Science.gov

Sample records for aggressive pediatric cancer

  1. Pediatric Thyroid Cancer

    MedlinePlus

    ... Marketplace Find an ENT Doctor Near You Pediatric Thyroid Cancer Pediatric Thyroid Cancer Patient Health Information News media ... and neck issues, should be consulted. Types of thyroid cancer in children: Papillary : This form of thyroid cancer ...

  2. Snapshot of Pediatric Cancers

    MedlinePlus

    ... and other central nervous system (CNS) tumors , and neuroblastoma , which are expected to account for more than ... in clinical trials in children with ALL and neuroblastoma. Selected Advances in Pediatric Cancers Research A comprehensive ...

  3. Breast Cancers Between Mammograms Have Aggressive Features

    Cancer.gov

    Breast cancers that are discovered in the period between regular screening mammograms—known as interval cancers—are more likely to have features associated with aggressive behavior and a poor prognosis than cancers found via screening mammograms.

  4. Temozolomide and radiation for aggressive pediatric central nervous system malignancies.

    PubMed

    Loh, Kenneth C; Willert, Jennifer; Meltzer, Hal; Roberts, William; Kerlin, Bryce; Kadota, Richard; Levy, Michael; White, Greg; Geddis, Amy; Schiff, Deborah; Martin, Laura; Yu, Alice; Kung, Faith; Spear, Matthew A

    2005-05-01

    This study describes the outcomes of children treated with combinations of temozolomide and radiation therapy for various aggressive central nervous system malignancies. Their age at diagnosis ranged from 1 to 15 years. Patients with focal disease were treated with concomitant temozolomide (daily 75 mg/m) and three-dimensional conformal radiotherapy in a dose that ranged from 50 to 54 Gy, followed by temozolomide (200 mg/m/d x 5 days/month in three patients, 150 mg/m x 5 days/ month in one patient). Patients with disseminated disease were treated with craniospinal radiation (39.6 Gy) before conformal boost. One patient received temozolomide (200 mg/m x 5 days/month) before craniospinal radiation, and one patient received temozolomide (daily 95 mg/m) concomitant with craniospinal radiation and a radiosurgical boost, followed by temozolomide (200 mg/m x 5 days/month). Three patients achieved a partial response during treatment, with two of these patients dying of progressive disease after treatment. One patient has no evidence of disease. Three patients achieved stable disease, with one of these patients dying of progressive disease after treatment. Toxicities observed included low-grade neutropenia, thrombocytopenia, and lymphopenia. The combination of temozolomide and radiotherapy appears to be well tolerated in a variety of treatment schemas for aggressive pediatric central nervous system malignancies. This information is of particular use in designing future studies, given the recent positive results in a randomized study examining the use of temozolomide concomitant with radiation in the treatment of adult glioblastoma.

  5. Survivin: an inhibitor of apoptosis in pediatric cancer.

    PubMed

    Fangusaro, Jason R; Caldas, Hugo; Jiang, Yuying; Altura, Rachel A

    2006-07-01

    Survivin is an inhibitor of apoptosis protein (IAP) expressed in a large number of adult malignancies. Its expression levels correlate with more aggressive disease and poor clinical outcome in many of these tumors. As its expression is restricted in normal adult differentiated tissues, it has become of great interest as both a tumor prognostic marker and as a potential biologic target for future anti-cancer therapies. Survivin expression and Survivin-based therapies have been examined in many of the more common pediatric malignancies. We present an overview of Survivin function and current research exploring its biologic and therapeutic roles in pediatric tumors.

  6. Cancer vaccines: emphasis on pediatric cancers.

    PubMed

    Guinipero, Terri; Finn, Olivera J

    2010-01-01

    The success that vaccines have had in the fight with infectious diseases has not been mirrored in their use in the fight against cancer. The major differences are that cancer vaccines have been tested in the therapeutic rather than the prophylactic setting, and in older adults rather than in the pediatric population. Cancers, as well as current standard treatments, are highly immunosuppressive, which further compromises the success of therapeutic vaccines. Cancer is considered to be primarily a disease of the older age and yet many children suffer from or succumb to cancers such as leukemias, glioblastomas, neuroblastomas and sarcomas. Standard therapy, even when curative, is accompanied by serious side effects, including secondary tumors later in life. Due to the greater capacity of a young immune system to recover after cancer treatment, therapeutic vaccines are expected to have a better chance to elicit protective immunity and prevent cancer recurrence in children. In this review, we discuss the current efforts at designing and testing cancer vaccines in children with the focus on specific tumor antigens expressed by pediatric cancers.

  7. Pediatric papillary thyroid cancer: current management challenges

    PubMed Central

    Verburg, Frederik A; Van Santen, Hanneke M; Luster, Markus

    2017-01-01

    Although with a standardized incidence of 0.54 cases per 100,000 persons, differentiated thyroid cancer (DTC) is a rare disease in children and adolescents, it nonetheless concerns ~1.4% of all pediatric malignancies. Furthermore, its incidence is rising. Due to the rarity and long survival of pediatric DTC patients, in most areas of treatment little evidence exists. Treatment of pediatric DTC is therefore littered with controversies, many questions therefore remain open regarding the optimal management of pediatric papillary thyroid cancer (PTC), and many challenges remain unsolved. In the present review, we aim to provide an overview of these challenging areas of patient and disease management in pediatric PTC patients. Data on diagnosis, surgery, radionuclide, and endocrine therapy are discussed, and the controversies therein are highlighted. PMID:28096684

  8. Molecular Targeted Therapies of Aggressive Thyroid Cancer

    PubMed Central

    Ferrari, Silvia Martina; Fallahi, Poupak; Politti, Ugo; Materazzi, Gabriele; Baldini, Enke; Ulisse, Salvatore; Miccoli, Paolo; Antonelli, Alessandro

    2015-01-01

    Differentiated thyroid carcinomas (DTCs) that arise from follicular cells account >90% of thyroid cancer (TC) [papillary thyroid cancer (PTC) 90%, follicular thyroid cancer (FTC) 10%], while medullary thyroid cancer (MTC) accounts <5%. Complete total thyroidectomy is the treatment of choice for PTC, FTC, and MTC. Radioiodine is routinely recommended in high-risk patients and considered in intermediate risk DTC patients. DTC cancer cells, during tumor progression, may lose the iodide uptake ability, becoming resistant to radioiodine, with a significant worsening of the prognosis. The lack of specific and effective drugs for aggressive and metastatic DTC and MTC leads to additional efforts toward the development of new drugs. Several genetic alterations in different molecular pathways in TC have been shown in the past few decades, associated with TC development and progression. Rearranged during transfection (RET)/PTC gene rearrangements, RET mutations, BRAF mutations, RAS mutations, and vascular endothelial growth factor receptor 2 angiogenesis pathways are some of the known pathways determinant in the development of TC. Tyrosine kinase inhibitors (TKIs) are small organic compounds inhibiting tyrosine kinases auto-phosphorylation and activation, most of them are multikinase inhibitors. TKIs act on the aforementioned molecular pathways involved in growth, angiogenesis, local, and distant spread of TC. TKIs are emerging as new therapies of aggressive TC, including DTC, MTC, and anaplastic thyroid cancer, being capable of inducing clinical responses and stabilization of disease. Vandetanib and cabozantinib have been approved for the treatment of MTC, while sorafenib and lenvatinib for DTC refractory to radioiodine. These drugs prolong median progression-free survival, but until now no significant increase has been observed on overall survival; side effects are common. New efforts are made to find new more effective and safe compounds and to personalize the therapy in

  9. Tumor Tension Induces Persistent Inflammation and Promotes Breast Cancer Aggression

    DTIC Science & Technology

    2015-10-01

    Award Number: W81XWH-14-1-0056 TITLE: Tumor Tension Induces Persistent Inflammation and Promotes Breast Cancer Aggression PRINCIPAL INVESTIGATOR...Breast Cancer Aggression 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) 5d. PROJECT NUMBER Ori Maller and Valerie M. Weaver email...ECM stiffening cooperate with inflammatory signaling to facilitate immune evasion and promote breast cancer aggression . In this progress report, I

  10. Pharmacology and pharmacogenetics of pediatric ADHD with associated aggression: a review.

    PubMed

    Patel, Bianca D; Barzman, Drew H

    2013-12-01

    Attention deficit hyperactivity disorder (ADHD) is often associated with symptoms of aggression in children and adolescents. Clinically, this is complex because aggression can be from hyperactivity and impulsivity, or could be a distinct symptom from a comorbid diagnosis. Past research has recommended first treating the primary disorder of ADHD. Stimulants are the most common treatment for pediatric ADHD, which can be helpful in decreasing aggressive behaviors. Alpha-adrenergic agonists and atomoxetine (ATX) are non-stimulant medications for ADHD and aggression, but more research is necessary to compare these drugs to stimulants. If aggressive symptoms do not improve from treating the primary disorder, aggression can be treated separately. Risperidone, lithium, valproic acid, clonidine, and guanfacine have shown positive results in reducing aggression, but studies including children with aggression and ADHD are limited. The variability in treatment tolerability in patients has stimulated research in pharmacogenetics for ADHD. Although this field is still emerging, research has found evidence supporting a link between the response rate of methylphenidate and the dopamine transporter (DAT1) and a link between the metabolism rate of atomoxetine and hepatic cytochrome 450 isozymes. Pharmacogenetics may be relevant to ADHD and associated aggression. Further research in pharmacogenetics will strive to identify patterns of genetic variations that can tailor individual treatments.

  11. Targeting pediatric cancer stem cells with oncolytic virotherapy.

    PubMed

    Friedman, Gregory K; Cassady, Kevin A; Beierle, Elizabeth A; Markert, James M; Gillespie, G Yancey

    2012-04-01

    Cancer stem cells (CSCs), also termed "cancer-initiating cells" or "cancer progenitor cells," which have the ability to self-renew, proliferate, and maintain the neoplastic clone, have recently been discovered in a wide variety of pediatric tumors. These CSCs are thought to be responsible for tumorigenesis and tumor maintenance, aggressiveness, and recurrence due to inherent resistance to current treatment modalities such as chemotherapy and radiation. Oncolytic virotherapy offers a novel, targeted approach for eradicating pediatric CSCs using mechanisms of cell killing that differ from conventional therapies. Moreover, oncolytic viruses have the ability to target specific features of CSCs such as cell-surface proteins, transcription factors, and the CSC microenvironment. Through genetic engineering, a wide variety of foreign genes may be expressed by oncolytic viruses to augment the oncolytic effect. We review the current data regarding the ability of several types of oncolytic viruses (herpes simplex virus-1, adenovirus, reovirus, Seneca Valley virus, vaccinia virus, Newcastle disease virus, myxoma virus, vesicular stomatitis virus) to target and kill both CSCs and tumor cells in pediatric tumors. We highlight advantages and limitations of each virus and potential ways in which next-generation engineered viruses may target resilient CSCs.

  12. Fathering and the Pediatric Cancer Experience.

    DTIC Science & Technology

    1979-12-01

    dealing with parenting has to date emphasized mothers and their children. The mother, by popular acclaim, is the primary parent in actual household...addition to bi-weekly attendance at the pediatric oncology clinic, I attended a monthly parents group consisting of the parents of children with cancer...replacement therapy of blood and/or blood components, and admission to the pediatric inpatient units. Arrangements need to be made by one or both parents

  13. Aggressive thyroid cancer: targeted therapy with sorafenib.

    PubMed

    Corrado, Alda; Ferrari, Silvia M; Politti, Ugo; Mazzi, Valeria; Miccoli, Mario; Materazzi, Gabriele; Antonelli, Alessandro; Ulisse, Salvatore; Fallahi, Poupak; Miccoli, Paolo

    2017-03-01

    Sorafenib (Nexavar), is a multikinase inhibitor, which has demonstrated both antiproliferative and antiangiogenic properties in vitro and in vivo, inhibiting the activity of targets present in the tumoral cells (c-RAF [proto-oncogene serine/threonine-protein kinase], BRAF, (V600E)BRAF, c-KIT, and FMS-like tyrosine kinase 3) and in tumor vessels (c-RAF, vascular endothelial growth factor receptor [VEGFR]-2, VEGFR-3, and platelet-derived growth factor receptor β). Sorafenib was initially approved for the treatment of hepatocellular carcinoma and advanced renal cell carcinoma. Experimental studies have demonstrated that sorafenib has both antiproliferative and antiangiogenic properties in vitro and in vivo, against thyroid cancer cells. Furthermore, several completed (or ongoing) studies have evaluated the long-term efficacy and tolerability of sorafenib in patients with papillary, follicular and medullary aggressive thyroid cancer. The results of the different studies showed good clinical responses and stabilization of the disease and suggested that sorafenib is a promising therapeutic option in patients with advanced thyroid cancer that is not responsive to traditional therapeutic strategies (such as radioiodine). Currently, USA Food and Drug Administration has approved the use of sorafenib for metastatic differentiated thyroid cancer.

  14. Screening for Psychosocial Risk in Pediatric Cancer

    PubMed Central

    Kazak, Anne E.; Brier, Moriah; Alderfer, Melissa A.; Reilly, Anne; Parker, Stephanie Fooks; Rogerwick, Stephanie; Ditaranto, Susan; Barakat, Lamia P.

    2012-01-01

    Major professional organizations have called for psychosocial risk screening to identify specific psychosocial needs of children with cancer and their families and facilitate the delivery of appropriate evidence-based care to address these concerns. However, systematic screening of risk factors at diagnosis is rare in pediatric oncology practice. Subsequent to a brief summary of psychosocial risks in pediatric cancer and the rationale for screening, this review identified three screening models and two screening approaches (Distress Thermometer [DT], Psychosocial Assessment Tool [PAT]), among many more papers calling for screening. Implications of broadly implemented screening for all patients across treatment settings are discussed. PMID:22492662

  15. Screening for psychosocial risk in pediatric cancer.

    PubMed

    Kazak, Anne E; Brier, Moriah; Alderfer, Melissa A; Reilly, Anne; Fooks Parker, Stephanie; Rogerwick, Stephanie; Ditaranto, Susan; Barakat, Lamia P

    2012-11-01

    Major professional organizations have called for psychosocial risk screening to identify specific psychosocial needs of children with cancer and their families and facilitate the delivery of appropriate evidence-based care to address these concerns. However, systematic screening of risk factors at diagnosis is rare in pediatric oncology practice. Subsequent to a brief summary of psychosocial risks in pediatric cancer and the rationale for screening, this review identified three screening models and two screening approaches [Distress Thermometer (DT), Psychosocial Assessment Tool (PAT)], among many more articles calling for screening. Implications of broadly implemented screening for all patients across treatment settings are discussed.

  16. Vitamin D and Related Genes, Race and Prostate Cancer Aggressiveness

    DTIC Science & Technology

    2015-12-29

    vitamin D and genetic polymorphisms act synergistically to affect prostate cancer aggressiveness. We examined these associations among vitamin D...epidemiologic techniques for estimating odds of high aggressive prostate cancer according to vitamin D metabolites, PTH, calcium, phosphorus and genetic ...hypotheses a. Statistical analyses have been performed examining associations between 25(OH)D, 1,25(OH)2D, genetic polymorphisms and prostate cancer

  17. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    FAS activity in prostatectomy samples, intraprostatic lipid as measured by MRSI and prostate tumor aggressiveness. 3) To quantify key metabolic ...intermediates involved in lipid metabolism , mitochondrial function, inflammation, and apoptosis in the prostatectomy samples. 15. SUBJECT TERMS : none...vivo intraprostatic fat as measured by 1H MRSI, metabolic signatures of lipid oxidation and metabolism , and prostate cancer aggressiveness, our

  18. Targeting Aggressive Cancer Stem Cells in Glioblastoma

    PubMed Central

    Seymour, Tracy; Nowak, Anna; Kakulas, Foteini

    2015-01-01

    Glioblastoma (GBM) is the most common and fatal type of primary brain tumor. Gliosarcoma (GSM) is a rarer and more aggressive variant of GBM that has recently been considered a potentially different disease. Current clinical treatment for both GBM and GSM includes maximal surgical resection followed by post-operative radiotherapy and concomitant and adjuvant chemotherapy. Despite recent advances in treating other solid tumors, treatment for GBM and GSM still remains palliative, with a very poor prognosis and a median survival rate of 12–15 months. Treatment failure is a result of a number of causes, including resistance to radiotherapy and chemotherapy. Recent research has applied the cancer stem cells theory of carcinogenesis to these tumors, suggesting the existence of a small subpopulation of glioma stem-like cells (GSCs) within these tumors. GSCs are thought to contribute to tumor progression, treatment resistance, and tumor recapitulation post-treatment and have become the focus of novel therapy strategies. Their isolation and investigation suggest that GSCs share critical signaling pathways with normal embryonic and somatic stem cells, but with distinct alterations. Research must focus on identifying these variations as they may present novel therapeutic targets. Targeting pluripotency transcription factors, SOX2, OCT4, and Nanog homeobox, demonstrates promising therapeutic potential that if applied in isolation or together with current treatments may improve overall survival, reduce tumor relapse, and achieve a cure for these patients. PMID:26258069

  19. Caffeine Use: Association with Nicotine Use, Aggression, and Other Psychopathology in Psychiatric and Pediatric Outpatient Adolescents

    PubMed Central

    Martin, Catherine A.; Cook, Circe; Woodring, John H.; Burkhardt, Gretchen; Guenthner, Greg; Omar, Hatim A.; Kelly, Thomas H.

    2009-01-01

    The objective of this study was to evaluate the relationship between caffeine use, other drug use, and psychopathology in adolescents, using self-report measures. The study group consisted of 132 adolescents (average age 14.01 ± 2.06 years, 52% female, 19% African American, 5% other categories, 76% Caucasian). Most (47%) were recruited from a child psychiatry clinic with emphasis on youth with disruptive disorders, with 35% from an adolescent pediatric clinic with emphasis on prevention of risk-taking behavior and 18% from a pediatric clinic for families with limited resources. Subjects were consecutively recruited before or after regular clinic visits. Consent was obtained from parents and assent from the youth. High caffeine consumption was associated with daily cigarette use; aggressive behavior; conduct, attention deficit/hyperactivity, and social problems; and increased somatic complaints in adolescents. PMID:18516472

  20. Caffeine use: association with nicotine use, aggression, and other psychopathology in psychiatric and pediatric outpatient adolescents.

    PubMed

    Martin, Catherine A; Cook, Circe; Woodring, John H; Burkhardt, Gretchen; Guenthner, Greg; Omar, Hatim A; Kelly, Thomas H

    2008-05-22

    The objective of this study was to evaluate the relationship between caffeine use, other drug use, and psychopathology in adolescents, using self-report measures. The study group consisted of 132 adolescents (average age 14.01 +/- 2.06 years, 52% female, 19% African American, 5% other categories, 76% Caucasian). Most (47%) were recruited from a child psychiatry clinic with emphasis on youth with disruptive disorders, with 35% from an adolescent pediatric clinic with emphasis on prevention of risk-taking behavior and 18% from a pediatric clinic for families with limited resources. Subjects were consecutively recruited before or after regular clinic visits. Consent was obtained from parents and assent from the youth. High caffeine consumption was associated with daily cigarette use; aggressive behavior; conduct, attention deficit/hyperactivity, and social problems; and increased somatic complaints in adolescents.

  1. Genetic predisposition and screening in pediatric cancer.

    PubMed

    Pakakasama, Samart; Tomlinson, Gail E

    2002-12-01

    Pediatricians are often the health care providers who first detect the signs and symptoms of childhood cancer. Although pediatric malignancies are rare diseases, early diagnosis is an important factor leading to high cure rates of many types of cancers including retinoblastomara, Wilms' tumor, hepatoblastoma, rhabdomyosarcoma. thyroid carcinoma, and other solid tumors. A number of familial cancer syndromes present with childhood cancers that can be recognized or diagnosed by pediatricians. The genetic origins of several syndromes have been elucidated. Genetic testing is not yet available for all of these inherited cancers. A frequently updated list of genetic tests is available at www.genetests.org. The ordering and interpreting of genetic tests, however, is often best done by trained genetic counselors. The pediatrician will play a vital on-going role in following the at-risk child. In many of syndromes discussed, the cost effectiveness of the tests as well as that of any potential intervention needs further study. The role of the subtle genetic polymorphisms in pediatric tumorigenesis. many more of which will undoubtedly be described in the coming years, has not yet been translated into defined needs for interventions. Perhaps in the future it will be possible to understand the additive effect of multiple genetic polymorphisms and to determine genetic profiles of high cancer risk. Until suitable interventions are established, however, the study of genetic variability and cancer will await practical significance. Undoubtedly other major important cancer genes are yet to be discovered and characterized. An additional challenge is the counseling and management of children and adults who have a strong family history of cancer yet who do not have a recognizable syndrome. The role of the primary pediatrician is to recognize the major cancer genetic syndromes, to make appropriate referrals for genetic counseling and testing when indicated, and to ensure that adequate

  2. Two Susceptibility Loci Identified for Prostate Cancer Aggressiveness

    PubMed Central

    Berndt, Sonja I.; Wang, Zhaoming; Yeager, Meredith; Alavanja, Michael C.; Albanes, Demetrius; Amundadottir, Laufey; Andriole, Gerald; Freeman, Laura Beane; Campa, Daniele; Cancel-Tassin, Geraldine; Canzian, Federico; Cornu, Jean-Nicolas; Cussenot, Olivier; Diver, W. Ryan; Gapstur, Susan M.; Grönberg, Henrik; Haiman, Christopher A.; Henderson, Brian; Hutchinson, Amy; Hunter, David J.; Key, Timothy J.; Kolb, Suzanne; Koutros, Stella; Kraft, Peter; Le Marchand, Loic; Lindström, Sara; Machiela, Mitchell J.; Ostrander, Elaine A.; Riboli, Elio; Schumacher, Fred; Siddiq, Afshan; Stanford, Janet L.; Stevens, Victoria L.; Travis, Ruth C.; Tsilidis, Konstantinos K.; Virtamo, Jarmo; Weinstein, Stephanie; Wilkund, Fredrik; Xu, Jianfeng; Zheng, S. Lilly; Yu, Kai; Wheeler, William; Zhang, Han; Sampson, Joshua; Black, Amanda; Jacobs, Kevin; Hoover, Robert N; Tucker, Margaret; Chanock, Stephen J.

    2015-01-01

    Most men diagnosed with prostate cancer will experience indolent disease; hence discovering genetic variants that distinguish aggressive from non-aggressive prostate cancer is of critical clinical importance for disease prevention and treatment. In a multistage, case-only genome-wide association study of 12,518 prostate cancer cases, we identify two loci associated with Gleason score, a pathological measure of disease aggressiveness: rs35148638 at 5q14.3 (RASA1, P=6.49×10-9) and rs78943174 at 3q26.31 (NAALADL2, P=4.18×10-8). In a stratified case-control analysis, the SNP at 5q14.3 appears specific for aggressive prostate cancer (P=8.85×10-5) with no association for non-aggressive prostate cancer compared to controls (P=0.57). The proximity of these loci to genes involved in vascular disease suggests potential biological mechanisms worthy of further investigation. PMID:25939597

  3. Role of MicroRNA in Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-07-01

    AD_________________ Award Number: W81XWH-11-1-0491 TITLE: Role of MicroRNA in Aggressive Prostate... MicroRNA in Aggressive Prostate Cancer 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-11-1-0491 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Jer...action is not fully characterized. Using microRNA microarray screening, we found microRNA -363 (miR363) is significantly down regulated in several

  4. Biomarkers to Distinguish Aggressive Cancers from Non-aggressive or Non-progressing Cancer — EDRN Public Portal

    Cancer.gov

    Distinguishing aggressive cancers from non-aggressive or non-progressing cancers is an issue of both clinical and public health importance particularly for those cancers with an available screening test. With respect to breast cancer, mammographic screening has been shown in randomized trials to reduce breast cancer mortality, but given the limitations of its sensitivity and specificity some breast cancers are missed by screening. These so called interval detected breast cancers diagnosed between regular screenings are known to have a more aggressive clinical profile. In addition, of those cancers detected by mammography some are indolent while others are more likely to recur despite treatment. The pilot study proposed herein is highly responsive to the EDRN supplement titled “Biomarkers to Distinguish Aggressive Cancers from Nonaggressive or Non-progressing Cancers” in that it addresses both of the research objectives related to these issues outlined in the notice for this supplement: Aim 1: To identify biomarkers in tumor tissue related to risk of interval detected vs. mammography screen detected breast cancer focusing on early stage invasive disease. We will compare gene expression profiles using the whole genome-cDNA-mediated Annealing, Selection, extension and Ligation (DASL) assay of 50 screen detected cancers to those of 50 interval detected cancers. Through this approach we will advance our understanding of the molecular characteristics of interval vs. screen detected breast cancers and discover novel biomarkers that distinguish between them. Aim 2: To identify biomarkers in tumor tissue related to risk of cancer recurrence among patients with screen detected early stage invasive breast cancer. Using the DASL assay we will compare gene expression profiles from screen detected early stage breast cancer that either recurred within five years or never recurred within five years. These two groups of patients will be matched on multiple factors including

  5. Molecular Pathways Associated with Aggressiveness of Papillary Thyroid Cancer

    PubMed Central

    Benvenga, Salvatore; Koch, Christian A

    2014-01-01

    The most common thyroid malignancy is papillary thyroid cancer (PTC). Mortality rates from PTC mainly depend on its aggressiveness. Geno- and phenotyping of aggressive PTC has advanced our understanding of treatment failures and of potential future therapies. Unraveling molecular signaling pathways of PTC including its aggressive forms will hopefully pave the road to reduce mortality but also morbidity from this cancer. The mitogen-activated protein kinase and the phosphatidylinositol 3-kinase signaling pathway as well as the family of RAS oncogenes and BRAF as a member of the RAF protein family and the aberrant expression of microRNAs miR-221, miR-222, and miR-146b all play major roles in tumor initiation and progression of aggressive PTC. Small molecule tyrosine kinase inhibitors targeting BRAF-mediated events, vascular endothelial growth factor receptors, RET/PTC rearrangements, and other molecular targets, show promising results to improve treatment of radioiodine resistant, recurrent, and aggressive PTC. PMID:24955023

  6. Role of MicroRNA in Aggressive Prostate Cancer

    DTIC Science & Technology

    2013-07-01

    SUBTITLE Role of microRNA in aggressive prostate cancer 5a. CONTRACT NUMBER W81XWH-11-1-0491 5b. GRANT NUMBER 5c. PROGRAM ELEMENT NUMBER... cancer lesion, we applied ISH on formalin-fixed paraffin embedded (FFPE) tissue . We first confirmed the specificity of miR363 probe using benign...with prostate cancer development. REPORTABLE OUTCOMES Lo, U., Pong, R.C., Tseng, S.F., Hsieh, J.T. (2013) MicroRNA -363 regulated by a novel

  7. MicroRNA in Prostate Cancer Racial Disparities and Aggressiveness

    DTIC Science & Technology

    2014-10-01

    Detroit, MI. Little is known about the role of microRNAs ( miRNAs ) and their biogenesis in prostate cancer (PCa), and less is understood about the possible...AWARD NUMBER: W81XWH-13-1-0477 TITLE: MicroRNA in Prostate Cancer Racial Disparities and Aggressiveness PRINCIPAL INVESTIGATOR: Cathryn...ADDRESS. 1. REPORT DATE 2014 2. REPORT TYPE Annual 3. DATES COVERED 30 Sept 2013-29 Sept 2014 4. TITLE AND SUBTITLE MicroRNA in Prostate Cancer Racial

  8. Effect of Statins and Anticoagulants on Prostate Cancer Aggressiveness

    SciTech Connect

    Alizadeh, Moein; Sylvestre, Marie-Pierre; Zilli, Thomas; Van Nguyen, Thu; Guay, Jean-Pierre; Bahary, Jean-Paul; Taussky, Daniel

    2012-07-15

    Purpose: Statins and anticoagulants (ACs) have both been associated with a less-aggressive prostate cancer (PCa) and a better outcome after treatment of localized PCa. The results of these studies might have been confounded because patients might often take both medications. We examined their respective influence on PCa aggressiveness at initial diagnosis. Materials and Methods: We analyzed 381 patients treated with either external beam radiotherapy or brachytherapy for low-risk (n = 152), intermediate-risk (n = 142), or high-risk (n = 87) localized PCa. Univariate and multivariate logistic regression analyses were used to investigate an association between these drug classes and prostate cancer aggressiveness. We tested whether the concomitant use of statins and ACs had a different effect than that of either AC or statin use alone. Results: Of the 381 patients, 172 (45.1%) were taking statins and 141 (37.0%) ACs; 105 patients (27.6%) used both. On univariate analysis, the statin and AC users were associated with the prostate-specific antigen (PSA) level (p = .017) and National Comprehensive Cancer Network risk group (p = .0022). On multivariate analysis, statin use was associated with a PSA level <10 ng/mL (odds ratio, 2.9; 95% confidence interval, 1.3-6.8; p = .012) and a PSA level >20 ng/mL (odds ratio, 0.29; 95% confidence interval, 0.08-0.83; p = .03). The use of ACs was associated with a PSA level >20 ng/mL (odds ratio, 0.13; 95% confidence interval, 0.02-0.59, p = .02). Conclusion: Both AC and statins have an effect on PCa aggressiveness, with statins having a more stringent relationship with the PSA level, highlighting the importance of considering statin use in studies of PCa aggressiveness.

  9. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    saturation bands (six for fat and two for water) were used to minimize lipid/water contamination to the VOI. The 2D MRSI sequence details are: TR/TE... fat as measured by in-vivo imaging using proton magnetic resonance spectroscopy imaging in the prediction of prostate disease aggressiveness...histology, in-vivo intraprostatic fat as measured by 1H MRSI, metabolic signatures of lipid oxidation and metabolism, and prostate cancer

  10. microRNA in Prostate Cancer Racial Disparities and Aggressiveness

    DTIC Science & Technology

    2015-10-01

    final analyses. 15. SUBJECT TERMS prostate cancer, microRNA, racial disparities, African American, genetic polymorphisms, biochemical recurrence...is to identify novel genetic and epigenetic factors that might contribute significantly to racial/ethnic disparity in PCa risk and progression. We...related miRNAs and PCa aggressiveness, and 3) determine the associations between genetic polymorphisms in miRNA biogenesis pathway genes and plasma levels

  11. Vitamin D and Related Genes, Race, and Prostate Cancer Aggressiveness

    DTIC Science & Technology

    2014-10-01

    SUBTITLE 5a. CONTRACT NUMBER Vitamin D and Related Genes, Race, and Prostate Cancer 5b. GRANT NUMBER W81XWH-11-1-0568 Aggressiveness 5c. PROGRAM...examine whether altered vitamin D status (as measured by serum metabolites and by functional polymorphisms within genes related to vitamin D...potential to provide insights into a chronically underserved population carrying an unequal burden of disease. 15. SUBJECT TERMS Vitamin D, prostate

  12. Neuropilin 2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    AWARD NUMBER: W81XWH-12-1-0308 TITLE: Neuropilin-2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer PRINCIPAL...14Aug2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Neuropilin-2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer 5b. GRANT... aggressive prostate cancer. Cancer Discov 2(10):906-921. 3. Gualberto A & Pollak M (2009) Emerging role of insulin-like growth factor receptor inhibitors in

  13. Low spinophilin expression enhances aggressive biological behavior of breast cancer

    PubMed Central

    Ress, Anna Lena; Aigelsreiter, Ariane; Schauer, Silvia; Wagner, Karin; Langsenlehner, Tanja; Resel, Margit; Gerger, Armin; Ling, Hui; Ivan, Cristina; Calin, George Adrian; Hoefler, Gerald; Rinner, Beate; Pichler, Martin

    2015-01-01

    Spinophilin, a putative tumor suppressor gene, has been shown to be involved in the pathogenesis of certain types of cancer, but its role has never been systematically explored in breast cancer. In this study, we determined for the first time the expression pattern of spinophilin in human breast cancer molecular subtypes (n = 489) and correlated it with survival (n = 921). We stably reduced spinophilin expression in breast cancer cells and measured effects on cellular growth, apoptosis, anchorage-independent growth, migration, invasion and self-renewal capacity in vitro and metastases formation in vivo. Microarray profiling was used to determine the most abundantly expressed genes in spinophilin-silenced breast cancer cells. Spinophilin expression was significantly lower in basal-like breast cancer (p<0.001) and an independent poor prognostic factor in breast cancer patients (hazard ratio = 1.93, 95% confidence interval: 1.24-3.03; p = 0.004) A reduction of spinophilin levels increased cellular growth in breast cancer cells (p<0.05), without influencing activation of apoptosis. Anchorage-independent growth, migration and self-renewal capacity in vitro and metastatic potential in vivo were also significantly increased in spinophilin-silenced cells (p<0.05). Finally, we identified several differentially expressed genes in spinophilin-silenced cells. According to our data, low levels of spinophilin are associated with aggressive behavior of breast cancer. PMID:25857299

  14. The Antihelmintic Drug Pyrvinium Pamoate Targets Aggressive Breast Cancer

    PubMed Central

    Xu, Wei; Lacerda, Lara; Debeb, Bisrat G.; Atkinson, Rachel L.; Solley, Travis N.; Li, Li; Orton, Darren; McMurray, John S.; Hang, Brian I.; Lee, Ethan; Klopp, Ann H.; Ueno, Naoto T.; Reuben, James M.; Krishnamurthy, Savitri; Woodward, Wendy A.

    2013-01-01

    WNT signaling plays a key role in the self-renewal of tumor initiation cells (TICs). In this study, we used pyrvinium pamoate (PP), an FDA-approved antihelmintic drug that inhibits WNT signaling, to test whether pharmacologic inhibition of WNT signaling can specifically target TICs of aggressive breast cancer cells. SUM-149, an inflammatory breast cancer cell line, and SUM-159, a metaplastic basal-type breast cancer cell line, were used in these studies. We found that PP inhibited primary and secondary mammosphere formation of cancer cells at nanomolar concentrations, at least 10 times less than the dose needed to have a toxic effect on cancer cells. A comparable mammosphere formation IC50 dose to that observed in cancer cell lines was obtained using malignant pleural effusion samples from patients with IBC. A decrease in activity of the TIC surrogate aldehyde dehydrogenase was observed in PP-treated cells, and inhibition of WNT signaling by PP was associated with down-regulation of a panel of markers associated with epithelial-mesenchymal transition. In vivo, intratumoral injection was associated with tumor necrosis, and intraperitoneal injection into mice with tumor xenografts caused significant tumor growth delay and a trend toward decreased lung metastasis. In in vitro mammosphere-based and monolayer-based clonogenic assays, we found that PP radiosensitized cells in monolayer culture but not mammosphere culture. These findings suggest WNT signaling inhibition may be a feasible strategy for targeting aggressive breast cancer. Investigation and modification of the bioavailability and toxicity profile of systemic PP are warranted. PMID:24013655

  15. Students with Pediatric Cancer: A Prescription for School Success

    ERIC Educational Resources Information Center

    Hay, Genevieve H.; Nabors, Martha L.; Sullivan, Alexandra; Zygmund, Allyson

    2015-01-01

    Due to medical advances, many students with acute chronic illnesses, like pediatric cancer, are able to attend school. The professional literature reflects the need for reform of educational strategies for children facing cancer treatment and who will be absent for extended periods of time. In order to promote successful educational services and…

  16. Tumor reactive stroma in cholangiocarcinoma: The fuel behind cancer aggressiveness

    PubMed Central

    Brivio, Simone; Cadamuro, Massimiliano; Strazzabosco, Mario; Fabris, Luca

    2017-01-01

    Cholangiocarcinoma (CCA) is a highly aggressive epithelial malignancy still carrying a dismal prognosis, owing to early lymph node metastatic dissemination and striking resistance to conventional chemotherapy. Although mechanisms underpinning CCA progression are still a conundrum, it is now increasingly recognized that the desmoplastic microenvironment developing in conjunction with biliary carcinogenesis, recently renamed tumor reactive stroma (TRS), behaves as a paramount tumor-promoting driver. Indeed, once being recruited, activated and dangerously co-opted by neoplastic cells, the cellular components of the TRS (myofibroblasts, macrophages, endothelial cells and mesenchymal stem cells) continuously rekindle malignancy by secreting a huge variety of soluble factors (cyto/chemokines, growth factors, morphogens and proteinases). Furthermore, these factors are long-term stored within an abnormally remodeled extracellular matrix (ECM), which in turn can deleteriously mold cancer cell behavior. In this review, we will highlight evidence for the active role played by reactive stromal cells (as well as by the TRS-associated ECM) in CCA progression, including an overview of the most relevant TRS-derived signals possibly fueling CCA cell aggressiveness. Hopefully, a deeper knowledge of the paracrine communications reciprocally exchanged between cancer and stromal cells will steer the development of innovative, combinatorial therapies, which can finally hinder the progression of CCA, as well as of other cancer types with abundant TRS, such as pancreatic and breast carcinomas.

