer during follow-up to 2013. Of these, 1347 cases were among women who completed a questionnaire about their diet during adolescence (ages 13-18). Total fruit consumption during adolescence was associated with a lower risk of breast cancer. The hazard ratio was 0.75 (95% confidence interval 0.62 to 0.90; P=0.01 for trend) for the highest (median intake 2.9 servings/day) versus the lowest (median intake 0.5 serving/day) fifth of intake. The association for fruit intake during adolescence was independent of adult fruit intake. There was no association between risk and total fruit intake in early adulthood and total vegetable intake in either adolescence or early adulthood. Higher early adulthood intake of fruits and vegetables rich in α carotene was associated with lower risk of premenopausal breast cancer. The hazard ratio was 0.82 (0.70 to 0.96) for the highest fifth (median intake 0.5 serving/day) versus the lowest fifth (median intake 0.03 serving/day) intake. The association with adolescent fruit intake was stronger for both estrogen and progesterone receptor negative cancers than estrogen and progesterone receptor positive cancers (P=0.02 for heterogeneity). For individual fruits and vegetables, greater consumption of apple, banana, and grapes during adolescence and oranges and kale during early adulthood was significantly associated with a reduced risk of breast cancer. Fruit juice intake in adolescence or early adulthood was not associated with risk. Conclusion There is an association between higher fruit intake and lower risk of breast cancer. Food choices during adolescence might be particularly important. PMID:27170029

Endoscopic ultrasonography in the management of esophageal cancer

NASA Astrophysics Data System (ADS)

Trowers, Eugene A.

2000-05-01

Precise tumor-staging is critical in the management of early esophageal caner. Endoscopic ultrasound (EUS) allows the endoscopist a view beyond the esophageal wall which opens the door to a variety of new gastroenterologic techniques. Endoscopic mucosal resection, laser photoablation and photodynamic therapy may be successfully employed in early esophageal cancer management. Combination radiation therapy and chemotherapy have shown better responses in advanced cancer. Expandable metallic stents may also provide palliation with inoperable esophageal cancer. The efficacy of EUS in the management of esophageal cancer is critically reviewed.

Association of Matrix Metalloproteinase-1 Polymorphisms with Risk of COPD and Lung Cancer and Survival in Lung Cancer

PubMed Central

ENEWOLD, LINDSEY; MECHANIC, LEAH E.; BOWMAN, ELISE D.; PLATZ, ELIZABETH A.; ALBERG, ANTHONY J.

2013-01-01

Background The primary risk factor for chronic obstructive pulmonary disease (COPD) and non-small cell lung cancer (NSCLC) is cigarette smoking but shared susceptibility factors, such as variations in the matrix metalloproteinase-1 (MMP1) gene, may also underlie both diseases. Materials and Methods Cases with prevalent COPD (n=167), incident NSCLC (n=242), or prevalent COPD plus incident NSCLC (n=128) were compared to disease-free controls (n=338) to assess six MMP1 polymorphisms. The association between these polymorphisms and survival in NSCLC was also evaluated. Results Rs11292517 among African-Americans [odds ratio (OR)=5.48, 95% confidence interval (CI)=1.17–25.72] and rs2071230 among Caucasians (OR=2.51, 95% CI=1.09–5.77) appeared to be associated with NSCLC risk in the presence of COPD. Rs470558 appeared to be associated with survival in NSCLC among African-Americans (hazard ratio=3.94; 95%CI=1.14–13.63). No associations remained after adjusting for multiple comparisons. Conclusion Polymorphisms in MMP1 were not consistently associated with prevalent COPD or incident NSCLC nor with survival in NSCLC. PMID:22993337

Computer-aided discovery of biological activity spectra for anti-aging and anti-cancer olive oil oleuropeins.

PubMed

Corominas-Faja, Bruna; Santangelo, Elvira; Cuyàs, Elisabet; Micol, Vicente; Joven, Jorge; Ariza, Xavier; Segura-Carretero, Antonio; García, Jordi; Menendez, Javier A

2014-09-01

Aging is associated with common conditions, including cancer, diabetes, cardiovascular disease, and Alzheimer's disease. The type of multi-targeted pharmacological approach necessary to address a complex multifaceted disease such as aging might take advantage of pleiotropic natural polyphenols affecting a wide variety of biological processes. We have recently postulated that the secoiridoids oleuropein aglycone (OA) and decarboxymethyl oleuropein aglycone (DOA), two complex polyphenols present in health-promoting extra virgin olive oil (EVOO), might constitute a new family of plant-produced gerosuppressant agents. This paper describes an analysis of the biological activity spectra (BAS) of OA and DOA using PASS (Prediction of Activity Spectra for Substances) software. PASS can predict thousands of biological activities, as the BAS of a compound is an intrinsic property that is largely dependent on the compound's structure and reflects pharmacological effects, physiological and biochemical mechanisms of action, and specific toxicities. Using Pharmaexpert, a tool that analyzes the PASS-predicted BAS of substances based on thousands of "mechanism-effect" and "effect-mechanism" relationships, we illuminate hypothesis-generating pharmacological effects, mechanisms of action, and targets that might underlie the anti-aging/anti-cancer activities of the gerosuppressant EVOO oleuropeins.

DEspR roles in tumor vasculo-angiogenesis, invasiveness, CSC-survival and anoikis resistance: a 'common receptor coordinator' paradigm.

PubMed

Herrera, Victoria L; Decano, Julius L; Tan, Glaiza A; Moran, Ann M; Pasion, Khristine A; Matsubara, Yuichi; Ruiz-Opazo, Nelson

2014-01-01

A priori, a common receptor induced in tumor microvessels, cancer cells and cancer stem-like cells (CSCs) that is involved in tumor angiogenesis, invasiveness, and CSC anoikis resistance and survival, could underlie contemporaneous coordination of these events rather than assume stochasticity. Here we show that functional analysis of the dual endothelin1/VEGFsignal peptide receptor, DEspR, (formerly named Dear, Chr.4q31.2) supports the putative common receptor paradigm in pancreatic ductal adenocarcinoma (PDAC) and glioblastoma (GBM) selected for their invasiveness, CD133+CSCs, and polar angiogenic features. Unlike normal tissue, DEspR is detected in PDAC and GBM microvessels, tumor cells, and CSCs isolated from PDAC-Panc1 and GBM-U87 cells. DEspR-inhibition decreased angiogenesis, invasiveness, CSC-survival and anoikis resistance in vitro, and decreased Panc1-CSC and U87-CSC xenograft tumor growth, vasculo-angiogenesis and invasiveness in nude(nu/nu) rats, suggesting that DEspR activation would coordinate these tumor progression events. As an accessible, cell-surface 'common receptor coordinator', DEspR-inhibition defines a novel targeted-therapy paradigm for pancreatic cancer and glioblastoma.

DEspR Roles in Tumor Vasculo-Angiogenesis, Invasiveness, CSC-Survival and Anoikis Resistance: A ‘Common Receptor Coordinator’ Paradigm

PubMed Central

Herrera, Victoria L.; Decano, Julius L.; Tan, Glaiza A.; Moran, Ann M.; Pasion, Khristine A.; Matsubara, Yuichi; Ruiz-Opazo, Nelson

2014-01-01

A priori, a common receptor induced in tumor microvessels, cancer cells and cancer stem-like cells (CSCs) that is involved in tumor angiogenesis, invasiveness, and CSC anoikis resistance and survival, could underlie contemporaneous coordination of these events rather than assume stochasticity. Here we show that functional analysis of the dual endothelin1/VEGFsignal peptide receptor, DEspR, (formerly named Dear, Chr.4q31.2) supports the putative common receptor paradigm in pancreatic ductal adenocarcinoma (PDAC) and glioblastoma (GBM) selected for their invasiveness, CD133+CSCs, and polar angiogenic features. Unlike normal tissue, DEspR is detected in PDAC and GBM microvessels, tumor cells, and CSCs isolated from PDAC-Panc1 and GBM-U87 cells. DEspR-inhibition decreased angiogenesis, invasiveness, CSC-survival and anoikis resistance in vitro, and decreased Panc1-CSC and U87-CSC xenograft tumor growth, vasculo-angiogenesis and invasiveness in nudenu/nu rats, suggesting that DEspR activation would coordinate these tumor progression events. As an accessible, cell-surface ‘common receptor coordinator’, DEspR-inhibition defines a novel targeted-therapy paradigm for pancreatic cancer and glioblastoma. PMID:24465725

The Immune Landscape of Non-Small Cell Lung Cancer: Utility of Cytologic and Histologic Samples Obtained Through Minimally Invasive Pulmonary Procedures.

PubMed

Beattie, Jason; Yarmus, Lonny; Wahidi, Momen M; Rivera, M Patricia; Gilbert, Christopher; Maldonado, Fabien; Czarnecka, Kasia; Argento, Angela; Chen, Alexander; Herth, Felix; Sterman, Daniel H

2018-05-14

The success of immune checkpoint inhibitors and the discovery of useful biomarkers to predict response to these agents is shifting much of the focus of personalized care for non-small cell lung cancer towards harnessing the immune response. With further advancement, more effective immunotherapy options will emerge along with more useful biomarkers. Paradoxically, minimally invasive small biopsy and cytology specimens have become the primary method for diagnosis of patients with advanced disease, as well for initial diagnosis and staging in earlier stage disease. For the benefit of these patients, we will continue to learn how to do more with less. In this perspective, we review aspects of immunobiology that underlie the current state of the art of existing and emerging immunologic biomarkers that hold potential to enhance the care of patients with non-small cell lung cancer. We address practical considerations for acquiring patient samples that accurately reflect disease immune status. We also propose a paradigm shift wherein the most important sample types that need to be proven in pioneering basic science and translation work and subsequent clinical trials are the specimens most often obtained clinically.

Nanostructured materials with plasmonic nanobiosensors for early cancer detection: A past and future prospect.

PubMed

Sugumaran, Sathish; Jamlos, Mohd Faizal; Ahmad, Mohd Noor; Bellan, Chandar Shekar; Schreurs, Dominique

2018-02-15

Early cancer detection and treatment is an emerging and fascinating field of plasmonic nanobiosensor research. It paves to enrich a life without affecting living cells leading to a possible survival of the patient. This review describes a past and future prospect of an integrated research field on nanostructured metamaterials, microwave transmission, surface plasmonic resonance, nanoantennas, and their manifested versatile properties with nano-biosensors towards early cancer detection to preserve human health. Interestingly, (i) microwave transmission shows more advantages than other electromagnetic radiation in reacting with biological tissues, (ii) nanostructured metamaterial (Au) with special properties like size and shape can stimulate plasmonic effects, (iii) plasmonic based nanobiosensors are to explore the efficacy for early cancer tumour detection or single molecular detection and (iv) nanoantenna wireless communication by using microwave inverse scattering nanomesh (MISN) technique instead of conventional techniques can be adopted to characterize the microwave scattered signals from the biomarkers. It reveals that the nanostructured material with plasmonic nanobiosensor paves a fascinating platform towards early detection of cancer tumour and is anticipated to be exploited as a magnificent field in the future. Copyright © 2017 Elsevier B.V. All rights reserved.

[Primary safety analysis of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients].

PubMed

Zhou, Ning-Ning; Teng, Xiao-Yu; Liu, Dong-Geng; Xu, Ran; Guan, Zhong-Zhen

2008-12-01

It has been proved that trastuzumab has clinical activity in early and advanced breast cancer with Her2-overexpression. This study was to analyze the safety of trastuzumab after adjuvant chemotherapy in 30 Chinese Her2-positive early breast cancer patients. Trastuzumab was administrated after adjuvant chemotherapy every 21 days. The initial dose was 8 mg/kg, and the subsequent dose was 6 mg/kg, for four to 35 cycles (medium 18 cycles). The side effects of these patients, especially cardiotoxicity, were analyzed. Thirty patients with Her2-positive early breast cancer were entered into the study. The average treatment period was one year (range nine weeks to two years). Two patients had shivering and fever during the first infusion with trastuzumab. Left ventricular ejection fraction (LVEF) level dropped in 18 cases after treatment with trastuzumab, half of which decreased more then 10%û however, no cardiac failure was observed. The post-surgical treatment of trastuzumab in Chinese patients with Her2-positive early breast cancer shows a satisfactory safety profile. However, the potential cardiotoxicity of trastuzumab should be carefully monitored during therapy.

Knowledge, attitude and practices of women in maldives related to the risk factors, prevention and early detection of cervical cancer.

PubMed

Basu, Partha; Hassan, Salma; Fileeshia, Fathmath; Mohamed, Sizna; Nahoodha, Aminath; Shiuna, Aminath; Sulaiman, Asma Ibrahim; Najeeb, Nazeera; Saleem, Fathmath Jeehan

2014-01-01

A population-based cervical cancer screening program using visual inspection with acetic acid was launched in Maldives in 2014. Our study aimed to assess the knowledge, attitude and practices of women in relation to risk factors of cervical cancer, early detection of the disease and its prevention. The questionnaire based survey was conducted among 20 to 50 year old women, systematically sampled to represent three regions of Maldives. Trained investigators interviewed a total of 2,845 women at home. The prevalence of the risk factors of cervical cancer like early age at marriage and childbirth, multiple marriages, multiple marriages of the husbands, and multiple pregnancies was high. More women knew about breast cancer than cervical cancer. Even among the small number of women who knew of cervical cancer, only 34.6% had the knowledge of at least one early symptom. Very few women knew that the cancer could be prevented by any test. Only 6.2% of the women reported having ever undergone a Pap smear. Many women had the misconception that cervical cancer was infectious. In Maldives the younger women have high literacy rate due to the policy of universal free education and those with higher levels of education had improved knowledge of cervical cancer and its risk factors. The prevalence of risk factors also reduced with improved literacy. Awareness about risk factors and prevention of cervical cancer is limited among Maldivian women in spite of having high exposure to some of the risk factors. A universal literacy program in the country has helped to improve the knowledge of cervical cancer prevention and to reduce the exposure to various risk factors in the younger population.

Essential medicines for breast cancer in low and middle income countries.

PubMed

Bazargani, Y T; de Boer, A; Schellens, J H M; Leufkens, H G M; Mantel-Teeuwisse, Aukje K

2015-08-18

Breast cancer is the most common type of cancer among women worldwide. In low and middle-income countries (LMICs), appropriate selection of medicines on national essential medicines lists (NEMLs) is a first step towards adequate access to treatment. We studied selection of systemic treatments for breast cancer on NEMLs and assessed its alignment with treatment guidelines for different types of early and advanced breast cancer. Furthermore, influence of country characteristics on the selection was investigated. NEMLs from 75 LMICs were studied for inclusion of all components of therapy in each stage of breast cancer according to international consensus guidelines. The results were then grouped by income level, WHO region and the NEMLs' release date. Non parametric tests were used for statistical analysis. Unlike HER2-targeted therapies (<10%), aromatase inhibitors (12%) and taxanes (28%); tamoxifen and first generation chemotherapeutic regimens (e.g., anthracycline-based regimens) were frequently found in the NEMLs (71-78%). Consequently, all components of treatment for "Luminal A" early breast cancer and non HER2 overexpressed advanced breast cancer were found on the NEMLs of over 70% of countries. However, 40% of the low income countries did not have all the components of therapy for any type of early breast cancer in their NEMLs, and adequate treatment of HER2 overexpressed breast cancer was hardly possible with the current selections. Recent NEMLs were more aligned with the guidelines (p < 0.05). Eastern Mediterranean and African regions less frequently incorporated all components of breast cancer treatment in their NEMLs. Alignment of selection with guidelines' recommendations was inconsistent for different types of early and advanced breast cancer in NEMLs. Regular updates and more attention to clinical guidelines is therefore recommended.

Mindfulness Meditation or Survivorship Education in Improving Behavioral Symptoms in Younger Stage 0-III Breast Cancer Survivors (Pathways to Wellness)

ClinicalTrials.gov

2018-02-15

Cancer Survivor; Early-Stage Breast Carcinoma; Stage 0 Breast Cancer; Stage IA Breast Cancer; Stage IB Breast Cancer; Stage IIA Breast Cancer; Stage IIB Breast Cancer; Stage IIIA Breast Cancer; Stage IIIB Breast Cancer; Stage IIIC Breast Cancer

Pancreatic Cancer Early Detection Program

ClinicalTrials.gov

2017-05-12

Pancreatic Cancer; Pancreas Cancer; Pancreatic Adenocarcinoma; Familial Pancreatic Cancer; BRCA 1/2; HNPCC; Lynch Syndrome; Hereditary Pancreatitis; FAMMM; Familial Atypical Multiple Mole Melanoma; Peutz Jeghers Syndrome

DCP's Early Detection Research Guides Future Science | Division of Cancer Prevention

Cancer.gov

Early detection research funded by the NCI's Division of Cancer Prevention has positively steered both public health and clinical outcomes, and set the stage for findings in the next generation of research. |

Construction of a novel multi-gene assay (42-gene classifier) for prediction of late recurrence in ER-positive breast cancer patients.

PubMed

Tsunashima, Ryo; Naoi, Yasuto; Shimazu, Kenzo; Kagara, Naofumi; Shimoda, Masashi; Tanei, Tomonori; Miyake, Tomohiro; Kim, Seung Jin; Noguchi, Shinzaburo

2018-05-04

Prediction models for late (> 5 years) recurrence in ER-positive breast cancer need to be developed for the accurate selection of patients for extended hormonal therapy. We attempted to develop such a prediction model focusing on the differences in gene expression between breast cancers with early and late recurrence. For the training set, 779 ER-positive breast cancers treated with tamoxifen alone for 5 years were selected from the databases (GSE6532, GSE12093, GSE17705, and GSE26971). For the validation set, 221 ER-positive breast cancers treated with adjuvant hormonal therapy for 5 years with or without chemotherapy at our hospital were included. Gene expression was assayed by DNA microarray analysis (Affymetrix U133 plus 2.0). With the 42 genes differentially expressed in early and late recurrence breast cancers in the training set, a prediction model (42GC) for late recurrence was constructed. The patients classified by 42GC into the late recurrence-like group showed a significantly (P = 0.006) higher late recurrence rate as expected but a significantly (P = 1.62 × E-13) lower rate for early recurrence than non-late recurrence-like group. These observations were confirmed for the validation set, i.e., P = 0.020 for late recurrence and P = 5.70 × E-5 for early recurrence. We developed a unique prediction model (42GC) for late recurrence by focusing on the biological differences between breast cancers with early and late recurrence. Interestingly, patients in the late recurrence-like group by 42GC were at low risk for early recurrence.