  17. Characterization of aggressive prostate cancer using ultrasound RF time series

    NASA Astrophysics Data System (ADS)

    Khojaste, Amir; Imani, Farhad; Moradi, Mehdi; Berman, David; Siemens, D. Robert; Sauerberi, Eric E.; Boag, Alexander H.; Abolmaesumi, Purang; Mousavi, Parvin

    2015-03-01

    Prostate cancer is the most prevalently diagnosed and the second cause of cancer-related death in North American men. Several approaches have been proposed to augment detection of prostate cancer using different imaging modalities. Due to advantages of ultrasound imaging, these approaches have been the subject of several recent studies. This paper presents the results of a feasibility study on differentiating between lower and higher grade prostate cancer using ultrasound RF time series data. We also propose new spectral features of RF time series to highlight aggressive prostate cancer in small ROIs of size 1 mm × 1 mm in a cohort of 19 ex vivo specimens of human prostate tissue. In leave-one-patient-out cross-validation strategy, an area under accumulated ROC curve of 0.8 has been achieved with overall sensitivity and specificity of 81% and 80%, respectively. The current method shows promising results on differentiating between lower and higher grade of prostate cancer using ultrasound RF time series.

  18. Highly prevalent TERT promoter mutations in aggressive thyroid cancers.

    PubMed

    Liu, Xiaoli; Bishop, Justin; Shan, Yuan; Pai, Sara; Liu, Dingxie; Murugan, Avaniyapuram Kannan; Sun, Hui; El-Naggar, Adel K; Xing, Mingzhao

    2013-08-01

    Mutations 1 295 228 C>T and 1 295 250 C>T (termed C228T and C250T respectively), corresponding to -124 C>T and -146 C>T from the translation start site in the promoter of the telomerase reverse transcriptase (TERT) gene, have recently been reported in human cancers, but not in thyroid cancers yet. We explored these mutations in thyroid cancers by genomic sequencing of a large number of primary tumor samples. We found the C228T mutation in 0 of 85 (0.0%) benign thyroid tumors, 30 of 257 (11.7%) papillary thyroid cancers (PTC), 9 of 79 (11.4%) follicular thyroid cancers (FTC), 3 of 8 (37.5%) poorly differentiated thyroid cancers (PDTC), 23 of 54 (42.6%) anaplastic thyroid cancers (ATC), and 8 of 12 (66.7%) thyroid cancer cell lines. The C250T mutation was uncommon, but mutually exclusive with the C228T mutation, and the two mutations were collectively found in 11 of 79 (13.9%) FTC, 25 of 54 (46.3%) ATC, and 11 of 12 (91.7%) thyroid cancer cell lines. Among PTC variants, the C228T mutation was found in 4 of 13 (30.8%) tall-cell PTC (TCPTC), 23 of 187 (12.3%) conventional PTC, and 2 of 56 (3.6%) follicular variant PTC samples. No TERT mutation was found in 16 medullary thyroid cancer samples. The C228T mutation was associated with the BRAF V600E mutation in PTC, being present in 19 of 104 (18.3%) BRAF mutation-positive PTC vs 11 of 153 (7.2%) the BRAF mutation-negative PTC samples (P=0.0094). Conversely, BRAF mutation was found in 19 of 30 (63.3%) C228T mutation-positive PTC vs 85 of 227 (37.4%) C228T mutation-negative PTC samples (P=0.0094). We thus for the first time, to our knowledge, demonstrate TERT promoter mutations in thyroid cancers, that are particularly prevalent in the aggressive thyroid cancers TCPTC, PDTC, ATC and BRAF mutation-positive PTC, revealing a novel genetic background for thyroid cancers.

  19. MMSET is overexpressed in cancers: Link with tumor aggressiveness

    SciTech Connect

    Kassambara, Alboukadel; Klein, Bernard Moreaux, Jerome

    2009-02-20

    MMSET is expressed ubiquitously in early development and its deletion is associated with the malformation syndrome called Wolf-Hirschhorn syndrome. It is involved in the t(4; 14) (p16; q32) chromosomal translocation, which is the second most common translocation in multiple myeloma (MM) and is associated with the worst prognosis. MMSET expression has been shown to promote cellular adhesion, clonogenic growth and tumorigenicity in multiple myeloma. MMSET expression has been recently shown to increase with ascending tumor proliferation activity in glioblastoma multiforme. These data demonstrate that MMSET could be implicated in tumor emergence and/or progression. Therefore, we compared the expression of MMSET in 40 human tumor types - brain, epithelial, lymphoid - to that of their normal tissue counterparts using publicly available gene expression data, including the Oncomine Cancer Microarray database. We found significant overexpression of MMSET in 15 cancers compared to their normal counterparts. Furthermore MMSET is associated with tumor aggressiveness or prognosis in many types of these aforementioned cancers. Taken together, these data suggest that MMSET potentially acts as a pathogenic agent in many cancers. The identification of the targets of MMSET and their role in cell growth and survival will be key to understand how MMSET is associated with tumor development.

  20. Bioenergetics of Stromal Cells As a Predictor of Aggressive Prostate Cancer

    DTIC Science & Technology

    2015-09-01

    1 AD______________ AWARD NUMBER: W81XWH-14-1-0255 TITLE: BIOENERGETICS OF STROMAL CELLS AS A PREDICTOR OF AGGRESSIVE PROSTATE CANCER...31 Aug 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Bioenergetics Of Stromal Cells As A Predictor Of Aggressive Prostate Cancer” 5b. GRANT NUMBER...form and rapidly falls below the normal as they become aggressive in prostate tumorigenesis. We have validated this in five prostate cancer cell

  1. Screening for Novel Germline Rare Mutations Associated with Aggressive Prostate Cancer

    DTIC Science & Technology

    2015-12-01

    AWARD NUMBER: W81XWH-13-1-0348 TITLE: “Screening for Novel Germline Rare Mutations Associated with Aggressive Prostate Cancer ” PRINCIPAL...TITLE AND SUBTITLE “Screening for Novel Germline Rare Mutations Associated with Aggressive Prostate Cancer ” 5a. CONTRACT NUMBER 5b. GRANT NUMBER...Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT Prostate cancer is the most common noncutaneous cancer in males in the U.S. While the major indolent form

  2. Pediatric Malignancies, Treatment Outcomes and Abandonment of Pediatric Cancer Treatment in Zambia

    PubMed Central

    Slone, Jeremy S.; Chunda-Liyoka, Catherine; Perez, Marta; Mutalima, Nora; Newton, Robert; Chintu, Chifumbe; Kankasa, Chipepo; Chipeta, James; Heimburger, Douglas C.; Vermund, Sten H.; Friedman, Debra L.

    2014-01-01

    Background There exist significant challenges to the receipt of comprehensive oncologic treatment for children diagnosed with cancer in sub-Saharan Africa. To better define those challenges, we investigated treatment outcomes and risk factors for treatment abandonment in a cohort of children diagnosed with cancer at the University Teaching Hospital (UTH), the site of the only pediatric oncology ward in Zambia. Methods Using an established database, a retrospective cohort study was conducted of children aged 0–15 years admitted to the pediatric oncology ward between July 2008 and June 2010 with suspected cancer. Diagnosis, mode of diagnosis, treatment outcome, and risk factors for abandonment of treatment were abstracted from this database and clinical medical records. Results Among 162 children treated at the UTH during the study time period that met inclusion criteria, only 8.0% completed a treatment regimen with most of the patients dying during treatment or abandoning care. In multivariable analysis, shorter distance from home to the UTH was associated with a lower risk of treatment abandonment (Adjusted Odds Ratio [aOR] = 0.48 (95% confidence interval [CI] 0.23–0.97). Conversely maternal education less than secondary school was associated with increased risk for abandonment (aOR = 1.65; 95% CI 1.05–2.58). Conclusions Despite availability of dedicated pediatric oncology treatment, treatment completion rates are poor, due in part to the logistical challenges faced by families, low educational status, and significant distance from the hospital. Alternative treatment delivery strategies are required to bring effective pediatric oncology care to the patients in need, as their ability to come to and remain at a central tertiary care facility for treatment is limited. We suggest that the extensive system now in place in most of sub-Saharan Africa that sustains life-long antiretroviral therapy for children with human immunodeficiency virus (HIV) infection

  3. Brief Family-Focused Intervention on the Pediatric Cancer Unit.

    ERIC Educational Resources Information Center

    Friedrich, William N.; Copeland, Donna R.

    1983-01-01

    Suggests that behavioral problems that frequently occur in pediatric cancer treatment settings, such as food refusal and the resistance to treatment, can be successfully treated utilizing family therapy techniques. Presents the theoretical background that supports this mode of intervention and several case studies. (Author/WAS)

  4. Psychosocial Aspects of Siblings' Experiences of Pediatric Cancer.

    ERIC Educational Resources Information Center

    Shapiro, Marla; Brack, Gregory

    1994-01-01

    Identified those aspects of experiences of siblings of children with cancer that might have impact on school functioning. Also examined extent to which parents and siblings concurred in their reports of siblings' psychosocial functioning and adjustment. Findings from 15 children and adults attending pediatric oncology camp revealed that most…

  5. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    PubMed Central

    2012-01-01

    Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants) or stromal vascular fraction (SVF) from paired fat samples of periprostatic (PP) and pre-peritoneal visceral (VIS) anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs) 2 and 9 activity. The effects of those conditioned media (CM) on growth and migration of hormone-refractory (PC-3) and hormone-sensitive (LNCaP) prostate cancer cells were measured. Results We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF) as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration. Conclusions Our

  6. PEG-3, a nontransforming cancer progression gene, is a positive regulator of cancer aggressiveness and angiogenesis.

    PubMed

    Su, Z Z; Goldstein, N I; Jiang, H; Wang, M N; Duigou, G J; Young, C S; Fisher, P B

    1999-12-21

    Cancer is a progressive disease culminating in acquisition of metastatic potential by a subset of evolving tumor cells. Generation of an adequate blood supply in tumors by production of new blood vessels, angiogenesis, is a defining element in this process. Although extensively investigated, the precise molecular events underlying tumor development, cancer progression, and angiogenesis remain unclear. Subtraction hybridization identified a genetic element, progression elevated gene-3 (PEG-3), whose expression directly correlates with cancer progression and acquisition of oncogenic potential by transformed rodent cells. We presently demonstrate that forced expression of PEG-3 in tumorigenic rodent cells, and in human cancer cells, increases their oncogenic potential in nude mice as reflected by a shorter tumor latency time and the production of larger tumors with increased vascularization. Moreover, inhibiting endogenous PEG-3 expression in progressed rodent cancer cells by stable expression of an antisense expression vector extinguishes the progressed cancer phenotype. Cancer aggressiveness of PEG-3 expressing rodent cells correlates directly with increased RNA transcription, elevated mRNA levels, and augmented secretion of vascular endothelial growth factor (VEGF). Furthermore, transient ectopic expression of PEG-3 transcriptionally activates VEGF in transformed rodent and human cancer cells. Taken together these data demonstrate that PEG-3 is a positive regulator of cancer aggressiveness, a process regulated by augmented VEGF production. These studies also support an association between expression of a single nontransforming cancer progression-inducing gene, PEG-3, and the processes of cancer aggressiveness and angiogenesis. In these contexts, PEG-3 may represent an important target molecule for developing cancer therapeutics and inhibitors of angiogenesis.

  7. A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict Aggressive Phenotype of Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-12-1-0535 TITLE: A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict Aggressive Phenotype of Prostate...30Sep2014 - 29Sep2015 4. TITLE AND SUBTITLE: A Multiplex Cancer/Testis Antigen-Based Biomarker Panel to Predict Aggressive Phenotype of Prostate...different between aggressive and indolent tumors. For the third year of the grant, we evaluated the gene expression of these 8 CTAs in PCa and benign

  8. Glucose promotes breast cancer aggression and reduces metformin efficacy

    PubMed Central

    Wahdan-Alaswad, Reema; Fan, Zeying; Edgerton, Susan M; Liu, Bolin; Deng, Xin-Sheng; Arnadottir, Sigrid Salling; Richer, Jennifer K; Anderson, Steven M; Thor, Ann D

    2013-01-01

    Metformin treatment has been associated with a decrease in breast cancer risk and improved survival. Metformin induces complex cellular changes, resulting in decreased tumor cell proliferation, reduction of stem cells, and apoptosis. Using a carcinogen-induced rodent model of mammary tumorigenesis, we recently demonstrated that overfeeding in obese animals is associated with a 50% increase in tumor glucose uptake, increased proliferation, and tumor cell reprogramming to an “aggressive” metabolic state. Metformin significantly inhibited these pro-tumorigenic effects. We hypothesized that a dynamic relationship exists between chronic energy excess (glucose by dose) and metformin efficacy/action. Media glucose concentrations above 5 mmol/L was associated with significant increase in breast cancer cell proliferation, clonogenicity, motility, upregulation/activation of pro-oncogenic signaling, and reduction in apoptosis. These effects were most significant in triple-negative breast cancer (TNBC) cell lines. High-glucose conditions (10 mmol/L or above) significantly abrogated the effects of metformin. Mechanisms of metformin action at normal vs. high glucose overlapped but were not identical; for example, metformin reduced IGF-1R expression in both the HER2+ SK-BR-3 and TNBC MDA-MB-468 cell lines more significantly at 5, as compared with 10 mmol/L glucose. Significant changes in gene profiles related to apoptosis, cellular processes, metabolic processes, and cell proliferation occurred with metformin treatment in cells grown at 5 mmol/L glucose, whereas under high-glucose conditions, metformin did not significantly increase apoptotic/cellular death genes. These data indicate that failure to maintain glucose homeostasis may promote a more aggressive breast cancer phenotype and alter metformin efficacy and mechanisms of action. PMID:24107633

  9. Profilin 1 is a Potential Biomarker for Bladder Cancer Aggressiveness*

    PubMed Central

    Zoidakis, Jerome; Makridakis, Manousos; Zerefos, Panagiotis G.; Bitsika, Vasiliki; Esteban, Sergio; Frantzi, Maria; Stravodimos, Konstantinos; Anagnou, Nikolaos P.; Roubelakis, Maria G.; Sanchez-Carbayo, Marta; Vlahou, Antonia

    2012-01-01

    Of the most important clinical needs for bladder cancer (BC) management is the identification of biomarkers for disease aggressiveness. Urine is a “gold mine” for biomarker discovery, nevertheless, with multiple proteins being in low amounts, urine proteomics becomes challenging. In the present study we applied a fractionation strategy of urinary proteins based on the use of immobilized metal affinity chromatography for the discovery of biomarkers for aggressive BC. Urine samples from patients with non invasive (two pools) and invasive (two pools) BC were subjected to immobilized metal affinity chromatography fractionation and eluted proteins analyzed by 1D-SDS-PAGE, band excision and liquid chromatography tandem MS. Among the identified proteins, multiple corresponded to proteins with affinity for metals and/or reported to be phosphorylated and included proteins with demonstrated association with BC such as MMP9, fibrinogen forms, and clusterin. In agreement to the immobilized metal affinity chromatography results, aminopeptidase N, profilin 1, and myeloblastin were further found to be differentially expressed in urine from patients with invasive compared with non invasive BC and benign controls, by Western blot or Elisa analysis, nevertheless exhibiting high interindividual variability. By tissue microarray analysis, profilin 1 was found to have a marked decrease of expression in the epithelial cells of the invasive (T2+) versus high risk non invasive (T1G3) tumors with occasional expression in stroma; importantly, this pattern strongly correlated with poor prognosis and increased mortality. The functional relevance of profilin 1 was investigated in the T24 BC cells where blockage of the protein by the use of antibodies resulted in decreased cell motility with concomitant decrease in actin polymerization. Collectively, our study involves the application of a fractionation method of urinary proteins and as one main result of this analysis reveals the

  10. Basic Research and Progress against Pediatric Cancer

    Cancer.gov

    An infographic about the importance of basic research for making progress against childhood cancers. Shows the milestones that led to development and approval of dinutuximab (Unituxin®) to treat neuroblastoma, a cancer seen mainly in children.

  11. Association between Serum 25-Hydroxy-Vitamin D and Aggressive Prostate Cancer in African American Men

    PubMed Central

    Nelson, Shakira M.; Batai, Ken; Ahaghotu, Chiledum; Agurs-Collins, Tanya; Kittles, Rick A.

    2016-01-01

    African American men have higher incidence rates of aggressive prostate cancer, where high levels of calcium and serum vitamin D deficient levels play a role in the racial differences in incidence. In this study, we examined associations of serum vitamin D with aggressive prostate cancer to improve our understanding of higher susceptibility of aggressive disease in this racial cohort. From Howard University Hospital, 155 African American men with clinically-identified prostate cancer were identified; 46 aggressive cases, and 58 non-aggressive cases. Serum vitamin D was assessed from fasting blood samples, and total calcium intake was assessed using the Block Food Frequency Questionnaire. Vitamin D receptor polymorphisms from three different loci were genotyped; rs731236, rs1544410, and rs11568820. Multivariate logistic regression models were used to determine odds ratios (OR) and 95% confidence intervals (CI) comparing aggressive to non-aggressive prostate cancer. Vitamin D deficiency (<20 ng/mL) significantly increased risk of aggressive disease (OR: 3.1, 95% CI: 1.03–9.57, p-value = 0.04). Stratification by total calcium showed high calcium levels (≥800 mg/day) modified this association (OR: 7.3, 95% CI: 2.15–47.68, p-interaction = 0.03). Genetic variant rs11568820 appeared to increase the magnitude of association between deficient serum vitamin D and aggressive prostate cancer (OR: 3.64, 95% CI: 1.12–11.75, p-value = 0.05). These findings suggest that high incidence of aggressive prostate cancer risk in African American men may be due in-part to deficient levels of serum vitamin D. Other factors, including genetics, should be considered for future studies. PMID:28036013

  12. Whole-body MRI in pediatric patients with cancer.

    PubMed

    Guimarães, Marcos Duarte; Noschang, Julia; Teixeira, Sara Reis; Santos, Marcel Koenigkam; Lederman, Henrique Manoel; Tostes, Vivian; Kundra, Vikas; Oliveira, Alex Dias; Hochhegger, Bruno; Marchiori, Edson

    2017-02-10

    Cancer is the leading cause of natural death in the pediatric populations of developed countries, yet cure rates are greater than 70% when a cancer is diagnosed in its early stages. Recent advances in magnetic resonance imaging methods have markedly improved diagnostic and therapeutic approaches, while avoiding the risks of ionizing radiation that are associated with most conventional radiological methods, such as computed tomography and positron emission tomography/computed tomography. The advent of whole-body magnetic resonance imaging in association with the development of metabolic- and function-based techniques has led to the use of whole-body magnetic resonance imaging for the screening, diagnosis, staging, response assessment, and post-therapeutic follow-up of children with solid sporadic tumours or those with related genetic syndromes. Here, the advantages, techniques, indications, and limitations of whole-body magnetic resonance imaging in the management of pediatric oncology patients are presented.

  13. Cancer-associated fibroblast-derived annexin A6+ extracellular vesicles support pancreatic cancer aggressiveness

    PubMed Central

    Leca, Julie; Martinez, Sébastien; Lac, Sophie; Nigri, Jérémy; Secq, Véronique; Rubis, Marion; Bressy, Christian; Lavaut, Marie-Noelle; Dusetti, Nelson; Loncle, Céline; Roques, Julie; Pietrasz, Daniel; Bousquet, Corinne; Garcia, Stéphane; Granjeaud, Samuel; Ouaissi, Mehdi; Bachet, Jean Baptiste; Iovanna, Juan L.; Zimmermann, Pascale; Vasseur, Sophie

    2016-01-01

    The intratumoral microenvironment, or stroma, is of major importance in the pathobiology of pancreatic ductal adenocarcinoma (PDA), and specific conditions in the stroma may promote increased cancer aggressiveness. We hypothesized that this heterogeneous and evolving compartment drastically influences tumor cell abilities, which in turn influences PDA aggressiveness through crosstalk that is mediated by extracellular vesicles (EVs). Here, we have analyzed the PDA proteomic stromal signature and identified a contribution of the annexin A6/LDL receptor-related protein 1/thrombospondin 1 (ANXA6/LRP1/TSP1) complex in tumor cell crosstalk. Formation of the ANXA6/LRP1/TSP1 complex was restricted to cancer-associated fibroblasts (CAFs) and required physiopathologic culture conditions that improved tumor cell survival and migration. Increased PDA aggressiveness was dependent on tumor cell–mediated uptake of CAF-derived ANXA6+ EVs carrying the ANXA6/LRP1/TSP1 complex. Depletion of ANXA6 in CAFs impaired complex formation and subsequently impaired PDA and metastasis occurrence, while injection of CAF-derived ANXA6+ EVs enhanced tumorigenesis. We found that the presence of ANXA6+ EVs in serum was restricted to PDA patients and represents a potential biomarker for PDA grade. These findings suggest that CAF–tumor cell crosstalk supported by ANXA6+ EVs is predictive of PDA aggressiveness, highlighting a therapeutic target and potential biomarker for PDA. PMID:27701147

  14. Evaluation of protein biomarkers of prostate cancer aggressiveness

    PubMed Central

    2014-01-01

    Background Prognostic multibiomarker signatures in prostate cancer (PCa) may improve patient management and provide a bridge for developing novel therapeutics and imaging methods. Our objective was to evaluate the association between expression of 33 candidate protein biomarkers and time to biochemical failure (BF) after prostatectomy. Methods PCa tissue microarrays were constructed representing 160 patients for whom clinicopathologic features and follow-up data after surgery were available. Immunohistochemistry for each of 33 proteins was quantified using automated digital pathology techniques. Relationships between clinicopathologic features, staining intensity, and time to BF were assessed. Predictive modeling using multiple imputed datasets was performed to identify the top biomarker candidates. Results In univariate analyses, lymph node positivity, surgical margin positivity, non-localized tumor, age at prostatectomy, and biomarkers CCND1, HMMR, IGF1, MKI67, SIAH2, and SMAD4 in malignant epithelium were significantly associated with time to BF. HMMR, IGF1, and SMAD4 remained significantly associated with BF after adjusting for clinicopathologic features while additional associations were observed for HOXC6 and MAP4K4 following adjustment. In multibiomarker predictive models, 3 proteins including HMMR, SIAH2, and SMAD4 were consistently represented among the top 2, 3, 4, and 5 most predictive biomarkers, and a signature comprised of these proteins best predicted BF at 3 and 5 years. Conclusions This study provides rationale for investigation of HMMR, HOXC6, IGF1, MAP4K4, SIAH2, and SMAD4 as biomarkers of PCa aggressiveness in larger cohorts. PMID:24708576

  15. What Pediatric Primary Care Clinicians Can Do When Confronting Aggressive Youth

    PubMed Central

    Stringham, Peter; Spivak, Howard

    1994-01-01

    Violence is a serious problem confronting primary care practitioners. This paper presents office-based primary, secondary and tertiary prevention strategies for dealing with relationship and street violence and gives practical skills for practitioners to respond to patients who are aggressive. PMID:19313103

  16. Pediatric Necrotizing Fasciitis: Restitutio Ad Integrum after Early Diagnosis and Aggressive Surgical Treatment

    PubMed Central

    Lemaréchal, Angela; Zundel, Sabine; Szavay, Philipp

    2016-01-01

    Necrotizing fasciitis (NF) is a severe, life-threatening infectious condition. Diagnosis is difficult due to unspecific symptoms yet crucial for favorable outcomes. We report a case of a 1 year old, previously healthy boy, where early suspicion of NF led to prompt aggressive therapy and consecutive restitutio ad integrum. PMID:28035291

  17. Probing HER2-PUMA and EGFR-PUMA Crosstalks in Aggressive Breast Cancer

    DTIC Science & Technology

    2012-09-01

    AWARD NUMBER: W81XWH-11-1-0600 TITLE: Probing HER2- PUMA and EGFR- PUMA Crosstalks in Aggressive...COVERED 1 Sep 2011 – 31 Aug 2012 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER Probing HER2- PUMA and EGFR- PUMA Crosstalks in Aggressive Breast Cancer 5b...on novel significant findings made from the initial Idea Award. We discovered that proapoptotic PUMA protein is highly expressed in the breast cancer

  18. The camp experience for siblings of pediatric cancer patients.

    PubMed

    Hancock, Lauren

    2011-01-01

    Siblings of pediatric cancer patients experience difficulties coping and adapting to the experience of a cancer diagnosis. A variety of emotional and behavioral changes as well as somatic complaints have been reported. Children describe many negative changes after their sibling is diagnosed with cancer. Many social supports and therapeutic interventions have been proposed for siblings, one of which is a camp experience. The literature has demonstrated that camps have a positive impact and offer siblings of children with cancer a supportive peer environment. Camp encourages discussion with peers and health care providers and facilitates participation in activities that improve knowledge, social confidence, and self-esteem. Nurses can help siblings by recommending camp experiences, volunteering at camps, and adding a camp experiences to existing sibling support programs.

  19. Geographic and environmental factors in pediatric cancer

    SciTech Connect

    Gordis, L.

    1986-07-15

    It is important to determine the relative contributions of genetic and environmental factors to the etiology of childhood cancer in order to elucidate the pathogenic mechanisms involved and to develop effective means of primary prevention. Geographic differences in cancer incidence as well as changes in incidence over calendar time have long been used to generate clues to possible etiologic agents. The important role of genetic factors in childhood cancer is clear, and is exemplified by the observations in retinoblastoma. The importance of the contributions of environmental factors in general and of specific factors in particular, to the etiology of cancers in children, has proven more difficult to determine. A variety of environmental factors have been implicated to varying degrees in the etiology of different childhood cancers. These factors include physical agents such as radiation, chemical agents such as nitrosamines, and organic solvents, and infectious agents such as the Epstein-Barr virus. The observations that certain compounds may act as teratogens when a prenatal exposure occurs early in pregnancy and as carcinogens when the exposure occurs late in pregnancy, suggests that there may be a continuum of teratogenesis and carcinogenesis. This finding has major implications for the possible biologic mechanisms that could be involved in childhood cancers and for the design of future research of their etiology and prevention. The etiology of childhood cancer should be viewed as an interaction of environmental factors to which the child or his parent were exposed together with varying degrees of genetically determined susceptibility of the child to the carcinogenic effects of these factors.

  20. Receipt of Life-Sustaining Treatments for Taiwanese Pediatric Patients Who Died of Cancer in 2001 to 2010: A Retrospective Cohort Study.

    PubMed

    Hung, Yen-Ni; Liu, Tsang-Wu; Lin, Dong-Tsamn; Chen, Yueh-Chih; Chen, Jen-Shi; Tang, Siew Tzuh

    2016-04-01

    Aggressive life-sustaining treatments have the potential to be continued beyond benefit, but have seldom been systematically/nationally explored in pediatric cancer patients. Furthermore, factors predisposing children dying of cancer to receive life-sustaining treatments at end of life (EOL) have never been investigated in a population-based study. This population-based study explored determinants of receiving life-sustaining treatments in pediatric cancer patients' last month of life. For this retrospective cohort study, we used administrative data on 1603 Taiwanese pediatric cancer patients who died in 2001 to 2010. Individual patient-level data were linked with encrypted identification numbers from the National Register of Deaths Database, Cancer Registration System database, National Health Insurance claims datasets, and Database of Medical Care Institutions Status. Life-sustaining treatments included intensive care unit (ICU) care, cardiopulmonary resuscitation (CPR), and mechanical ventilation. Associations of patient, physician, hospital, and regional factors with receiving ICU care, CPR, and mechanical ventilation in the last month of life were evaluated by multilevel generalized linear mixed models. In their last month of life, 22.89%, 46.48%, and 61.45% of pediatric cancer patients received CPR, mechanical ventilation, and ICU care, respectively, with no significant decreasing trends from 2001 to 2010. Patients were more likely to receive all three identified life-sustaining treatments at EOL if they were diagnosed with a hematologic malignancy or a localized disease, died within 1 year of diagnosis, and received care from a pediatrician. Receipt of ICU care or mechanical ventilation increased with increasing EOL-care intensity of patients' primary hospital, whereas use of mechanical ventilation decreased with increasing quartile of hospice beds in the patients' primary hospital region. Taiwanese pediatric cancer patients received aggressive life

  1. Highly and moderately aggressive mouse ovarian cancer cell lines exhibit differential gene expression

    PubMed Central

    Zhang, Wensheng; Kale, Shubha P.; McFerrin, Harris; Davenport, Ian; Wang, Guangdi; Skripnikova, Elena; Li, Xiao-Lin; Bowen, Nathan J.; McDaniels, Leticia B; Meng, Yuan-Xiang; Polk, Paula; Liu, Yong-Yu; Zhang, Qian-Jin

    2017-01-01

    Patients with advanced epithelial ovarian cancer often experience disease recurrence after standard therapies, a critical factor in determining their five-year survival rate. Recent reports indicated that long-term or short-term survival is associated with varied gene expression of cancer cells. Thus, identification of novel prognostic biomarkers should be considered. Since the mouse genome is similar to the human genome, we explored potential prognostic biomarkers using two groups of mouse ovarian cancer cell lines (group 1: IG-10, IG-10pw, and IG-10pw/agar; group 2: IG-10 clones 2, 3, and 11) which display highly and moderately aggressive phenotypes in vivo. Mice injected with these cell lines have different survival time and rates, capacities of tumor, and ascites formations, reflecting different prognostic potentials. Using an Affymetrix Mouse Genome 430 2.0 Array, a total of 181 genes were differentially expressed (P<0.01) by at least twofold between two groups of the cell lines. Of the 181 genes, 109 and 72 genes were overexpressed in highly and moderately aggressive cell lines, respectively. Analysis of the 109 and 72 genes using Ingenuity Pathway Analysis (IPA) tool revealed two cancer-related gene networks. One was associated with the highly aggressive cell lines and affiliated with MYC gene, and another was associated with the moderately aggressive cell lines and affiliated with the androgen receptor (AR). Finally, the gene enrichment analysis indicated that the overexpressed 89 genes (out of 109 genes) in highly aggressive cell lines had a function annotation in the David database. The cancer-relevant significant gene ontology (GO) terms included Cell cycle, DNA metabolic process, and Programmed cell death. None of the genes from a set of the 72 genes overexpressed in the moderately aggressive cell lines had a function annotation in the David database. Our results suggested that the overexpressed MYC and 109 gene set represented highly aggressive ovarian

  2. Genome-wide network analysis of Wnt signaling in three pediatric cancers

    NASA Astrophysics Data System (ADS)

    Bao, Ju; Lee, Ho-Jin; Zheng, Jie J.

    2013-10-01

    Genomic structural alteration is common in pediatric cancers, and analysis of data generated by the Pediatric Cancer Genome Project reveals such tumor-related alterations in many Wnt signaling-associated genes. Most pediatric cancers are thought to arise within developing tissues that undergo substantial expansion during early organ formation, growth and maturation, and Wnt signaling plays an important role in this development. We examined three pediatric tumors--medullobastoma, early T-cell precursor acute lymphoblastic leukemia, and retinoblastoma--that show multiple genomic structural variations within Wnt signaling pathways. We mathematically modeled this pathway to investigate the effects of cancer-related structural variations on Wnt signaling. Surprisingly, we found that an outcome measure of canonical Wnt signaling was consistently similar in matched cancer cells and normal cells, even in the context of different cancers, different mutations, and different Wnt-related genes. Our results suggest that the cancer cells maintain a normal level of Wnt signaling by developing multiple mutations.

  3. Genome-wide network analysis of Wnt signaling in three pediatric cancers.

    PubMed

    Bao, Ju; Lee, Ho-Jin; Zheng, Jie J

    2013-10-17

    Genomic structural alteration is common in pediatric cancers, and analysis of data generated by the Pediatric Cancer Genome Project reveals such tumor-related alterations in many Wnt signaling-associated genes. Most pediatric cancers are thought to arise within developing tissues that undergo substantial expansion during early organ formation, growth and maturation, and Wnt signaling plays an important role in this development. We examined three pediatric tumors-medullobastoma, early T-cell precursor acute lymphoblastic leukemia, and retinoblastoma-that show multiple genomic structural variations within Wnt signaling pathways. We mathematically modeled this pathway to investigate the effects of cancer-related structural variations on Wnt signaling. Surprisingly, we found that an outcome measure of canonical Wnt signaling was consistently similar in matched cancer cells and normal cells, even in the context of different cancers, different mutations, and different Wnt-related genes. Our results suggest that the cancer cells maintain a normal level of Wnt signaling by developing multiple mutations.

  4. Spermine and Citrate as Metabolic Biomarkers for Assessing Prostate Cancer Aggressiveness

    PubMed Central

    Giskeødegård, Guro F.; Bertilsson, Helena; Selnæs, Kirsten M.; Wright, Alan J.; Bathen, Tone F.; Viset, Trond; Halgunset, Jostein; Angelsen, Anders; Gribbestad, Ingrid S.; Tessem, May-Britt

    2013-01-01

    Separating indolent from aggressive prostate cancer is an important clinical challenge for identifying patients eligible for active surveillance, thereby reducing the risk of overtreatment. The purpose of this study was to assess prostate cancer aggressiveness by metabolic profiling of prostatectomy tissue and to identify specific metabolites as biomarkers for aggressiveness. Prostate tissue samples (n = 158, 48 patients) with a high cancer content (mean: 61.8%) were obtained using a new harvesting method, and metabolic profiles of samples representing different Gleason scores (GS) were acquired by high resolution magic angle spinning magnetic resonance spectroscopy (HR-MAS). Multivariate analysis (PLS, PLS-DA) and absolute quantification (LCModel) were used to examine the ability to predict cancer aggressiveness by comparing low grade (GS = 6, n = 30) and high grade (GS≥7, n = 81) cancer with normal adjacent tissue (n = 47). High grade cancer tissue was distinguished from low grade cancer tissue by decreased concentrations of spermine (p = 0.0044) and citrate (p = 7.73·10−4), and an increase in the clinically applied (total choline+creatine+polyamines)/citrate (CCP/C) ratio (p = 2.17·10−4). The metabolic profiles were significantly correlated to the GS obtained from each tissue sample (r = 0.71), and cancer tissue could be distinguished from normal tissue with sensitivity 86.9% and specificity 85.2%. Overall, our findings show that metabolic profiling can separate aggressive from indolent prostate cancer. This holds promise for the benefit of applying in vivo magnetic resonance spectroscopy (MRS) within clinical MR imaging investigations, and HR-MAS analysis of transrectal ultrasound-guided biopsies has a potential as an additional diagnostic tool. PMID:23626811

  5. Imaging Prostatic Lipids to Distinguish Aggressive Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    this application, we propose to build upon our current work to determine the association between fatty acid synthase (FAS) overexpression and...Mechanisms linking fatty acid synthase overexpression, lipid accumulation, lipid oxidation, and tumor aggressiveness will be explored using...INTRODUCTION: Mounting evidence suggests that dysregulation of fatty acid synthase (FAS), the rate limiting multienzyme in the de novo formation of free

  6. Risk of Total and Aggressive Prostate Cancer and Pesticide Use in the Agricultural Health Study

    PubMed Central

    Koutros, Stella; Beane Freeman, Laura E.; Lubin, Jay H.; Heltshe, Sonya L.; Andreotti, Gabriella; Barry, Kathryn Hughes; DellaValle, Curt T.; Hoppin, Jane A.; Sandler, Dale P.; Lynch, Charles F.; Blair, Aaron; Alavanja, Michael C. R.

    2013-01-01

    Because pesticides may operate through different mechanisms, the authors studied the risk of prostate cancer associated with specific pesticides in the Agricultural Health Study (1993–2007). With 1,962 incident cases, including 919 aggressive prostate cancers among 54,412 applicators, this is the largest study to date. Rate ratios and 95% confidence intervals were calculated by using Poisson regression to evaluate lifetime use of 48 pesticides and prostate cancer incidence. Three organophosphate insecticides were significantly associated with aggressive prostate cancer: fonofos (rate ratio (RR) for the highest quartile of exposure (Q4) vs. nonexposed = 1.63, 95% confidence interval (CI): 1.22, 2.17; Ptrend < 0.001); malathion (RR for Q4 vs. nonexposed = 1.43, 95% CI: 1.08, 1.88; Ptrend = 0.04); and terbufos (RR for Q4 vs. nonexposed = 1.29, 95% CI: 1.02, 1.64; Ptrend = 0.03). The organochlorine insecticide aldrin was also associated with increased risk of aggressive prostate cancer (RR for Q4 vs. nonexposed = 1.49, 95% CI: 1.03, 2.18; Ptrend = 0.02). This analysis has overcome several limitations of previous studies with the inclusion of a large number of cases with relevant exposure and detailed information on use of specific pesticides at 2 points in time. Furthermore, this is the first time specific pesticides are implicated as risk factors for aggressive prostate cancer. PMID:23171882

  7. Aggressive Surgery in Palliative Setting of Lung Cancer: Is it Helpful?

    PubMed Central

    Byregowda, Suman; Prabhash, Kumar; Puri, Ajay; Joshi, Amit; Noronha, Vanita; Patil, Vijay M; Panda, Pankaj Kumar; Gulia, Ashish

    2016-01-01

    With increase in survival and progression-free survival in the advanced metastatic cancers, the expectation of quality of life (QOL) has increased dramatically. Palliative care plays a vital role in the management of these advanced cancer patients. At present scenario, palliative care in advanced cancer has seen a completely different approach. Aggressive surgical procedures have been performed to improve the QOL in the advanced cancer patients. We report a case of advanced lung cancer with pathological femur fracture, treated with extensive total femur replacement surgery to provide better QOL. PMID:27803575

  8. Microvascular Channel Device to Study Aggressiveness in Prostate Cancer Metastasis

    DTIC Science & Technology

    2014-08-01

    E-selectin ligands and prostate cancer bone metastasis (Barthel et al., 2007; Barthel et al., 2008; Dimitroff et al., 2005; Gout et al., 2008). In...Vesuna, F., et al. (2013). The Twist Box Domain is Required for Twist1-induced Prostate Cancer Metastasis. Mol Cancer Res. Gout , S., Morin, C., Houle, F...by triggering p38 and ERK MAPK activation. Cancer research 66, 9117-9124. Gout , S., Tremblay, P. L., and Huot, J. (2008). Selectins and selectin

  9. Geography and the Burden of Care in Pediatric Cancers

    PubMed Central

    Fluchel, Mark N.; Kirchhoff, Anne C.; Bodson, Julia; Sweeney, Carol; Edwards, Sandra L.; Ding, Qian; Stoddard, Gregory J.; Kinney, Anita Y.

    2016-01-01

    Background Childhood cancers typically require rigorous treatment at specialized centers in urban areas, which can create substantial challenges for families residing in remote communities. We evaluated the impact of residence and travel time on the burden of care for families of childhood cancer patients. Procedure We conducted a cross-sectional, self-administered survey of 354 caregivers of pediatric cancer patients at a children’s hospital serving a seven state area. Measures included the impact of cancer treatment on relocation, employment, schooling and finances. We evaluated these domains by rural/urban residence and travel time (>1 hour and >2 hours) to the hospital in multivariable regression models. Results Of the 29% of caregivers who reported moving residences since their child was diagnosed, 33% reported that the move was due to their child’s cancer. Rural and remote (e.g., >1 hour travel time) caregivers missed more days of work during the first month after diagnosis than did urban and local caregivers, however, these differences did not persist over the first six months of therapy. One-third of caregivers reported quitting or changing jobs as a direct result of their child being diagnosed with cancer. Rural respondents had greater out-of-pocket travel expenses and reported a significantly greater perceived financial burden. Rural patients missed more school days and were at an increased risk of having to repeat a grade. Conclusions Childhood cancer has an appreciable impact on the lives of patients and caregivers. The burden is greater for those living far from a treatment center. PMID:25131518

  10. Mutations in PUMA Gene Cause Prostate Cancer Development and Aggressiveness

    DTIC Science & Technology

    2006-11-01

    Stephen Thibodeau , Mayo Clinic, Rochester MN, to obtain de-identified clinical samples which were isolated from the PCa patients with the association...between chromosome 19q13 and PCa aggressiveness (1). Drs. Thibodeau and Schaid (PI’s another collaborator) have been collaborating for many years and...the amplified sequences were bona fide PUMA. Furthermore, during the course of study, we initiated a new collaboration with Dr. Stephen Thibodeau

  11. Human Breast Cancer Invasion and Aggression Correlates with ECM Stiffening and Immune Cell Infiltration

    PubMed Central

    Acerbi, I; Cassereau, L; Dean, I; Shi, Q; Au, A; Park, C; Chen, YY; Liphardt, J; Hwang, ES; Weaver, VM

    2015-01-01

    Tumors are stiff and data suggest that the extracellular matrix stiffening that correlates with experimental mammary malignancy drives tumor invasion and metastasis. Nevertheless, the relationship between tissue and extracellular matrix stiffness and human breast cancer progression and aggression remains unclear. We undertook a biophysical and biochemical assessment of stromal-epithelial interactions in noninvasive, invasive and normal adjacent human breast tissue and in breast cancers of increasingly aggressive subtype. Our analysis revealed that human breast cancer transformation is accompanied by an incremental increase in collagen deposition and a progressive linearization and thickening of interstitial collagen. The linearization of collagen was visualized as an overall increase in tissue birefringence and was most striking at the invasive front of the tumor where the stiffness of the stroma and cellular mechanosignaling were the highest. Amongst breast cancer subtypes we found that the stroma at the invasive region of the more aggressive Basal-like and Her2 tumor subtypes was the most heterogeneous and the stiffest when compared to the less aggressive Luminal A and B subtypes. Intriguingly, we quantified the greatest number of infiltrating macrophages and the highest level of TGF beta signaling within the cells at the invasive front. We also established that stroma stiffness and the level of cellular TGF beta signaling positively correlated with each other and with the number of infiltrating tumor-activated, macrophages, which was highest in the more aggressive tumor subtypes. These findings indicate that human breast cancer progression and aggression, collagen linearization and stromal stiffening are linked and implicate tissue inflammation and TGF beta. PMID:25959051

  12. Are we missing an opportunity for cancer prevention? Human papillomavirus vaccination for survivors of pediatric and young adult cancers.

    PubMed

    Temkin, Sarah M; Seibel, Nita L

    2015-10-01

    Survivors of pediatric and young adult cancers remain at risk for subsequent diseases, including those related to human papillomavirus (HPV) infection. Prevention of HPV acquisition through vaccination has become possible over the last decade. HPV vaccines have been shown to be safe and effective, yet rates of vaccination among childhood cancer survivors have remained low. Multiple factors, including stronger advocacy for this intervention from providers, could potentially increase vaccination and lead to lower HPV disease burdens for childhood cancer survivors. Health care providers for survivors of pediatric and adolescent cancers should prioritize counseling for HPV vaccination at follow-up visits. Cancer 2015;121:3435-43. © 2015 American Cancer Society.

  13. Overexpression of α (1,6) fucosyltransferase associated with aggressive prostate cancer.

    PubMed

    Wang, Xiangchun; Chen, Jing; Li, Qing Kay; Peskoe, Sarah B; Zhang, Bai; Choi, Caitlin; Platz, Elizabeth A; Zhang, Hui

    2014-10-01

    Aberrant protein glycosylation is known to be associated with the development of cancers. The aberrant glycans are produced by the combined actions of changed glycosylation enzymes, substrates and transporters in glycosylation synthesis pathways in cancer cells. To identify glycosylation enzymes associated with aggressive prostate cancer (PCa), we analyzed the difference in the expression of glycosyltransferase genes between aggressive and non-aggressive PCa. Three candidate genes encoding glycosyltransferases that were elevated in aggressive PCa were subsequently selected. The expression of the three candidates was then further evaluated in androgen-dependent (LNCaP) and androgen-independent (PC3) PCa cell lines. We found that the protein expression of one of the glycosyltransferases, α (1,6) fucosyltransferase (FUT8), was only detected in PC3 cells, but not in LNCaP cells. We further showed that FUT8 protein expression was elevated in metastatic PCa tissues compared to normal prostate tissues. In addition, using tissue microarrays, we found that FUT8 overexpression was statistically associated with PCa with a high Gleason score. Using PC3 and LNCaP cells as models, we found that FUT8 overexpression in LNCaP cells increased PCa cell migration, while loss of FUT8 in PC3 cells decreased cell motility. Our results suggest that FUT8 may be associated with aggressive PCa and thus is potentially useful for its prognosis.

  14. Pediatrics

    NASA Technical Reports Server (NTRS)

    Spackman, T. J.

    1978-01-01

    The utilization of the Lixiscope in pediatrics was investigated. The types of images that can presently be obtained are discussed along with the problems encountered. Speculative applications for the Lixiscope are also presented.

  15. Kilovoltage Imaging Doses in the Radiotherapy of Pediatric Cancer Patients

    SciTech Connect

    Deng Jun; Chen Zhe; Roberts, Kenneth B.; Nath, Ravinder

    2012-04-01

    Purpose: To investigate doses induced by kilovoltage cone-beam computed tomography (kVCBCT) to pediatric cancer patients undergoing radiotherapy, as well as strategies for dose reduction. Methods and Materials: An EGS4 Monte Carlo code was used to calculate three-dimensional dose deposition due to kVCBCT on 4 pediatric cancer patients. Absorbed doses to various organs were analyzed for both half-fan and full-fan modes. Clinical conditions, such as distance from organ at risk (OAR) to CBCT field border, kV peak energy, and testicular shielding, were studied. Results: The mean doses induced by one CBCT scan operated at 125 kV in half-fan mode to testes, liver, kidneys, femoral heads, spinal cord, brain, eyes, lens, and optical nerves were 2.9, 4.7, 7.7, 10.5, 8.8, 7.6, 7.7, 7.8, and 7.2 cGy, respectively. Increasing the distances from OARs to CBCT field border greatly reduced the doses to OARs, ranging from 33% reduction for spinal cord to 2300% reduction for testes. As photon beam energy increased from 60 to 125 kV, the dose increase due to kVCBCT ranged from 170% for lens to 460% for brain and spinal cord. A testicular shielding made of 1-cm cerrobend could reduce CBCT doses down to 31%, 51%, 68%, and 82%, respectively, for 60, 80, 100, and 125 kV when the testes lay within the CBCT field. Conclusions: Generally speaking, kVCBCT deposits much larger doses to critical structures in children than in adults, usually by a factor of 2 to 3. Increasing the distances from OARs to CBCT field border greatly reduces doses to OARs. Depending on OARs, kVCBCT-induced doses increase linearly or exponentially with photon beam energy. Testicular shielding works more efficiently at lower kV energies. On the basis of our study, it is essential to choose an appropriate scanning protocol when kVCBCT is applied to pediatric cancer patients routinely.

  16. Cannabidiol as a novel inhibitor of Id-1 gene expression in aggressive breast cancer cells.

    PubMed

    McAllister, Sean D; Christian, Rigel T; Horowitz, Maxx P; Garcia, Amaia; Desprez, Pierre-Yves

    2007-11-01

    Invasion and metastasis of aggressive breast cancer cells is the final and fatal step during cancer progression, and is the least understood genetically. Clinically, there are still limited therapeutic interventions for aggressive and metastatic breast cancers available. Clearly, effective and nontoxic therapies are urgently required. Id-1, an inhibitor of basic helix-loop-helix transcription factors, has recently been shown to be a key regulator of the metastatic potential of breast and additional cancers. Using a mouse model, we previously determined that metastatic breast cancer cells became significantly less invasive in vitro and less metastatic in vivo when Id-1 was down-regulated by stable transduction with antisense Id-1. It is not possible at this point, however, to use antisense technology to reduce Id-1 expression in patients with metastatic breast cancer. Here, we report that cannabidiol (CBD), a cannabinoid with a low-toxicity profile, could down-regulate Id-1 expression in aggressive human breast cancer cells. The CBD concentrations effective at inhibiting Id-1 expression correlated with those used to inhibit the proliferative and invasive phenotype of breast cancer cells. CBD was able to inhibit Id-1 expression at the mRNA and protein level in a concentration-dependent fashion. These effects seemed to occur as the result of an inhibition of the Id-1 gene at the promoter level. Importantly, CBD did not inhibit invasiveness in cells that ectopically expressed Id-1. In conclusion, CBD represents the first nontoxic exogenous agent that can significantly decrease Id-1 expression in metastatic breast cancer cells leading to the down-regulation of tumor aggressiveness.

  17. A Targetable GATA2-IGF2 Axis Confers Aggressiveness in Lethal Prostate Cancer

    PubMed Central

    Vidal, Samuel J.; Rodriguez-Bravo, Veronica; Quinn, S. Aidan; Rodriguez-Barrueco, Ruth; Lujambio, Amaia; Williams, Estrelania; Sun, Xiaochen; de la Iglesia-Vicente, Janis; Lee, Albert; Readhead, Ben; Chen, Xintong; Galsky, Matthew; Esteve, Berta; Petrylak, Daniel P.; Dudley, Joel T.; Rabadan, Raul; Silva, Jose M.; Hoshida, Yujin; Lowe, Scott W.; Cordon-Cardo, Carlos; Domingo-Domenech, Josep

    2015-01-01

    SUMMARY Elucidating the determinants of aggressiveness in lethal prostate cancer may stimulate therapeutic strategies that improve clinical outcomes. We used experimental models and clinical databases to identify GATA2 as a regulator of chemotherapy resistance and tumorigenicity in this context. Mechanistically, direct upregulation of the growth hormone IGF2 emerged as a mediator of the aggressive properties regulated by GATA2. IGF2 in turn activated IGF1R and INSR as well as a downstream polykinase program. The characterization of this axis prompted a combination strategy whereby dual IGF1R/INSR inhibition restored the efficacy of chemotherapy and improved survival in preclinical models. These studies reveal a GATA2-IGF2 aggressiveness axis in lethal prostate cancer and identify a therapeutic opportunity in this challenging disease. PMID:25670080

  18. Prediction of Aggressive Human Prostate Cancer by Cathepsin B

    DTIC Science & Technology

    2008-03-01

    for CB was added to the wells. Following several washes to remove unbound antibody-enzyme reagent, a substrate solution HRP (horse- radish ...prostate cancer. Clin Cancer Res 6: 3430-3433, 2000. 8 Guo Y, Sigman DB, Borkowski A and Kyprianou N: Racial differences in prostate cancer growth ...cystatins in tumor growth and progression. Biol Chem Hoppe Seyler 1990;371 Suppl:193-198. 39. Yan S, Sloane BF. Molecular regulation of human cathepsin B

  19. Chronic psychological stress and its impact on the development of aggressive breast cancer

    PubMed Central

    Cormanique, Thayse Fachin; de Almeida, Lirane Elize Defante Ferreto; Rech, Cynthia Alba; Rech, Daniel; Herrera, Ana Cristina da Silva do Amaral; Panis, Carolina

    2015-01-01

    Objective To investigate the clinicopathological findings of women diagnosed with breast cancer and study the impact of chronic psychological stress on the pathological characteristics of these tumors. Methods We investigated a cohort composed of women diagnosed with breast cancer and divided into two groups. One group was categorized as presenting with chronic psychological stress (by using the Self-Reporting Questionnaire − SRQ-20). Another group of women with breast cancer, but with no previous history of chronic psychological stress, comprised the Control Group. Clinical and pathological data were assessed. Results Women presenting with a history of chronic distress were significantly overweight when compared to the Control Group. Furthermore, it was observed that these stressed women also had a significant percentage of aggressive breast cancer subtype, the HER2 amplified tumor, which could be putatively associated with the loss of immunosurveillance. Conclusion Our findings suggested an interaction among chronic psychological stress, overweight, and the development of more aggressive breast tumors. PMID:26466057

  20. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types.

    PubMed

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P; Brabletz, Thomas

    2016-02-15

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a 'common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings.

  1. ZEB1 turns into a transcriptional activator by interacting with YAP1 in aggressive cancer types

    PubMed Central

    Lehmann, Waltraut; Mossmann, Dirk; Kleemann, Julia; Mock, Kerstin; Meisinger, Chris; Brummer, Tilman; Herr, Ricarda; Brabletz, Simone; Stemmler, Marc P.; Brabletz, Thomas

    2016-01-01

    Early dissemination, metastasis and therapy resistance are central hallmarks of aggressive cancer types and the leading cause of cancer-associated deaths. The EMT-inducing transcriptional repressor ZEB1 is a crucial stimulator of these processes, particularly by coupling the activation of cellular motility with stemness and survival properties. ZEB1 expression is associated with aggressive behaviour in many tumour types, but the potent effects cannot be solely explained by its proven function as a transcriptional repressor of epithelial genes. Here we describe a direct interaction of ZEB1 with the Hippo pathway effector YAP, but notably not with its paralogue TAZ. In consequence, ZEB1 switches its function to a transcriptional co-activator of a ‘common ZEB1/YAP target gene set', thereby linking two pathways with similar cancer promoting effects. This gene set is a predictor of poor survival, therapy resistance and increased metastatic risk in breast cancer, indicating the clinical relevance of our findings. PMID:26876920

  2. Radiation, Atherosclerotic Risk Factors, and Stroke Risk in Survivors of Pediatric Cancer: A Report From the Childhood Cancer Survivor Study

    SciTech Connect

    Mueller, Sabine; Fullerton, Heather J.; Stratton, Kayla; Leisenring, Wendy; Weathers, Rita E.; Stovall, Marilyn; Armstrong, Gregory T.; Goldsby, Robert E.; Packer, Roger J.; Sklar, Charles A.; Bowers, Daniel C.; Robison, Leslie L.; Krull, Kevin R.

    2013-07-15

    Purpose: To test the hypotheses that (1) the increased risk of stroke conferred by childhood cranial radiation therapy (CRT) persists into adulthood; and (2) atherosclerotic risk factors further increase the stroke risk in cancer survivors. Methods and Materials: The Childhood Cancer Survivor Study is a multi-institutional retrospective cohort study of 14,358 5-year survivors of childhood cancer and 4023 randomly selected sibling controls with longitudinal follow-up. Age-adjusted incidence rates of self-reported late-occurring (≥5 years after diagnosis) first stroke were calculated. Multivariable Cox proportional hazards models were used to identify independent stroke predictors. Results: During a mean follow-up of 23.3 years, 292 survivors reported a late-occurring stroke. The age-adjusted stroke rate per 100,000 person-years was 77 (95% confidence interval [CI] 62-96), compared with 9.3 (95% CI 4-23) for siblings. Treatment with CRT increased stroke risk in a dose-dependent manner: hazard ratio 5.9 (95% CI 3.5-9.9) for 30-49 Gy CRT and 11.0 (7.4-17.0) for 50+ Gy CRT. The cumulative stroke incidence in survivors treated with 50+ Gy CRT was 1.1% (95% CI 0.4-1.8%) at 10 years after diagnosis and 12% (95% CI 8.9-15.0%) at 30 years. Hypertension increased stroke hazard by 4-fold (95% CI 2.8-5.5) and in black survivors by 16-fold (95% CI 6.9-36.6). Conclusion: Young adult pediatric cancer survivors have an increased stroke risk that is associated with CRT in a dose-dependent manner. Atherosclerotic risk factors enhanced this risk and should be treated aggressively.

  3. HES6 promotes prostate cancer aggressiveness independently of Notch signalling.

    PubMed

    Carvalho, Filipe L F; Marchionni, Luigi; Gupta, Anuj; Kummangal, Basheer A; Schaeffer, Edward M; Ross, Ashley E; Berman, David M

    2015-07-01

    Notch signalling is implicated in the pathogenesis of a variety of cancers, but its role in prostate cancer is poorly understood. However, selected Notch pathway members are overrepresented in high-grade prostate cancers. We comprehensively profiled Notch pathway components in prostate cells and found prostate cancer-specific up-regulation of NOTCH3 and HES6. Their expression was particularly high in androgen responsive lines. Up- and down-regulating Notch in these cells modulated expression of canonical Notch targets, HES1 and HEY1, which could also be induced by androgen. Surprisingly, androgen treatment also suppressed Notch receptor expression, suggesting that androgens can activate Notch target genes in a receptor-independent manner. Using a Notch-sensitive Recombination signal binding protein for immunoglobulin kappa J region (RBPJ) reporter assay, we found that basal levels of Notch signalling were significantly lower in prostate cancer cells compared to benign cells. Accordingly pharmacological Notch pathway blockade did not inhibit cancer cell growth or viability. In contrast to canonical Notch targets, HES6, a HES family member known to antagonize Notch signalling, was not regulated by Notch signalling, but relied instead on androgen levels, both in cultured cells and in human cancer tissues. When engineered into prostate cancer cells, reduced levels of HES6 resulted in reduced cancer cell invasion and clonogenic growth. By molecular profiling, we identified potential roles for HES6 in regulating hedgehog signalling, apoptosis and cell migration. Our results did not reveal any cell-autonomous roles for canonical Notch signalling in prostate cancer. However, the results do implicate HES6 as a promoter of prostate cancer progression.

  4. Probing HER2-PUMA and EGFR-PUMA Crosstalks in Aggressive Breast Cancer

    DTIC Science & Technology

    2013-09-01

    AD_________________ Award Number: W81XWH-11-1-0600 TITLE: Probing HER2- PUMA and EGFR- PUMA ...AND SUBTITLE Probing HER2- PUMA and EGFR- PUMA Crosstalks in Aggressive Breast Canccer Cancer 5a. CONTRACT NUMBER W81XWH-11-1-0600 er 5b. GRANT...Award. We discovered that proapoptotic PUMA protein is highly expressed in the breast cancer cell lines and patient tumors that overexpress HER2 and/or

  5. Pedican: an online gene resource for pediatric cancers with literature evidence.

    PubMed

    Zhao, Min; Ma, Lei; Liu, Yining; Qu, Hong

    2015-06-15

    Pediatric cancer (PC), that is cancer occurring in children, is the leading cause of death among children worldwide, with an incidence of 175,000 per year. Elucidating the genetic abnormalities and underlying cellular mechanisms may provide less toxic curative treatments. Therefore, it is important to understand the pathology of pediatric cancer at the genetic, genomic and epigenetic level. To unveil the cellular complexity of PC, we have developed a database of pediatric cancers (Pedican), the first literature-based pediatric gene data resource by comprehensive literature curation and data integration. In the current release, Pedican contains 735 human genes, 88 gene fusion and 24 chromosome abnormal events curated from 2245 PubMed abstracts. Pedican provides detailed annotations for each gene, such as Entrez gene information, involved pathways, protein-protein interactions, mutations, gene expression, methylation sites, TF regulation, and post-translational modification. Additionally Pedican has a user-friendly web interface, which allows sophisticated text query, sequence searches, and browsing by highlighted literature evidence and hundreds of cancer types. Overall, our curated pediatric cancer-related gene list maps the genomic and cellular landscape for various pediatric cancers, providing a valuable resource for further experiment design. The Pedican is available at http://pedican.bioinfo-minzhao.org/.

  6. Neuropathic Pain Referrals to a Multidisciplinary Pediatric Cancer Pain Service

    PubMed Central

    Anghelescu, Doralina L.; Faughnan, Lane G.; Popenhagen, Mark P.; Oakes, Linda L.; Pei, Deqing; Burgoyne, Laura L.

    2012-01-01

    Objectives Neuropathic pain (NP) in children with cancer is not well characterized. We describe the prevalence of NP and the characteristics, duration of follow-up, and interventions provided for NP among patients referred to a pediatric oncology center’s pain management service. Methods Retrospective review of patient data from a 3.5-year period. Results Fifteen percent (66/439) of all referrals to our pain service were for NP (56/323 patients, 17%; 34 male, 22 female). The NP patient group had 1401 clinical visits (778 inpatient visits [55.5%] and 623 outpatient visits [44.5%]). Patients with NP had a significantly greater mean number of pain visits per consult (p=0.008) and significantly more days (median) of pain service follow-up (p <0.001) than did other patients. The most common cause of NP was cancer treatment rather than the underlying malignancy. Pharmacological management of NP was complex, often comprising 3 medications. Nonpharmacological approaches were used for 57.6% of NP referrals. Discussion NP is less frequently encountered than non-NP in children with cancer; nevertheless, it is more difficult to treat, requiring longer follow up, more clinical visits, complex pharmacological management, and the frequent addition of non-pharmacological interventions. PMID:24602431

  7. PKCα expression is a marker for breast cancer aggressiveness

    PubMed Central

    2010-01-01

    Background Protein kinase C (PKC) isoforms are potential targets for breast cancer therapy. This study was designed to evaluate which PKC isoforms might be optimal targets for different breast cancer subtypes. Results In two cohorts of primary breast cancers, PKCα levels correlated to estrogen and progesterone receptor negativity, tumor grade, and proliferative activity, whereas PKCδ and PKCε did not correlate to clinicopathological parameters. Patients with PKCα-positive tumors showed poorer survival than patients with PKCα-negative tumors independently of other factors. Cell line studies demonstrated that PKCα levels are high in MDA-MB-231 and absent in T47D cells which proliferated slower than other cell lines. Furthermore, PKCα silencing reduced proliferation of MDA-MB-231 cells. PKCα inhibition or downregulation also reduced cell migration in vitro. Conclusions PKCα is a marker for poor prognosis of breast cancer and correlates to and is important for cell functions associated with breast cancer progression. PMID:20398285

  8. NIH scientists map gene changes driving tumors in common pediatric soft-tissue cancer

    Cancer.gov

    Scientists have mapped the genetic changes that drive tumors in rhabdomyosarcoma, a pediatric soft-tissue cancer, and found that the disease is characterized by two distinct genotypes. The genetic alterations identified in this malignancy could be useful

  9. The 19q12 bladder cancer GWAS signal: association with cyclin E function and aggressive disease

    PubMed Central

    Fu, Yi-Ping; Kohaar, Indu; Moore, Lee E.; Lenz, Petra; Figueroa, Jonine D.; Tang, Wei; Porter-Gill, Patricia; Chatterjee, Nilanjan; Scott-Johnson, Alexandra; Garcia-Closas, Montserrat; Muchmore, Brian; Baris, Dalsu; Paquin, Ashley; Ylaya, Kris; Schwenn, Molly; Apolo, Andrea B.; Karagas, Margaret R.; Tarway, McAnthony; Johnson, Alison; Mumy, Adam; Schned, Alan; Guedez, Liliana; Jones, Michael A.; Kida, Masatoshi; Monawar Hosain, GM; Malats, Nuria; Kogevinas, Manolis; Tardon, Adonina; Serra, Consol; Carrato, Alfredo; Garcia-Closas, Reina; Lloreta, Josep; Wu, Xifeng; Purdue, Mark; Andriole, Gerald L.; Grubb, Robert L.; Black, Amanda; Landi, Maria T.; Caporaso, Neil E.; Vineis, Paolo; Siddiq, Afshan; Bueno-de-Mesquita, H. Bas; Trichopoulos, Dimitrios; Ljungberg, Börje; Severi, Gianluca; Weiderpass, Elisabete; Krogh, Vittorio; Dorronsoro, Miren; Travis, Ruth C.; Tjønneland, Anne; Brennan, Paul; Chang-Claude, Jenny; Riboli, Elio; Prescott, Jennifer; Chen, Constance; De Vivo, Immaculata; Govannucci, Edward; Hunter, David; Kraft, Peter; Lindstrom, Sara; Gapstur, Susan M.; Jacobs, Eric J.; Diver, W. Ryan; Albanes, Demetrius; Weinstein, Stephanie J.; Virtamo, Jarmo; Kooperberg, Charles; Hohensee, Chancellor; Rodabough, Rebecca J.; Cortessis, Victoria K.; Conti, David V.; Gago-Dominguez, Manuela; Stern, Mariana C.; Pike, Malcolm C.; Van Den Berg, David; Yuan, Jian-Min; Haiman, Christopher A.; Cussenot, Olivier; Cancel-Tassin, Geraldine; Roupret, Morgan; Comperat, Eva; Porru, Stefano; Carta, Angela; Pavanello, Sofia; Arici, Cecilia; Mastrangelo, Giuseppe; Grossman, H. Barton; Wang, Zhaoming; Deng, Xiang; Chung, Charles C.; Hutchinson, Amy; Burdette, Laurie; Wheeler, William; Fraumeni, Joseph; Chanock, Stephen J.; Hewitt, Stephen M.; Silverman, Debra T.; Rothman, Nathaniel; Prokunina-Olsson, Ludmila

    2014-01-01

    A genome-wide association study (GWAS) of bladder cancer identified a genetic marker rs8102137 within the 19q12 region as a novel susceptibility variant. This marker is located upstream of the CCNE1 gene, which encodes cyclin E, a cell cycle protein. We performed genetic fine mapping analysis of the CCNE1 region using data from two bladder cancer GWAS (5,942 cases and 10,857 controls). We found that the original GWAS marker rs8102137 represents a group of 47 linked SNPs (with r2≥0.7) associated with increased bladder cancer risk. From this group we selected a functional promoter variant rs7257330, which showed strong allele-specific binding of nuclear proteins in several cell lines. In both GWAS, rs7257330 was associated only with aggressive bladder cancer, with a combined per-allele odds ratio (OR) =1.18 (95%CI=1.09-1.27, p=4.67×10−5 vs. OR =1.01 (95%CI=0.93-1.10, p=0.79) for non-aggressive disease, with p=0.0015 for case-only analysis. Cyclin E protein expression analyzed in 265 bladder tumors was increased in aggressive tumors (p=0.013) and, independently, with each rs7257330-A risk allele (ptrend=0.024). Over-expression of recombinant cyclin E in cell lines caused significant acceleration of cell cycle. In conclusion, we defined the 19q12 signal as the first GWAS signal specific for aggressive bladder cancer. Molecular mechanisms of this genetic association may be related to cyclin E over-expression and alteration of cell cycle in carriers of CCNE1 risk variants. In combination with established bladder cancer risk factors and other somatic and germline genetic markers, the CCNE1 variants could be useful for inclusion into bladder cancer risk prediction models. PMID:25320178

  10. Prediction of Aggressive Human Prostate Cancer by Cathepsin B

    DTIC Science & Technology

    2006-03-01

    microdisection (LCM) in this task is in progress. Prostate cancer (PC), and benign prostatic hyperplasia ( BPH ) as control samples, were collected at the...antigen (PSA) levels in less than five years even though the post-RP pathology report did not detect cancer cell invasion to prostate margin/capsule...design of prospective studies. Biopsies showed significantly higher levels of CB to SA ratios than BPH . 15. SUBJECT TERMS African and White American Men

  11. Molecular Innovations Towards Theranostics of Aggressive Prostate Cancer

    DTIC Science & Technology

    2013-09-01

    quantitative PET imaging of PSMA expression in prostate cancer. 15. SUBJECT TERMS 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF...design for noninvasive assessment of prostate specific membrane antigen ( PSMA ) expression in prostate cancer. • We have published two peer-reviewed...other is on the use of our proposed bifunctional chelator system to exploit the multivalent effect for the detection of PSMA . REPORTABLE OUTCOMES

  12. Development of targeted therapy in uterine serous carcinoma, a biologically aggressive variant of endometrial cancer.

    PubMed

    El-Sahwi, Karim S; Schwartz, Peter E; Santin, Alessandro D

    2012-01-01

    Endometrial cancer (EC) is the most common female genital malignancy in the USA. Most carcinomas arising from the uterus are estrogen dependent and are associated with obesity and hypertension. They are designated type I ECs and typically, due to their early diagnosis secondary to postmenopausal bleeding, have a good prognosis. By contrast, type II ECs develop in older patients, are not hormone dependent and are responsible for most recurrences and deaths from EC. Uterine serous cancer constitutes up to 10% of all endometrial tumors, and represents the most biologically aggressive variant of type II EC. This article will describe the most salient molecular markers that have been identified in uterine serous cancer, thus far with emphasis on the use of erbB2 (HER2/neu) as the first of a series of therapeutic markers for the treatment of this highly-aggressive subset of ECs.

  13. Unusual aggressive breast cancer: metastatic malignant phyllodes tumor.

    PubMed

    Singer, Adam; Tresley, Jonathan; Velazquez-Vega, Jose; Yepes, Monica

    2013-02-01

    For the year of 2012, it has been estimated that breast cancer will account for the greatest number of newly diagnosed cancers and the second highest proportion of cancer related deaths among women. Breast cancer, while often lumped together as one disease, represents a diverse group of malignancies with different imaging findings, histological appearances and behavior. While most invasive primary breast cancers are epithelial derived adenocarcinomas, rare neoplasms such as the phyllodes tumor may arise from mesenchymal tissue. Compared to the breast adenocarcinoma, the phyllodes tumor tends to affect a younger population, follows a different clinical course, is associated with different imaging and histological findings and is managed distinctively. There may be difficulty in differentiating the phyllodes tumor from a large fibroadenoma, but the mammographer plays a key role in reviewing the clinical and imaging data in order to arrive at the correct diagnosis. Early diagnosis with proper surgical management can often cure non-metastatic phyllodes tumors. However, in rare cases where metastasis occurs, prognosis tends to be poor. This report describes the presentation, imaging findings and management of a metastatic malignant phyllodes tumor.

  14. Enriched CD44(+)/CD24(-) population drives the aggressive phenotypes presented in triple-negative breast cancer (TNBC).

    PubMed

    Ma, Fei; Li, Huihui; Wang, Haijuan; Shi, Xiuqing; Fan, Ying; Ding, Xiaoyan; Lin, Chen; Zhan, Qimin; Qian, Haili; Xu, Binghe

    2014-10-28

    The mechanism underlying the aggressive behaviors of triple negative breast cancer (TNBC) is not well characterized yet. The association between cancer stem cell (CSC) population and the aggressive behaviors of TNBC has not been established. We found the CD44(+)/CD24(-) cell population was enriched in TNBC tissues and cell lines, with a higher capacity of proliferation, migration, invasion and tumorigenicity as well as lower adhesion ability. The CD44(+)/CD24(-) cell population with cancer stem cell-like properties may play an important role in the aggressive behaviors of TNBC. This discovery may lead to new therapeutic strategies targeting CD44(+)/CD24(-) cell population in TNBC.

  15. Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

    DTIC Science & Technology

    2013-09-01

    objective is to develop dendrimer -based theranostic agent with prostate cancer specificity and positron emission tomography imaging capability that...The goal of this project is to construct dendrimer nanoconjuate containing a prostate specific cell permeation peptide, peptide therapeutic(s) and...bifunctional chelator for PET imaging. Dr. Simanek’s laboratory will make dendrimers that bear functional handles for conjugation with imaging

  16. Making Aggressive Prostate Cancer Quiescent by Abrogating Cholesterol Esterification

    DTIC Science & Technology

    2015-10-01

    precursor to hormone synthesis. While cholesterol accumulation is known to be a hallmark of atherosclerosis , its exact role in cancer progression...molecule inhibitors of cholesterol accumulation, e.g. avasimibe, have gone through clinical trials to treat atherosclerosis but failed due to the lack of

  17. Calcium intake, polymorphisms of the calcium-sensing receptor, and recurrent/aggressive prostate cancer

    PubMed Central

    Binder, Moritz; Shui, Irene M.; Wilson, Kathryn M.; Penney, Kathryn L.; Mucci, Lorelei A.; Kibel, Adam S.