Metachronous Lung Cancer: Clinical Characteristics and Effects of Surgical Treatment.

PubMed

Rzechonek, Adam; Błasiak, Piotr; Muszczyńska-Bernhard, Beata; Pawełczyk, Konrad; Pniewski, Grzegorz; Ornat, Maciej; Grzegrzółka, Jędrzej; Brzecka, Anna

2018-01-01

The occurrence of a second lung tumor after surgical removal of lung cancer usually indicates a lung cancer metastasis, but sometimes a new lesion proves to be a new primary lung cancer, i.e., metachronous lung cancer. The goal of the present study was to conduct a clinical evaluation of patients with metachronous lung cancer and lung cancer metastasis, and to compare the early and distant outcomes of surgical treatment in both cancer types. There were 26 age-matched patients with lung cancer metastases and 23 patients with metachronous lung cancers, who underwent a second lung cancer resection. We evaluated the histological type of a resected cancer, the extent of thoracosurgery, the frequency of early postoperative complications, and the probability of 5-year survival after the second operation. The findings were that metachronous lung cancer was adenocarcinoma in 52% of patients, with a different histopathological pattern from that of the primary lung cancer in 74% of patients. In both cancer groups, mechanical resections were the most common surgery type (76% of all cases), with anatomical resections such as segmentectomy, lobectomy, or pneumectomy being much rarer conducted. The incidence of early postoperative complications in metachronous lung cancer and lung cancer metastasis (30% vs. 31%, respectively) and the probability of 5-year survival after resection of either cancer tumor (60.7% vs. 50.9%, respectively) were comparable. In conclusion, patients undergoing primary lung cancer surgery require a long-term follow-up due to the risk of metastatic or metachronous lung cancer. The likelihood of metachronous lung cancer and pulmonary lung cancer metastases, the incidence of postoperative complications, and the probability of 5-year survival after resection of metachronous lung cancer or lung cancer metastasis are similar.

Epithelial stem cells and intestinal cancer.

PubMed

Tan, Shawna; Barker, Nick

2015-06-01

The mammalian intestine is comprised of an epithelial layer that serves multiple functions in order to maintain digestive activity as well as intestinal homeostasis. This epithelial layer contains highly proliferative stem cells which facilitate its characteristic rapid regeneration. How these stem cells contribute to tissue repair and normal homeostasis are actively studied, and while we have a greater understanding of the molecular mechanisms and cellular locations that underlie stem cell regulation in this tissue, much still remains undiscovered. This review describes epithelial stem cells in both intestinal and non-intestinal tissues, as well as the strategies that have been used to further characterize the cells. Through a discussion of the current understanding of intestinal self-renewal and tissue regeneration in response to injury, we focus on how dysregulation of critical signaling pathways results in potentially oncogenic aberrations, and highlight issues that should be addressed in order for effective intestinal cancer therapies to be devised. Copyright © 2014 Elsevier Ltd. All rights reserved.

Rhomboid family member 2 regulates cytoskeletal stress-associated Keratin 16

PubMed Central

Maruthappu, Thiviyani; Chikh, Anissa; Fell, Benjamin; Delaney, Paul J.; Brooke, Matthew A.; Levet, Clemence; Moncada-Pazos, Angela; Ishida-Yamamoto, Akemi; Blaydon, Diana; Waseem, Ahmad; Leigh, Irene M.; Freeman, Matthew; Kelsell, David P.

2017-01-01

Keratin 16 (K16) is a cytoskeletal scaffolding protein highly expressed at pressure-bearing sites of the mammalian footpad. It can be induced in hyperproliferative states such as wound healing, inflammation and cancer. Here we show that the inactive rhomboid protease RHBDF2 (iRHOM2) regulates thickening of the footpad epidermis through its interaction with K16. K16 expression is absent in the thinned footpads of irhom2−/− mice compared with irhom2+/+mice, due to reduced keratinocyte proliferation. Gain-of-function mutations in iRHOM2 underlie Tylosis with oesophageal cancer (TOC), characterized by palmoplantar thickening, upregulate K16 with robust downregulation of its type II keratin binding partner, K6. By orchestrating the remodelling and turnover of K16, and uncoupling it from K6, iRHOM2 regulates the epithelial response to physical stress. These findings contribute to our understanding of the molecular mechanisms underlying hyperproliferation of the palmoplantar epidermis in both physiological and disease states, and how this ‘stress' keratin is regulated. PMID:28128203

Photoaging and skin cancer: Is the inflammasome the missing link?

PubMed

Awad, Fawaz; Assrawi, Eman; Louvrier, Camille; Jumeau, Claire; Giurgea, Irina; Amselem, Serge; Karabina, Sonia-Athina

2018-03-12

Photoaging and epithelial skin tumorigenesis are complex processes triggered mainly by UV radiation from chronic sun exposure. This leads to DNA damage and reactive oxygen species (ROS) production, which initiate an inflammatory response that alters cell structure and function. Changes in cell homeostasis and ROS production activate intracellular multiprotein platforms called inflammasomes. Inflammasomes nucleate around cytoplasmic receptors mainly of the NLR (nucleotide-binding domain and leucine-rich repeat) family and regulate caspase-1-dependant secretion of pro-inflammatory interleukin (IL)1β and IL18 cytokines, and an inflammatory form of death named pyroptosis. NLRP1 inflammasomes have taken centre stage in skin biology, as mutations in NLRP1 underlie the genetic etiology of dermatological diseases and increase the susceptibility to skin cancer. Targeting inflammasome(s) might be an important approach to improve skin inflammation, photoaging and reduce the risk of epithelial skin tumorigenesis. In this context, we discuss the potential implication of NLRP1 and NLRP3 inflammasomes. Copyright © 2018 Elsevier B.V. All rights reserved.

The study of esophageal cancer in an early stage by using Raman spectroscopy

NASA Astrophysics Data System (ADS)

Ishigaki, Mika; Taketani, Akinori; Maeda, Yasuhiro; Andriana, Bibin B.; Ishihara, Ryu; Sato, Hidetoshi

2013-02-01

The esophageal cancer is a disease with a high mortality. In order to lead a higher survival rate five years after the cancer's treatment, we inevitably need a method to diagnose the cancer in an early stage and support the therapy. Raman spectroscopy is one of the most powerful techniques for the purpose. In the present study, we apply Raman spectroscopy to obtain ex vivo spectra of normal and early tumor human esophageal sample. The result of principal component analysis indicates that the tumor tissue is associated with a decrease in tryptophan concentration. Furthermore, we can predict the tissue type with 80% accuracy by linear discriminant analysis which model is made by tryptophan bands.

DNA Nanotechnology for Cancer Diagnosis and Therapy.

PubMed

Chen, Tianshu; Ren, Lingjie; Liu, Xiaohao; Zhou, Mengru; Li, Lingling; Xu, Jingjing; Zhu, Xiaoli

2018-06-05

Cancer is one of the leading causes of mortality worldwide, because of the lack of accurate diagnostic tools for the early stages of cancer. Thus, early diagnosis, which provides important information for a timely therapy of cancer, is of great significance for controlling the development of the disease and the proliferation of cancer cells and for improving the survival rates of patients. To achieve the goals of early diagnosis and timely therapy of cancer, DNA nanotechnology may be effective, since it has emerged as a valid technique for the fabrication of various nanoscale structures and devices. The resultant DNA-based nanoscale structures and devices show extraordinary performance in cancer diagnosis, owing to their predictable secondary structures, small sizes, and high biocompatibility and programmability. In particular, the rapid development of DNA nanotechnologies, such as molecular assembly technologies, endows DNA-based nanomaterials with more functionalization and intellectualization. Here, we summarize recent progress made in the development of DNA nanotechnology for the fabrication of functional and intelligent nanomaterials and highlight the prospects of this technology in cancer diagnosis and therapy.

[China expert consensus on the management of dyslipidemia in postmenopausal patients with early-stage breast cancer].

PubMed

2017-01-23

Estrogen has an impact on the type of lipoproteins and the blood lipid levels, thus protecting the cardiovascular system. Postmenopausal breast cancer patients suffer a significant decrease in estrogen levels due to both physiological changes and the use of drugs, and thus have a higher risk of atherosclerotic cardiovascular diseases. Therefore, strict lipid management is required for postmenopausal breast cancer patients receiving endocrine therapy. However, no guidelines have been developed in terms of lipid management and intervention for postmenopausal breast cancer patients. The Chinese expert group of multidisciplinary management of dyslipidemia in breast cancer patients with endocrine therapy, after deep investigation into the management of dyslipidemia in postmenopausal patients with early-stage breast cancer, has developed the China Expert Consensus on Dyslipidemia Management in Postmenopausal Patients with Early-stage Breast Cancer. The Consensus clearly defines the goals and measures of interventions for dyslipidemia, hoping to effectively reduce the risk of atherosclerotic cardiovascular disease in postmenopausal breast cancer patients and further improve the long-term survival of the patients.