    2015-01-01

    Purpose To assess whether calcium intake and common genetic variants of the calcium-sensing receptor (CASR) are associated with either aggressive prostate cancer (PCa) or disease recurrence after prostatectomy. Methods Calcium intake at diagnosis was assessed, and 65 common single-nucleotide polymorphisms (SNPs) in CASR were genotyped in 886 prostatectomy patients. We investigated the association between calcium intake and CASR variants with both PCa recurrence and aggressiveness (defined as Gleason score ≥4 + 3, stage ≥pT3, or nodal-positive disease). Results A total of 285 men had aggressive disease and 91 experienced recurrence. A U-shaped relationship between calcium intake and both disease recurrence and aggressiveness was observed. Compared to the middle quintile, the HR for disease recurrence was 3.07 (95 % CI 1.41–6.69) for the lowest quintile and 3.21 (95 % CI 1.47–7.00) and 2.97 (95 % CI 1.37–6.45) for the two upper quintiles, respectively. Compared to the middle quintile, the OR for aggressive disease was 1.80 (95 % CI 1.11–2.91) for the lowest quintile and 1.75 (95 % CI 1.08–2.85) for the highest quintile of calcium intake. The main effects of CASR variants were not associated with PCa recurrence or aggressiveness. In the subgroup of patients with moderate calcium intake, 31 SNPs in four distinct blocks of high linkage disequilibrium were associated with PCa recurrence. Conclusions We observed a protective effect of moderate calcium intake for PCa aggressiveness and recurrence. While CASR variants were not associated with these outcomes in the entire cohort, they may be associated with disease recurrence in men with moderate calcium intakes. PMID:26407952

  18. Molecular Innovations Toward Theranostics of Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    to develop dendrimer -based theranostic agent with prostate cancer specificity and positron emission tomography imaging capability that can prevent...laboratories to develop a new molecular medicine. The goal of this project is to construct dendrimer nanoconjuate containing a prostate specific...cell permeation peptide, peptide therapeutic(s) and bifunctional chelator for PET imaging. Dr. Simanek’s laboratory will make dendrimers that bear

  19. Microvascular Channel Device to Study Aggressiveness in Prostate Cancer Metastasis

    DTIC Science & Technology

    2013-06-01

    leukocyte like’ cells to be transported through the blood stream to their metastatic destinations (1). Like leukocytes, prostate cancer ( PRCA ) cells...for the dynamic flow-based E-selectin+SDF-1 coated microtubes, which can capture PRCA cells and allow us to study the circulating tumor cell...1 dyne/cm2 is the best possible combination to collect the smallest most potent PRCA cells from the tube based circulation model (preliminary data

  20. Microvascular Channel Device to Study Aggressiveness in Prostate Cancer Metastasis

    DTIC Science & Technology

    2013-06-01

    Prostate Cancer ( PRCA ) cells preferentially adhere and roll on bone marrow endothelial cells (BMECs) (2, 3) where abundant E-selectin is expressed (4...successfully established parameters’ for the dynamic flow-based E-selectin+SDF-1 coated microtubes, which can capture PRCA cells and allow us to study the...ml of SDF-1β with shear stress 1 dyne/cm2 is the best possible combination to collect the smallest more potent PRCA cells from the tube based

  1. Microvascular Channel Device to Study Aggressiveness in Prostate Cancer Metastasis

    DTIC Science & Technology

    2012-06-01

    stream to their metastatic destinations (1). Like leukocytes, Prostate Cancer ( PRCA ) cells preferentially adhere and roll on bone marrow endothelial...microtubes, which can capture PRCA cells and allow us to study the circulating tumor cell behavior and its contribution to tumor metastasis. It was...the smallest more potent PRCA cells from the tube based circulation model (preliminary data). We used this selectin and SDF-1β coated micro-renathane

  2. A novel non-canonical Wnt signature for prostate cancer aggressiveness.

    PubMed

    Sandsmark, Elise; Hansen, Ailin Falkmo; Selnæs, Kirsten M; Bertilsson, Helena; Bofin, Anna M; Wright, Alan J; Viset, Trond; Richardsen, Elin; Drabløs, Finn; Bathen, Tone F; Tessem, May-Britt; Rye, Morten B

    2017-02-07

    Activation of the Canonical Wnt pathway (CWP) has been linked to advanced and metastatic prostate cancer, whereas the Wnt5a-induced non-canonical Wnt pathway (NCWP) has been associated with both good and poor prognosis. A newly discovered NCWP, Wnt5/Fzd2, has been shown to induce epithelial-to-mesenchymal transition (EMT) in cancers, but has not been investigated in prostate cancer. The aim of this study was to investigate if the CWP and NCWP, in combination with EMT, are associated with metabolic alterations, aggressive disease and biochemical recurrence in prostate cancer. An initial analysis was performed using integrated transcriptomics, ex vivo and in vivo metabolomics, and histopathology of prostatectomy samples (n=129), combined with at least five-year follow-up. This analysis detected increased activation of NCWP through Wnt5a/ Fzd2 as the most common mode of Wnt activation in prostate cancer. This activation was associated with increased expression of EMT markers and higher Gleason score. The transcriptional association between NCWP and EMT was confirmed in five other publicly available patient cohorts (1519 samples in total). A novel gene expression signature of concordant activation of NCWP and EMT (NCWP-EMT) was developed, and this signature was significantly associated with metastasis and shown to be a significant predictor of biochemical recurrence. The NCWP-EMT signature was also associated with decreased concentrations of the metabolites citrate and spermine, which have previously been linked to aggressive prostate cancer. Our results demonstrate the importance of NCWP and EMT in prostate cancer aggressiveness, suggest a novel gene signature for improved risk stratification, and give new molecular insight.

  3. Aggressive surgical resection for concomitant liver and lung metastasis in colorectal cancer

    PubMed Central

    Lee, Sung Hwan; Kim, Sung Hyun; Lim, Jin Hong; Kim, Sung Hoon; Lee, Jin Gu; Kim, Dae Joon; Choi, Gi Hong; Choi, Jin Sub

    2016-01-01

    Backgrounds/Aims Aggressive surgical resection for hepatic metastasis is validated, however, concomitant liver and lung metastasis in colorectal cancer patients is equivocal. Methods Clinicopathologic data from January 2008 through December 2012 were retrospectively reviewed in 234 patients with colorectal cancer with concomitant liver and lung metastasis. Clinicopathologic factors and survival data were analyzed. Results Of the 234 patients, 129 (55.1%) had synchronous concomitant liver and lung metastasis from colorectal cancer and 36 (15.4%) had metachronous metastasis. Surgical resection was performed in 33 patients (25.6%) with synchronous and 6 (16.7%) with metachronous metastasis. Surgical resection showed better overall survival in both groups (synchronous, p=0.001; metachronous, p=0.028). In the synchronous metastatic group, complete resection of both liver and lung metastatic lesions had better survival outcomes than incomplete resection of two metastatic lesions (p=0.037). The primary site of colorectal cancer and complete resection were significant prognostic factors (p=0.06 and p=0.003, respectively). Conclusions Surgical resection for hepatic and pulmonary metastasis in colorectal cancer can improve complete remission and survival rate in resectable cases. Colorectal cancer with concomitant liver and lung metastasis is not a poor prognostic factor or a contraindication for surgical treatments, hence, an aggressive surgical approach may be recommended in well-selected resectable cases. PMID:27621747

  4. Neuropilin-2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-09-01

    AWARD NUMBER: W81XWH-12- 1 -0308 TITLE: Neuropilin-2: Novel Biomarker and Therapeutic Target for Aggressive Prostate Cancer...information is estimated to average 1 hour per response, including the time for reviewing instructions, searching existing data sources, gathering and...information if it does not display a currently valid OMB control number. PLEASE DO NOT RETURN YOUR FORM TO THE ABOVE ADDRESS. 1 . REPORT DATE September

  5. Study in mice shows that an aggressive type of breast cancer is linked to an inflammatory protein

    Cancer.gov

    Aberrant expression of an inflammatory protein, nitric oxide synthase 2 (NOS2), may enhance the progression and metastasis of an aggressive and less common form of breast cancer, known as the estrogen receptor-negative type of disease.

  6. Hypnosis as an Adjunct Treatment for Distress Associated with Pediatric Cancer Procedures.

    ERIC Educational Resources Information Center

    White, Jerre Lee

    This paper reviews research literature pertaining to the pain and anxiety associated with pediatric cancer and the use of hypnosis as an adjunct treatment. It is noted that pain and anxiety are most often associated with the procedural treatment of cancer, and that the literature suggests that both pain and anxiety are multi-faceted constructs.…

  7. The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers.

    PubMed

    Bertucci, François; Finetti, Pascal; Birnbaum, Daniel; Mamessier, Emilie

    2016-03-01

    Analysis of PDL1 mRNA expression in ∼5,500 breast cancers showed PDL1 upregulation in 38% of basal tumors and 38% of inflammatory breast cancers (IBC). Upregulation, associated with signs of strong cytotoxic local immune response, was associated with a better survival in the basal or triple-negative subtypes, and with a better pathological response to chemotherapy in these subtypes and IBC. Reactivation of dormant tumor-infiltrating lymphocytes (TILs) by PD1/PDL1-inhibitors represents a promising strategy in these aggressive tumors.

  8. The PD1/PDL1 axis, a promising therapeutic target in aggressive breast cancers

    PubMed Central

    Bertucci, François; Finetti, Pascal; Birnbaum, Daniel; Mamessier, Emilie

    2016-01-01

    ABSTRACT Analysis of PDL1 mRNA expression in ∼5,500 breast cancers showed PDL1 upregulation in 38% of basal tumors and 38% of inflammatory breast cancers (IBC). Upregulation, associated with signs of strong cytotoxic local immune response, was associated with a better survival in the basal or triple-negative subtypes, and with a better pathological response to chemotherapy in these subtypes and IBC. Reactivation of dormant tumor-infiltrating lymphocytes (TILs) by PD1/PDL1-inhibitors represents a promising strategy in these aggressive tumors. PMID:27141340

  9. Screening for Novel Germline Rare Mutations Associated with Aggressive Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    Schmidt S., Peshkin L., et al. A method and server for predicting damaging missense mutations. Nat Methods. 7, 248-249 (2010). Akbari MR, Trachtenberg...Inst. 2012 Aug 1;104(16):1260-2. Epub 2012 Jul 9. Castro E. G.C.L., Olmos D., et al. Correlation of germ-line BRCA2 mutations with aggressive...prostate cancer. Clin Cancer Res. 16, 2115-2121 (2010). 20    Hammer GE, Gonzalez F, Champsaur M, Cado D, Shastri N. The aminopeptidase ERAAP shapes the

  10. Emergency Point-of-Care Ultrasound Detection of Cancer in the Pediatric Emergency Department.

    PubMed

    Jamjoom, Roaa S; Etoom, Yousef; Solano, Tanya; Desjardins, Marie-Pier; Fischer, Jason W

    2015-08-01

    The use of point-of-care ultrasound in the pediatric emergency department is evolving beyond conventional applications as users become more expert with the technology. In this case series, we describe the potential utility of recognizing abnormal anatomy to impact care in the context of possible cancer in pediatric patients. We describe 4 patients with Langerhans histiocytosis, neuroblastoma, Wilms tumor, and rhabdomyosarcoma, in which point-of-care ultrasound was used to facilitate the diagnoses.

  11. A Systems Genetics Approach Identifies CXCL14, ITGAX, and LPCAT2 as Novel Aggressive Prostate Cancer Susceptibility Genes

    PubMed Central

    Andreas, Jonathan; Patel, Shashank J.; Zhang, Suiyuan; Chines, Peter; Elkahloun, Abdel; Chandrasekharappa, Settara; Gutkind, J. Silvio; Molinolo, Alfredo A.; Crawford, Nigel P. S.

    2014-01-01

    Although prostate cancer typically runs an indolent course, a subset of men develop aggressive, fatal forms of this disease. We hypothesize that germline variation modulates susceptibility to aggressive prostate cancer. The goal of this work is to identify susceptibility genes using the C57BL/6-Tg(TRAMP)8247Ng/J (TRAMP) mouse model of neuroendocrine prostate cancer. Quantitative trait locus (QTL) mapping was performed in transgene-positive (TRAMPxNOD/ShiLtJ) F2 intercross males (n = 228), which facilitated identification of 11 loci associated with aggressive disease development. Microarray data derived from 126 (TRAMPxNOD/ShiLtJ) F2 primary tumors were used to prioritize candidate genes within QTLs, with candidate genes deemed as being high priority when possessing both high levels of expression-trait correlation and a proximal expression QTL. This process enabled the identification of 35 aggressive prostate tumorigenesis candidate genes. The role of these genes in aggressive forms of human prostate cancer was investigated using two concurrent approaches. First, logistic regression analysis in two human prostate gene expression datasets revealed that expression levels of five genes (CXCL14, ITGAX, LPCAT2, RNASEH2A, and ZNF322) were positively correlated with aggressive prostate cancer and two genes (CCL19 and HIST1H1A) were protective for aggressive prostate cancer. Higher than average levels of expression of the five genes that were positively correlated with aggressive disease were consistently associated with patient outcome in both human prostate cancer tumor gene expression datasets. Second, three of these five genes (CXCL14, ITGAX, and LPCAT2) harbored polymorphisms associated with aggressive disease development in a human GWAS cohort consisting of 1,172 prostate cancer patients. This study is the first example of using a systems genetics approach to successfully identify novel susceptibility genes for aggressive prostate cancer. Such approaches will

  12. Targeting uPAR with antagonistic recombinant human antibodies in aggressive breast cancer.

    PubMed

    LeBeau, Aaron M; Duriseti, Sai; Murphy, Stephanie T; Pepin, Francois; Hann, Byron; Gray, Joe W; VanBrocklin, Henry F; Craik, Charles S

    2013-04-01

    Components of the plasminogen activation system, which are overexpressed in aggressive breast cancer subtypes, offer appealing targets for development of new diagnostics and therapeutics. By comparing gene expression data in patient populations and cultured cell lines, we identified elevated levels of the urokinase plasminogen activation receptor (uPAR, PLAUR) in highly aggressive breast cancer subtypes and cell lines. Recombinant human anti-uPAR antagonistic antibodies exhibited potent binding in vitro to the surface of cancer cells expressing uPAR. In vivo these antibodies detected uPAR expression in triple negative breast cancer (TNBC) tumor xenografts using near infrared imaging and (111)In single-photon emission computed tomography. Antibody-based uPAR imaging probes accurately detected small disseminated lesions in a tumor metastasis model, complementing the current clinical imaging standard (18)F-fluorodeoxyglucose at detecting non-glucose-avid metastatic lesions. A monotherapy study using the antagonistic antibodies resulted in a significant decrease in tumor growth in a TNBC xenograft model. In addition, a radioimmunotherapy study, using the anti-uPAR antibodies conjugated to the therapeutic radioisotope (177)Lu, found that they were effective at reducing tumor burden in vivo. Taken together, our results offer a preclinical proof of concept for uPAR targeting as a strategy for breast cancer diagnosis and therapy using this novel human antibody technology.

  13. Inherited Variants in the Chemokine CCL2 Gene and Prostate Cancer Aggressiveness in a Caucasian Cohort

    PubMed Central

    Sun, Tong; Lee, Gwo-Shu Mary; Oh, William K.; Freedman, Matthew L.; Pomerantz, Mark; Pienta, Kenneth J.; Kantoff, Philip W.

    2010-01-01

    Purpose Though C-C chemokine ligand 2 (CCL2) has been demonstrated to play a pivotal role in prostate cancer tumorigenesis and invasion, the role of inherited variation in the CCL2 gene in prostate cancer progression and metastases remains unanswered. This study is aimed to determine the influence of CCL2 germline variants on prostate cancer aggressiveness. Experimental Design We performed an association study between six single nucleotide polymorphisms (SNPs) in the CCL2 gene and prostate cancer clinicopathologic variables in a large hospital based Caucasian patient cohort (N =4073). Results Genetic variantion at CCL2 is associated with markers of disease aggressiveness. Three SNPs, each in strong linkage disequilibrium, are associated with a higher (>7) biopsy Gleason score: CCL2-1811 A/G, −2835A/C and +3726 T/C (P =0.01, 0.03 and 0.04 respectively). The CCL2 −1811 G allele is addionally associated with advanced pathologic stages in patients who underwent radical prostatectomy (P = 0.04). In haplotype analysis, we found that the frequency of a common haplotype, H5, was higher among patients with D’Amico good risk features (Ppermutation = 0.04). Conclusions These results support the influence of CCL2 variants on prostate cancer development and progression. PMID:21135144

  14. Associations between vitamin D deficiency and risk of aggressive breast cancer in African-American women.

    PubMed

    Yao, Song; Ambrosone, Christine B

    2013-07-01

    Although breast cancer incidence in the US is highest for women of European ancestry (EA), women of African ancestry (AA) have higher incidence of cancer diagnosed before age 40 and tumors with more aggressive features (high grade and negative for estrogen receptor (ER), progesterone receptor (PR) and human epidermal growth factor receptor (HER2)), which precludes targeted therapies and leads to poorer outcomes. It is unclear what underlies these disparities. It has been hypothesized that dark skin with high melanin content is the ancestral skin color of origin, with adaptation to northern environs resulting in lighter skin. Although intense sunlight in sub-Saharan Africa may compensate for low sun absorption through skin, an urban or western lifestyle may result in less synthesis of vitamin D with higher skin pigmentation. Laboratory and preclinical data indicate that vitamin D is involved in preventing breast carcinogenesis and progression. Vitamin D receptor (VDR) knock-out mice are more likely to develop tumors that are ER-negative, and we have shown that serum levels of 25OHD are lowest among EA women with triple-negative tumors (negative for ER, PR and HER2); and among non-cancer patients, vitamin D levels are lower in AAs than in EAs. Thus, it is plausible to hypothesize that low vitamin D levels could be associated with the higher prevalence of more aggressive tumors among AA women. In this paper, we review the current literature on vitamin D and aggressive breast cancer subtypes, discuss vitamin D in AA women from a perspective of evolution and adaption, and examine the potential role of vitamin D in cancer racial disparities. We present our recently published data showing two single nucleotide polymorphisms in vitamin D catabolic enzyme CYP24A1 associated with higher risk of estrogen ER-negative risk in AA than in EA women. The relationship of vitamin D with breast cancer risk may be subtype-specific, with emerging evidence of stronger effects of vitamin

  15. Lectin chromatography/mass spectrometry discovery workflow identifies putative biomarkers of aggressive breast cancers.

    PubMed

    Drake, Penelope M; Schilling, Birgit; Niles, Richard K; Prakobphol, Akraporn; Li, Bensheng; Jung, Kwanyoung; Cho, Wonryeon; Braten, Miles; Inerowicz, Halina D; Williams, Katherine; Albertolle, Matthew; Held, Jason M; Iacovides, Demetris; Sorensen, Dylan J; Griffith, Obi L; Johansen, Eric; Zawadzka, Anna M; Cusack, Michael P; Allen, Simon; Gormley, Matthew; Hall, Steven C; Witkowska, H Ewa; Gray, Joe W; Regnier, Fred; Gibson, Bradford W; Fisher, Susan J

    2012-04-06

    We used a lectin chromatography/MS-based approach to screen conditioned medium from a panel of luminal (less aggressive) and triple negative (more aggressive) breast cancer cell lines (n=5/subtype). The samples were fractionated using the lectins Aleuria aurantia (AAL) and Sambucus nigra agglutinin (SNA), which recognize fucose and sialic acid, respectively. The bound fractions were enzymatically N-deglycosylated and analyzed by LC-MS/MS. In total, we identified 533 glycoproteins, ∼90% of which were components of the cell surface or extracellular matrix. We observed 1011 glycosites, 100 of which were solely detected in ≥3 triple negative lines. Statistical analyses suggested that a number of these glycosites were triple negative-specific and thus potential biomarkers for this tumor subtype. An analysis of RNaseq data revealed that approximately half of the mRNAs encoding the protein scaffolds that carried potential biomarker glycosites were up-regulated in triple negative vs luminal cell lines, and that a number of genes encoding fucosyl- or sialyltransferases were differentially expressed between the two subtypes, suggesting that alterations in glycosylation may also drive candidate identification. Notably, the glycoproteins from which these putative biomarker candidates were derived are involved in cancer-related processes. Thus, they may represent novel therapeutic targets for this aggressive tumor subtype.

  16. A cancer-causing gene is positively correlated with male aggression in Xiphophorus cortezi

    PubMed Central

    Fernandez, André A.

    2010-01-01

    The persistence of seemingly maladaptive genes in organisms challenges evolutionary biological thought. In Xiphophorus fishes, certain melanin patterns form malignant melanomas due to a cancer-causing gene (Xiphophorus melanoma receptor kinase; Xmrk), which arose several millions years ago from unequal meiotic recombination. Xiphophorus melanomas are male biased and induced by androgens however male behavior and Xmrk genotype has not been investigated. This study found that male X. cortezi with the spotted caudal (Sc) pattern, from which melanomas originate, displayed increased aggression in mirror image trials. Furthermore, Xmrk males (regardless of Sc phenotype) bit and performed more agonistic displays than Xmrk deficient males. Male aggressive response decreased when males viewed their Sc image as compared to their non-Sc image. Collectively, these results indicate that Xmrk males experience a competitive advantage over wild-type males and that intrasexual selection could be an important component in the evolutionary maintenance of this oncogene within Xiphophorus. PMID:20021547

  17. Vincristine-induced peripheral neuropathy in pediatric cancer patients

    PubMed Central

    Mora, Erika; Smith, Ellen M Lavoie; Donohoe, Clare; Hertz, Daniel L

    2016-01-01

    Vincristine is a chemotherapeutic agent that is a component of many combination regimens for a variety of malignancies, including several common pediatric tumors. Vincristine treatment is limited by a progressive sensorimotor peripheral neuropathy. Vincristine-induced peripheral neuropathy (VIPN) is particularly challenging to detect and monitor in pediatric patients, in whom the side effect can diminish long term quality of life. This review summarizes the current state of knowledge regarding VIPN, focusing on its description, assessment, prediction, prevention, and treatment. Significant progress has been made in our knowledge about VIPN incidence and progression, and tools have been developed that enable clinicians to reliably measure VIPN in pediatric patients. Despite these successes, little progress has been made in identifying clinically useful predictors of VIPN or in developing effective approaches for VIPN prevention or treatment in either pediatric or adult patients. Further research is needed to predict, prevent, and treat VIPN to maximize therapeutic benefit and avoid unnecessary toxicity from vincristine treatment. PMID:27904761

  18. Is the European pediatric medicine regulation working for children and adolescents with cancer?

    PubMed

    Vassal, Gilles; Geoerger, Birgit; Morland, Bruce

    2013-03-15

    The European Pediatric Medicine Regulation was launched in 2007 to provide better medicines for children. Five years later, the number of new anticancer drugs in early development in the pediatric population remains low, and most children with cancer are still largely denied access to innovative drugs in Europe, as compared with the United States. We analyzed individual pediatric investigation plan (PIP) and waiver decisions for oncology drugs and all oncology drugs that have been approved for marketing authorization since 2007 in Europe. Among the 45 approved PIPs, 33% concern leukemias and lymphomas, 29% solid tumors, 13% brain tumors, and 20% a drug for supportive care. No specific PIP exists for life-threatening diseases such as high-risk neuroblastoma, whereas there are several PIPs in extremely rare malignancies in children and adolescents such as gastrointestinal stromal tumor, melanoma, thyroid cancer, and chronic myeloid leukemia. This paradoxical situation is due to approval of a PIP being driven by the adult indication. Twenty-six of 28 authorized new oncology drugs have a potentially relevant mechanism of action for pediatric malignancies, but 50% have been waived because the adult condition does not occur in children. The most striking example is crizotinib. Implementation of the pediatric regulation should no longer be driven by the adult indication but should be guided instead by the biology of pediatric tumors and the mechanism of action of a drug. This change will be achievable through voluntary PIPs submitted by Pharma or revocation of the oncology class waiver list.

  19. Novel targeted therapies in uterine serous carcinoma, an aggressive variant of endometrial cancer.

    PubMed

    Menderes, Gulden; Clark, Mitchell; Santin, Alessandro D

    2016-04-01

    Uterine serous carcinoma (USC) is a rare but aggressive subtype of endometrial cancer. Although it represents only 10% of all endometrial cancer cases, USC accounts for up to 40% of all endometrial cancer-related recurrences and subsequent deaths. With such a dismal prognosis, there is an expanding role for novel targeted approaches in the treatment of USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. The results emphasize the relevance of these novel therapeutic targets for biologic therapy of USC, which will be reviewed in this article.

  20. Translating microRNAs into biomarkers: What is new for pediatric cancer?

    PubMed

    de Carvalho, Ivna Néria Silva Ribamar; de Freitas, Renata Mendes; Vargas, Fernando Regla

    2016-05-01

    Since their discovery in 2008, cell-free circulating microRNAs have been considered potential biomarkers for various conditions, including pediatric cancer. Diagnosis of pediatric cancer still relies on clinical signs, which sometimes may be non-specific or appear at later stages. Thus, there is a need for a better understanding of molecules that allow a less invasive, early and effective method of cancer diagnosis. Despite the efforts of many researches to set specific miRNAs to be routinely used as diagnostic molecules, no miR has been currently utilized so far. In this study, we review the recent discoveries on circulating miRNAs in blood of patients suffering from the following pediatric cancers: osteosarcoma, rhabdomyosarcoma, Wilms tumor, acute myeloid leukemia, acute lymphocytic leukemia, retinoblastoma and neuroblastoma. We also focus on the roles of circulating miRs in tumorigenesis pathways, the methodological approaches used to detect and quantify circulating miRs, and discuss the challenges in using them routinely as biomarkers for pediatric cancers.

  1. Ectopic Activation of Germline and Placental Genes Identifies Aggressive Metastasis-Prone Lung Cancers

    PubMed Central

    Rousseaux, Sophie; Debernardi, Alexandra; Jacquiau, Baptiste; Vitte, Anne-Laure; Vesin, Aurélien; Nagy-Mignotte, Hélène; Moro-Sibilot, Denis; Brichon, Pierre-Yves; Lantuejoul, Sylvie; Hainaut, Pierre; Laffaire, Julien; de Reyniès, Aurélien; Beer, David G.; Timsit, Jean-François; Brambilla, Christian; Brambilla, Elisabeth; Khochbin, Saadi

    2016-01-01

    Activation of normally silent tissue-specific genes and the resulting cell “identity crisis” are the unexplored consequences of malignant epigenetic reprogramming. We designed a strategy for investigating this reprogramming, which consisted of identifying a large number of tissue-restricted genes that are epigenetically silenced in normal somatic cells and then detecting their expression in cancer. This approach led to the demonstration that large-scale “off-context” gene activations systematically occur in a variety of cancer types. In our series of 293 lung tumors, we identified an ectopic gene expression signature associated with a subset of highly aggressive tumors, which predicted poor prognosis independently of the TNM (tumor size, node positivity, and metastasis) stage or histological subtype. The ability to isolate these tumors allowed us to reveal their common molecular features characterized by the acquisition of embryonic stem cell/germ cell gene expression profiles and the down-regulation of immune response genes. The methodical recognition of ectopic gene activations in cancer cells could serve as a basis for gene signature–guided tumor stratification, as well as for the discovery of oncogenic mechanisms, and expand the understanding of the biology of very aggressive tumors. PMID:23698379

  2. A Neighborhood-Wide Association Study (NWAS): Example of prostate cancer aggressiveness

    PubMed Central

    Lynch, Shannon M.; Mitra, Nandita; Ross, Michelle; Newcomb, Craig; Dailey, Karl; Jackson, Tara; Zeigler-Johnson, Charnita M.; Riethman, Harold; Branas, Charles C.; Rebbeck, Timothy R.

    2017-01-01

    Purpose Cancer results from complex interactions of multiple variables at the biologic, individual, and social levels. Compared to other levels, social effects that occur geospatially in neighborhoods are not as well-studied, and empiric methods to assess these effects are limited. We propose a novel Neighborhood-Wide Association Study(NWAS), analogous to genome-wide association studies(GWAS), that utilizes high-dimensional computing approaches from biology to comprehensively and empirically identify neighborhood factors associated with disease. Methods Pennsylvania Cancer Registry data were linked to U.S. Census data. In a successively more stringent multiphase approach, we evaluated the association between neighborhood (n = 14,663 census variables) and prostate cancer aggressiveness(PCA) with n = 6,416 aggressive (Stage≥3/Gleason grade≥7 cases) vs. n = 70,670 non-aggressive (Stage<3/Gleason grade<7) cases in White men. Analyses accounted for age, year of diagnosis, spatial correlation, and multiple-testing. We used generalized estimating equations in Phase 1 and Bayesian mixed effects models in Phase 2 to calculate odds ratios(OR) and confidence/credible intervals(CI). In Phase 3, principal components analysis grouped correlated variables. Results We identified 17 new neighborhood variables associated with PCA. These variables represented income, housing, employment, immigration, access to care, and social support. The top hits or most significant variables related to transportation (OR = 1.05;CI = 1.001–1.09) and poverty (OR = 1.07;CI = 1.01–1.12). Conclusions This study introduces the application of high-dimensional, computational methods to large-scale, publically-available geospatial data. Although NWAS requires further testing, it is hypothesis-generating and addresses gaps in geospatial analysis related to empiric assessment. Further, NWAS could have broad implications for many diseases and future precision medicine studies focused on multilevel

  3. Preclinical Models Provide Scientific Justification and Translational Relevance for Moving Novel Therapeutics into Clinical Trials for Pediatric Cancer.

    PubMed

    Langenau, David M; Sweet-Cordero, Alejandro; Wechsler-Reya, Robert J; Dyer, Michael A

    2015-12-15

    Despite improvements in survival rates for children with cancer since the 1960s, progress for many pediatric malignancies has slowed over the past two decades. With the recent advances in our understanding of the genomic landscape of pediatric cancer, there is now enthusiasm for individualized cancer therapy based on genomic profiling of patients' tumors. However, several obstacles to effective personalized cancer therapy remain. For example, relatively little data from prospective clinical trials demonstrate the selective efficacy of molecular-targeted therapeutics based on somatic mutations in the patient's tumor. In this commentary, we discuss recent advances in preclinical testing for pediatric cancer and provide recommendations for providing scientific justification and translational relevance for novel therapeutic combinations for childhood cancer. Establishing rigorous criteria for defining and validating druggable mutations will be essential for the success of ongoing and future clinical genomic trials for pediatric malignancies.

  4. Coffee consumption and prostate cancer aggressiveness among African and Caucasian Americans in a population-based study.

    PubMed

    Arab, Lenore; Su, L Joseph; Steck, Susan E; Ang, Alfonso; Fontham, Elizabeth T H; Bensen, Jeannette T; Mohler, James L

    2012-01-01

    This study evaluated the relationship between caffeinated and decaffeinated coffee and prostate cancer (CaP) aggressiveness using data from a population-based incident CaP study within the North Carolina-Louisiana Prostate Cancer Project (PCaP). Classification of CaP aggressiveness at diagnosis was based on clinical criteria for 1,049 African-American (AA) and 1,083 Caucasian-American (CA) research subjects. Coffee consumption was measured using a modified NCI Dietary History Questionnaire. No significant associations were found between CaP aggressiveness and consumption of either caffeinated or decaffeinated coffee. The OR for high aggressive CaP among consumers of more than 4 cups per day was 0.92 (95%CI = 0.61, 1.39), compared to non-coffee-drinkers. Results stratified by race found no significant associations and no noticeable trends in either AAs (P for trend = 0. 62) or CAs (P for trend = 0.42). In contrast to a recent report on a select population that has less complete information on CaP aggressiveness suggesting that coffee prevents aggressive CaP, this rapid case ascertainment population-based study, in a biracial population with differing risks of CaP did not demonstrate a protective relationship between high coffee consumption and risk of high aggressive CaP.

  5. Cognitive/Attentional Distraction in the Control of Conditioned Nausea in Pediatric Cancer Patients Receiving Chemotherapy.

    ERIC Educational Resources Information Center

    Redd, William H.; And Others

    1987-01-01

    Investigated use of cognitive/attentional distraction (via commercially available video games) to control conditioned nausea in pediatric cancer patients receiving chemotherapy. Video game-playing resulted in significantly less nausea. The introduction and withdrawal of the opportunity to play video games produced significant changes (reduction…

  6. Pediatric cancer gone viral. Part I: strategies for utilizing oncolytic herpes simplex virus-1 in children.

    PubMed

    Cripe, Timothy P; Chen, Chun-Yu; Denton, Nicholas L; Haworth, Kellie B; Hutzen, Brian; Leddon, Jennifer L; Streby, Keri A; Wang, Pin-Yi; Markert, James M; Waters, Alicia M; Gillespie, George Yancey; Beierle, Elizabeth A; Friedman, Gregory K

    Progress for improving outcomes in pediatric patients with solid tumors remains slow. In addition, currently available therapies are fraught with numerous side effects, often causing significant life-long morbidity for long-term survivors. The use of viruses to kill tumor cells based on their increased vulnerability to infection is gaining traction, with several viruses moving through early and advanced phase clinical testing. The prospect of increased efficacy and decreased toxicity with these agents is thus attractive for pediatric cancer. In part I of this two-part review, we focus on strategies for utilizing oncolytic engineered herpes simplex virus (HSV) to target pediatric malignancies. We discuss mechanisms of action, routes of delivery, and the role of preexisting immunity on antitumor efficacy. Challenges to maximizing oncolytic HSV in children are examined, and we highlight how these may be overcome through various arming strategies. We review the preclinical and clinical evidence demonstrating safety of a variety of oncolytic HSVs. In Part II, we focus on the antitumor efficacy of oncolytic HSV in pediatric tumor types, pediatric clinical advances made to date, and future prospects for utilizing HSV in pediatric patients with solid tumors.

  7. HER2 overcomes PTEN (loss)-induced senescence to cause aggressive prostate cancer

    PubMed Central

    Ahmad, Imran; Patel, Rachana; Singh, Lukram Babloo; Nixon, Colin; Seywright, Morag; Barnetson, Robert J.; Brunton, Valerie G.; Muller, William J.; Edwards, Joanne; Sansom, Owen J.; Leung, Hing Y.

    2011-01-01

    Prostate cancer (CaP) is the most common cancer among adult men in the Western world. Better insight into its tumor-activating pathways may facilitate the development of targeted therapies. In this study, we show that patients who develop prostate tumors with low levels of PTEN and high levels of HER2/3 have a poor prognosis. This is functionally relevant, as targeting Her2 activation to the murine prostate cooperates with Pten loss and drives CaP progression. Mechanistically, this is associated with activation of the MAPK pathway and abrogation of the Pten loss-induced cellular senescence program. Importantly, inhibition of MEK function strongly suppressed proliferation within these tumors by restoring the Pten loss-induced cellular senescence program. Taken together, these data suggest that stratification of CaP patients for HER2/3 and PTEN status could identify patients with aggressive CaP who may respond favorably to MEK inhibition. PMID:21930937

  8. Targeted therapy in uterine serous carcinoma: an aggressive variant of endometrial cancer.

    PubMed

    Black, Jonathan D; English, Diana P; Roque, Dana M; Santin, Alessandro D

    2014-01-01

    Uterine serous carcinoma (USC) is a highly aggressive variant of endometrial cancer. Although it only represents less than 10% of all cases, it accounts for a disproportionate number of deaths from endometrial cancer. Comprehensive surgical staging followed by carboplatin and paclitaxel chemotherapy represents the mainstay of USC therapy. Vaginal cuff brachytherapy is also of potential benefit in USC. Recent whole-exome sequencing studies have demonstrated gain of function of the HER2/NEU gene, as well as driver mutations in the PIK3CA/AKT/mTOR and cyclin E/FBXW7 oncogenic pathways in a large number of USCs. These results emphasize the relevance of these novel therapeutic targets for biologic therapy of chemotherapy-resistant recurrent USC.