Self-assembled polymeric nanoparticles as new, smart contrast agents for cancer early detection using magnetic resonance imaging.

PubMed

Mouffouk, Fouzi; Simão, Teresa; Dornelles, Daniel F; Lopes, André D; Sau, Pablo; Martins, Jorge; Abu-Salah, Khalid M; Alrokayan, Salman A; Rosa da Costa, Ana M; dos Santos, Nuno R

2015-01-01

Early cancer detection is a major factor in the reduction of mortality and cancer management cost. Here we developed a smart and targeted micelle-based contrast agent for magnetic resonance imaging (MRI), able to turn on its imaging capability in the presence of acidic cancer tissues. This smart contrast agent consists of pH-sensitive polymeric micelles formed by self-assembly of a diblock copolymer (poly(ethyleneglycol-b-trimethylsilyl methacrylate)), loaded with a gadolinium hydrophobic complex ((t)BuBipyGd) and exploits the acidic pH in cancer tissues. In vitro MRI experiments showed that (t)BuBipyGd-loaded micelles were pH-sensitive, as they turned on their imaging capability only in an acidic microenvironment. The micelle-targeting ability toward cancer cells was enhanced by conjugation with an antibody against the MUC1 protein. The ability of our antibody-decorated micelles to be switched on in acidic microenvironments and to target cancer cells expressing specific antigens, together with its high Gd(III) content and its small size (35-40 nm) reveals their potential use for early cancer detection by MRI.

Optical diagnostic of breast cancer using Raman, polarimetric and fluorescence spectroscopy

NASA Astrophysics Data System (ADS)

Anwar, Shahzad; Firdous, Shamaraz; Rehman, Aziz-ul; Nawaz, Muhammed

2015-04-01

We presented the optical diagnostic of normal and cancerous human breast tissues using Raman, polarimetric and fluorescence spectroscopic techniques. Breast cancer is the second leading cause of cancer death among women worldwide. Optical diagnostics of cancer offered early intervention and the greatest chance of cure. Spectroscopic data were collected from freshly excised surgical specimens of normal tissues with Raman bands at 800, 1171 and 1530 cm-1 arising mainly by lipids, nucleic acids, proteins, carbohydrates and amino acids. For breast cancer, Raman bands are observed at 1070, 1211, 1495, 1583 and 1650 cm-1. Results demonstrate that the spectra of normal tissue are dominated by lipids and amino acids. Polarization decomposition of the Mueller matrix and confocal microscopic fluorescence provides detailed description of cancerous tissue and distinguishes between the normal and malignant one. Based on these findings, we successfully differentiate normal and malignant breast tissues at an early stage of disease. There is a need to develop a new tool for noninvasive, real-time diagnosis of tissue abnormalities and a test procedure for detecting breast cancer at an early stage.

Nanoparticle-based Paclitaxel vs Solvent-based Paclitaxel as Part of Neoadjuvant Chemotherapy for Early Breast Cancer (GeparSepto)

ClinicalTrials.gov

2016-10-11

Tubular Breast Cancer Stage II; Mucinous Breast Cancer Stage II; Breast Cancer Female NOS; Invasive Ductal Breast Cancer; Tubular Breast Cancer Stage III; HER-2 Positive Breast Cancer; Inflammatory Breast Cancer Stage IV; Inflammatory Breast Cancer

Specific PET Imaging Probes for Early Detection of Prostate Cancer Metastases

DTIC Science & Technology

2010-05-01

penetrating cell membranes. In one of our studies using such a peptide to deliver a therapeutic moiety to various prostate cancer cell lines, we...to exploit this group of peptides for the early detection of prostate tumor metastases. Promisingly, in our preliminary studies , th e peptide lab...cancer. Based on one of our studies using a polyarginine (NH2GR11) to deliver a therapeutic moiety to various prostate cancer cell lines, we hypothesize

Co-Operation Between FADD and Bin1 in Prostate Cancer Apoptosis

DTIC Science & Technology

2005-04-01

an early step in prostate (and also breast ) cancer development, it may represent an early link between cell growth 9 DAMD17-03-1-0049 PI Andrew M...apoptosis is combined. TRAIL-induced autophagy occurs prostate cancer research programs grants DAMD17-02-1-0612 and DAMD17- during breast epithelial cell...Hahn, W. C., and Weinberg, R. A. (2001). Human breast are involved in mammalian cell immortalization, including cancer cells generated by oncogenic

Long-Term Outcomes of Alternative Brachytherapy Techniques for Early Prostate Cancer. Addendum

DTIC Science & Technology

2008-10-01

radical prostatectomy. The National Medicare Experience: 1988-1990 (updated June 1993). Urology 1993;42:622-9. 3. Litwin MS, Hays RD, Fink A, Ganz PA...implantation for early-stage prostatic cancer. J Clin Oncol 1999;17:517-22. 33. Brandeis JM, Litwin MS, Burnison CM, Reiter RE. Quality of life outcomes after...combination radiotherapy for patients with prostate cancer. I-125 implant followed by external-beam radiation. Cancer 1995;75:2383-91. 35. Litwin M

Surgical treatment for apparent early stage endometrial cancer

PubMed Central

2014-01-01

Most experts would agree that the standard surgical treatment for endometrial cancer includes a hysterectomy and bilateral salpingo-oophorectomy; however, the benefit of full surgical staging with lymph node dissection in patients with apparent early stage disease remains a topic of debate. Recent prospective data and advances in laparoscopic techniques have transformed this disease into one that can be successfully managed with minimally invasive surgery. This review will discuss the current surgical management of apparent early stage endometrial cancer and some of the new techniques that are being incorporated. PMID:24596812

Stepwise radical endoscopic resection for Barrett's esophagus with early neoplasia: report on a Brussels' cohort.

PubMed

Pouw, R E; Peters, F P; Sempoux, C; Piessevaux, H; Deprez, P H

2008-11-01

The aim of this retrospective study was to assess safety and efficacy of stepwise radical endoscopic resection (SRER) in patients with Barrett's esophagus with high-grade intraepithelial neoplasia (HGIN) or early cancer. Patients undergoing SRER between 2000 and 2006 were retrospectively evaluated. Patients with Barrett's esophagus who also had HGIN or early cancer were included if they had no signs of submucosal infiltration or metastases. SRER was performed using the cap-technique, at 8-week intervals until all Barrett's esophagus was removed. Follow-up endoscopy was scheduled every 6 months. A total of 34 patients were included (31 male, mean 67 years, median Barrett's dimensions C1M4). HGIN / early cancer was eradicated in all patients in a median of two endoscopic resection sessions (IQR 1-2 sessions). Twelve patients underwent additional argon plasma coagulation for small islets or an irregular Z-line. Barrett's esophagus was eradicated in 28 patients (82 %). Complications occurred in 3/34 patients (9 %): two perforations, one delayed bleeding. In all, 19 patients (56 %) developed dysphagia, which was resolved with dilatation or stent placement. During a median follow-up period of 23 months (IQR 15 - 41 months), HGIN / early cancer recurred in three patients (9 %): two were retreated with endoscopic resection and one patient was referred for curative surgery. Five patients (15 %) had recurrence of nondysplastic Barrett's esophagus. At the end of the follow-up period all patients were free of HGIN / early cancer (one patient after surgery), and 23 patients (68 %) had complete endoscopic and histological eradication of Barrett's esophagus. SRER resulted in complete eradication of HGIN/early cancer in all patients, and eradication of Barrett's esophagus in a majority of cases. A significant number of patients develop dysphagia, which can be successfully treated endoscopically.

Surfactant protein DNA methylation: A new entrant in the field of lung cancer diagnostics? (Review)

PubMed Central

Vaid, Mudit; Floros, Joanna

2010-01-01

Lung cancer is a major cause of cancer-related mortality in both men and women. A 5-year survival of lung cancer patients is only 15% with a negative correlation between progressively advanced lung cancer stage and a 5-year survival period. The only chance for cure is surgical resection if done at the early stage of the disease. Therefore, an early diagnosis and a better prediction of prognosis could decrease mortality. An early diagnosis could provide the opportunity for a therapeutic intervention early in the course of the disease. Genetic alterations in the cancer genome include aneuploidy, deletions and amplifications of chromosomal regions, loss of heterozygosity (LOH), microsatellite alterations, point mutations and aberrant promoter methylation. Of the various types of genetic alterations (i.e. gene amplifications, allele deletions, point mutations or deletions and methylation) reported in different tumor types, aberrant promoter methylation of genes is recent and is the focus of the present review. Specifically, we will briefly review the role of promoter methylation in various malignancies and then focus on lung cancer diagnosis and promoter gene methylation with emphasis on the methylation status of genes of the innate host defense, namely the surfactant proteins A and D. PMID:19082436

Tumor-associated macrophages drive spheroid formation during early transcoelomic metastasis of ovarian cancer