  9. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer.

    PubMed

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R; Tang, Dean G

    2016-02-29

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features.

  10. Stem cell and neurogenic gene-expression profiles link prostate basal cells to aggressive prostate cancer

    PubMed Central

    Zhang, Dingxiao; Park, Daechan; Zhong, Yi; Lu, Yue; Rycaj, Kiera; Gong, Shuai; Chen, Xin; Liu, Xin; Chao, Hsueh-Ping; Whitney, Pamela; Calhoun-Davis, Tammy; Takata, Yoko; Shen, Jianjun; Iyer, Vishwanath R.; Tang, Dean G.

    2016-01-01

    The prostate gland mainly contains basal and luminal cells constructed as a pseudostratified epithelium. Annotation of prostate epithelial transcriptomes provides a foundation for discoveries that can impact disease understanding and treatment. Here we describe a genome-wide transcriptome analysis of human benign prostatic basal and luminal epithelial populations using deep RNA sequencing. Through molecular and biological characterizations, we show that the differential gene-expression profiles account for their distinct functional properties. Strikingly, basal cells preferentially express gene categories associated with stem cells, neurogenesis and ribosomal RNA (rRNA) biogenesis. Consistent with this profile, basal cells functionally exhibit intrinsic stem-like and neurogenic properties with enhanced rRNA transcription activity. Of clinical relevance, the basal cell gene-expression profile is enriched in advanced, anaplastic, castration-resistant and metastatic prostate cancers. Therefore, we link the cell-type-specific gene signatures to aggressive subtypes of prostate cancer and identify gene signatures associated with adverse clinical features. PMID:26924072

  11. Fludarabine, cyclophosphamide, doxorubicin (FCD), and rituximab: a remission induction therapy for aggressive pediatric post-transplant lymphoproliferative disease (PTLD).

    PubMed

    Giraldi, Eugenia; Provenzi, Massimo; Fiocchi, Roberto; Colledan, Michele; Cornelli, Pieremilio; Torre, Giuliano; Rambaldi, Alessandro; Conter, Valentino

    2011-08-01

    Management of aggressive, usually late-occurring, post-transplant lymphoproliferative disorders (PTLDs), a life-threatening complication after solid organ transplants, remains controversial. Four children affected by aggressive CD20+ PTLDs received a chemo-immunotherapy regimen for remission induction based on fludarabine, cyclophosphamide, doxorubicin, and rituximab, associated with a rapid discontinuation of immunosuppression (IS). Subsequent consolidation chemotherapy consisted of Berlin-Frankfurt-Münster-modified blocks. All patients achieved a complete remission, which persisted for 25, 68+, 80+, and 103+ months after diagnosis. Therapy was well tolerated. No patients developed allograft rejection during PTLD treatment. Our experience suggests that this chemo-immunotherapeutic approach may be an effective treatment strategy while allowing for a concomitant discontinuation of IS.

  12. GALNT6 expression enhances aggressive phenotypes of ovarian cancer cells by regulating EGFR activity.

    PubMed

    Lin, Tzu-Chi; Chen, Syue-Ting; Huang, Min-Chuan; Huang, John; Hsu, Chia-Lang; Juan, Hsueh-Fen; Lin, Ho-Hsiung; Chen, Chi-Hau

    2017-03-28

    Ovarian cancer is the most lethal of the gynecologic malignancies. N-acetylgalactosaminyltransferase 6 (GALNT6), an enzyme that mediates the initial step of mucin type-O glycosylation, has been reported to regulate mammary carcinogenesis. However, the expression and role of GALNT6 in ovarian cancer are still unclear. Here we showed that high GALNT6 expression correlates with increased recurrence, lymph node metastasis, and chemoresistance in ovarian endometrioid and clear cell carcinomas; and higher GALNT6 levels are significantly associated with poorer patient survivals. GALNT6 knockdown with two independent siRNAs significantly suppressed viability, migration, and invasion of ovarian cancer cells. Using phospho-RTK array and Western blot analyses, we identified EGFR as a critical target of GALNT6. GALNT6 knockdown decreased phosphorylation of EGFR, whereas GALNT6 overexpression increased the phosphorylation. Lectin pull-down assays with Vicia villosa agglutinin (VVA) indicated that GALNT6 was able to modify O-glycans on EGFR. Moreover, the GALNT6-enhanced invasive behavior was significantly reversed by erlotinib, an EGFR inhibitor. Our results suggest that GALNT6 expression is associated with poor prognosis of ovarian cancer and enhances the aggressive behavior of ovarian cancer cells by regulating EGFR activity.

  13. Mitochondrial oncobioenergetic index: A potential biomarker to predict progression from indolent to aggressive prostate cancer.

    PubMed

    Vayalil, Praveen K; Landar, Aimee

    2015-12-15

    Mitochondrial function is influenced by alterations in oncogenes and tumor suppressor genes and changes in the microenvironment occurring during tumorigenesis. Therefore, we hypothesized that mitochondrial function will be stably and dynamically altered at each stage of the prostate tumor development. We tested this hypothesis in RWPE-1 cells and its tumorigenic clones with progressive malignant characteristics (RWPE-1 < WPE-NA22 < WPE-NB14 < WPE-NB11 < WPE-NB26) using high-throughput respirometry. Our studies demonstrate that mitochondrial content do not change with increasing malignancy. In premalignant cells (WPE-NA22 and WPE-NB14), OXPHOS is elevated in presence of glucose or glutamine alone or in combination compared to RWPE-1 cells and decreases with increasing malignancy. Glutamine maintained higher OXPHOS than glucose and suggests that it may be an important substrate for the growth and proliferation of prostate epithelial cells. Glycolysis significantly increases with malignancy and follow a classical Warburg phenomenon. Fatty acid oxidation (FAO) is significantly lower in tumorigenic clones and invasive WPE-NB26 does not utilize FAO at all. In this paper, we introduce for the first time the mitochondrial oncobioenergetic index (MOBI), a mathematical representation of oncobioenergetic profile of a cancer cell, which increases significantly upon transformation into localized premalignant form and rapidly falls below the normal as they become aggressive in prostate tumorigenesis. We have validated this in five prostate cancer cell lines and MOBI appears to be not related to androgen dependence or mitochondrial content, but rather dependent on the stage of the cancer. Altogether, we propose that MOBI could be a potential biomarker to distinguish aggressive cancer from that of indolent disease.

  14. Metabolic coupling in urothelial bladder cancer compartments and its correlation to tumor aggressiveness

    PubMed Central

    Afonso, Julieta; Santos, Lúcio L.; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2016-01-01

    abstract Monocarboxylate transporters (MCTs) are vital for intracellular pH homeostasis by extruding lactate from highly glycolytic cells. These molecules are key players of the metabolic reprogramming of cancer cells, and evidence indicates a potential contribution in urothelial bladder cancer (UBC) aggressiveness and chemoresistance. However, the specific role of MCTs in the metabolic compartmentalization within bladder tumors, namely their preponderance on the tumor stroma, remains to be elucidated. Thus, we evaluated the immunoexpression of MCTs in the different compartments of UBC tissue samples (n = 111), assessing the correlations among them and with the clinical and prognostic parameters. A significant decrease in positivity for MCT1 and MCT4 occurred from normoxic toward hypoxic regions. Significant associations were found between the expression of MCT4 in hypoxic tumor cells and in the tumor stroma. MCT1 staining in normoxic tumor areas, and MCT4 staining in hypoxic regions, in the tumor stroma and in the blood vessels were significantly associated with UBC aggressiveness. MCT4 concomitant positivity in hypoxic tumor cells and in the tumor stroma, as well as positivity in each of these regions concomitant with MCT1 positivity in normoxic tumor cells, was significantly associated with an unfavourable clinicopathological profile, and predicted lower overall survival rates among patients receiving platinum-based chemotherapy. Our results point to the existence of a multi-compartment metabolic model in UBC, providing evidence of a metabolic coupling between catabolic stromal and cancer cells’ compartments, and the anabolic cancer cells. It is urgent to further explore the involvement of this metabolic coupling in UBC progression and chemoresistance. PMID:26636903

  15. In vivo NCL targeting affects breast cancer aggressiveness through miRNA regulation

    PubMed Central

    Palmieri, Dario; De Luca, Luciana; Consiglio, Jessica; You, Jia; Rocci, Alberto; Talabere, Tiffany; Piovan, Claudia; Lagana, Alessandro; Cascione, Luciano; Guan, Jingwen; Gasparini, Pierluigi; Balatti, Veronica; Nuovo, Gerard; Coppola, Vincenzo; Hofmeister, Craig C.; Marcucci, Guido; Byrd, John C.; Volinia, Stefano; Shapiro, Charles L.; Freitas, Michael A.

    2013-01-01

    Numerous studies have described the altered expression and the causal role of microRNAs (miRNAs) in human cancer. However, to date, efforts to modulate miRNA levels for therapeutic purposes have been challenging to implement. Here we find that nucleolin (NCL), a major nucleolar protein, posttranscriptionally regulates the expression of a specific subset of miRNAs, including miR-21, miR-221, miR-222, and miR-103, that are causally involved in breast cancer initiation, progression, and drug resistance. We also show that NCL is commonly overexpressed in human breast tumors and that its expression correlates with that of NCL-dependent miRNAs. Finally, inhibition of NCL using guanosine-rich aptamers reduces the levels of NCL-dependent miRNAs and their target genes, thus reducing breast cancer cell aggressiveness both in vitro and in vivo. These findings illuminate a path to novel therapeutic approaches based on NCL-targeting aptamers for the modulation of miRNA expression in the treatment of breast cancer. PMID:23610125

  16. Pediatric Blood Cancer Survivors and Tobacco Use across Adolescence and Emerging Adulthood: A Narrative Review

    PubMed Central

    Masiero, Marianna; Riva, Silvia; Fioretti, Chiara; Pravettoni, Gabriella

    2016-01-01

    Scholars underline the pivotal role of tobacco cigarette smoking in carcinogenesis process for blood tumors. A controversial debate is represented by the diffusion of tobacco use in young cancer survivors that had a previous diagnosis of blood tumor during the childhood. Compared with their peers, scientific evidence highlights that pediatric survivors have more difficult to give-up cigarette smoking. Furthermore, tobacco-smoking is frequently linked with others risk behaviors as drinking or substance abuse. In reviewing the main knowledge on this topic, authors affirm the need for increasing research on blood cancer survivors in order to depict psychological characteristics of pediatric blood cancer survivors. Improving health decision-making skills in young survivors could reduce the risk to adopt un-healthy behaviors and increase psychological wellbeing. Furthermore, authors propose tailored antismoking interventions based on the knowledge of the psychological and cognitive factors that support smoking during the transition toward emerging-adulthood. PMID:27047419

  17. Distress among hospitalized pediatric cancer patients modified by pet-therapy intervention to improve quality of life.

    PubMed

    Urbanski, Beth L; Lazenby, Mark

    2012-01-01

    This state of the science, integrative literature review focuses on animal-facilitated therapy (AFT) and the benefits provided to quality of life in hospitalized pediatric oncology patients. Results showed physiological and psychological benefits in pediatric inpatients settings. AFT has been shown to decrease pain, change vital signs, provide distraction, decrease fear, increase socialization, increase pleasure and decrease emotional distress in hospitalized pediatric patients. AFT needs to be implemented with appropriate medical discretion, but for the appropriate high-risk patients, AFT can improve quality of life. Pain, adjustment difficulties, mood changes and symptom management can be improved in inpatient pediatric cancer patients receiving AFT, thus improving overall quality of life.

  18. [Implementation of the unified model of presenting cancer diagnosis in Polish pediatric onco-hematology centers].

    PubMed

    Samardakiewicz, Marzena; Kowalczyk, Jerzy R; Mazurowa, Mieczysława; Budziński, Waldemar; Antonowicz, Małgorzata; Borysławska, Anna; Szweda, Elzbieta; Groth, Anna; Pyka, Małgorzata; Figurska, Martyna; Chybicka, Alicja; Rokicka-Milewska, Roma; Matysiak, Michał; Balwierz, Walentyna; Sońta-Jakimczyk, Danuta; Balcerska, Anna; Wachowiak, Jacek

    2004-01-01

    Presentation of full information related to diagnosis of children with cancer should be one of principles in pediatric oncology. Multidisciplinary approach to each newly diagnosed child and its parents contributes to improving this standard. The Polish Pediatric Leukemia and Lymphoma Group is engaged in these activities since 1998 and it resulted in implementation of several SIOP recommendations in most of Polish pediatric oncohematology centers. The unified model of presentation of diagnosis for a child, parents and family was of an importance and the efforts to introduce it in all cooperating centers was undertaken. Proposed model of informing consists of several steps. Procedure should be individually tailored according to natural history of the disease and characteristics of the family. The purpose of the study was to evaluate the informing procedure in 60 children with newly diagnosed neoplasmatic disease.

  19. Association of prostate volume with incidence and aggressiveness of prostate cancer

    PubMed Central

    Al-Khalil, Shadi; Ibilibor, Christine; Cammack, James Thomas; de Riese, Werner

    2016-01-01

    Objective The aim of this study was to investigate the possible correlation between prostate volume and aggressiveness and incidence of prostate cancer (PCa). Patients and methods A chart review of a cohort of 448 consecutive prostate biopsy-naive men was performed. These men underwent at least a 12-core biopsy at our institution due to increased prostate-specific antigen serum levels (>4 ng/mL) and/or suspicious findings on digital rectal examination during the period between 2008 and 2013. Transrectal ultrasound was used to determine the prostate volume. Results The positive biopsy rate was 66% for patients with a prostate volume of ≤35 cc and 40% for patients with a prostate volume of ≥65 cc (P<0.001). Of the 110 patients testing positive on biopsy with a volume of ≤35 cc, 10 patients (9.1%) had a Gleason score of ≥8. Of the 27 patients testing positive on biopsy with a volume of ≥65 cc, only 1 patient (3.7%) had a Gleason score of ≥8. Conclusion These results suggest that there may be an association between prostate volume and the incidence and aggressiveness of PCa. The larger the prostate, the lower the positive biopsy rate for PCa and the lower the Gleason score. PMID:27822463

  20. Identification of Cell Surface Proteins as Potential Immunotherapy Targets in 12 Pediatric Cancers

    PubMed Central

    Orentas, Rimas J.; Yang, James J.; Wen, Xinyu; Wei, Jun S.; Mackall, Crystal L.; Khan, Javed

    2012-01-01

    Technological advances now allow us to rapidly produce CARs and other antibody-derived therapeutics targeting cell surface receptors. To maximize the potential of these new technologies, relevant extracellular targets must be identified. The Pediatric Oncology Branch of the NCI curates a freely accessible database of gene expression data for both pediatric cancers and normal tissues, through which we have defined discrete sets of over-expressed transcripts in 12 pediatric cancer subtypes as compared to normal tissues. We coupled gene expression profiles to current annotation databases (i.e., Affymetrix, Gene Ontology, Entrez Gene), in order to categorize transcripts by their sub-cellular location. In this manner we generated a list of potential immune targets expressed on the cell surface, ranked by their difference from normal tissue. Global differences from normal between each of the pediatric tumor types studied varied, indicating that some malignancies expressed transcript sets that were more highly diverged from normal tissues than others. The validity of our approach is seen by our findings for pre-B cell ALL, where targets currently in clinical trials were top-ranked hits (CD19, CD22). For some cancers, reagents already in development could potentially be applied to a new disease class, as exemplified by CD30 expression on sarcomas. Moreover, several potential new targets shared among several pediatric solid tumors are herein identified, such as MCAM (MUC18), metadherin (MTDH), and glypican-2 (GPC2). These targets have been identified at the mRNA level and are yet to be validated at the protein level. The safety of targeting these antigens has yet to be demonstrated and therefore the identified transcripts should be considered preliminary candidates for new CAR and therapeutic antibody targets. Prospective candidate targets will be evaluated by proteomic analysis including Westerns and immunohistochemistry of normal and tumor tissues. PMID:23251904

  1. Anti-influenza neuraminidase inhibitor oseltamivir phosphate induces canine mammary cancer cell aggressiveness.

    PubMed

    de Oliveira, Joana T; Santos, Ana L; Gomes, Catarina; Barros, Rita; Ribeiro, Cláudia; Mendes, Nuno; de Matos, Augusto J; Vasconcelos, M Helena; Oliveira, Maria José; Reis, Celso A; Gärtner, Fátima

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness.

  2. Aggressive resection of frequent peritoneal recurrences in colorectal cancer contributes to long-term survival

    PubMed Central

    Komori, Koji; Kinoshita, Takashi; Taihei, Oshiro; Ito, Seiji; Abe, Tetsuya; Senda, Yoshiki; Misawa, Kazunari; Ito, Yuich; Uemura, Norihisa; Natsume, Seiji; Kawakami,, Jiro; Ouchi, Akira; Tsutsuyama, Masayuki; Hosoi, Takahiro; Shigeyoshi, Itaru; Akazawa, Tomoyuki; Hayashi, Daisuke; Tanaka, Hideharu; Shimizu, Yasuhiro

    2016-01-01

    ABSTRACT We report a long-term survivor of colorectal cancer who underwent aggressive, frequent resection for peritoneal recurrences. A 58-year-old woman was diagnosed with descending colon cancer. Resection of the descending colon along with lymph node dissection was performed in September 2006. The pathological findings revealed Stage IIA colorectal cancer. The following peritoneal recurrences were removed: two in July 2007, two in the omental fat and two in the pouch of Douglas in June 2008 resected by low anterior resection of the rectum, one in the uterus and right ovarian recurrence resected via bilateral adnexectomy and Hartmann’s procedure in May 2011, and one in the ascending colon by partial resection of the colon wall in December 2011. Postoperative adjuvant chemotherapy (uracil and tegafur/leucovorin, fluorouracil/levofolinate/oxaliplatin/bevacizumab, 5-fluorouracil/leucovorin/bevacizumab, irinotecan/bevacizumab, and irinotecan/panitumumab) was administered. The patient did not desire postoperative adjuvant chemotherapy after the fourth operation. The long-term survival was 6 years and 7 months. PMID:28008206

  3. Anti-Influenza Neuraminidase Inhibitor Oseltamivir Phosphate Induces Canine Mammary Cancer Cell Aggressiveness

    PubMed Central

    de Oliveira, Joana T.; Santos, Ana L.; Gomes, Catarina; Barros, Rita; Ribeiro, Cláudia; Mendes, Nuno; de Matos, Augusto J.; Vasconcelos, M. Helena; Oliveira, Maria José; Reis, Celso A.; Gärtner, Fátima

    2015-01-01

    Oseltamivir phosphate is a widely used anti-influenza sialidase inhibitor. Sialylation, governed by sialyltransferases and sialidases, is strongly implicated in the oncogenesis and progression of breast cancer. In this study we evaluated the biological behavior of canine mammary tumor cells upon oseltamivir phosphate treatment (a sialidase inhibitor) in vitro and in vivo. Our in vitro results showed that oseltamivir phosphate impairs sialidase activity leading to increased sialylation in CMA07 and CMT-U27 canine mammary cancer cells. Surprisingly, oseltamivir phosphate stimulated, CMT-U27 cell migration and invasion capacity in vitro, in a dose-dependent manner. CMT-U27 tumors xenograft of oseltamivir phosphate-treated nude mice showed increased sialylation, namely α2,6 terminal structures and SLe(x) expression. Remarkably, a trend towards increased lung metastases was observed in oseltamivir phosphate-treated nude mice. Taken together, our findings revealed that oseltamivir impairs canine mammary cancer cell sialidase activity, altering the sialylation pattern of canine mammary tumors, and leading, surprisingly, to in vitro and in vivo increased mammary tumor aggressiveness. PMID:25850034

  4. Comprehensive functional analysis of the tousled-like kinase 2 frequently amplified in aggressive luminal breast cancers

    PubMed Central

    Kim, Jin-Ah; Tan, Ying; Wang, Xian; Cao, Xixi; Veeraraghavan, Jamunarani; Liang, Yulong; Edwards, Dean P.; Huang, Shixia; Pan, Xuewen; Li, Kaiyi; Schiff, Rachel; Wang, Xiao-Song

    2016-01-01

    More aggressive and therapy-resistant oestrogen receptor (ER)-positive breast cancers remain a great clinical challenge. Here our integrative genomic analysis identifies tousled-like kinase 2 (TLK2) as a candidate kinase target frequently amplified in ∼10.5% of ER-positive breast tumours. The resulting overexpression of TLK2 is more significant in aggressive and advanced tumours, and correlates with worse clinical outcome regardless of endocrine therapy. Ectopic expression of TLK2 leads to enhanced aggressiveness in breast cancer cells, which may involve the EGFR/SRC/FAK signalling. Conversely, TLK2 inhibition selectively inhibits the growth of TLK2-high breast cancer cells, downregulates ERα, BCL2 and SKP2, impairs G1/S cell cycle progression, induces apoptosis and significantly improves progression-free survival in vivo. We identify two potential TLK2 inhibitors that could serve as backbones for future drug development. Together, amplification of the cell cycle kinase TLK2 presents an attractive genomic target for aggressive ER-positive breast cancers. PMID:27694828

  5. One in Four Questioned Children Faces Problems Regarding Reintegration Into Physical Education at School After Treatment for Pediatric Cancer.

    PubMed

    Kesting, Sabine V; Götte, Miriam; Seidel, Corinna C; Rosenbaum, Dieter; Boos, Joachim

    2016-04-01

    Resumption of physical activity and reintegration into social surroundings after treatment for pediatric cancer is of high importance to recover from the burden of disease and treatment and to positively influence long-term health outcomes. Eighty-three children who had completed intensive treatment for pediatric cancer were surveyed regarding their participation in physical education at school (PES). The results show a concerning low rate of participation, particularly in children treated for pediatric bone tumors, and associated barriers. Reported reasons for quitting PES seem to be conquerable by individual and entity-related support to enable participation according to the children's desire.

  6. Enhancement of the Efficacy of Conventional Anticancer Compounds through the Repression of SNAI Proteins in Aggressive Breast Cancer Cells

    DTIC Science & Technology

    2012-09-01

    vitamin D and anti-estrogens in human breast cancer tissues; (b) To determine the effects of alterations of the levels of SNAI proteins in breast...determine the effects of alterations of the levels of SNAI proteins in breast cancer cells on their sensitivity towards vitamin D and/or 4HT; and (3) To...diminish their aggressiveness but also make these cells sensitive to the inhibition of some of the conventional anticancer agents such as vitamin D and

  7. RB loss contributes to aggressive tumor phenotypes in MYC-driven triple negative breast cancer.

    PubMed

    Knudsen, Erik S; McClendon, A Kathleen; Franco, Jorge; Ertel, Adam; Fortina, Paolo; Witkiewicz, Agnieszka K

    2015-01-01

    Triple negative breast cancer (TNBC) is characterized by multiple genetic events occurring in concert to drive pathogenic features of the disease. Here we interrogated the coordinate impact of p53, RB, and MYC in a genetic model of TNBC, in parallel with the analysis of clinical specimens. Primary mouse mammary epithelial cells (mMEC) with defined genetic features were used to delineate the combined action of RB and/or p53 in the genesis of TNBC. In this context, the deletion of either RB or p53 alone and in combination increased the proliferation of mMEC; however, the cells did not have the capacity to invade in matrigel. Gene expression profiling revealed that loss of each tumor suppressor has effects related to proliferation, but RB loss in particular leads to alterations in gene expression associated with the epithelial-to-mesenchymal transition. The overexpression of MYC in combination with p53 loss or combined RB/p53 loss drove rapid cell growth. While the effects of MYC overexpression had a dominant impact on gene expression, loss of RB further enhanced the deregulation of a gene expression signature associated with invasion. Specific RB loss lead to enhanced invasion in boyden chambers assays and gave rise to tumors with minimal epithelial characteristics relative to RB-proficient models. Therapeutic screening revealed that RB-deficient cells were particularly resistant to agents targeting PI3K and MEK pathway. Consistent with the aggressive behavior of the preclinical models of MYC overexpression and RB loss, human TNBC tumors that express high levels of MYC and are devoid of RB have a particularly poor outcome. Together these results underscore the potency of tumor suppressor pathways in specifying the biology of breast cancer. Further, they demonstrate that MYC overexpression in concert with RB can promote a particularly aggressive form of TNBC.

  8. Glycoprotein Biomarkers for the Early Detection of Aggressive Prostate Cancer — EDRN Public Portal

    Cancer.gov

    The Early Detection Research Network of the NCI is charged with the discovery, development and validation of biomarkers for early detection and prognosis related to neoplastic disease. Our laboratory is an NCI EDRN (U01CA152813) working on "Glycoprotein biomarkers for the early detection of aggressive prostate cancer". This EDRN administratiVE! supplement is a collaboration with Robert Veltri on his project to identify men with very low risk (indolent) prostate cancer (CaP) at the diagnostic biopsy at selection for active surveillance (AS). We will assess biopsy tissue using quantitative nuclear histomorphometric measurements and molecular biomarkers to predict an unexpected catastrophic CaP in such men with indolent CaP. At Johns Hopkins Hospital w1e use the Epstein criteria that includes; PSA density (PSAD) <0.15 ng/mVcm3, Gleason score SS, S2 cons involved with cancer, and ::;;SO% of any core involved with cancer to select AS. Our approach will study 140 AS men (70 with a expected outcome and 70 with a disastrous outcome) using nuclear histomorphometry and pre-qualified biomarkers quantified by digital microscopy. Previously, our laboratory combined measurements of DNA content and (-2)pPSA in the serum and (-5,-?)pPSA in biopsy tissue to identify 7/10 men that would fail surveillance based on the primary diagnostic biopsy. We now will devHiop a clinical, morphological and biomarker 'signature' for identifying severe aggressive disease from a AS diagnostic biopsy. Our approach will combine nuclear morphometry measured by digital microscopy with a unique biopsy tissue biomarker profile (DNA content, Ki67, Her2neu, CACND1 and periostin). Fc•r the molecular targets we will us•e a multiplex tissue blot (MTB) immunohistochemistry method. The Aims o'f our work include 1) to utilize retrospective archival biopsy material from 70 AS cases where the outcome was unexpected and disastrous and collect an equal number of AS cases (n=140) and perform assays for morphology

  9. Historical Trends in the Use of Radiation Therapy for Pediatric Cancers: 1973-2008

    SciTech Connect

    Jairam, Vikram; Roberts, Kenneth B.; Yu, James B.

    2013-03-01

    Purpose: This study was undertaken to assess historical trends in the use of radiation therapy (RT) for pediatric cancers over the past 4 decades. Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database of the 9 original tumor registries (SEER-9) was queried to identify patients aged 0 to 19 years with acute lymphoblastic leukemia, acute myeloid leukemia, bone and joint cancer, cancer of the brain and nervous system, Hodgkin lymphoma, neuroblastoma, non-Hodgkin lymphoma, soft tissue cancer, Wilms tumor, or retinoblastoma from 1973 to 2008. Patients were grouped into 4-year time epochs. The number and percentage of patients who received RT as part of their initial treatment were calculated per epoch by each diagnosis group from 1973 to 2008. Results: RT use for acute lymphoblastic leukemia, non-Hodgkin lymphoma, and retinoblastoma declined sharply from 57%, 57%, and 30% in 1973 to 1976 to 11%, 15%, and 2%, respectively, in 2005 to 2008. Similarly, smaller declines in RT use were also seen in brain cancer (70%-39%), bone cancer (41%-21%), Wilms tumor (75%-53%), and neuroblastoma (60%-25%). RT use curves for Wilms tumor and neuroblastoma were nonlinear with nadirs in 1993 to 1996 at 39% and 19%, respectively. There were minimal changes in RT use for Hodgkin lymphoma, soft tissue cancer, or acute myeloid leukemia, roughly stable at 72%, 40%, and 11%, respectively. Almost all patients treated with RT were given external beam RT exclusively. However, from 1985 to 2008, treatments involving brachytherapy, radioisotopes, or combination therapy increased in frequency, comprising 1.8%, 4.6%, and 11.9% of RT treatments in brain cancer, soft tissue cancer, and retinoblastoma, respectively. Conclusions: The use of RT is declining over time in 7 of 10 pediatric cancer categories. A limitation of this study is a potential under-ascertainment of RT use in the SEER-9 database including the delayed use of RT.

  10. Is Birthweight Associated with Total and Aggressive/Lethal Prostate Cancer Risks? A Systematic Review and Meta-analysis

    PubMed Central

    Zhou, Cindy Ke; Sutcliffe, Siobhan; Welsh, Judith; Mackinnon, Karen; Kuh, Diana; Hardy, Rebecca; Cook, Michael B.

    2016-01-01

    Background It has been hypothesized that intrauterine exposures are important for subsequent prostate cancer risk. Prior epidemiological studies have used birthweight as a proxy of cumulative intrauterine exposures to test this hypothesis, but results have been inconsistent partly due to limited statistical power. Methods We investigated birthweight in relation to prostate cancer in the Medical Research Council (MRC) National Survey of Health and Development (NSHD) using Cox proportional hazards models. We then conducted a meta-analysis of birthweight in relation to total and aggressive/lethal prostate cancer risks, combining results from the NSHD analysis with 13 additional studies on this relationship identified from a systematic search in four major scientific literature databases through January 2015. Results Random-effects models found that each kg increase in birthweight was positively associated with total (OR=1.02, 95%CI=1.00, 1.05; I2=13%) and aggressive/lethal prostate cancer (OR=1.08, 95%CI=0.99, 1.19; I2=40%). Sensitivity analyses restricted to studies with birthweight extracted from medical records demonstrated stronger positive associations with total (OR=1.11, 95%CI=1.03, 1.19; I2=0%) and aggressive/lethal (OR=1.37, 95%CI=1.09, 1.74; I2=0%) prostate cancer. These studies heavily overlapped with those based in Nordic countries. Conclusion This study provides evidence that heavier birthweight may be associated with modest increased risks of total and aggressive/lethal prostate cancer, which supports the hypothesis that intrauterine exposures may be related to subsequent prostate cancer risks. PMID:26930450

  11. A mixed methods assessment of coping with pediatric cancer

    PubMed Central

    Alderfer, Melissa A.; Deatrick, Janet A.; Marsac, Meghan L.

    2014-01-01

    The purpose of this study was to describe child coping and parent coping assistance with cancer-related stressors during treatment. Fifteen children (aged 6-12) with cancer and their parents (N = 17) completed semi-structured interviews and self-report measures to assess coping and coping assistance. Results suggest families utilized a broad array of approach and avoidance strategies to manage cancer and its treatment. Quantitative and qualitative assessments provided complementary and unique contributions to understanding coping among children with cancer and their parents. Using a mixed methods approach to assess coping provides a richer understanding of families’ experiences, which can better inform clinical practice. PMID:24428250

  12. A meta-analytic review of the influence of pediatric cancer on parent and family functioning.

    PubMed

    Pai, Ahna L H; Greenley, Rachel Neff; Lewandowski, Amy; Drotar, Dennis; Youngstrom, Eric; Peterson, Catherine Cant

    2007-09-01

    This study used meta-analytic methods to compare the functioning of parents of children with cancer to parents of physically healthy children or normative samples. A meta-analysis using fixed effects, weighted least squares methods was conducted on 29 studies examining psychological distress and marital and family functioning among parents of children with cancer. Mothers and fathers of children newly diagnosed with cancer reported significantly greater distress than comparison samples. Mothers reported greater distress than fathers up to 12 months postdiagnosis. Mothers of children with cancer reported higher levels of family conflict than mothers of healthy children. Findings suggest that pediatric cancer impacts parents' perceptions of self- and family functioning, especially within the 1st year following diagnosis.

  13. Nanotechnology and Pediatric Cancer: Prevention, Diagnosis and Treatment

    PubMed Central

    Zare-Zardini, H; Amiri, A; Shanbedi, M; Taheri-Kafrani, A; Sadri, Z; Ghanizadeh, F; Neamatzadeh, H; Sheikhpour, R; Keyvani Boroujeni, F; Masoumi Dehshiri, R; Hashemi, A; Aminorroaya, MM; Dehgahnzadeh, MR; Shahriari, Sh

    2015-01-01

    Despite development of new approaches for the treatment of cancer disease, it is the second cause of mortality in world. Annually, 30000 persons die in Iran due to cancer diseases. Eighty percent of cancer patients are children which about 50% children lead to death. Given the high rate of cancer-related death, the new approaches for prevention, control, early diagnosis, and treatment of this disease seem necessary. Investigation of new strategies is the major challenge for scientists at recent century. Nanotechnology as a new scientific field with novel and small compounds utilized different fields over the past ten years especially in medicine. This science has come to the forefront in the areas of medical diagnostics, imaging, and therapeutic scheduls. Therefore, it has the potential applications for cancer detection and therapy. This review will discuss the therapeutic applications of different nano-materials in diagnosis, imaging, and delivery of therapeutic agents for the treatment of cancer with a major focus on their applications for the treatment of cancer and cancer- related diseases in children. The advancements in established nanoparticle technologies such as liposomes, polymer micelles, and functionalization regarding tumor targeting and controlled release strategies as well as drug delivery were discussed. It will also review the blood toxicity of used nanostructures. PMID:26985357

  14. Environmental factors and risk of aggressive prostate cancer among a population of New Zealand men - a genotypic approach.

    PubMed

    Vaidyanathan, Venkatesh; Naidu, Vijay; Kao, Chi Hsiu-Juei; Karunasinghe, Nishi; Bishop, Karen S; Wang, Alice; Pallati, Radha; Shepherd, Phillip; Masters, Jonathan; Zhu, Shuotun; Goudie, Megan; Krishnan, Mohanraj; Jabed, Anower; Marlow, Gareth; Narayanan, Ajit; Ferguson, Lynnette R

    2017-03-28

    Prostate cancer is one of the most significant health concerns for men worldwide. Numerous researchers carrying out molecular diagnostics have indicated that genetic interactions with biological and behavioral factors play an important role in the overall risk and prognosis of this disease. Single nucleotide polymorphisms (SNPs) are increasingly becoming strong biomarker candidates to identify susceptibility to prostate cancer. We carried out a gene × environment interaction analysis linked to aggressive and non-aggressive prostate cancer (PCa) with a number of SNPs. By using this method, we identified the susceptible alleles in a New Zealand population, and examined the interaction with environmental factors. We have identified a number of SNPs that have risk associations both with and without environmental interaction. The results indicate that certain SNPs are associated with disease vulnerability based on behavioral factors. The list of genes with SNPs identified as being associated with the risk of PCa in a New Zealand population is provided in the graphical abstract.

  15. ZNF503/Zpo2 drives aggressive breast cancer progression by down-regulation of GATA3 expression.

    PubMed

    Shahi, Payam; Wang, Chih-Yang; Lawson, Devon A; Slorach, Euan M; Lu, Angela; Yu, Ying; Lai, Ming-Derg; Gonzalez Velozo, Hugo; Werb, Zena

    2017-03-21

    The transcription factor GATA3 is the master regulator that drives mammary luminal epithelial cell differentiation and maintains mammary gland homeostasis. Loss of GATA3 is associated with aggressive breast cancer development. We have identified ZNF503/ZEPPO2 zinc-finger elbow-related proline domain protein 2 (ZPO2) as a transcriptional repressor of GATA3 expression and transcriptional activity that induces mammary epithelial cell proliferation and breast cancer development. We show that ZPO2 is recruited to GATA3 promoter in association with ZBTB32 (Repressor of GATA, ROG) and that ZBTB32 is essential for down-regulation of GATA3 via ZPO2. Through this modulation of GATA3 activity, ZPO2 promotes aggressive breast cancer development. Our data provide insight into a mechanism of GATA3 regulation, and identify ZPO2 as a possible candidate gene for future diagnostic and therapeutic strategies.

  16. Loss of RasGAP Tumor Suppressors Underlies the Aggressive Nature of Luminal B Breast Cancers.

    PubMed

    Olsen, Sarah Naomi; Wronski, Ania; Castaño, Zafira; Dake, Benjamin; Malone, Clare; De Raedt, Thomas; Enos, Miriam; DeRose, Yoko S; Zhou, Wenhui; Guerra, Stephanie; Loda, Massimo; Welm, Alana; Partridge, Ann H; McAllister, Sandra S; Kuperwasser, Charlotte; Cichowski, Karen

    2017-02-01

    Luminal breast cancers are typically estrogen receptor-positive and generally have the best prognosis. However, a subset of luminal tumors, namely luminal B cancers, frequently metastasize and recur. Unfortunately, the causal events that drive their progression are unknown, and therefore it is difficult to identify individuals who are likely to relapse and should receive escalated treatment. Here, we identify a bifunctional RasGAP tumor suppressor whose expression is lost in almost 50% of luminal B tumors. Moreover, we show that two RasGAP genes are concomitantly suppressed in the most aggressive luminal malignancies. Importantly, these genes cooperatively regulate two major oncogenic pathways, RAS and NF-κB, through distinct domains, and when inactivated drive the metastasis of luminal tumors in vivo Finally, although the cooperative effects on RAS drive invasion, NF-κB activation triggers epithelial-to-mesenchymal transition and is required for metastasis. Collectively, these studies reveal important mechanistic insight into the pathogenesis of luminal B tumors and provide functionally relevant prognostic biomarkers that may guide treatment decisions.

  17. One Thousand Genomes Imputation in the National Cancer Institute Breast and Prostate Cancer Cohort Consortium Aggressive Prostate Cancer Genome-wide Association Study

    PubMed Central

    Machiela, Mitchell J.; Chen, Constance; Liang, Liming; Diver, W. Ryan; Stevens, Victoria L.; Tsilidis, Konstantinos K.; Haiman, Christopher A.; Chanock, Stephen J.; Hunter, David J.; Kraft, Peter

    2014-01-01

    BACKGROUND Genotype imputation substantially increases available markers for analysis in genome-wide association studies (GWAS) by leveraging linkage disequilibrium from a reference panel. We sought to (i) investigate the performance of imputation from the August 2010 release of the 1000 Genomes Project (1000GP) in an existing GWAS of prostate cancer, (ii) look for novel associations with prostate cancer risk, (iii) fine-map known prostate cancer susceptibility regions using an approximate Bayesian framework and stepwise regression, and (iv) compare power and efficiency of imputation and de novo sequencing. METHODS We used 2,782 aggressive prostate cancer cases and 4,458 controls from the NCI Breast and Prostate Cancer Cohort Consortium aggressive prostate cancer GWAS to infer 5.8 million well-imputed autosomal single nucleotide polymorphisms. RESULTS Imputation quality, as measured by correlation between imputed and true allele counts, was higher among common variants than rare variants. We found no novel prostate cancer associations among a subset of 1.2 million well-imputed low-frequency variants. At a genome-wide sequencing cost of $2,500, imputation from SNP arrays is a more powerful strategy than sequencing for detecting disease associations of SNPs with minor allele frequencies above 1%. CONCLUSIONS 1000GP imputation provided dense coverage of previously-identified prostate cancer susceptibility regions, highlighting its potential as an inexpensive first-pass approach to fine-mapping in regions such as 5p15 and 8q24. Our study shows 1000GP imputation can accurately identify low-frequency variants and stresses the importance of large sample size when studying these variants. PMID:23255287

  18. Challenges identifying genetic determinants of pediatric cancers--the childhood leukemia experience.

    PubMed

    Sinnett, Daniel; Labuda, Damian; Krajinovic, Maja

    2006-01-01

    Pediatric cancers affect approximately 1 in every 500 children before the age of 15. Little is known about the etiology of this heterogeneous group of diseases despite the fact they constitute the major cause of death by disease among this population. Because of its relatively high prevalence, most of the work done in pediatric oncogenetics has been focused on leukemias, particularly acute lymphoblastic leukemia (ALL). Although it is now well accepted that genetic variation plays a significant role in determining individual's cancer susceptibility, few studies have explored genetic susceptibility to childhood leukemia with respect to common polymorphisms. The biochemical and genetic mechanisms contributing to cancer susceptibility are numerous and can be grouped into broad categories: (1) cellular growth and differentiation, (2) DNA replication and repair, (3) metabolism of carcinogens (4) apoptosis, (5) oxidative stress response and (6) cell cycle. To evaluate whether candidate genes in these pathways are involved in childhood leukemogenesis, we conducted case-control studies. We showed that leukemogenesis in children may be associated with DNA variants in some of these genes and that the combination of genotypes seems to be more predictive of risk than either of them independently. We also observed that, at least at some loci, the parental genetics might be important in predicting the risk of cancer in this pediatric model of a complex disease. Taken together, these results indicate that the investigation of a single enzyme and/or a single genotype might not be sufficient to explain the etiology of childhood leukemia because of the complexity of the environment and that of the inter-individual variability in cancer susceptibility.

  19. Rac3 induces a molecular pathway triggering breast cancer cell aggressiveness: differences in MDA-MB-231 and MCF-7 breast cancer cell lines

    PubMed Central

    2013-01-01

    Background Rho GTPases are involved in cellular functions relevant to cancer. The roles of RhoA and Rac1 have already been established. However, the role of Rac3 in cancer aggressiveness is less well understood. Methods This work was conducted to analyze the implication of Rac3 in the aggressiveness of two breast cancer cell lines, MDA-MB-231 and MCF-7: both express Rac3, but MDA-MB-231 expresses more activated RhoA. The effect of Rac3 in cancer cells was also compared with its effect on the non-tumorigenic mammary epithelial cells MCF-10A. We analyzed the consequences of Rac3 depletion by anti-Rac3 siRNA. Results Firstly, we analyzed the effects of Rac3 depletion on the breast cancer cells’ aggressiveness. In the invasive MDA-MB-231 cells, Rac3 inhibition caused a marked reduction of both invasion (40%) and cell adhesion to collagen (84%), accompanied by an increase in TNF-induced apoptosis (72%). This indicates that Rac3 is involved in the cancer cells’ aggressiveness. Secondly, we investigated the effects of Rac3 inhibition on the expression and activation of related signaling molecules, including NF-κB and ERK. Cytokine secretion profiles were also analyzed. In the non-invasive MCF-7 line; Rac3 did not influence any of the parameters of aggressiveness. Conclusions This discrepancy between the effects of Rac3 knockdown in the two cell lines could be explained as follows: in the MDA-MB-231 line, the Rac3-dependent aggressiveness of the cancer cells is due to the Rac3/ERK-2/NF-κB signaling pathway, which is responsible for MMP-9, interleukin-6, -8 and GRO secretion, as well as the resistance to TNF-induced apoptosis, whereas in the MCF-7 line, this pathway is not functional because of the low expression of NF-κB subunits in these cells. Rac3 may be a potent target for inhibiting aggressive breast cancer. PMID:23388133

  20. Ultrasound and Biomarker Tests in Predicting Cancer Aggressiveness in Tissue Samples of Patients With Bladder Cancer

    ClinicalTrials.gov

    2016-06-09

    Bladder Papillary Urothelial Carcinoma; Stage 0a Bladder Urothelial Carcinoma; Stage 0is Bladder Urothelial Carcinoma; Stage I Bladder Cancer With Carcinoma In Situ; Stage I Bladder Urothelial Carcinoma; Stage II Bladder Urothelial Carcinoma; Stage III Bladder Urothelial Carcinoma; Stage IV Bladder Urothelial Carcinoma

  1. Germline Mutations in Predisposition Genes in Pediatric Cancer

    PubMed Central

    Edmonson, Michael N.; Gruber, Tanja A.; Easton, John; Hedges, Dale; Ma, Xiaotu; Zhou, Xin; Yergeau, Donald A.; Wilkinson, Mark R.; Vadodaria, Bhavin; Chen, Xiang; McGee, Rose B.; Hines-Dowell, Stacy; Nuccio, Regina; Quinn, Emily; Shurtleff, Sheila A.; Rusch, Michael; Patel, Aman; Becksfort, Jared B.; Wang, Shuoguo; Weaver, Meaghann S.; Ding, Li; Mardis, Elaine R.; Wilson, Richard K.; Gajjar, Amar; Ellison, David W.; Pappo, Alberto S.; Pui, Ching-Hon; Downing, James R.

    2016-01-01

    BACKGROUND The prevalence and spectrum of predisposing mutations among children and adolescents with cancer are largely unknown. Knowledge of such mutations may improve the understanding of tumorigenesis, direct patient care, and enable genetic counseling of patients and families. METHODS In 1120 patients younger than 20 years of age, we sequenced the whole genomes (in 595 patients), whole exomes (in 456), or both (in 69). We analyzed the DNA sequences of 565 genes, including 60 that have been associated with autosomal dominant cancer-predisposition syndromes, for the presence of germline mutations. The pathogenicity of the mutations was determined by a panel of medical experts with the use of cancer-specific and locus-specific genetic databases, the medical literature, computational predictions, and second hits identified in the tumor genome. The same approach was used to analyze data from 966 persons who did not have known cancer in the 1000 Genomes Project, and a similar approach was used to analyze data from an autism study (from 515 persons with autism and 208 persons without autism). RESULTS Mutations that were deemed to be pathogenic or probably pathogenic were identified in 95 patients with cancer (8.5%), as compared with 1.1% of the persons in the 1000 Genomes Project and 0.6% of the participants in the autism study. The most commonly mutated genes in the affected patients were TP53 (in 50 patients), APC (in 6), BRCA2 (in 6), NF1 (in 4), PMS2 (in 4), RB1 (in 3), and RUNX1 (in 3). A total of 18 additional patients had protein-truncating mutations in tumor-suppressor genes. Of the 58 patients with a predisposing mutation and available information on family history, 23 (40%) had a family history of cancer. CONCLUSIONS Germline mutations in cancer-predisposing genes were identified in 8.5% of the children and adolescents with cancer. Family history did not predict the presence of an underlying predisposition syndrome in most patients. (Funded by the American

  2. Pediatric cancer and the internet: exploring the gap in doctor-parents communication.

    PubMed

    Domínguez, Martí; Sapiña, Lucía

    2015-03-01

    The aim of this study is to examine the use of the Internet to obtain information by parents of children with cancer and how pediatric oncologists understand this new scenario and the shifting relationship between patients and doctors. With this goal in mind, we conducted two surveys: one was answered by 110 parents of pediatric cancer patients and another one was answered by 74 oncologists, members of the Spanish Society of Pediatric Hematology and Oncology (SEHOP). Less than half of the surveyed parents (44.5%) looked for information on the Internet, while 55.5% preferred not to do it. In addition, 87.3% of the parents explain that their doctors did not recommend any Internet resources. Among the oncologists' sample, 68.9% of the respondents did not recommend seeking information on the Internet, but they would consider it desirable for the patients to be guided in the search (82.4%). These results show some degree of dissent between the parents' needs and the oncologists' attitudes. Higher interaction between these two agents would be recommended in order to achieve better information and cooperation in the therapeutic protocols.

  3. Clinical and Neurobiological Perspectives of Empowering Pediatric Cancer Patients Using Videogames

    PubMed Central

    Govender, Meveshni; Bowen, Randy C.; German, Massiell L.; Bulaj, Grzegorz

    2015-01-01

    Abstract Pediatric oncology patients often experience fatigue and physical and mental deconditioning during and following chemotherapy treatments, contributing to diminished quality of life. Patient empowerment is a core principle of patient-centered care and reflects one's ability to positively affect his or her own health behavior and health status. Empowerment interventions may enhance patients' internal locus of control, resilience, coping skills, and self-management of symptoms related to disease and therapy. Clinical and technological advancements in therapeutic videogames and mobile medical applications (mobile health) can facilitate delivery of the empowerment interventions for medical purposes. This review summarizes clinical strategies for empowering pediatric cancer patients, as well as their relationship with developing a “fighting spirit” in physical and mental health. To better understand physiological aspects of empowerment and to elucidate videogame-based intervention strategies, brain neuronal circuits and neurotransmitters during stress, fear, and resilience are also discussed. Neuroimaging studies point to the role of the reward system pathways in resilience and empowerment in patients. Taken together, videogames and mobile health applications open translational research opportunities to develop and deliver empowerment interventions to pediatric cancer patients and also to those with other chronic diseases. PMID:26287927

  4. Clinical and Neurobiological Perspectives of Empowering Pediatric Cancer Patients Using Videogames.

    PubMed

    Govender, Meveshni; Bowen, Randy C; German, Massiell L; Bulaj, Grzegorz; Bruggers, Carol S

    2015-10-01

    Pediatric oncology patients often experience fatigue and physical and mental deconditioning during and following chemotherapy treatments, contributing to diminished quality of life. Patient empowerment is a core principle of patient-centered care and reflects one's ability to positively affect his or her own health behavior and health status. Empowerment interventions may enhance patients' internal locus of control, resilience, coping skills, and self-management of symptoms related to disease and therapy. Clinical and technological advancements in therapeutic videogames and mobile medical applications (mobile health) can facilitate delivery of the empowerment interventions for medical purposes. This review summarizes clinical strategies for empowering pediatric cancer patients, as well as their relationship with developing a "fighting spirit" in physical and mental health. To better understand physiological aspects of empowerment and to elucidate videogame-based intervention strategies, brain neuronal circuits and neurotransmitters during stress, fear, and resilience are also discussed. Neuroimaging studies point to the role of the reward system pathways in resilience and empowerment in patients. Taken together, videogames and mobile health applications open translational research opportunities to develop and deliver empowerment interventions to pediatric cancer patients and also to those with other chronic diseases.

  5. Family rituals, financial burden, and mothers' adjustment in pediatric cancer.

    PubMed

    Santos, Susana; Crespo, Carla; Canavarro, M Cristina; Alderfer, Melissa A; Kazak, Anne E

    2016-12-01

    The financial burden of childhood cancer may contribute to the distress that parents experience during and after treatment. Inconsistent relationships between financial burden and parental psychological distress highlight the need to identify psychosocial factors that may moderate this relationship. In this study, we aimed to determine if family ritual meaning moderates the relationship between financial burden and anxiety and depression symptoms among mothers of children with cancer. Portuguese mothers of children with cancer on-treatment and off-treatment (N = 244) completed measures of financial burden, anxiety and depression symptoms, and family ritual meaning. Moderating effects were tested using hierarchical multiple regression analyses. Family ritual meaning buffered the effect of financial burden on anxiety, but not on depression symptoms. The relationship between financial burden and anxiety symptoms was not significant when mothers endorsed higher levels of family ritual meaning. Although preliminary, the current findings suggest that high levels of perceived family ritual meaning may constitute a protective factor against the effect of financial burden on mothers' anxiety symptoms. Promoting family ritual meaning might be an effective approach to reducing anxiety symptoms of mothers of children with cancer in the context of financial burden. (PsycINFO Database Record

  6. Phenotypic changes of acid adapted cancer cells push them toward aggressiveness in their evolution in the tumor microenvironment.

    PubMed

    Damaghi, Mehdi; Gillies, Robert

    2016-09-16

    The inter- and intra-tumoral metabolic phenotypes of tumors are heterogeneous, and this is related to microenvironments that select for increased glycolysis. Increased glycolysis leads to decreased pH, and these local microenvironment effects lead to further selection. Hence, heterogeneity of phenotypes is an indirect consequence of altering microenvironments during carcinogenesis. In early stages of growth, tumors are stratified, with the most aggressive cells developing within the acidic interior of the tumor. However, these cells eventually find themselves at the tumor edge, where they invade into the normal tissue via acid-mediated invasion. We believe acid adaptation during the evolution of cancer cells in their niche is a Rubicon that, once crossed, allows cells to invade into and outcompete normal stromal tissue. In this study, we illustrate some acid-induced phenotypic changes due to acidosis resulting in more aggressiveness and invasiveness of cancer cells.

  7. Oncogenic miR-181a/b affect the DNA damage response in aggressive breast cancer

    PubMed Central

    Bisso, Andrea; Faleschini, Michela; Zampa, Federico; Capaci, Valeria; De Santa, Jacopo; Santarpia, Libero; Piazza, Silvano; Cappelletti, Vera; Daidone, Mariagrazia; Agami, Reuven; Del Sal, Giannino

    2013-01-01

    Breast cancer is a heterogeneous tumor type characterized by a complex spectrum of molecular aberrations, resulting in a diverse array of malignant features and clinical outcomes. Deciphering the molecular mechanisms that fuel breast cancer development and act as determinants of aggressiveness is a primary need to improve patient management. Among other alterations, aberrant expression of microRNAs has been found in breast cancer and other human tumors, where they act as either oncogenes or tumor suppressors by virtue of their ability to finely modulate gene expression at the post-transcriptional level. In this study, we describe a new role for miR-181a/b as negative regulators of the DNA damage response in breast cancer, impacting on the expression and activity of the stress-sensor kinase ataxia telangiectasia mutated (ATM). We report that miR-181a and miR-181b were overexpressed in more aggressive breast cancers, and their expression correlates inversely with ATM levels. Moreover we demonstrate that deregulated expression of miR-181a/b determines the sensitivity of triple-negative breast cancer cells to the poly-ADP-ribose-polymerase1 (PARP1) inhibition. These evidences suggest that monitoring the expression of miR-181a/b could be helpful in tailoring more effective treatments based on inhibition of PARP1 in breast and other tumor types. PMID:23656790

  8. CD44v6 promotes β-catenin and TGF-β expression, inducing aggression in ovarian cancer cells.

    PubMed

    Wang, Jing; Xiao, Ling; Luo, Chen-Hui; Zhou, Hui; Zeng, Liang; Zhong, Jingmin; Tang, Yan; Zhao, Xue-Heng; Zhao, Min; Zhang, Yi

    2015-05-01

    A high expression of CD44v6 has been reported in numerous malignant cancers, including stomach, prostate, lung and colon. However, the pathological role and the regulatory mechanisms of CD44v6 have yet to be elucidated. In the present study, the expression levels of CD44v6 were shown to be significantly higher in ovarian cancer tissues, as compared with adjacent normal tissues. Furthermore, the upregulated expression levels of CD44v6 were correlated with disease recurrence and poor survival in patients. The expression of CD44v6 was knocked down in the CAOV3 ovarian cell line, by transfection of a specific small hairpin RNA. The present study showed a correlation between the aggression, viability, invasion and migration of the ovarian cancer cells, with the expression of CD44v6. In addition, the expression of CD44v6 was positively correlated with the expression levels of β‑catenin and tumor growth factor‑β, which indicates that the effects of CD44v6 on ovarian cancer cell aggression may be mediated by these two signaling pathways. In conclusion, the present study provides a novel insight into the association between CD44v6 expression and ovarian cancer. CD44v6 may provide a novel target for the prognosis and treatment of ovarian cancer.

  9. βIII-tubulin overexpression is linked to aggressive tumor features and genetic instability in urinary bladder cancer.

    PubMed

    Hinsch, Andrea; Chaker, Aref; Burdelski, Christian; Koop, Christina; Tsourlakis, Maria Christina; Steurer, Stefan; Rink, Michael; Eichenauer, Till Simon; Wilczak, Waldemar; Wittmer, Corinna; Fisch, Margit; Simon, Ronald; Sauter, Guido; Büschek, Franziska; Clauditz, Till; Minner, Sarah; Jacobsen, Frank

    2017-03-01

    Development of genetic instability is a hallmark of tumor progression. Type III β-tubulin (TUBB3) is a component of microtubules involved in chromosome segregation. Its overexpression has been linked to adverse features of urinary bladder cancer. To investigate the role of TUBB3 for development of genetic instability, we compared TUBB3 expression with histopathological features and surrogate markers of genetic instability and tumor aggressiveness; copy number changes of HER2, TOP2A, CCND1, RAF1, and FGFR1; nuclear accumulation of p53, and cell proliferation in a tissue microarray (TMA) with more than 700 bladder cancers. TUBB3 expression was linked to high-grade and advanced-stage cancers (P<.0001), rapid cell proliferation (P<.0001), presence of multiple gene copy number alterations (P=.0008), and nuclear accumulation of p53 (P=.0008). Strong TUBB3 staining was found in 43% of urothelial cancers harboring copy number alterations as compared with 28% of genetically stable cancers, and in 50% of p53-positive cancers as compared with 30% of p53-negative tumors. The fraction of tumors with concomitant TUBB3 and p53 positivity increased with tumor stage and grade: 2% in pTaG1-2, 11% in pTaG3, 17% in pT1G2, 23% in pT1G3, and 32% in pT2-4 cancers (P<.0001). Importantly, strong TUBB3 overexpression was detectable in about 20% of low-grade, noninvasive cancers. In summary, our study demonstrates that TUBB3 overexpression is linked to an aggressive subtype of urinary bladder cancers, which is characterized by increased genetic instability, p53 alterations, and rapid cell proliferation. Detection of TUBB3 overexpression in genetically stable, low-grade, and noninvasive bladder cancers may be clinically useful to identify patients requiring particular close monitoring.

  10. Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer.

    PubMed

    Ferrara, Fortunato; Staquicini, Daniela I; Driessen, Wouter H P; D'Angelo, Sara; Dobroff, Andrey S; Barry, Marc; Lomo, Lesley C; Staquicini, Fernanda I; Cardó-Vila, Marina; Soghomonyan, Suren; Alauddin, Mian M; Flores, Leo G; Arap, Marco A; Lauer, Richard C; Mathew, Paul; Efstathiou, Eleni; Aparicio, Ana M; Troncoso, Patricia; Navone, Nora M; Logothetis, Christopher J; Marchiò, Serena; Gelovani, Juri G; Sidman, Richard L; Pasqualini, Renata; Arap, Wadih

    2016-10-24

    Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC.

  11. Role of miR-139 as a surrogate marker for tumor aggression in breast cancer.

    PubMed

    Dai, Hongyan; Gallagher, Dan; Schmitt, Sarah; Pessetto, Ziyan Y; Fan, Fang; Godwin, Andrew K; Tawfik, Ossama

    2017-03-01

    MicroRNAs are non-protein coding molecules that play a key role in oncogenesis, tumor progression, and metastasis in many types of malignancies including breast cancer. In the current study, we studied the expression of microRNA-139-5p (miR-139) in invasive ductal carcinoma (IDC) of the breast and correlated its expression with tumor grade, molecular subtype, hormonal status, human epidermal growth factor receptor 2 status, proliferation index, tumor size, lymph node status, patient's age, and overall survival in 74 IDC cases. In addition, we compared and correlated miR-139 expression in 18 paired serum and tissue samples from patients with IDC to assess its value as a serum marker. Our data showed that miR-139 was down-regulated in all tumor tissue samples compared with control. More pronounced down-regulation was seen in tumors that were higher grade, estrogen receptor negative, progesterone receptor negative, more proliferative, or larger in size (P < .05). Although not statistically significant, lower miR-139 level was frequently associated with human epidermal growth factor receptor 2 overexpression. In addition, significantly lower miR-139 tissue level was seen in patients who were deceased (P = .027), although older age (>50 years) and positive local nodal disease did not adversely affect miR-139 expression. In contrast, serum miR-139 profile of the patients appeared similar to that of normal control. In conclusion, our study demonstrated that down-regulation of miR-139 was associated with aggressive tumor behavior and disease progression in breast cancer. miR-139 may serve as a risk assessment biomarker in tailoring treatment options.

  12. Targeted molecular-genetic imaging and ligand-directed therapy in aggressive variant prostate cancer

    PubMed Central

    Ferrara, Fortunato; Staquicini, Daniela I.; Driessen, Wouter H. P.; D’Angelo, Sara; Dobroff, Andrey S.; Barry, Marc; Lomo, Lesley C.; Staquicini, Fernanda I.; Cardó-Vila, Marina; Soghomonyan, Suren; Alauddin, Mian M.; Flores, Leo G.; Arap, Marco A.; Lauer, Richard C.; Mathew, Paul; Efstathiou, Eleni; Aparicio, Ana M.; Troncoso, Patricia; Navone, Nora M.; Logothetis, Christopher J.; Marchiò, Serena; Gelovani, Juri G.; Sidman, Richard L.; Pasqualini, Renata; Arap, Wadih

    2016-01-01

    Aggressive variant prostate cancers (AVPC) are a clinically defined group of tumors of heterogeneous morphologies, characterized by poor patient survival and for which limited diagnostic and treatment options are currently available. We show that the cell surface 78-kDa glucose-regulated protein (GRP78), a receptor that binds to phage-display-selected ligands, such as the SNTRVAP motif, is a candidate target in AVPC. We report the presence and accessibility of this receptor in clinical specimens from index patients. We also demonstrate that human AVPC cells displaying GRP78 on their surface could be effectively targeted both in vitro and in vivo by SNTRVAP, which also enabled specific delivery of siRNA species to tumor xenografts in mice. Finally, we evaluated ligand-directed strategies based on SNTRVAP-displaying adeno-associated virus/phage (AAVP) particles in mice bearing MDA-PCa-118b, a patient-derived xenograft (PDX) of castration-resistant prostate cancer bone metastasis that we exploited as a model of AVPC. For theranostic (a merging of the terms therapeutic and diagnostic) studies, GRP78-targeting AAVP particles served to deliver the human Herpes simplex virus thymidine kinase type-1 (HSVtk) gene, which has a dual function as a molecular-genetic sensor/reporter and a cell suicide-inducing transgene. We observed specific and simultaneous PET imaging and treatment of tumors in this preclinical model of AVPC. Our findings demonstrate the feasibility of GPR78-targeting, ligand-directed theranostics for translational applications in AVPC. PMID:27791181

  13. [The current situation of adolescents with cancer in pediatric hematology-oncology units in Spain. Results of a national survey].

    PubMed

    Lassaletta, A; Andión, M; Garrido-Colino, C; Gutierrez-Carrasco, I; Echebarria-Barona, A; Almazán, F; López-Ibor, B; Ortega-Acosta, M J

    2013-04-01

    Little attention was paid to adolescents with Cancer in Spain up to 2010. In 2011 an "Adolescents with Cancer Committee" was established by the Spanish Society of Pediatric Hemato-Oncology (SEHOP) to care for the needs of these patients. The aim of this national survey was to outline the present situation of adolescents with cancer in Spanish Pediatric Hemato-Oncology units. A web based survey assessed institutional management of adolescents with cancer. The survey was personally sent to one member of the staff of each Pediatric Hemato-Oncology unit in Spain. It included questions about epidemiology, management, psycho-social coverage, specific facilities, and follow up of these patients. A total of 40 institutions out of 41 responded to the survey (overall response rate 98%). Fifty-six percent of the institutions had patients over 14, but only 36% of the institutions treated patients up to 18 years old. Only 25.6% of the units have more than 40 new pediatric cases every year. The percentage of patients between 14 and 18 years of age is below 10% in most of the units (77%). In 30.8% and 48.7% of the institutions, pediatric hemato-oncologists treat adolescents with hematological and solid tumors, respectively. The rest of the patients are seen by adult oncologists. There is only one institution that has a physician specifically dedicated to adolescent patients, and only two units have a "teenager's room". Only 2 units have a psychologist specifically trained to treat adolescents with cancer. The survey shows that most adolescents with cancer in Spain between 14 and 18 years of age are treated by adult oncologists. Most pediatric institutions still do not have specific facilities and psychosocial support for adolescents. The SEHOP is working hard in order to improve the quality of cancer care, and the quality of survival of this population.

  14. Estrogen-dependent signaling in a molecularly distinct subclass of aggressive prostate cancer

    PubMed Central

    Setlur, Sunita R.; Mertz, Kirsten D.; Hoshida, Yujin; Demichelis, Francesca; Lupien, Mathieu; Perner, Sven; Sboner, Andrea; Pawitan, Yudi; Andrén, Ove; Johnson, Laura A.; Tang, Jeff; Adami, Hans-Olov; Calza, Stefano; Chinnaiyan, Arul M.; Rhodes, Daniel; Tomlins, Scott; Fall, Katja; Mucci, Lorelei A.; Kantoff, Philip W; Stampfer, Meir J.; Andersson, Swen-Olof; Varenhorst, Eberhard; Johansson, Jan-Erik; Brown, Myles; Golub, Todd R.; Rubin, Mark A.

    2011-01-01

    Background The majority of prostate cancers harbor gene fusions of the 5′-untranslated region of the androgen-regulated transmembrane protease, serine 2 (TMPRSS2) promoter with erythroblast transformation specific (ETS) transcription factor family members. The common v-ets erythroblastosis virus E26 oncogene homolog [avian] (TMPRSS2–ERG) fusion is associated with a more aggressive clinical phenotype, implying the existence of a distinct subclass of prostate cancer defined by this fusion. Methods We used cDNA-mediated annealing, selection, ligation, and extension to determine the expression profiles of 6144 transcriptionally informative genes in archived biopsy samples from 455 prostate cancer patients in the Swedish Watchful Waiting cohort (1987–1999) and the US-based Physicians Health Study cohort (1983–2003). A gene expression signature for prostate cancers with the TMPRSS2-ERG fusion was determined using partitioning and classification models and used in computational functional analysis. Cell proliferation and TMPRSS2-ERG expression in androgen receptor–negative (NCI-H660) and –positive (VCaP-ERβ) prostate cancer cells after treatment with vehicle or estrogenic compounds were assessed by viability assays and quantitative polymerase chain reaction, respectively. All statistical tests were two-sided. Results We identified an 87-gene expression signature that distinguishes TMPRSS2-ERG fusion prostate cancer as a discrete molecular entity (area under the curve = 0.80, 95% confidence interval [CI] = 0.792 to 0.81; P<.001). Computational analysis suggested that this fusion signature was associated with estrogen receptor (ER) signaling. Viability of NCI-H660 cells decreased after treatment with estrogen (viability normalized to day 0, estrogen vs vehicle at day 8, mean = 2.04 vs 3.40, difference = 1.36, 95% CI = 1.12 to 1.62) or ERβ agonist (ERβ agonist vs vehicle at day 8, mean = 1.86 vs 3.40, difference = 1.54, 95% CI = 1.39 to 1.69) but increased

  15. Parent Perspectives on Family-Based Psychosocial Interventions in Pediatric Cancer: A Mixed-Methods Approach

    PubMed Central

    Hocking, Matthew C.; Kazak, Anne E.; Schneider, Stephanie; Barkman, Darlene; Barakat, Lamia P.; Deatrick, Janet A.

    2014-01-01

    Family-based interventions in pediatric cancer face challenges associated with integrating psychosocial care into a period of intensive treatment and escalating stress. Little research has sought input from parents on the role of interventions delivered shortly after diagnosis. This mixed-methods study obtained parents’ perspectives on the potential role of family-based interventions. Twenty-five parents provided feedback on the structure and timing of psychosocial interventions via focus groups and a questionnaire. Qualitative analyses resulted in three themes that were illustrative of a traumatic stress framework: 1) tension between focusing on child with cancer and addressing other family needs, 2) factors influencing parents’ perception of a shared experience with other parents, and 3) the importance of matching interventions to the trajectory of parent adjustment. Quantitative data indicated that parents preferred intervention within six months of diagnosis, with almost half favoring within two months of diagnosis, and the majority wanted interventions targeted to parents only. Qualitative themes highlight the importance of using a traumatic stress framework to inform the development of family-based interventions for those affected by pediatric cancer. PMID:24337762

  16. Anthropometric and Biochemical Assessment of Nutritional Status in Pediatric Cancer Patients.

    PubMed

    İlhan, İnci Ergürhan; Sarı, Neriman; Yeşil, Şule; Eren, Tuba; Taçyıldız, Nurdan

    2015-01-01

    Children are at greater risk for malnutrition due to increased needs of nutrients to obtain appropriate growth, and they exhibit elevated substrate needs due to cancer and its treatment. This study aimed to report anthropometric and biochemical evaluation of nutritional status in children with cancer at initial presentation and during treatment. A prospective, controlled study was performed in the pediatric oncology department of a tertiary care center. Control group consisted of the siblings of patients. Weight, height, body mass index, triceps skinfold thickness, and serum levels of total protein, albumin, prealbumin, serum lipids, trace minerals, C-reactive protein (CRP), and vitamins were compared in patients and controls at initial presentation and at 6th month after the onset of treatment. According to weight for height, the frequency of malnutrition was 16% at initial presentation and 22% at 6th month. Triceps skinfold thickness was significantly thinner in patients than controls at both measurements. Patients had lower levels of prealbumin, albumin, iron, folate, zinc, and vitamin C and higher levels of ferritin, vitamin B12, and copper. Serum CRP levels were significantly higher in cancer patients at initial presentation and seemed to be correlated with copper levels. Compared with other patients, malnourished patients had significantly higher levels of vitamin B12 at 6th month. Results of the current study demonstrate that trace minerals, vitamins, and anthropometric measures may yield important clues for nutritional status and disease activity in pediatric oncology patients. However, validation and updating these potential markers warrant further trials on larger series.

  17. Candidiasis in pediatric patients with cancer interned in a university hospital

    PubMed Central

    De Carvalho Parahym, Ana Maria Rabelo; De Melo, Luciana Resende Bandeira; De Morais, Vera Lúcia Lins; Neves, Rejane Pereira

    2009-01-01

    Fungi are common causes of infection in immunocompromised patients. Candida species are frequently involved in these cases. In order to investigate candidiasis in pediatric patients with cancer, clinical samples were collected from one hundred and twenty two patients interned in the Oswaldo Cruz University Hospital in Recife, Brazil. Yeasts were isolated from thirty-four clinical samples. The species isolated were: Candida albicans (fourteen isolates), C. parapsilosis (nine isolates), C. guilliermondii (two isolates) and C. tropicalis (two isolates). We found that candidemia was most frequent in patients with malignant hematology and that C. parapsilosis infections caused the highest mortality. PMID:24031365

  18. Epigenetically upregulated WIPF1 plays a major role in BRAF V600E-promoted papillary thyroid cancer aggressiveness

    PubMed Central

    Zhang, Tao; Shen, Xiaopei; Liu, Rengyun; Zhu, Guangwu; Bishop, Justin; Xing, Mingzhao

    2017-01-01

    How the BRAF V600E mutation promotes the pathogenesis and aggressiveness of papillary thyroid cancer (PTC) is not completely understood. Here we explored a novel mechanism involving WASP interacting protein family member 1 (WIPF1). In PTC tumors, compared with the wild-type BRAF, BRAF V600E was associated with over-expression and hypomethylation of the WIPF1 gene. In thyroid cancer cell lines with wild-type BRAF, WIPF1 expression was robustly upregulated upon introduced expression of BRAF V600E (P=0.03) whereas the opposite was seen upon BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF V600E. Methylation of a functionally critical region of the WIPF1 promoter was decreased by expressing BRAF V600E in cells harboring the wild-type BRAF and increased by BRAF knockdown or treatment with BRAF V600E or MEK inhibitors in cells harboring BRAF V600E mutation. Under-expression and hypermethylation of WIPF1 induced by stable BRAF knockdown was reversed by DNA demethylating agent 5′-azadeoxycytidine. Knockdown of WIPF1 robustly inhibited anchorage-independent colony formation, migration, and invasion of thyroid cancer cells and suppressed xenograft thyroid cancer tumor growth and vascular invasion, mimicking the effects of BRAF knockdown. In human PTC tumors, WIPF1 expression was associated with extrathyroidal invasion (P=0.01) and lymph node metastasis (P=2.64E-05). In summary, BRAF V600E-activated MAP kinase pathway causes hypomethylation and overexpression of WIPF1; WIPF1 then functions like an oncoprotein to robustly promote aggressive cellular and tumor behaviors of PTC. This represents a novel mechanism in BRAF V600E-promoted PTC aggressiveness and identifies WIPF1 as a novel therapeutic target for thyroid cancer. PMID:27863429

  19. Cancer-specific uptake of a liganded protein nanocarrier targeting aggressive CXCR4(+) colorectal cancer models.

    PubMed

    Céspedes, María Virtudes; Unzueta, Ugutz; Álamo, Patricia; Gallardo, Alberto; Sala, Rita; Casanova, Isolda; Pavón, Miguel Angel; Mangues, María Antonia; Trías, Manuel; López-Pousa, Antonio; Villaverde, Antonio; Vázquez, Esther; Mangues, Ramon

    2016-10-01

    Unliganded drug-nanoconjugates accumulate passively in the tumor whereas liganded nanoconjugates promote drug internalization in tumor cells via endocytosis and increase antitumor efficacy. Whether or not tumor cell internalization associates with enhanced tumor uptake is still under debate. We here compared tumor uptake of T22-GFP-H6, a liganded protein carrier targeting the CXCR4 receptor, and the unliganded GFP-H6 carrier in subcutaneous and metastatic colorectal cancer models. T22-GFP-H6 had a higher tumor uptake in primary tumor and metastatic foci than GFP-H6, with no biodistribution or toxicity on normal tissues. T22-GFP-H6 was detected in target CXCR4(+) tumor cell cytosol whereas GFP-H6 was detected in tumor stroma. SDF1-α co-administration switched T22-GFP-H6 internalization from CXCR4(+) tumor epithelial cells to the stroma. Therefore, the incorporation of a targeting ligand promotes selective accumulation of the nanocarrier inside target tumor cells while increasing whole tumor uptake in a CXCR4-dependent manner, validating T22-GFP-H6 as a CXCR4-targeted drug carrier.