PubMed Central

Yin, Mingzhu; Li, Xia; Tan, Shu; Zhou, Huanjiao Jenny; Ji, Weidong; Bellone, Stefania; Xu, Xiaocao; Zhang, Haifeng; Santin, Alessandro D.; Lou, Ge

2016-01-01

Tumor-associated macrophages (TAMs) can influence ovarian cancer growth, migration, and metastasis, but the detailed mechanisms underlying ovarian cancer metastasis remain unclear. Here, we have shown a strong correlation between TAM-associated spheroids and the clinical pathology of ovarian cancer. Further, we have determined that TAMs promote spheroid formation and tumor growth at early stages of transcoelomic metastasis in an established mouse model for epithelial ovarian cancer. M2 macrophage–like TAMs were localized in the center of spheroids and secreted EGF, which upregulated αMβ2 integrin on TAMs and ICAM-1 on tumor cells to promote association between tumor cells and TAM. Moreover, EGF secreted by TAMs activated EGFR on tumor cells, which in turn upregulated VEGF/VEGFR signaling in surrounding tumor cells to support tumor cell proliferation and migration. Pharmacological blockade of EGFR or antibody neutralization of ICAM-1 in TAMs blunted spheroid formation and ovarian cancer progression in mouse models. These findings suggest that EGF secreted from TAMs plays a critical role in promoting early transcoelomic metastasis of ovarian cancer. As transcoelomic metastasis is also associated with many other cancers, such as pancreatic and colon cancers, our findings uncover a mechanism for TAM-mediated spheroid formation and provide a potential target for the treatment of ovarian cancer and other transcoelomic metastatic cancers. PMID:27721235

A case report of prostate cancer metastasis to the stomach resembling undifferentiated-type early gastric cancer.

PubMed

Inagaki, Chiaki; Suzuki, Takuto; Kitagawa, Yoshiyasu; Hara, Taro; Yamaguchi, Taketo

2017-08-07

Occurrence of metastatic cancer to the stomach is rare, particularly in patients with prostate cancer. Gastric metastasis generally presents as a solitary and submucosal lesion with a central depression. We describe a case of gastric metastasis arising from prostate cancer, which is almost indistinguishable from the undifferentiated-type gastric cancer. A definitive diagnosis was not made until endoscopic resection. On performing both conventional and magnifying endoscopies, the lesion appeared to be slightly depressed and discolored area and it could not be distinguished from undifferentiated early gastric cancer. Biopsy from the lesion was negative for immunohistochemical staining of prostate-specific antigen, a sensitive and specific marker for prostate cancer. Thus, false initial diagnosis of an early primary gastric cancer was made and endoscopic submucosal dissection was performed. Pathological findings from the resected specimen aroused suspicion of a metastatic lesion. Consequently, immunostaining was performed. The lesion was positive for prostate-specific acid phosphatase and negative for prostate-specific antigen, cytokeratin 7, and cytokeratin 20. Accordingly, the final diagnosis was a metastatic gastric lesion originating from prostate cancer. In this patient, the definitive diagnosis as a metastatic lesion was difficult due to its unusual endoscopic appearance and the negative stain for prostate-specific antigen. We postulate that both of these are consequences of hormonal therapy against prostate cancer.

About the Breast and Gynecologic Cancer Research Group | Division of Cancer Prevention

Cancer.gov

The Breast and Gynecologic Cancer Research Group conducts and fosters the development of research on the prevention and early detection of breast cancer, cervix and human papillomavirus (HPV)-related cancers, endometrial cancers, ovarian cancers, and precursor conditions related to these cancers. |

Bringing skin assessments to life using human patient simulation: an emphasis on cancer prevention and early detection.

PubMed

Kuhrik, Marilee; Seckman, Christy; Kuhrik, Nancy; Ahearn, Tina; Ercole, Patrick

2011-12-01

Skin cancer is the most common cancer in the United States, with about 1,000,000 people developing the disease each year. The incidence of melanoma has rapidly increased in young white women between the ages of 15-34 over the last three decades. While melanoma accounts for approximately 3% of skin cancers, it causes more than 75% of skin cancer deaths. Thorough skin assessments and awareness of new or changing appearance of skin lesions are critical to early detection and treatment of skin cancer, as well as teaching sun-protective behaviors. Educators created a novel approach to "bring to life" skin cancer assessment skills to promote awareness of prevention and early detection of skin cancer using moulage in a human patient simulation lab. Through the use of moulage-like lesions, simulated patients were evaluated and taught skin cancer prevention and early detection principles by baccalaureate nursing students. The average age of study participants (n = 104) was 26.50 years. The majority of responders were female. At the end of the lab, students' average responses to an evaluation based on program goals were very positive. Anecdotal comments affirmed positive student perceptions of their simulation experience. Data analyses indicated item means were consistently higher for upper-division students. The age and gender of students who participated in this study align with the NCI statistics on age and gender of the population with increased incidence of melanoma.

Cancer knowledge and misconceptions: a survey of immigrant Salvadorean women.

PubMed

Shankar, S; Figueroa-Valles, N

1999-01-01

This study assessed cancer knowledge, beliefs, and awareness of signs, symptoms, and early detection methods in immigrant Salvadorean women in the Washington, D.C. metropolitan area (DCMA). A face-to-face survey sampled 843 females aged 20 and above. Descriptive statistics were used to compute frequency of response for sociodemographic characteristics, beliefs, and awareness of signs, symptoms, and early detection methods. The sample's mean age was 34.5 years; 10% had no schooling, and 7.4% had more than a high school education. Sixty-six percent of the women worked full- or part-time; 16% had an annual income of $20,000 or more; and 26% reported having medical insurance. Thirty percent of the sample lacked knowledge of the etiology and spread of cancer. The statement, "Bumps on your body can cause cancer" was endorsed by 61.6%. Beliefs that "destiny cannot be changed" or "just about anything can cause cancer" were prevalent among 18.5%. "Cancer is a punishment from God" was believed by 10.9%. A general physical examination was the most frequent (82%) early detection method mentioned. The Pap test was identified by 24.2%, and mammography by 14%; 5.6% mentioned breast self examination. Similar to other Hispanics, immigrant Salvadorean women in DCMA demonstrated a lack of knowledge of cancer's signs and symptoms, and early detection methods of and beliefs about cancer. Educational programs designed specifically for immigrant Salvadorean women to increase their knowledge of cancer and prevention methods are essential.

An assessment of oral cancer curricula in dental hygiene programmes: implications for cancer control.

PubMed

Thacker, K K; Kaste, L M; Homsi, K D; LeHew, C W

2016-11-01

To assess oral cancer prevention and early detection curricula in Illinois associate-degree dental hygiene programmes and highlight global health applications. An email invitation was sent to each Illinois associate-degree granting dental hygiene programme's oral cancer contact to participate in a survey via a SurveyMonkey™ link to a 21-item questionnaire. Questions elicited background information on each programme and inquired about curriculum and methods used for teaching oral cancer prevention and early detection. Eight of the 12 (67%) programmes responded. Three (37.5%) reported having a specific oral cancer curriculum. Five (62.5%) require students to perform examinations for signs and symptoms of oral cancer at each clinic visit. Variations exist across the programmes in the number of patients each student sees annually and the number of oral cancer examinations each student performs before graduation. Seven programmes (87.5%) conduct early detection screening in community settings. All programmes included risk assessment associated with tobacco. All other risk factors measured were treated inconsistently. Significant differences in training and experience were reported across Illinois dental hygiene programmes. Training is neither standardized nor uniformly comprehensive. Students' preparation for delivering prevention and early detection services to their patients could be strengthened to ensure competence including reflection of risk factors and behaviours in a global context. Regular review of curricular guidelines and programme content would help dental hygienists meet the expectations of the Crete Declaration on Oral Cancer Prevention. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

Screening for Cancer

Cancer.gov

Cancer screening is checking for cancer in people who don't have symptoms. Screening tests can help doctors find and treat several types of cancer early, but cancer screening can have harms as well as benefits.

Human small breast epithelial mucin: the promise of a new breast tumor biomarker.

PubMed

Hubé, F; Mutawe, M; Leygue, E; Myal, Y

2004-12-01

Breast cancer remains one of the most frequently diagnosed cancers today. In developed countries, one in eight women is expected to present with breast cancer within her lifetime and an estimated 1,000,000 cases are detected each year worldwide (Canadian Cancer Statistics, http://www.cancer.ca/vgn/images/ portal/cit_86751114/14/33/1959864 11niw_stats2004_en.pdf). For women with recurrent disease, the median time of survival is about 2 years. Despite optimal surgery, adjuvant irradiation, hormonal treatment, and chemotherapy, approximately 30% of patients with localized breast cancer finally develop distant metastases. Early detection, which enables intervention at a localized and potentially curable stage, remains a central goal in breast cancer treatment. Indeed, the 5-year survival rate for women with breast cancer has been shown to increase dramatically when the disease is diagnosed at an early stage: from less than 25% in women with disseminated cancer to about 75% in patients with regional disease and over 95% in women with a localized tumor (Breast Cancer Facts and Figures, 2001-2002, http://www.cancer.org/downloads/STT/BrCaFF 2001.pdf). Unfortunately, only 60% of all breast cancers are diagnosed at a local stage. Any improvement in early detection through identification of tumor biomarkers would have a significant impact on reducing overall breast cancer mortality.

Genome-wide identification of novel expression signatures reveal distinct patterns and prevalence of binding motifs for p53, nuclear factor-κB and other signal transcription factors in head and neck squamous cell carcinoma

PubMed Central

Yan, Bin; Yang, Xinping; Lee, Tin-Lap; Friedman, Jay; Tang, Jun; Van Waes, Carter; Chen, Zhong

2007-01-01

Background Differentially expressed gene profiles have previously been observed among pathologically defined cancers by microarray technologies, including head and neck squamous cell carcinomas (HNSCCs). However, the molecular expression signatures and transcriptional regulatory controls that underlie the heterogeneity in HNSCCs are not well defined. Results Genome-wide cDNA microarray profiling of ten HNSCC cell lines revealed novel gene expression signatures that distinguished cancer cell subsets associated with p53 status. Three major clusters of over-expressed genes (A to C) were defined through hierarchical clustering, Gene Ontology, and statistical modeling. The promoters of genes in these clusters exhibited different patterns and prevalence of transcription factor binding sites for p53, nuclear factor-κB (NF-κB), activator protein (AP)-1, signal transducer and activator of transcription (STAT)3 and early growth response (EGR)1, as compared with the frequency in vertebrate promoters. Cluster A genes involved in chromatin structure and function exhibited enrichment for p53 and decreased AP-1 binding sites, whereas clusters B and C, containing cytokine and antiapoptotic genes, exhibited a significant increase in prevalence of NF-κB binding sites. An increase in STAT3 and EGR1 binding sites was distributed among the over-expressed clusters. Novel regulatory modules containing p53 or NF-κB concomitant with other transcription factor binding motifs were identified, and experimental data supported the predicted transcriptional regulation and binding activity. Conclusion The transcription factors p53, NF-κB, and AP-1 may be important determinants of the heterogeneous pattern of gene expression, whereas STAT3 and EGR1 may broadly enhance gene expression in HNSCCs. Defining these novel gene signatures and regulatory mechanisms will be important for establishing new molecular classifications and subtyping, which in turn will promote development of targeted therapeutics for HNSCC. PMID:17498291

Neural Crest Migration and Survival Are Susceptible to Morpholino-Induced Artifacts

PubMed Central

Jette, Cicely A.

2016-01-01

The neural crest (NC) is a stem cell-like embryonic population that is essential for generating and patterning the vertebrate body, including the craniofacial skeleton and peripheral nervous system. Defects in NC development underlie many birth defects and contribute to formation of some of the most malignant cancers in humans, such as melanoma and neuroblastoma. For these reasons, significant research efforts have been expended to identify genes that control NC development, as it is expected to lead to a deeper understanding of the genetic mechanisms controlling vertebrate development and identify new treatments for NC-derived diseases and cancers. However, a number of inconsistencies regarding gene function during NC development have emerged from comparative analyses of gene function between mammalian and non-mammalian systems (chick, frog, zebrafish). This poses a significant barrier to identification of single genes and/or redundant pathways to target in NC diseases. Here, we determine whether technical differences, namely morpholino-based approaches used in non-mammalian systems, could contribute to these discrepancies, by examining the extent to which NC phenotypes in fascin1a (fscn1a) morphant embryos are similar to or different from fscn1a null mutants in zebrafish. Analysis of fscn1a morphants showed that they mimicked early NC phenotypes observed in fscn1a null mutants; however, these embryos also displayed NC migration and derivative phenotypes not observed in null mutants, including accumulation of p53-independent cell death. These data demonstrate that morpholinos can cause seemingly specific NC migration and derivative phenotypes, and thus have likely contributed to the inconsistencies surrounding NC gene function between species. We suggest that comparison of genetic mutants between different species is the most rigorous method for identifying conserved genetic mechanisms controlling NC development and is critical to identify new treatments for NC diseases. PMID:28005909

Calcium homeostasis and organelle function in the pathogenesis of obesity and diabetes

PubMed Central

Arruda, Ana Paula; Hotamisligil, Gökhan S.

2015-01-01

Summary A number of chronic metabolic pathologies, including obesity, diabetes, cardiovascular disease, asthma, and cancer cluster together to present the greatest threat to human health. As research in this field has advanced, it has become clear that unresolved metabolic inflammation, organelle dysfunction, and other cellular and metabolic stresses underlie the development of these chronic metabolic diseases. However, the relationship between these systems and pathological mechanisms is poorly understood. Here, we will discuss the role of cellular Ca2+ homeostasis as a critical mechanism integrating the myriad of cellular and subcellular dysfunctional networks found in metabolic tissues such as liver and adipose tissue in the context of metabolic disease particularly in obesity and diabetes. PMID:26190652

Cellular and molecular mechanisms coordinating pancreas development.

PubMed

Bastidas-Ponce, Aimée; Scheibner, Katharina; Lickert, Heiko; Bakhti, Mostafa

2017-08-15

The pancreas is an endoderm-derived glandular organ that participates in the regulation of systemic glucose metabolism and food digestion through the function of its endocrine and exocrine compartments, respectively. While intensive research has explored the signaling pathways and transcriptional programs that govern pancreas development, much remains to be discovered regarding the cellular processes that orchestrate pancreas morphogenesis. Here, we discuss the developmental mechanisms and principles that are known to underlie pancreas development, from induction and lineage formation to morphogenesis and organogenesis. Elucidating such principles will help to identify novel candidate disease genes and unravel the pathogenesis of pancreas-related diseases, such as diabetes, pancreatitis and cancer. © 2017. Published by The Company of Biologists Ltd.

Arresting Evolution.

PubMed

Bull, James J; Barrick, Jeffrey E

2017-12-01

Evolution in the form of selective breeding has long been harnessed as a useful tool by humans. However, rapid evolution can also be a danger to our health and a stumbling block for biotechnology. Unwanted evolution can underlie the emergence of drug and pesticide resistance, cancer, and weeds. It makes live vaccines and engineered cells inherently unreliable and unpredictable, and therefore potentially unsafe. Yet, there are strategies that have been and can possibly be used to stop or slow many types of evolution. We review and classify existing population genetics-inspired methods for arresting evolution. Then, we discuss how genome editing techniques enable a radically new set of approaches to limit evolution. Copyright © 2017 The Authors. Published by Elsevier Ltd.. All rights reserved.

Mechanisms governing the health and performance benefits of exercise.

PubMed

Bishop-Bailey, D

2013-11-01

Humans are considered among the greatest if not the greatest endurance land animals. Over the last 50 years, as the population has become more sedentary, rates of cardiovascular disease and its associated risk factors such as obesity, type 2 diabetes and hypertension have all increased. Aerobic fitness is considered protective for all-cause mortality, cardiovascular disease, a variety of cancers, joint disease and depression. Here, I will review the emerging mechanisms that underlie the response to exercise, focusing on the major target organ the skeletal muscle system. Understanding the mechanisms of action of exercise will allow us to develop new therapies that mimic the protective actions of exercise. © 2013 The British Pharmacological Society.

Opportunities During Early Life for Cancer Prevention: Highlights From a Series of Virtual Meetings With Experts

PubMed Central

Holman, Dawn M.; Buchanan, Natasha D.

2018-01-01

Compelling evidence suggests that early life exposures can affect lifetime cancer risk. In 2014, the Centers for Disease Control and Prevention’s (CDC’s) Cancer Prevention Across the Lifespan Workgroup hosted a series of virtual meetings with select experts to discuss the state of the evidence linking factors during the prenatal period and early childhood to subsequent risk of both pediatric and adult cancers. In this article, we present the results from a qualitative analysis of the meeting transcripts and summarize themes that emerged from our discussions with meeting participants. Themes included the state of the evidence linking early life factors to cancer risk, research gaps and challenges, the level of evidence needed to support taking public health action, and the challenges of communicating complex, and sometimes conflicting, scientific findings to the public. Opportunities for collaboration among public health agencies and other stakeholders were identified during these discussions. Potential next steps for the CDC and its partners included advancing and building upon epidemiology and surveillance work, developing and using evidence from multiple sources to inform decision-making, disseminating and communicating research findings in a clear and effective way, and expanding collaborations with grantees and other partners. As the science on early life factors and cancer risk continues to evolve, there are opportunities for collaboration to translate science into actionable public health practice. PMID:27940972

Ovarian Cancer

MedlinePlus

... deaths than other female reproductive cancers. The sooner ovarian cancer is found and treated, the better your chance for recovery. But ovarian cancer is hard to detect early. Women with ovarian ...

Experimental Lung Cancer Drug Shows Early Promise | Poster

Cancer.gov

By Frank Blanchard, Staff Writer A first-of-its-kind drug is showing early promise in attacking certain lung cancers that are hard to treat because they build up resistance to conventional chemotherapy. The drug, CO-1686, performed well in a preclinical study involving xenograft and transgenic mice, as reported in the journal Cancer Discovery. It is now being evaluated for

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection

Cancer.gov

Utilizing Existing Clinical and Population Biospecimen Resources for Discovery or Validation of Markers for Early Cancer Detection, a 2013 workshop sponsored by the Epidemiology and Genomics Research Program.