  20. Inherited disorders as a risk factor and predictor of neurodevelopmental outcome in pediatric cancer.

    PubMed

    Ullrich, Nicole J

    2008-01-01

    Each year in the United States, an average of one to two children per 10,000 develop cancer. The etiology of most childhood cancer remains largely unknown but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition involving a germline genetic mutation or chromosomal aberration. Despite overall improved survival rates for children with cancer over recent decades, many patients experience neurological and neurocognitive complications during the course of their illness and/or as late effects of treatment. Improvements in therapy, longer survival times, and improved imaging techniques have all increased both the time that patients are at risk and the ability to detect such complications. How an underlying inherited disorder influences the incidence, timing, etiology, and treatment of such sequelae has not been extensively documented, but evidence exists for an increased risk for secondary malignancies and in some cases life-threatening sensitivity/toxicity to conventionally dosed cancer treatments, thus emphasizing the need for the early recognition of such syndromes. This review outlines the major tumor- and treatment-related neurodevelopmental sequelae in pediatric cancer patients, with particular attention to children with an underlying inheritable disorder.

  1. Shorter telomeres and high telomerase activity correlate with a highly aggressive phenotype in breast cancer cell lines.

    PubMed

    Ceja-Rangel, Hugo A; Sánchez-Suárez, Patricia; Castellanos-Juárez, Emilio; Peñaroja-Flores, Rubicelia; Arenas-Aranda, Diego J; Gariglio, Patricio; Benítez-Bribiesca, Luis

    2016-09-01

    Maintenance of telomere length is one function of human telomerase that is crucial for the survival of cancer cells and cancer progression. Both telomeres and telomerase have been proposed as possible biomarkers of cancer risk and cancer invasiveness; however, their clinical relevance is still under discussion. In order to improve our understanding of the relationship between telomere length and telomerase activity with cancer invasiveness, we studied telomere length as well as telomerase levels, activity, and intracellular localization in breast cancer cell lines with diverse invasive phenotypes. We found an apparently paradoxical coincidence of short telomeres and enhanced telomerase activity in the most invasive breast cancer cell lines. We also observed that hTERT intracellular localization could be correlated with its level of activity. There was no association between human telomerase reverse transcriptase (hTERT) protein expression levels and invasiveness. We propose that simultaneous evaluation of these two biomarkers-telomere length and telomerase activity-could be useful for the assessment of the invasive capacity and aggressiveness of tumor cells from breast cancer patients.

  2. Surveillance of bloodstream infections in pediatric cancer centers – what have we learned and how do we move on?

    PubMed Central

    Simon, Arne; Furtwängler, Rhoikos; Graf, Norbert; Laws, Hans Jürgen; Voigt, Sebastian; Piening, Brar; Geffers, Christine; Agyeman, Philipp; Ammann, Roland A.

    2016-01-01

    Pediatric patients receiving conventional chemotherapy for malignant disease face an increased risk of bloodstream infection (BSI). Since BSI may represent an acute life-threatening event in patients with profound immunosuppression, and show further negative impact on quality of life and anticancer treatment, the prevention of BSI is of paramount importance to improve and guarantee patients’ safety during intensive treatment. The great majority of all pediatric cancer patients (about 85%) have a long-term central venous access catheter in use (type Broviac or Port; CVAD). Referring to the current surveillance definitions a significant proportion of all BSI in pediatric patients with febrile neutropenia is categorized as CVAD-associated BSI. This state of the art review summarizes the epidemiology and the distinct pathogen profile of BSI in pediatric cancer patients from the perspective of infection surveillance. Problems in executing the current surveillance definition in this patient population are discussed and a new concept for the surveillance of BSI in pediatric cancer patients is outlined. PMID:27274442

  3. Successful emergency department interventions that reduce time to antibiotics in febrile pediatric cancer patients

    PubMed Central

    Spencer, Sandra; Nypaver, MIchele; Hebert, Katherine; Benner, Christopher; Stanley, Rachel; Cohen, Daniel; Rogers, Alexander; Goldstick, Jason; Mahajan, Prashant

    2017-01-01

    Children with cancer and fever are at high risk for sepsis related death. Rapid antibiotic delivery (< 60 minutes) has been shown to reduce mortality. We compared patient outcomes and describe interventions from three separate quality improvement (QI) projects conducted in three United States (US) tertiary care pediatric emergency departments (EDs) with the shared aim to reduce time to antibiotic (TTA) to < 60 minutes in febrile pediatric oncology patients (Temperature > 38.0 C). A secondary objective was to identify interventions amenable to translation to other centers. We conducted a post project analysis of prospectively collected observational data from children < 18 years visiting these EDs during independently conducted QI projects. Comparisons were made pre to post intervention periods within each institution. All interventions were derived independently using QI methods by each institution. Successful as well as unsuccessful interventions were described and common interventions adopted by all sites identified. A total of 1032 ED patient visits were identified from the three projects. Improvement in median TTA delivery (min) pre to post intervention(s) was 118.5–57.0 at site 1, 163.0–97.5 at site 2, and 188.0–111.5 at site 3 (p<.001 all sites). The eight common interventions were 1) Triage application of topical anesthetic 2) Rapid room placement & triage 3) Resuscitation room placement of ill appearing children 4) Close proximity to central line equipment 5) Antibiotic administration before laboratory analyses 6) Consensus clinical practice guideline establishment 7) Family pre-ED education for fever and 8) Staff project updates. This core set of eight low cost, high yield QI interventions were developed independently by the three ED's which led to substantial reduction in time to antibiotic delivery in children with cancer presenting with fever. These interventions may inform future QI initiatives in other settings caring for febrile pediatric

  4. Exome and deep sequencing of clinically aggressive neuroblastoma reveal somatic mutations that affect key pathways involved in cancer progression

    PubMed Central

    Lasorsa, Vito Alessandro; Formicola, Daniela; Pignataro, Piero; Cimmino, Flora; Calabrese, Francesco Maria; Mora, Jaume; Esposito, Maria Rosaria; Pantile, Marcella; Zanon, Carlo; De Mariano, Marilena; Longo, Luca; Hogarty, Michael D.; de Torres, Carmen; Tonini, Gian Paolo; Iolascon, Achille; Capasso, Mario

    2016-01-01

    The spectrum of somatic mutation of the most aggressive forms of neuroblastoma is not completely determined. We sought to identify potential cancer drivers in clinically aggressive neuroblastoma. Whole exome sequencing was conducted on 17 germline and tumor DNA samples from high-risk patients with adverse events within 36 months from diagnosis (HR-Event3) to identify somatic mutations and deep targeted sequencing of 134 genes selected from the initial screening in additional 48 germline and tumor pairs (62.5% HR-Event3 and high-risk patients), 17 HR-Event3 tumors and 17 human-derived neuroblastoma cell lines. We revealed 22 significantly mutated genes, many of which implicated in cancer progression. Fifteen genes (68.2%) were highly expressed in neuroblastoma supporting their involvement in the disease. CHD9, a cancer driver gene, was the most significantly altered (4.0% of cases) after ALK. Other genes (PTK2, NAV3, NAV1, FZD1 and ATRX), expressed in neuroblastoma and involved in cell invasion and migration were mutated at frequency ranged from 4% to 2%. Focal adhesion and regulation of actin cytoskeleton pathways, were frequently disrupted (14.1% of cases) thus suggesting potential novel therapeutic strategies to prevent disease progression. Notably BARD1, CHEK2 and AXIN2 were enriched in rare, potentially pathogenic, germline variants. In summary, whole exome and deep targeted sequencing identified novel cancer genes of clinically aggressive neuroblastoma. Our analyses show pathway-level implications of infrequently mutated genes in leading neuroblastoma progression. PMID:27009842

  5. An Assessment to Inform Pediatric Cancer Provider Development and Delivery of Survivor Care Plans.

    PubMed

    Warner, Echo L; Wu, Yelena P; Hacking, Claire C; Wright, Jennifer; Spraker-Perlman, Holly L; Gardner, Emmie; Kirchhoff, Anne C

    2015-12-01

    Current guidelines recommend all pediatric cancer survivors receive a survivor care plan (SCP) for optimal health management, yet clinical delivery of SCPs varies. We evaluated oncology providers' familiarity with and preferences for delivering SCPs to inform the implementation of a future SCP program at our institution. From November 2013 to April 2014, oncology providers from the Primary Children's Hospital in Salt Lake City, UT, completed a survey (n=41) and a 45-min focus group (n=18). Participants reported their familiarity with and training in SCP guidelines, opinions on SCPs, and barriers to delivering SCPs. As a secondary analysis, we examined differences in survey responses between physicians and nurses with Fisher's exact tests. Focus group transcripts and open-ended survey responses were content analyzed. Participants reported high familiarity with late effects of cancer treatment (87.8%) and follow-up care that cancer survivors should receive (82.5%). Few providers had delivered an SCP (oncologists 35.3% and nurses 5.0%; p=0.03). Barriers to providing SCPs included lack of knowledge (66.7%), SCP delivery is not expected in their clinic (53.9%), and no champion (48.7%). In qualitative comments, providers expressed that patient age variation complicated SCP delivery. Participants supported testing an SCP intervention program (95.1%) and felt this should be a team-based approach. Strategies for optimal delivery of SCPs are needed. Participants supported testing an SCP program to improve the quality of patient care. Team-based approaches, including nurses and physicians, that incorporate provider training on and support for SCP delivery are needed to improve pediatric cancer care.

  6. Statewide Longitudinal Hospital Use and Charges for Pediatric and Adolescent Patients With Cancer

    PubMed Central

    Kaul, Sapna; Barbeau, Bree; Wright, Jennifer; Fluchel, Mark; Kirchhoff, Anne C.; Nelson, Richard E.

    2015-01-01

    Purpose: We investigated longitudinal hospitalization outcomes (total charges, hospital days and admissions) among pediatric and adolescent patients with cancer compared with individuals from the general population without cancer using a novel and efficient three-step regression procedure. Methods: The statewide Utah Population Database, with linkages to the Utah Cancer Registry, was used to identify 1,651 patients who were diagnosed with cancer from 1996 to 2009 at ages 0 to 21 years. A comparison group of 4,953 same-sex and -age individuals was generated from birth certificates. Claims-based hospitalization data from 1996 to 2012 were retrieved from the Utah Department of Health. Using the regression method, we estimated survival (differences due to survival) and intensity (differences due to resource accumulation) effects of the cancer diagnosis on hospitalization outcomes within 10 years after diagnosis. Results: At 10 years after diagnosis, on average, patients with cancer incurred $51,723 (95% CI, $48,100 to $58,284) more in charges, spent 30 additional days (95% CI, 27.7 to 36.1 days) in the hospital, and had 5.7 (95% CI, 5.4 to 6.4) more admissions than the comparison group. Our analyses showed that the highest hospitalization burden occurred during the first 4 years of diagnosis. Patients with leukemia incurred the greatest hospitalization burden throughout the 10 years from diagnosis. Intensity effects explained the majority of differences in hospital outcomes. Conclusion: Our results suggest that children and adolescents who were diagnosed with cancer in 2014 in the United States will incur over $800 million more in hospital charges than individuals without cancer by 2024. Interventions to reduce this burden should be explored in conjunction with improving health and survival outcomes. PMID:26105667

  7. Psychoeducational Interventions with Pediatric Cancer Patients: Part II. Effects of Information and Skills Training on Health-Related Outcomes

    ERIC Educational Resources Information Center

    Beale, Ivan L.; Bradlyn, Andrew S.; Kato, Pamela M.

    2003-01-01

    In Part I of this paper, we described a model that was used as a framework for reviewing studies of psychoeducational interventions intended to influence illness- and treatment-related behaviors and attitudes in pediatric cancer patients. In Part II, we distinguish between interventions that attempt to influence patients' behaviors just by…

  8. Rise and fall of subclones from diagnosis to relapse in pediatric B-acute lymphoblastic leukaemia | Office of Cancer Genomics

    Cancer.gov

    There is incomplete understanding of genetic heterogeneity and clonal evolution during cancer progression. Here we use deep whole-exome sequencing to describe the clonal architecture and evolution of 20 pediatric B-acute lymphoblastic leukaemias from diagnosis to relapse. We show that clonal diversity is comparable at diagnosis and relapse and clonal survival from diagnosis to relapse is not associated with mutation burden.

  9. Gonadal function, fertility, and reproductive medicine in childhood and adolescent cancer patients: a national survey of Japanese pediatric endocrinologists

    PubMed Central

    Miyoshi, Yoko; Yorifuji, Tohru; Horikawa, Reiko; Takahashi, Ikuko; Nagasaki, Keisuke; Ishiguro, Hiroyuki; Fujiwara, Ikuma; Ito, Junko; Oba, Mari; Kawamoto, Hiroshi; Fujisaki, Hiroyuki; Kato, Masashi; Shimizu, Chikako; Kato, Tomoyasu; Matsumoto, Kimikazu; Sago, Haruhiko; Takimoto, Tetsuya; Okada, Hiroshi; Suzuki, Nao; Yokoya, Susumu; Ogata, Tsutomu; Ozono, Keiichi

    2016-01-01

    Abstract. An increasing number of pediatric cancer patients survive, and treatment-related infertility represents one of the most important issues for these patients. While official guidelines in Japan recommend long-term follow-up of childhood cancer survivors (CCSs), their gonadal function and fertility have not been clarified. To address this issue, we organized a working panel to compile evidence from long-term survivors who received treatments for cancer during childhood or adolescence. In collaboration with members of the CCS Committee of the Japanese Society for Pediatric Endocrinology (JSPE), we conducted a questionnaire survey regarding reproductive function in pediatric cancer patients. A cross-sectional survey was sent to 178 JSPE-certified councilors who were asked to self-evaluate the medical examinations they had performed. A total of 151 responses were obtained, revealing that 143 endocrinologists were involved in the care of CCSs. A quarter of the respondents reported having experienced issues during gonadal or reproductive examinations. Several survivors did not remember or fully understand the explanation regarding gonadal damage, and faced physical and psychological distress when discussing the risk of becoming infertile. Pediatric endocrinologists had anxieties regarding their patients’ infertility and the risk of miscarriage, premature birth, and delivery problems. Only a limited number of endocrinologists had experience with managing childbirth and fertility preservation. Many councilors mentioned the necessity for inter-disciplinary communication among healthcare providers. Both endocrinologists and oncologists should set and follow a uniform clinical guideline that includes management of fertility of CCSs. PMID:27212796

  10. Loss of miR-200c: A Marker of Aggressiveness and Chemoresistance in Female Reproductive Cancers

    PubMed Central

    Cochrane, Dawn R.; Howe, Erin N.; Spoelstra, Nicole S.; Richer, Jennifer K.

    2010-01-01

    We focus on unique roles of miR-200c in breast, ovarian, and endometrial cancers. Members of the miR-200 family target ZEB1, a transcription factor which represses E-cadherin and other genes involved in polarity. We demonstrate that the double negative feedback loop between miR-200c and ZEB1 is functional in some, but not all cell lines. Restoration of miR-200c to aggressive cancer cells causes a decrease in migration and invasion. These effects are independent of E-cadherin status. Additionally, we observe that restoration of miR-200c to ovarian cancer cells causes a decrease in adhesion to laminin. We have previously reported that reintroduction of miR-200c to aggressive cells that lack miR-200c expression restores sensitivity to paclitaxel. We now prove that this ability is a result of direct targeting of class III beta-tubulin (TUBB3). Introduction of a TUBB3 expression construct lacking the miR-200c target site into cells transfected with miR-200c mimic results in no change in sensitivity to paclitaxel. Lastly, we observe a decrease in proliferation in cells transfected with miR-200c mimic, and cells where ZEB1 is knocked down stably, demonstrating that the ability of miR-200c to enhance sensitivity to paclitaxel is not due to an increased proliferation rate. PMID:20049172

  11. Unilateral and Bilateral Breast Cancer in Women Surviving Pediatric Hodgkin's Disease

    SciTech Connect

    Basu, Swati K.; Schwartz, Cindy; Fisher, Susan G.; Hudson, Melissa M.; Tarbell, Nancy; Muhs, Ann; Marcus, Karen J.; Mendenhall, Nancy; Mauch, Peter; Kun, Larry E.; Constine, Louis S.

    2008-09-01

    Purpose: To define demographic and therapeutic associations with the risk of breast cancer in children treated for Hodgkin's disease (HD), particularly the frequency and interval to the development of contralateral breast cancer. Methods and Materials: All 398 female patients (<19 years) treated for HD in five institutions during the accrual period were evaluated. Mean follow-up was 16.9 years. The standardized incidence ratio (SIR) was calculated as the ratio of the observed number of cases to the expected number of cases, estimated using age-matched controls from the Surveillance, Epidemiology, and End Results database. Results: A total of 29 women developed breast cancer (25 invasive, 4 ductal carcinoma in situ; SIR, 37.25; 95% confidence interval, 24.96-53.64). Time to diagnosis was 9.4 to 36.1 years. Cumulative incidence was 24% at 30 years. Ten patients (34%) had bilateral disease (9 metachronous, 1 synchronous). The interval to contralateral breast cancer was 12 to 34 months. On univariate analysis, significant variables included stage of HD, mantle radiation dose, pelvic radiation (protective), and follow-up time. On multivariate analysis, early stage and older age at diagnosis of HD ({<=}12 vs. >12 years) were significant predictors of secondary breast cancer. Conclusions: Women surviving pediatric HD were found to have a 37-fold increase in the risk of breast cancer and a high likelihood of rapidly developing bilateral disease. Early-stage HD and age greater than 12 years at diagnosis of HD were independent risk factors. Higher radiation doses may augment risk, and pelvic radiation may be protective. Breast cancer screening methodology and frequency, plus the role of prophylaxis in patients with unilateral disease, require definition.

  12. TGF-β Regulates DNA Methyltransferase Expression in Prostate Cancer, Correlates with Aggressive Capabilities, and Predicts Disease Recurrence

    PubMed Central

    Helfand, Brian T.; Jang, Thomas L.; Sharma, Vidit; Kozlowski, James; Kuzel, Timothy Michael; Zhu, Lihua J.; Yang, Ximing J.; Javonovic, Borko; Guo, Yinglu; Lonning, Scott; Harper, Jay; Teicher, Beverly A.; Brendler, Charles; Yu, Nengwang; Catalona, William J.; Lee, Chung

    2011-01-01

    Background DNA methyltransferase (DNMT) is one of the major factors mediating the methylation of cancer related genes such as TGF-β receptors (TβRs). This in turn may result in a loss of sensitivity to physiologic levels of TGF-β in aggressive prostate cancer (CaP). The specific mechanisms of DNMT's role in CaP remain undetermined. In this study, we describe the mechanism of TGF-β-mediated DNMT in CaP and its association with clinical outcomes following radical prostatectomy. Methodology/Principal Findings We used human CaP cell lines with varying degrees of invasive capability to describe how TGF-β mediates the expression of DNMT in CaP, and its effects on methylation status of TGF-β receptors and the invasive capability of CaP in vitro and in vivo. Furthermore, we determined the association between DNMT expression and clinical outcome after radical prostatectomy. We found that more aggressive CaP cells had significantly higher TGF-β levels, increased expression of DNMT, but reduced TβRs when compared to benign prostate cells and less aggressive prostate cancer cells. Blockade of TGF-β signaling or ERK activation (p-ERK) was associated with a dramatic decrease in the expression of DNMT, which results in a coincident increase in the expression of TβRs. Blockade of either TGF-β signaling or DNMT dramatically decreased the invasive capabilities of CaP. Inhibition of TGF-β in an TRAMP-C2 CaP model in C57BL/6 mice using 1D11 was associated with downregulation of DNMTs and p-ERK and impairment in tumor growth. Finally, independent of Gleason grade, increased DNMT1 expression was associated with biochemical recurrence following surgical treatment for prostate cancer. Conclusions and Significance Our findings demonstrate that CaP derived TGF-β may induce the expression of DNMTs in CaP which is associated with methylation of its receptors and the aggressive potential of CaP. In addition, DNMTs is an independent predictor for disease recurrence after

  13. Communicating and Understanding the Purpose of Pediatric Phase I Cancer Trials

    PubMed Central

    Cousino, Melissa K.; Zyzanski, Stephen J.; Yamokoski, Amy D.; Hazen, Rebecca A.; Baker, Justin N.; Noll, Robert B.; Rheingold, Susan R.; Geyer, J. Russell; Alexander, Stewart C.; Drotar, Dennis; Kodish, Eric D.

    2012-01-01

    Purpose Quality informed consent should provide a clear understanding of the purpose of the research. Given the ethical challenges of pediatric phase I cancer trials, it is important to investigate physician-parent communication during informed consent conferences (ICCs) and parental understanding of the purpose of these studies. Methods In the multisite Informed Consent in Pediatric Phase I Cancer Trials study, 85 ICCs for phase I research between June 2008 and May 2011 were directly observed, and 60 parents were subsequently interviewed. The scientific purpose was defined as composite understanding of drug safety, dose finding, and dose escalation. We determined the frequency with which physicians explained these and other phase I–related concepts during the ICC. Parent interviews were analyzed to determine understanding. Results The child was present at 83 of 85 ICCs. Only 32% of parents demonstrated substantial understanding of the scientific purpose of phase I cancer trials; 35% demonstrated little or no understanding. Parents of higher socioeconomic status and racial majority status were more likely to understand the scientific purpose. Factors associated with understanding included physician explanation of the goal of the applicable phase I protocol offered (explained in 85% of ICCs) and explanation of the dose cohorts (explained in 43% of ICCs). Physicians explained drug safety in 23% of ICCs, dose finding in 52% of ICCs, and dose escalation in 53% of ICCs. Conclusion Many parents of children participating in phase I trials do not understand the purpose of these trials. Physician-parent communication about the purpose of phase I research is lacking during ICCs. PMID:23071225

  14. Identification of the transforming STRN-ALK fusion as a potential therapeutic target in the aggressive forms of thyroid cancer

    PubMed Central

    Kelly, Lindsey M.; Barila, Guillermo; Liu, Pengyuan; Evdokimova, Viktoria N.; Trivedi, Sumita; Panebianco, Federica; Gandhi, Manoj; Carty, Sally E.; Hodak, Steven P.; Luo, Jianhua; Dacic, Sanja; Yu, Yan P.; Nikiforova, Marina N.; Ferris, Robert L.; Altschuler, Daniel L.; Nikiforov, Yuri E.

    2014-01-01

    Thyroid cancer is a common endocrine malignancy that encompasses well-differentiated as well as dedifferentiated cancer types. The latter tumors have high mortality and lack effective therapies. Using a paired-end RNA-sequencing approach, we report the discovery of rearrangements involving the anaplastic lymphoma kinase (ALK) gene in thyroid cancer. The most common of these involves a fusion between ALK and the striatin (STRN) gene, which is the result of a complex rearrangement involving the short arm of chromosome 2. STRN-ALK leads to constitutive activation of ALK kinase via dimerization mediated by the coiled-coil domain of STRN and to a kinase-dependent, thyroid-stimulating hormone–independent proliferation of thyroid cells. Moreover, expression of STRN-ALK transforms cells in vitro and induces tumor formation in nude mice. The kinase activity of STRN-ALK and the ALK-induced cell growth can be blocked by the ALK inhibitors crizotinib and TAE684. In addition to well-differentiated papillary cancer, STRN-ALK was found with a higher prevalence in poorly differentiated and anaplastic thyroid cancers, and it did not overlap with other known driver mutations in these tumors. Our data demonstrate that STRN-ALK fusion occurs in a subset of patients with highly aggressive types of thyroid cancer and provide initial evidence suggesting that it may represent a therapeutic target for these patients. PMID:24613930

  15. Standard pediatric oncology data and information technology: necessities for cancer care management.

    PubMed

    Maserat, Elham; Rahimi, Mehrdad Mirza; Maserat, Elnaz; Zali, Mohamad Reza

    2011-01-01

    Cancer is the second leading cause of death in children and survivors require life time follow-up. There is a growing recognition of the need to base cancer control policies on accurate, detailed and timely information on cancer management and outcomes. Coordination and central documentation ensure quality of treatment and permit clinical and scientific investigations. The combined data thus obtained create a comprehensive picture of disease, leading to more effective prevention and cure. Medical information can be gathered, processed and analyzed in different ways and the importance of precise language cannot be overestimated. All medical activity arises from the ability to observe and communicate intelligibly and a lack of standardized documentation leads to insufficient integration of clinical work. The Minimal Standard data set is the result of a global effort to establish a common structure and vocabulary for electronic reports. In addition, information technology combines research aspects of decision support and clinical documentation, allowing formal representation of general protocols, calculating of a particular therapy for a patient, data acquisition in the clinics. Our aim in this papers is to stress the need for standard pediatric oncology data and information technology as an approach to cancer care management.

  16. PI3K/AKT pathway regulates E-cadherin and Desmoglein 2 in aggressive prostate cancer.

    PubMed

    Barber, Alison G; Castillo-Martin, Mireia; Bonal, Dennis M; Jia, Angela J; Rybicki, Benjamin A; Christiano, Angela M; Cordon-Cardo, Carlos

    2015-08-01

    Reduced expression of both classical and desmosomal cadherins has been associated with different types of carcinomas, including prostate cancer. This study aims to provide a comprehensive view of the role and regulation of cell-cell adhesion in prostate cancer aggressiveness by examining the functional implications of both E-cadherin and Desmoglein 2 (DSG2). E-cadherin expression was first examined using immunofluorescence in 50 normal prostate tissues and in a cohort of 414 prostate cancer patients. Correlation and survival analyses were performed to assess its clinical significance. In primary prostate cancer patients, reduced expression of both E-cadherin and DSG2 is significantly associated with an earlier biochemical recurrence. Transgenic DU145 E-cadherin knockdown and constitutively active AKT overexpression lines were generated. Functional implications of such genetic alterations were analyzed in vitro and in vivo, the latter by using tumorigenesis as well as extravasation and metastatic tumor formation assays. We observed that loss of E-cadherin leads to impaired primary and metastatic tumor formation in vivo, suggesting a tumor promoter role for E-cadherin in addition to its known role as a tumor suppressor. Activation of AKT leads to a significant reduction in E-cadherin expression and nuclear localization of Snail, suggesting a role for the PI3K/AKT signaling pathway in the transient repression of E-cadherin. This reduced expression may be regulated by separate mechanisms as neither the loss of E-cadherin nor activation of AKT significantly affected DSG2 expression. In conclusion, these findings illustrate the critical role of cell-cell adhesion in the progression to aggressive prostate cancer, through regulation by the PI3K pathway.

  17. Lentivirus-mediated RASSF1A expression suppresses aggressive phenotypes of gastric cancer cells in vitro and in vivo

    PubMed Central

    Zhou, P-H; Zheng, J-B; Wei, G-B; Wang, X-L; Wang, W; Chen, N-Z; Yu, J-H; Yao, J-F; Wang, H; Lu, S-Y; Sun, X-J

    2015-01-01

    Loss of Ras association domain family protein 1 isoform A (RASSF1A) expression is associated with the development of a variety of human cancers and the expression of carcinoembryonic antigen (CEA) frequently occurs in gastric cancer. This study investigated the effects of RASSF1A expression restoration using a hypoxia-inducible CEA promoter-driven vector on xenograft tumor growth in nude mice and on the in-vitro regulation of gastric cancer cell viability, cell cycle distribution, apoptosis, colony formation and invasion capacity. The data showed that the level of CEA mRNA and protein was much higher in gastric cancer SGC7901 cells than in a second gastric cancer cell line, MKN28, or in the MCF-10A normal epithelial breast cell line. RASSF1A expression was restored in SGC7901 cells compared with the negative control virus-infected SGC7910 cells. RASSF1A expression restoration significantly inhibited gastric cancer cell viability, colony formation and invasion capacity, but induced cell cycle arrest and apoptosis in vitro, especially under hypoxic culture conditions. At the gene level, restoration of RASSF1A expression under hypoxic culture conditions significantly suppressed matrix metalloproteinase-2 expression and prevented cyclinD1 expression. A nude mouse xenograft assay showed that the restoration of RASSF1A expression reduced gastric cancer xenograft formation and growth. In conclusion, the restoration of RASSF1A expression using a hypoxia-inducible and CEA promoter-driven vector suppressed aggressive phenotypes of gastric cancer cells in vitro and in vivo. These results suggest that LV-5HRE-CEAp-RASSF1A gene therapy may be a promising novel approach to treat advanced gastric cancer. PMID:26005859

  18. Diagnostic ability of %p2PSA and prostate health index for aggressive prostate cancer: a meta-analysis

    PubMed Central

    Wang, Wenying; Wang, Meilin; Wang, Li; Adams, Tamara S.; Tian, Ye; Xu, Jianfeng

    2014-01-01

    The role of [-2]proPSA (p2PSA) based diagnostic tests for the detection of aggressive prostate cancer (PCa) has not been fully evaluated. We conducted a meta-analysis to evaluate the diagnostic performance of p2PSA/free PSA (%p2PSA) and prostate health index (Phi) tests for PCa and to evaluate their ability in discriminating between aggressive and non-aggressive PCa. A total of 16 articles were included in this meta-analysis. For the detection of PCa, the pooled sensitivity, specificity, and AUC were 0.86 (95% CI, 0.84–0.87), 0.40 (95% CI, 0.39–042) and 0.72 (95% CI, 0.67–0.77) for %p2PSA respectively, and were 0.85 (95% CI, 0.83–0.86), 0.45 (95% CI, 0.44–0.47) and 0.70 (95% CI = 0.65–0.74) for Phi, respectively. In addition, the sensitivity for discriminating PCa between higher Gleason score (≥7) and lower Gleason score (<7) was 0.96 (95% CI, 0.93–0.98) and 0.90 (95% CI, 0.87–0.92) for %p2PSA and Phi respectively, and the specificity was low, only 0.09 (95% CI, 0.06–0.12) and 0.17 (95% CI, 0.14–0.19) for %p2PSA and Phi, respectively. Phi and %p2PSA have a high diagnostic accuracy rates and can be used in PCa diagnosis. Phi and %p2PSA may be useful as tumor markers in predicating patients harboring more aggressive disease and guiding biopsy decisions. PMID:24852453

  19. Sports in pediatric oncology: the role(s) of physical activity for children with cancer.

    PubMed

    Götte, Miriam; Taraks, Silke; Boos, Joachim

    2014-03-01

    Malignant disease and anticancer therapy dramatically affect daily life activities and participation in grassroots and high-performance sports. Specifically in childhood and adolescence such activities are relevant factors of individual development and social life. This review focuses on the inherent reduction of normal physical activity in pediatric oncology because this cutback additionally contributes to the level of burden of malignancies. Maintaining normality requires detailed analyses of disease-related and therapy-related restrictions and their justification. Relevant efforts should be stepped up to maintain physical activity levels during pediatric cancer therapy. Another aspect addresses direct therapeutic implications. Feasibility studies, nonrandomized as well as randomized investigations addressed therapeutic effects in acute hospital care, in bone marrow transplant settings, and in outpatient therapy. The overall summary shows positive effects on clinical and psychosocial outcome. Even if the basis of the data for children is still limited, there will be no doubt about a general impact of physical activity on acute side effects as well as late effects. In the areas of tension between context-related restrictions, the right to maintain normality wherever possible and the positive therapeutic and psychosocial perspectives of sports, strong efforts are needed to support physical activity wherever indicated, clarify contraindications, and overcome structural limitations.

  20. The ETS family member GABPα modulates androgen receptor signalling and mediates an aggressive phenotype in prostate cancer

    PubMed Central

    Sharma, Naomi L.; Massie, Charlie E.; Butter, Falk; Mann, Matthias; Bon, Helene; Ramos-Montoya, Antonio; Menon, Suraj; Stark, Rory; Lamb, Alastair D.; Scott, Helen E.; Warren, Anne Y.; Neal, David E.; Mills, Ian G.

    2014-01-01

    In prostate cancer (PC), the androgen receptor (AR) is a key transcription factor at all disease stages, including the advanced stage of castrate-resistant prostate cancer (CRPC). In the present study, we show that GABPα, an ETS factor that is up-regulated in PC, is an AR-interacting transcription factor. Expression of GABPα enables PC cell lines to acquire some of the molecular and cellular characteristics of CRPC tissues as well as more aggressive growth phenotypes. GABPα has a transcriptional role that dissects the overlapping cistromes of the two most common ETS gene fusions in PC: overlapping significantly with ETV1 but not with ERG target genes. GABPα bound predominantly to gene promoters, regulated the expression of one-third of AR target genes and modulated sensitivity to AR antagonists in hormone responsive and castrate resistant PC models. This study supports a critical role for GABPα in CRPC and reveals potential targets for therapeutic intervention. PMID:24753418

  1. A new goniothalamin N-acylated aza-derivative strongly downregulates mediators of signaling transduction associated with pancreatic cancer aggressiveness.

    PubMed

    Barcelos, Rosimeire Coura; Pelizzaro-Rocha, Karin Juliane; Pastre, Julio Cezar; Dias, Marina Pereira; Ferreira-Halder, Carmen Veríssima; Pilli, Ronaldo Aloise

    2014-11-24

    In this study, a novel concise series of molecules based on the structure of goniothalamin (1) was synthesized and evaluated against a highly metastatic human pancreatic cancer cell line (Panc-1). Among them, derivative 8 displayed a low IC50 value (2.7 μM) and its concentration for decreasing colony formation was 20-fold lower than goniothalamin (1). Both compounds reduced the levels of the receptor tyrosine kinase (AXL) and cyclin D1 which are known to be overexpressed in pancreatic cancer cells. Importantly, despite the fact that goniothalamin (1) and derivative 8 caused pancreatic cancer cell cycle arrest and cell death, only derivative 8 was able to downregulate pro-survival and proliferation pathways mediated by mitogen activated protein kinase ERK1/2. Another interesting finding was that Panc-1 cells treated with derivative 8 displayed a strong decrease in the transcription factor (c-Myc), hypoxia-inducible factor-1α (HIF-1α) and vascular endothelial growth factor (VEGF) protein levels. Notably, the molecular effects caused by derivative 8 might not be related to ROS generation, since no significant production of ROS was observed in low concentrations of this compound (from 1.5 up to 3 μM). Therefore, the downregulation of important mediators of pancreatic cancer aggressiveness by derivative 8 reveals its great potential for the development of new chemotherapeutic agents for pancreatic cancer treatment.