A deep learning method for early screening of lung cancer

NASA Astrophysics Data System (ADS)

Zhang, Kunpeng; Jiang, Huiqin; Ma, Ling; Gao, Jianbo; Yang, Xiaopeng

2018-04-01

Lung cancer is the leading cause of cancer-related deaths among men. In this paper, we propose a pulmonary nodule detection method for early screening of lung cancer based on the improved AlexNet model. In order to maintain the same image quality as the existing B/S architecture PACS system, we convert the original CT image into JPEG format image by analyzing the DICOM file firstly. Secondly, in view of the large size and complex background of CT chest images, we design the convolution neural network on basis of AlexNet model and sparse convolution structure. At last we train our models on the software named DIGITS which is provided by NVIDIA. The main contribution of this paper is to apply the convolutional neural network for the early screening of lung cancer and improve the screening accuracy by combining the AlexNet model with the sparse convolution structure. We make a series of experiments on the chest CT images using the proposed method, of which the sensitivity and specificity indicates that the method presented in this paper can effectively improve the accuracy of early screening of lung cancer and it has certain clinical significance at the same time.

Nanoparticle-facilitated functional and molecular imaging for the early detection of cancer

PubMed Central

Sivasubramanian, Maharajan; Hsia, Yu; Lo, Leu-Wei

2014-01-01

Cancer detection in its early stages is imperative for effective cancer treatment and patient survival. In recent years, biomedical imaging techniques, such as magnetic resonance imaging, computed tomography and ultrasound have been greatly developed and have served pivotal roles in clinical cancer management. Molecular imaging (MI) is a non-invasive imaging technique that monitors biological processes at the cellular and sub-cellular levels. To achieve these goals, MI uses targeted imaging agents that can bind targets of interest with high specificity and report on associated abnormalities, a task that cannot be performed by conventional imaging techniques. In this respect, MI holds great promise as a potential therapeutic tool for the early diagnosis of cancer. Nevertheless, the clinical applications of targeted imaging agents are limited due to their inability to overcome biological barriers inside the body. The use of nanoparticles has made it possible to overcome these limitations. Hence, nanoparticles have been the subject of a great deal of recent studies. Therefore, developing nanoparticle-based imaging agents that can target tumors via active or passive targeting mechanisms is desirable. This review focuses on the applications of various functionalized nanoparticle-based imaging agents used in MI for the early detection of cancer. PMID:25988156

MicroRNAs as biomarkers for early breast cancer diagnosis, prognosis and therapy prediction.

PubMed

Nassar, Farah J; Nasr, Rihab; Talhouk, Rabih

2017-04-01

Breast cancer is a major health problem that affects one in eight women worldwide. As such, detecting breast cancer at an early stage anticipates better disease outcome and prolonged patient survival. Extensive research has shown that microRNA (miRNA) are dysregulated at all stages of breast cancer. miRNA are a class of small noncoding RNA molecules that can modulate gene expression and are easily accessible and quantifiable. This review highlights miRNA as diagnostic, prognostic and therapy predictive biomarkers for early breast cancer with an emphasis on the latter. It also examines the challenges that lie ahead in their use as biomarkers. Noteworthy, this review addresses miRNAs reported in patients with early breast cancer prior to chemotherapy, radiotherapy, surgical procedures or distant metastasis (unless indicated otherwise). In this context, miRNA that are mentioned in this review were significantly modulated using more than one statistical test and/or validated by at least two studies. A standardized protocol for miRNA assessment is proposed starting from sample collection to data analysis that ensures comparative analysis of data and reproducibility of results. Copyright © 2016 Elsevier Inc. All rights reserved.

LASER BIOLOGY AND MEDICINE: Combination of fluorescence imaging and local spectrophotometry in fluorescence diagnostics of early cancer of larynx and bronchi

NASA Astrophysics Data System (ADS)

Sokolov, Vladimir V.; Filonenko, E. V.; Telegina, L. V.; Boulgakova, N. N.; Smirnov, V. V.

2002-11-01

The results of comparative studies of autofluorescence and 5-ALA-induced fluorescence of protoporphyrin IX, used in the diagnostics of early cancer of larynx and bronchi, are presented. The autofluorescence and 5-ALA-induced fluorescence images of larynx and bronchial tissues are analysed during the endoscopic study. The method of local spectrophotometry is used to verify findings obtained from fluorescence images. It is shown that such a combined approach can be efficiently used to improve the diagnostics of precancer and early cancer, to detect a primary multiple tumours, as well as for the diagnostics of a residual tumour or an early recurrence after the endoscopic, surgery or X-ray treatment. The developed approach allows one to minimise the number of false-positive results and to reduce the number of biopsies, which are commonly used in the white-light bronchoscopy search for occult cancerous loci.

[Early detection of breast and cervical cancer among indigenous communities in Morelos, Mexico].

PubMed

Campero, Lourdes; Atienzo, Erika E; Marín, Eréndira; de la Vara-Salazar, Elvia; Pelcastre-Villafuerte, Blanca; González, Guillermo

2014-01-01

To analyze the perception in relation to when and how to perform actions for the early detection of breast and cervical cancer among women and health care providers in communities with a high percentage of indigenous population in Morelos, Mexico. Ten health providers and 58 women users of health services were interviewed which have a first level of attention in five communities. The analysis was developed under the approach of the Grounded Theory. Providers are poorly informed about current regulations and specific clinical indications for the detection of cervical and breast cancer. Few practice health literacy under intercultural sensitization. The users have imprecise or wrong notions of the early detection. The need for training in adherence to norms is evident. It is urgent to assume a culturally relevant approach to enable efficient communication and promote health literacy for early detection of these two cancers.

Nanotechnology: Emerging Developments and Early Detection of Cancer. A Two-Day Workshop Sponsored by the National Cancer Institute and the National Institute of Standards and Technology, August 30–31 2001, on the National Institute of Standards and Technology Campus, Gaithersburg, MD, USA

PubMed Central

Zullo, Steven J.; Srivastava, Sudhir; Looney, J. Patrick; Barker, Peter E.

2002-01-01

A recent meeting jointly sponsored by the National Cancer Institute (NCI) and National Institute of Standards and Technology (NIST) brought together researchers active in nanotechnology and cancer molecular biology to discuss and evaluate the interface between disciplines. Emerging areas where nanotechnologies may impact cancer prevention and early cancer detection were elaborated by key researchers who catalyzed interdisciplinary dialogue aimed at fostering cross-discipline communications and future collaboration. PMID:12590168

6 Common Cancers - Prostate Cancer

MedlinePlus

... Bar Home Current Issue Past Issues 6 Common Cancers - Prostate Cancer Past Issues / Spring 2007 Table of Contents For ... early screening. Photo: AP Photo/Danny Moloshok Prostate Cancer The prostate gland is a walnut-sized structure ...

Chronological shifts and changing causes of death after radiotherapy for early-stage oral cancer.

PubMed

Fujisawa, Rina; Shibuya, Hitoshi; Harata, Naoki; Yuasa-Nakagawa, Keiko; Toda, Kazuma; Hayashi, Keiji

2014-02-01

Following recent improvements in the curability of oral cancer, chronological shifts and changes in the causes of death after treatment have been observed. We conducted a review of the post-treatment causes of death following radiotherapy for oral cancers. The medical records of 966 patients with early-stage (stage I and II) oral cancer treated at our institute between 1980 and 2001 were reviewed, and the chronological shifts and changes in the causes of death after radiotherapy were assessed. Of the 966 patients enrolled in this study, 365 have died to date. Two hundred and eleven patients died of their primary malignancy; 193 of these deaths occurred within 5 years of treatment for the primary oral cancer. The second most frequent cause of death was second primary cancer (n = 90). Twenty-three patients with head and neck cancers and 18 patients with esophageal cancers died within 10 years of radiotherapy, and six patients with lung cancers died after more than 10 years. Within the first 5 years following treatment, the major cause of death was the primary oral cancer. After 5-10 years, a second primary cancer, such as head and neck cancer or esophageal cancer, became the leading cause of death. Over a 10-year period, the proportion of deaths from a second primary cancer in the lung was significant. We have demonstrated that there are chronological shifts and changes in the causes of death following treatment for early-stage oral cancer.

Stillbirth, early death and neonatal morbidity among offspring of female cancer survivors.

PubMed

Madanat-Harjuoja, Laura-Maria; Lähteenmäki, Päivi M; Dyba, Tadeusz; Gissler, Mika; Boice, John D; Malila, Nea

2013-08-01

Increased awareness of the adverse effects of cancer treatments has prompted the development of fertility preserving regimens for the growing population of cancer survivors who desire to have children of their own. We conducted a registry-based study to evaluate the risk of stillbirth, early death and neonatal morbidity among children of female cancer survivors (0-34 years at diagnosis) compared with children of female siblings. A total of 3501 and 16 908 children of female cancer patients and siblings, respectively, were linked to the national medical birth and cause-of-death registers. The risk of stillbirth or early death was not significantly increased among offspring of cancer survivors as compared to offspring of siblings: the risk [Odds Ratio (OR)] of early neonatal death, i.e. mortality within the first week was 1.35, with a 95% confidence interval (CI) of 0.58-3.18, within 28 days 1.40, 95% CI 0.46-4.24 and within the first year of life 1.11, 95% CI 0.64-1.93 after adjustment for the main explanatory variables. All these risk estimates were reduced towards one after further adjustment for duration of pregnancy. Measures of serious neonatal morbidity were not significantly increased among the children of survivors. However, there was a significant increase in the monitoring of children of cancer survivors for neonatal conditions (OR 1.56, 95% CI 1.35-1.80), which persisted even after correcting for duration of pregnancy, that might be related to parental cancer and its treatment or increased surveillance among the children. Offspring of cancer survivors were more likely to require monitoring or care in a neonatal intensive care unit, but the risk of early death or stillbirth was not increased after adjustment for prematurity. Due to the rarity of the mortality outcomes studied, collaborative studies may be helpful in ruling out the possibility of an increased risk among offspring of cancer survivors.

Slow Gait Speed Is an Independent Predictor of Early Death in Older Cancer Outpatients: Results from a Prospective Cohort Study.

PubMed

Pamoukdjian, F; Lévy, V; Sebbane, G; Boubaya, M; Landre, T; Bloch-Queyrat, C; Paillaud, E; Zelek, L

2017-01-01

To assess the predictive value of gait speed for early death in older outpatients with cancer. Prospective bicentric observational cohort study. The Physical Frailty in Elder Cancer patients (PF-EC) study (France). One hundred and ninety outpatients with cancer during the first 6 months of follow up in the PF-EC study. The association between usual gait speed over 4 m alone (GS) or included in the short physical performance battery (SPPB) and overall survival within 6 months following a comprehensive geriatric assessment (CGA). A Cox proportional-hazard regression model was performed in non-survivors for clinical factors from the CGA, along with c reactive protein (CRP). Two models were created to assess GS alone and from inclusion in the SPPB. The mean age was 80.6 years, and 50.5% of the participants were men. Death occurred in 11% (n=22) of the participants within the 6 month follow up period. Of these participants, 98% had solid cancers, and 33% had a metastatic disease. A GS < 0.8 m/s (HR=5.6, 95%CI=1.6-19.7, p=0.007), a SPPB < 9 (HR=5.8, 95%CI=1.6-20.9, p=0.007) and a CRP of 50 mg/l or greater (p<0.0001) were significantly associated with early death in the two multivariate analyses. Cancer site and extension were not significantly associated with early death. Walking tests are associated with early death within the 6 month follow up period after a CGA independent of cancer site and cancer extension. GS alone < 0.8 m/s is at least as efficacious as the SPPB in predicting this outcome. GS alone could be used routinely as a marker of early death to adapt oncologic therapeutics. Further studies are needed to validate these preliminary data.

Integrated Genomic and Epigenomic Analysis of Breast Cancer Brain Metastasis

PubMed Central

Salhia, Bodour; Kiefer, Jeff; Ross, Julianna T. D.; Metapally, Raghu; Martinez, Rae Anne; Johnson, Kyle N.; DiPerna, Danielle M.; Paquette, Kimberly M.; Jung, Sungwon; Nasser, Sara; Wallstrom, Garrick; Tembe, Waibhav; Baker, Angela; Carpten, John; Resau, Jim; Ryken, Timothy; Sibenaller, Zita; Petricoin, Emanuel F.; Liotta, Lance A.; Ramanathan, Ramesh K.; Berens, Michael E.; Tran, Nhan L.

2014-01-01

The brain is a common site of metastatic disease in patients with breast cancer, which has few therapeutic options and dismal outcomes. The purpose of our study was to identify common and rare events that underlie breast cancer brain metastasis. We performed deep genomic profiling, which integrated gene copy number, gene expression and DNA methylation datasets on a collection of breast brain metastases. We identified frequent large chromosomal gains in 1q, 5p, 8q, 11q, and 20q and frequent broad-level deletions involving 8p, 17p, 21p and Xq. Frequently amplified and overexpressed genes included ATAD2, BRAF, DERL1, DNMTRB and NEK2A. The ATM, CRYAB and HSPB2 genes were commonly deleted and underexpressed. Knowledge mining revealed enrichment in cell cycle and G2/M transition pathways, which contained AURKA, AURKB and FOXM1. Using the PAM50 breast cancer intrinsic classifier, Luminal B, Her2+/ER negative, and basal-like tumors were identified as the most commonly represented breast cancer subtypes in our brain metastasis cohort. While overall methylation levels were increased in breast cancer brain metastasis, basal-like brain metastases were associated with significantly lower levels of methylation. Integrating DNA methylation data with gene expression revealed defects in cell migration and adhesion due to hypermethylation and downregulation of PENK, EDN3, and ITGAM. Hypomethylation and upregulation of KRT8 likely affects adhesion and permeability. Genomic and epigenomic profiling of breast brain metastasis has provided insight into the somatic events underlying this disease, which have potential in forming the basis of future therapeutic strategies. PMID:24489661

Socioecological perspectives on cervical cancer and cervical cancer screening among Asian American women.

PubMed

Lee, Jongwon; Carvallo, Mauricio

2014-10-01

Although cervical cancer is one of the most commonly diagnosed cancers among Vietnamese American women (VAW) and Korean American women (KAW), both groups consistently report much lower rates of cervical cancer screening compared with other Asian ethnic subgroups and non-Hispanic Whites. This study aimed to explore multilevel factors that may underlie low screening rates among VAW and KAW living in a city where their ethnic communities are relatively small. The socioecological model was used as a conceptual framework. Thirty participants were conveniently recruited from ethnic beauty salons run by VA and KA cosmetologists in Albuquerque, New Mexico. The participants' average age was 44.6 years (SD = .50; range = 21-60). Most participants were married (80 %) and employed (73.3 %), and had health insurance (83.3 %). A qualitative interview was conducted in Vietnamese or Korean and transcribed verbatim. A thematic content analysis was used to identify major codes, categories, and patterns across the transcripts. The study identified several factors at the individual (e.g., pregnancy, poverty, personality), interpersonal (e.g., family responsibility, mother as influential referent), and community (e.g., lack of availability, community size) levels. The study sheds light on four major areas that must be taken into consideration in the development of culturally appropriate, community-based interventions aimed to reduce disparities in cervical cancer screening among ethnic minority women in the United States: (1) ethnic community size and geographic location; (2) cross-cultural similarities and dissimilarities; (3) targeting of not only unmarried young women, but also close referents; and (4) utilization of trusted resources within social networks.

Early Palliative Care With Standard Care or Standard Care Alone in Improving Quality of Life of Patients With Incurable Lung or Non-colorectal Gastrointestinal Cancer and Their Family Caregivers

ClinicalTrials.gov

2017-04-19

Liver Cancer; Anxiety Disorder; Depression; Small Cell Lung Cancer; Extrahepatic Bile Duct Cancer; Malignant Mesothelioma; Pancreatic Cancer; Esophageal Cancer; Gastric Cancer; Non-small Cell Lung Cancer

Spatiotemporal proteomic analyses during pancreas cancer progression identifies serine/threonine stress kinase 4 (STK4) as a novel candidate biomarker for early stage disease.

PubMed

Mirus, Justin E; Zhang, Yuzheng; Hollingsworth, Michael A; Solan, Joell L; Lampe, Paul D; Hingorani, Sunil R

2014-12-01

Pancreas cancer, or pancreatic ductal adenocarcinoma, is the deadliest of solid tumors, with a five-year survival rate of <5%. Detection of resectable disease improves survival rates, but access to tissue and other biospecimens that could be used to develop early detection markers is confounded by the insidious nature of pancreas cancer. Mouse models that accurately recapitulate the human condition allow disease tracking from inception to invasion and can therefore be useful for studying early disease stages in which surgical resection is possible. Using a highly faithful mouse model of pancreas cancer in conjunction with a high-density antibody microarray containing ∼2500 antibodies, we interrogated the pancreatic tissue proteome at preinvasive and invasive stages of disease. The goal was to discover early stage tissue markers of pancreas cancer and follow them through histologically defined stages of disease using cohorts of mice lacking overt clinical signs and symptoms and those with end-stage metastatic disease, respectively. A panel of seven up-regulated proteins distinguishing pancreas cancer from normal pancreas was validated, and their levels were assessed in tissues collected at preinvasive, early invasive, and moribund stages of disease. Six of the seven markers also differentiated pancreas cancer from an experimental model of chronic pancreatitis. The levels of serine/threonine stress kinase 4 (STK4) increased between preinvasive and invasive stages, suggesting its potential as a tissue biomarker, and perhaps its involvement in progression from precursor pancreatic intraepithelial neoplasia to pancreatic ductal adenocarcinoma. Immunohistochemistry of STK4 at different stages of disease revealed a dynamic expression pattern further implicating it in early tumorigenic events. Immunohistochemistry of a panel of human pancreas cancers confirmed that STK4 levels were increased in tumor epithelia relative to normal tissue. Overall, this integrated approach yielded several tissue markers that could serve as signatures of disease stage, including early (resectable), and therefore clinically meaningful, stages. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.