  2. Familial risk of childhood cancer and tumors in the Li-Fraumeni spectrum in the Utah Population Database: implications for genetic evaluation in pediatric practice.

    PubMed

    Curtin, Karen; Smith, Ken R; Fraser, Alison; Pimentel, Richard; Kohlmann, Wendy; Schiffman, Joshua D

    2013-11-15

    We used the Utah Population Database to examine risk of cancer in relatives of 4,482 pediatric cancer cases (≤18 years old) diagnosed from 1966 to 2009 compared to matched population controls. We quantified cancer risk in relatives of children with cancer to determine evidence of familial aggregation and to inform risk assessment and counseling for families. Odds ratios that reflect risk were obtained using conditional logistic regression models adjusting for number of biological relatives, their degree of genetic relatedness and their person-years at risk. First-degree relatives (primarily siblings) of pediatric cases faced a twofold increased risk of a cancer diagnosis before age 19, which extended to their second-degree relatives (p < 10(-4), respectively). Furthermore, first-degree relatives of children diagnosed before age 5 had a 3.6-fold increased risk of developing pediatric cancer (p < 10(-7)), second-degree relatives of very young (under age 5) cases were at 2.5-fold risk (p < 10(-4)) and third-degree relatives were at twofold risk (P < 10(-3)) of childhood cancer. Although first-degree relatives of pediatric cases have a slight increased risk of adult tumors, when they do develop cancer they have a 1.7-fold risk of developing a tumor in the Li-Fraumeni spectrum. Our findings support the hypothesis of familial aggregation in pediatric cancer and suggest that a higher percent of childhood cancers may be related to hereditary syndromes than are adult cancers. We encourage the collection of a family medical history that is routinely updated for all pediatric cancer patients, and that families with early-onset adult cancers or clusters of several cancers are referred for genetic counseling.

  3. Familial risk of childhood cancer and tumors in the Li-Fraumeni spectrum in the Utah Population Database: Implications for genetic evaluation in pediatric practice

    PubMed Central

    Curtin, Karen; Smith, Ken R.; Fraser, Alison; Pimentel, Richard; Kohlmann, Wendy; Schiffman, Joshua D.

    2014-01-01

    We used the Utah Population Database to examine risk of cancer in relatives of 4,482 pediatric cancer cases (≤ 18 years old) diagnosed from 1966 to 2009 compared to matched population controls. We quantified cancer risk in relatives of children with cancer to determine evidence of familial aggregation and to inform risk assessment and counseling for families. Odds ratios that reflect risk were obtained using conditional logistic regression models adjusting for number of biological relatives, their degree of genetic relatedness and their person-years at risk. First-degree relatives (primarily siblings) of pediatric cases faced a twofold increased risk of a cancer diagnosis before age 19, which extended to their second-degree relatives (p < 10–, respectively). Furthermore, first-degree relatives of children diagnosed before age 5 had a 3.6-fold increased risk of developing pediatric cancer (p < 10–), second-degree relatives of very young (under age 5) cases were at 2.5-fold risk (p < 10–) and third-degree relatives were at twofold risk (P < 1023) of childhood cancer. Although first-degree relatives of pediatric cases have a slight increased risk of adult tumors, when they do develop cancer they have a 1.7-fold risk of developing a tumor in the Li-Fraumeni spectrum. Our findings support the hypothesis of familial aggregation in pediatric cancer and suggest that a higher percent of childhood cancers may be related to hereditary syndromes than are adult cancers. We encourage the collection of a family medical history that is routinely updated for all pediatric cancer patients, and that families with early-onset adult cancers or clusters of several cancers are referred for genetic counseling. PMID:23661176

  4. Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in Aggressiveness of Prostate Cancer

    DTIC Science & Technology

    2015-10-01

    AWARD NUMBER: W81XWH-14-1-0453 TITLE: Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in Aggressiveness of...COVERED 15 Sep 2014 - 14 Sep 2015 4. TITLE AND SUBTITLE Genetic Variations in SLCO Transporter Genes Contributing to Racial Disparity in...proposed studies are expected to (1) identify genetic variations in the genes of androgen transporters that are associated with the racial differences in

  5. Aggressiveness Niche: Can It Be the Foster Ground for Cancer Metastasis Precursors?

    PubMed Central

    2016-01-01

    The relationship between tumor initiation and tumor progression can follow a linear projection in which all tumor cells are equally endowed with the ability to progress into metastasis. Alternatively, not all tumor cells are equal genetically and/or epigenetically, and only few cells are induced to become metastatic tumor cells. The location of these cells within the tumor can also impact the fate of these cells. The most inner core of a tumor where an elevated pressure of adverse conditions forms, such as necrosis-induced inflammation and hypoxia-induced immunosuppressive environment, seems to be the most fertile ground to generate such tumor cells with metastatic potential. Here we will call this necrotic/hypoxic core the “aggressiveness niche” and will present data to support its involvement in generating these metastatic precursors. Within this niche, interaction of hypoxia-surviving cells with the inflammatory microenvironment influenced by newly recruited mesenchymal stromal cells (MSCs), tumor-associated macrophages (TAMs), and other types of cells and the establishment of bidirectional interactions between them elevate the aggressiveness of these tumor cells. Additionally, immune evasion properties induced in these cells most likely contribute in the formation and maintenance of such aggressiveness niche. PMID:27493669

  6. Relevance of ID3-TCF3-CCND3 pathway mutations in pediatric aggressive B-cell lymphoma treated according to the NHL-BFM protocols.

    PubMed

    Rohde, Marius; Bonn, Bettina R; Zimmermann, Martin; Lange, Jonas; Möricke, Anja; Klapper, Wolfram; Oschlies, Ilske; Szczepanowski, Monika; Nagel, Inga; Schrappe, Martin; Loeffler, Markus; Siebert, Reiner; Reiter, Alfred; Burkhardt, Birgit

    2017-02-16

    Mature B-cell Non-Hodgkin lymphoma is the most common subtype of Non-Hodgkin lymphoma in childhood and adolescence. B-cell Non-Hodgkin lymphoma are further classified into histological subtypes, with Burkitt lymphoma and Diffuse large B-cell lymphoma being the most common subgroups in pediatric patients. Translocations involving the MYC oncogene are known as relevant but not sufficient hit for Burkitt lymphoma pathogenesis. Recently published large-scale next-generation sequencing studies unveiled sets of additional recurrently mutated genes in samples of pediatric and adult B-cell Non-Hodgkin lymphoma patients. ID3, TCF3 and CCND3 are potential drivers of Burkitt-lymphomagenesis. In the present study frequency and clinical relevance of mutations in ID3, TCF3 and CCND3 were analyzed within a well-defined cohort of 84 uniformly diagnosed and treated pediatric B-cell Non-Hodgkin lymphoma patients of the Berlin-Frankfurt-Munster group (NHL-BFM). Mutation frequency was 78% (ID3), 13% (TCF3) and 36% (CCND3) in Burkitt lymphoma (including Burkitt leukemia). ID3 and CCND3 mutations were associated with more advanced stages of the disease in MYC rearrangement positive Burkitt lymphoma. In conclusion ID3-TCF3-CCND3 pathway genes are mutated in more than 88% of MYC-rearranged pediatric B-cell Non-Hodgkin lymphoma and the pathway may represent a highly relevant second hit of Burkitt lymphoma pathogenesis especially in children and adolescents.

  7. Characterization of Desmoglein Expression in the Normal Prostatic Gland. Desmoglein 2 Is an Independent Prognostic Factor for Aggressive Prostate Cancer

    PubMed Central

    Barber, Alison G.; Castillo-Martin, Mireia; Bonal, Dennis M.; Rybicki, Benjamin A.; Christiano, Angela M.; Cordon-Cardo, Carlos

    2014-01-01

    Purpose The expression of desmogleins (DSGs), which are known to be crucial for establishing and maintaining the cell-cell adhesion required for tissue integrity, has been well characterized in the epidermis and hair follicle; however, their expression in other epithelial tissues such as prostate is poorly understood. Although downregulation of classical cadherins, such as E-cadherin, has been described in prostate cancer tissue samples, the expression of desmogleins has only been previously reported in prostate cancer cell lines. In this study we characterized desmoglein expression in normal prostate tissues, and further investigated whether Desmoglein 2 (DSG2) expression specifically can serve as a potential clinical prognostic factor for patients diagnosed with primary prostate cancer. Experimental Design We utilized immunofluorescence to examine DSG2 expression in normal prostate (n = 50) and in a clinically well-characterized cohort of prostate cancer patients (n = 414). Correlation of DSG2 expression with clinico-pathological characteristics and biochemical recurrence was analyzed to assess its clinical significance. Results These studies revealed that DSG2 and DSG4 were specifically expressed in prostatic luminal cells, whereas basal cells lack their expression. In contrast, DSG1 and DSG3 were not expressed in normal prostate epithelium. Further analyses of DSG2 expression in prostate cancer revealed that reduced levels of this biomarker were a significant independent marker of poor clinical outcome. Conclusion Here we report for the first time that a low DSG2 expression phenotype is a useful prognostic biomarker of tumor aggressiveness and may serve as an aid in identifying patients with clinically significant prostate cancer. PMID:24896103

  8. LASP1-S100A11 axis promotes colorectal cancer aggressiveness by modulating TGFβ/Smad signaling

    PubMed Central

    Niu, Ya; Shao, Ziyun; Wang, Hui; Yang, Jiaqi; Zhang, Feifei; Luo, Yuhao; Xu, Lijun; Ding, Yanqing; Zhao, Liang

    2016-01-01

    LIM and SH3 protein 1(LASP1) can promote colorectal cancer (CRC) progression and metastasis, but the mechanism remains unclear. Here, we show that LASP1 interacts with S100 calcium binding protein A11(S100A11) and enhances its expression in CRC. LASP1-S100A11 axis is essential for TGFβ-mediated epithelial-mesenchymal transition (EMT) and cell aggressive phenotype. Clinically, S100A11 is overexpressed in CRC tissues and localized in both the cytoplasm and the nucleus of CRC cells. Overexpression of S100A11 in cytoplasmic and nuclear subcellular compartments is associated with tumor metastasis and poor prognosis of CRC patients. Introduction of cytoplasmic and nuclear S100A11 promotes aggressive phenotypes of CRC cells in vitro as well as growth and metastasis of CRC xenografts, whereas suppressing S100A11 abrogates these effects. Furthermore, we identify flotillin-1 (FLOT1) and histone H1 as downstream factors for cytoplasmic and nuclear pathway of S100A11, which are required for LASP1-S100A11 axis-mediated EMT and CRC progression. These findings indicate S100A11, combined with LASP1, plays a critical role in promoting CRC metastasis via its subcellular effectors, FLOT1 and histone H1. PMID:27181092

  9. Bloodstream infections and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City.

    PubMed

    Avilés-Robles, Martha; Ojha, Rohit P; González, Miriam; Ojeda-Diezbarroso, Karla; Dorantes-Acosta, Elisa; Jackson, Bradford E; Johnson, Kyle M; Caniza, Miguela A

    2014-11-01

    We assessed the association between bloodstream infections (BSIs) and inpatient length of stay among pediatric cancer patients with febrile neutropenia in Mexico City. The estimated length of stay for BSIs was 19 days, which corresponded with a 100% (95% confidence limits, 60%-160%) relative increase in the length of stay compared with patients for whom no pathogen was identified. Feasible options for reducing the length of stay should be considered to alleviate patient and resource burden.

  10. TNRC9 downregulates BRCA1 expression and promotes breast cancer aggressiveness.

    PubMed

    Shan, Jingxuan; Dsouza, Shoba P; Bakhru, Sasha; Al-Azwani, Eman K; Ascierto, Maria L; Sastry, Konduru S; Bedri, Shahinaz; Kizhakayil, Dhanya; Aigha, Idil I; Malek, Joel; Al-Bozom, Issam; Gehani, Salah; Furtado, Stacia; Mathiowitz, Edith; Wang, Ena; Marincola, Francesco M; Chouchane, Lotfi

    2013-05-01

    Although the linkage between germline mutations of BRCA1 and hereditary breast/ovarian cancers is well established, recent evidence suggests that altered expression of wild-type BRCA1 might contribute to the sporadic forms of breast cancer. The breast cancer gene trinucleotide-repeat-containing 9 (TNRC9; TOX3) has been associated with disease susceptibility but its function is undetermined. Here, we report that TNRC9 is often amplified and overexpressed in breast cancer, particularly in advanced breast cancer. Gene amplification was associated with reduced disease-free and metastasis-free survival rates. Ectopic expression of TNRC9 increased breast cancer cell proliferation, migration, and survival after exposure to apoptotic stimuli. These phenotypes were associated with tumor progression in a mouse model of breast cancer. Gene expression profiling, protein analysis, and in silico assays of large datasets of breast and ovarian cancer samples suggested that TNRC9 and BRCA1 expression were inversely correlated. Notably, we found that TNRC9 bound to both the BRCA1 promoter and the cAMP-responsive element-binding protein (CREB) complex, a regulator of BRCA1 transcription. In support of this connection, expression of TNRC9 downregulated expression of BRCA1 by altering the methylation status of its promoter. Our studies unveil a function for TNRC9 in breast cancer that highlights a new paradigm in BRCA1 regulation.

  11. Novel Nuclear Localization of Fatty Acid Synthase Correlates with Prostate Cancer Aggressiveness

    PubMed Central

    Madigan, Allison A.; Rycyna, Kevin J.; Parwani, Anil V.; Datiri, Yeipyeng J.; Basudan, Ahmed M.; Sobek, Kathryn M.; Cummings, Jessica L.; Basse, Per H.; Bacich, Dean J.; O'Keefe, Denise S.

    2015-01-01

    Fatty acid synthase is up-regulated in a variety of cancers, including prostate cancer. Up-regulation of fatty acid synthase not only increases production of fatty acids in tumors but also contributes to the transformed phenotype by conferring growth and survival advantages. In addition, increased fatty acid synthase expression in prostate cancer correlates with poor prognosis, although the mechanism(s) by which this occurs are not completely understood. Because fatty acid synthase is expressed at low levels in normal cells, it is currently a major target for anticancer drug design. Fatty acid synthase is normally found in the cytosol; however, we have discovered that it also localizes to the nucleus in a subset of prostate cancer cells. Analysis of the fatty acid synthase protein sequence indicated the presence of a nuclear localization signal, and subcellular fractionation of LNCaP prostate cancer cells, as well as immunofluorescent confocal microscopy of patient prostate tumor tissue and LNCaPs confirmed nuclear localization of this protein. Finally, immunohistochemical analysis of prostate cancer tissue indicated that nuclear localization of fatty acid synthase correlates with Gleason grade, implicating a potentially novel role in prostate cancer progression. Possible clinical implications include improving the accuracy of prostate biopsies in the diagnosis of low- versus intermediate-risk prostate cancer and the uncovering of novel metabolic pathways for the therapeutic targeting of androgen-independent prostate cancer. PMID:24907642

  12. BTG1 expression correlates with pathogenesis, aggressive behaviors and prognosis of gastric cancer: a potential target for gene therapy.

    PubMed

    Zheng, Hua-chuan; Li, Jing; Shen, Dao-fu; Yang, Xue-feng; Zhao, Shuang; Wu, Ya-zhou; Takano, Yasuo; Sun, Hong-zhi; Su, Rong-jian; Luo, Jun-sheng; Gou, Wen-feng

    2015-08-14

    Here, we found that BTG1 overexpression inhibited proliferation, migration and invasion, induced G2/M arrest, differentiation, senescence and apoptosis in BGC-823 and MKN28 cells (p < 0.05). BTG1 transfectants showed a higher mRNA expression of Cyclin D1 and Bax, but a lower mRNA expression of cdc2, p21, mTOR and MMP-9 than the control and mock (p < 0.05). After treated with cisplatin, MG132, paclitaxel and SAHA, both BTG1 transfectants showed lower mRNA viability and higher apoptosis than the control in both time- and dose-dependent manners (p < 0.05) with the hypoexpression of chemoresistance-related genes (slug, CD147, GRP78, GRP94, FBXW7 TOP1, TOP2 and GST-π). BTG1 expression was restored after 5-aza-2'-deoxycytidine treatment in gastric cancer cells. BTG1 expression was statistically lower in gastric cancer than non-neoplastic mucosa and metastatic cancer in lymph node (p < 0.05). BTG1 expression was positively correlated with depth of invasion, lymphatic and venous invasion, lymph node metastasis, TNM staging and worse prognosis (p < 0.05). The diffuse-type carcinoma showed less BTG1 expression than intestinal- and mixed-type ones (p < 0.05). BTG1 overexpression suppressed tumor growth and lung metastasis of gastric cancer cells by inhibiting proliferation, enhancing autophagy and apoptosis in xenograft models. It was suggested that down-regulated BTG1 expression might promote gastric carcinogenesis partially due to its promoter methylation. BTG1 overexpression might reverse the aggressive phenotypes and be employed as a potential target for gene therapy of gastric cancer.

  13. Integrating Palliative Care in Pediatric Oncology: An Evolving Paradigm for Comprehensive Cancer Care

    PubMed Central

    Levine, Deena R.; Johnson, Liza-Marie; Snyder, Angela; Wiser, Robert K.; Gibson, Deborah; Kane, Javier R.; Baker, Justin N.

    2017-01-01

    Background The demonstrated benefit of integrating palliative care (PC) into cancer treatment has triggered an increased need for PC services. The trajectory of integrating PC in comprehensive cancer centers, particularly pediatric centers, is unknown. We describe our eight-year experience of initiating and establishing PC with the Quality of Life Service (QoLS) at St. Jude Children’s Research Hospital. Patients and Methods We retrospectively reviewed records of patients seen by the QoLS (n= 615) from March 2007 to December 2014. Variables analyzed for each year, using descriptive statistics, included diagnostic groups, QoLS encounters, goals of care, duration of survival, and location of death. Results Total QoLS patient encounters increased from 58 (2007) to 1297 (2014), new consults increased from 17 (2007) to 115 (2014), and mean encounters per patient increased from 5.06 (2007) to 16.11 (2014). Goal of care at initial consultation shifted from primarily comfort to an increasing goal of cure. The median number of days from initial consult to death increased from 52 days (2008) to 223 days (2014). A trend toward increased outpatient location of death was noted with 42% outpatient deaths in 2007 increasing to a majority in each subsequent year (range 51–74%). Hospital-wide, patients receiving PC services before death increased from approximately 50% to nearly 100%. Conclusions Since its inception, the QoLS experienced a dramatic rise in referrals and encounters per patient, utilization by all clinical services, a trend toward earlier consultation and longer term follow-up, increasing outpatient location of death, and near-universal PC involvement at the end-of-life. The successful integration of PC in a comprehensive cancer center, and resulting potential for improved care provision over time, can serve as a model for other programs on a broad scale. PMID:27283167

  14. Genetic Variations in Mitochondria and Prostate Cancer Aggressiveness and Progression in Caucasian and African American Men

    DTIC Science & Technology

    2014-07-01

    SUBJECT TERMS Mitochondrial DNAs prostate cancer 16. SECURITY CLASSIFICATION OF: 17. LIMITATION OF ABSTRACT 18. NUMBER OF PAGES 6 19a. NAME OF...6 4 Introduction The mitochondrial genome is highly polymorphic among individuals and exhibits significant... mitochondrial DNA sequencing to identify novel genetic variants in AA and CA prostate cancer patients. A subset of the study population from PCaP

  15. Prolonged and repetitive exposure to Porphyromonas gingivalis increases aggressiveness of oral cancer cells by promoting acquisition of cancer stem cell properties.

    PubMed

    Ha, Na Hee; Woo, Bok Hee; Kim, Da Jeong; Ha, Eun Sin; Choi, Jeom Il; Kim, Sung Jo; Park, Bong Soo; Lee, Ji Hye; Park, Hae Ryoun

    2015-12-01

    Periodontitis is the most common chronic inflammatory condition occurring in the human oral cavity, but our knowledge on its contribution to oral cancer is rather limited. To define crosstalk between chronic periodontitis and oral cancer, we investigated whether Porphyromonas gingivalis, a major pathogen of chronic periodontitis, plays a role in oral cancer progression. To mimic chronic irritation by P. gingivalis in the oral cavity, oral squamous cell carcinoma (OSCC) cells were infected with P. gingivalis twice a week for 5 weeks. Repeated infection of oral cancer cells by P. gingivalis resulted in morphological changes of host cancer cells into an elongated shape, along with the decreased expression of epithelial cell markers, suggesting acquisition of an epithelial-to-mesenchymal transition (EMT) phenotype. The prolonged exposure to P. gingivalis also promoted migratory and invasive properties of OSCC cells and provided resistance against a chemotherapeutic agent, all of which are described as cellular characteristics undergoing EMT. Importantly, long-term infection by P. gingivalis induced an increase in the expression level of CD44 and CD133, well-known cancer stem cell markers, and promoted the tumorigenic properties of infected cancer cells compared to non-infected controls. Furthermore, increased invasiveness of P. gingivalis-infected OSCC cells was correlated with enhanced production of matrix metalloproteinase (MMP)-1 and MMP-10 that was stimulated by interleukin-8 (IL-8) release. This is the first report demonstrating that P. gingivalis can increase the aggressiveness of oral cancer cells via epithelial-mesenchymal transition-like changes and the acquisition of stemness, implicating P. gingivalis as a potential bacterial risk modifier.

  16. Role of androgen metabolism genes CYP1B1, PSA/KLK3, and CYP11alpha in prostate cancer risk and aggressiveness.

    PubMed

    Cicek, Mine S; Liu, Xin; Casey, Graham; Witte, John S

    2005-09-01

    Candidate genes involved with androgen metabolism have been hypothesized to affect the risk of prostate cancer. To further investigate this, we evaluated the relationship between prostate cancer and multiple potentially functional polymorphisms in three genes involved in androgen metabolism: CYP1B1 (two single nucleotide polymorphisms: 355G/T and 4326C/G), prostate-specific antigen (PSA/KLK3 (three single nucleotide polymorphisms: -158A/G, -4643G/A, and -5412C/T), and CYP11alpha [(tttta)(n) repeat], using a moderately large (n = 918) sibling-based case-control population. When looking at all subjects combined, no association was observed between any polymorphism-or their haplotypes-and prostate cancer risk. However, among men with more aggressive prostate cancer, the CYP1B1 355G/T variant was positively associated with disease: carrying one or two T alleles gave odds ratios (OR) of 1.90 [95% confidence interval (95% CI), 1.09-3.31; P = 0.02] and 3.73 (95% CI, 1.39-10.0; P = 0.009), respectively. Similarly, carrying the CYP1B1 355T-4326C haplotype was positively associated with prostate cancer among men with high aggressive disease (P = 0.01). In addition, the PSA -158G/-158G genotype was positively associated with prostate cancer among men with less aggressive disease (OR, 2.71; 95% CI, 1.06-6.94; P = 0.04). Our findings suggest that CYP1B1 and PSA variants may affect the risk of prostate cancer and tumor aggressiveness.

  17. Down regulation of ADAM33 as a Predictive Biomarker of Aggressive Breast Cancer

    PubMed Central

    Manica, Graciele C. M.; Ribeiro, Caroline F.; Oliveira, Marco A. S. de; Pereira, Isabela T.; Chequin, Andressa; Ramos, Edneia A. S.; Klassen, Liliane M. B.; Sebastião, Ana Paula M.; Alvarenga, Larissa M.; Zanata, Silvio M.; Noronha, Lucia De; Rabinovich, Iris; Costa, Fabricio F.; Souza, Emanuel M.; Klassen, Giseli

    2017-01-01

    Breast cancer is a heterogeneous disease with differences in its clinical, molecular and biological features. Traditionally, immunohistochemical markers together with clinicopathologic parameters are used to classify breast cancer and to predict disease outcome. Triple-negative breast cancer (TNBC) is a particular type of breast cancer that is defined by a lack of expression of hormonal receptors and the HER2 gene. Most cases of TNBC also have a basal-like phenotype (BLBC) with expression of cytokeratin 5/6 and/or EGFR. A basal marker alone is insufficient for a better understanding of the tumor biology of TNBC. In that regard, the ADAM33 gene is silenced by DNA hypermethylation in breast cancer, which suggests that ADAM33 might be useful as a molecular marker. In the present study, we have produced monoclonal antibodies against the ADAM33 protein and have investigated the role of ADAM33 protein in breast cancer. We used 212 breast tumor samples and lower levels of ADAM33 were correlated with TNBC and basal-like markers. A lower level of ADAM33 was also correlated with shorter overall survival and metastasis-free survival and was considered an independent prognostic factor suggesting that ADAM33 is a novel molecular biomarker of TNBC and BLBC that might be useful as a prognostic factor. PMID:28294120

  18. Down regulation of ADAM33 as a Predictive Biomarker of Aggressive Breast Cancer.

    PubMed

    Manica, Graciele C M; Ribeiro, Caroline F; Oliveira, Marco A S de; Pereira, Isabela T; Chequin, Andressa; Ramos, Edneia A S; Klassen, Liliane M B; Sebastião, Ana Paula M; Alvarenga, Larissa M; Zanata, Silvio M; Noronha, Lucia De; Rabinovich, Iris; Costa, Fabricio F; Souza, Emanuel M; Klassen, Giseli

    2017-03-15

    Breast cancer is a heterogeneous disease with differences in its clinical, molecular and biological features. Traditionally, immunohistochemical markers together with clinicopathologic parameters are used to classify breast cancer and to predict disease outcome. Triple-negative breast cancer (TNBC) is a particular type of breast cancer that is defined by a lack of expression of hormonal receptors and the HER2 gene. Most cases of TNBC also have a basal-like phenotype (BLBC) with expression of cytokeratin 5/6 and/or EGFR. A basal marker alone is insufficient for a better understanding of the tumor biology of TNBC. In that regard, the ADAM33 gene is silenced by DNA hypermethylation in breast cancer, which suggests that ADAM33 might be useful as a molecular marker. In the present study, we have produced monoclonal antibodies against the ADAM33 protein and have investigated the role of ADAM33 protein in breast cancer. We used 212 breast tumor samples and lower levels of ADAM33 were correlated with TNBC and basal-like markers. A lower level of ADAM33 was also correlated with shorter overall survival and metastasis-free survival and was considered an independent prognostic factor suggesting that ADAM33 is a novel molecular biomarker of TNBC and BLBC that might be useful as a prognostic factor.

  19. Phosphoinositide 3-kinase targeting by the β galactoside binding protein cytokine negates akt gene expression and leads aggressive breast cancer cells to apoptotic death

    PubMed Central

    Wells, Valerie; Mallucci, Livio

    2009-01-01

    Introduction Phosphoinositide 3-kinase (PI3K)-activated signalling has a critical role in the evolution of aggressive tumourigenesis and is therefore a prime target for anticancer therapy. Previously we have shown that the β galactoside binding protein (βGBP) cytokine, an antiproliferative molecule, induces functional inhibition of class 1A and class 1B PI3K. Here, we have investigated whether, by targeting PI3K, βGBP has therapeutic efficacy in aggressive breast cancer cells where strong mitogenic input is fuelled by overexpression of the ErbB2 (also known as HER/neu, for human epidermal growth factor receptor 2) oncoprotein receptor and have used immortalised ductal cells and non-aggressive mammary cancer cells, which express ErbB2 at low levels, as controls. Methods Aggressive BT474 and SKBR3 cancer cells where ErbB2 is overexpressed, MCF10A immortalised ductal cells and non-invasive MCF-7 cancer cells which express low levels of ErbB2, both in their naive state and when forced to mimic aggressive behaviour, were used. Class IA PI3K was immunoprecipitated and the conversion of phosphatidylinositol (4,5)-biphosphate (PIP2) to phosphatidylinositol (3,4,5)-trisphosphate (PIP3) assessed by ELISA. The consequences of PI3K inhibition by βGBP were analysed at proliferation level, by extracellular signal-regulated kinase (ERK) activation, by akt gene expression and by apoptosis. Apoptosis was documented by changes in mitochondrial membrane potential, alteration of the plasma membrane, caspase 3 activation and DNA fragmentation. Phosphorylated and total ERK were measured by Western blot analysis and akt mRNA levels by Northern blot analysis. The results obtained with the BT474 and SKBR3 cells were validated in the MCF10A ductal cells and in non-invasive MCF-7 breast cancer cells forced into mimicking the in vitro behaviour of the BT474 and SKBR3 cells. Results In aggressive breast cancer cells, where mitogenic signalling is enforced by the ErbB2 oncoprotein receptor

  20. Selective participation of c-Jun with Fra-2/c-Fos promotes aggressive tumor phenotypes and poor prognosis in tongue cancer

    PubMed Central

    Gupta, Shilpi; Kumar, Prabhat; Kaur, Harsimrut; Sharma, Nishi; Saluja, Daman; Bharti, Alok C.; Das, Bhudev C.

    2015-01-01

    Tongue squamous cell carcinoma (TSCC) is most aggressive head and neck cancer often associated with HR-HPV infection. The role of AP-1 which is an essential regulator of HPV oncogene expression and tumorigenesis is not reported in tongue cancer. One hundred tongue tissue biopsies comprising precancer, cancer and adjacent controls including two tongue cancer cell lines were employed to study the role of HPV infection and AP-1 family proteins. An exclusive prevalence (28%) of HR-HPV type 16 was observed mainly in well differentiated tongue carcinomas (78.5%). A higher expression and DNA binding activity of AP-1 was observed in tongue tumors and cancer cell lines with c-Fos and Fra-2 as the major binding partners forming the functional AP-1 complex but c-Jun participated only in HPV negative and poorly differentiated carcinoma. Knocking down of Fra-2 responsible for aggressive tongue tumorigenesis led to significant reduction in c-Fos, c-Jun, MMP-9 and HPVE6/E7 expression but Fra-1 and p53 were upregulated. The binding and expression of c-Fos/Fra-2 increased as a function of severity of tongue lesions, yet selective participation of c-Jun appears to promote poor differentiation and aggressive tumorigenesis only in HPV negative cases while HPV infection leads to well differentiation and better prognosis preferably in nonsmokers. PMID:26581505

  1. Oridonin Ring A-Based Diverse Constructions of Enone Functionality: Identification of Novel Dienone Analogues Effective for Highly Aggressive Breast Cancer by Inducing Apoptosis

    PubMed Central

    Ding, Chunyong; Zhang, Yusong; Chen, Haijun; Yang, Zhengduo; Wild, Christopher; Ye, Na; Ester, Corbin D.; Xiong, Ailian; White, Mark A.; Shen, Qiang; Zhou, Jia

    2013-01-01

    Oridonin (1) has attracted considerable attention in recent years due to its unique and safe anticancer pharmacological profile. Nevertheless, it exhibits moderate to poor effects against highly aggressive cancers including triple-negative and drug-resistant breast cancer cells. Herein, we report the rational design and synthesis of novel dienone derivatives with an additional α,β-unsaturated ketone system diversely installed in the A-ring based on this class of natural scaffold that features dense functionalities and stereochemistry-rich frameworks. Efficient and regioselective enone construction strategies have been established. Meanwhile, a unique 3,7-rearrangement reaction was identified to furnish an unprecedented dienone scaffold. Intriguingly, these new analogues have been demonstrated to significantly induce apoptosis and inhibit colony formation with superior antitumor effects against aggressive and drug-resistant breast cancer cells in vitro and in vivo, while also exhibiting comparable or lower toxicity to normal human mammary epithelial cells in comparison with 1. PMID:24128046

  2. Oridonin ring A-based diverse constructions of enone functionality: identification of novel dienone analogues effective for highly aggressive breast cancer by inducing apoptosis.

    PubMed

    Ding, Chunyong; Zhang, Yusong; Chen, Haijun; Yang, Zhengduo; Wild, Christopher; Ye, Na; Ester, Corbin D; Xiong, Ailian; White, Mark A; Shen, Qiang; Zhou, Jia

    2013-11-14

    Oridonin (1) has attracted considerable attention in recent years because of its unique and safe anticancer pharmacological profile. Nevertheless, it exhibits moderate to poor effects against highly aggressive cancers including triple-negative and drug-resistant breast cancer cells. Herein, we report the rational design and synthesis of novel dienone derivatives with an additional α,β-unsaturated ketone system diversely installed in the A-ring based on this class of natural scaffold that features dense functionalities and stereochemistry-rich frameworks. Efficient and regioselective enone construction strategies have been established. Meanwhile, a unique 3,7-rearrangement reaction was identified to furnish an unprecedented dienone scaffold. Intriguingly, these new analogues have been demonstrated to significantly induce apoptosis and inhibit colony formation with superior antitumor effects against aggressive and drug-resistant breast cancer cells in vitro and in vivo while also exhibiting comparable or lower toxicity to normal human mammary epithelial cells in comparison with 1.

  3. Risk analysis, diagnosis and management of gastrointestinal mucositis in pediatric cancer patients.

    PubMed

    Kuiken, Nicoline S S; Rings, Edmond H H M; Tissing, Wim J E

    2015-04-01

    Mucositis is a complex inflammatory reaction of the mucous membranes of the alimentary tract upon chemotherapy and radiotherapy treatment in oncology patients. Mucositis can be subdivided in oral and gastrointestinal mucositis (GI mucositis). The damage to the gastrointestinal tract compromises the intestinal function and thereby the nutritional status and the quality of life, and eventually affects survival. The literature on GI mucositis focuses mainly on adults. This review focuses on data available on GI mucositis in pediatric cancer patients. An evaluation of the clinical presentation and consequences of GI mucositis in children is outlined. The review summarizes key issues for clinicians with respect to risk analysis for developing mucositis and the diagnosis of this condition in children. Information on these issues is obtained from clinical trials in children and adults, and from animal models. Diagnostic tools and assessment of severity of GI mucositis in children is elaborated on. Furthermore, the clinical management of the symptoms and consequences of GI mucositis in children, with specific focus on nutritional support, are discussed.

  4. Clinical value of digital image analysis in the diagnosis of urinary bladder cancer, particularly in aggressive tumors: a preliminary report.

    PubMed

    Borkowski, T; Monika Dulewicz, A; Borkowski, A; Piętka, D; Radziszewski, P

    2016-06-01

    The aim of the project was to evaluate the clinical value of a computer analysis of cytological specimen images obtained from urine and bladder washing samples. Three sample types (voided urine, catheterized urine and bladder washing) from 59 patients with primary or recurrent tumor were analyzed. All patients underwent cystoscopy and biopsy or resection. The histological results were compared with the results of the image analyzing computer system of collected urine samples. The consistency between the computer diagnosis and the clinical or histological diagnosis both in the presence and absence of cancer was as follows: 77% for voided urine samples, 72.5% for catheterized urine samples and 78% for bladder washing samples. The specificity of the method at the standard pathology level was 71%, and the sensitivity was 83%. The positive and negative predictive values (PPV and NPV) were 87.5% and 63% respectively. The sensitivity for G3 or CIS or T2 or T3 tumors reached nearly 100%. Computer analysis of urine provided correct diagnoses in cancer and control patients with the sensitivity of 83% and specificity of 71% and gave excellent results in aggressive tumors such as T2, T3, G3 and in CIS.

  5. 5′-AMP-activated Protein Kinase (AMPK) Supports the Growth of Aggressive Experimental Human Breast Cancer Tumors*

    PubMed Central

    Laderoute, Keith R.; Calaoagan, Joy M.; Chao, Wan-ru; Dinh, Dominc; Denko, Nicholas; Duellman, Sarah; Kalra, Jessica; Liu, Xiaohe; Papandreou, Ioanna; Sambucetti, Lidia; Boros, Laszlo G.

    2014-01-01

    Rapid tumor growth can establish metabolically stressed microenvironments that activate 5′-AMP-activated protein kinase (AMPK), a ubiquitous regulator of ATP homeostasis. Previously, we investigated the importance of AMPK for the growth of experimental tumors prepared from HRAS-transformed mouse embryo fibroblasts and for primary brain tumor development in a rat model of neurocarcinogenesis. Here, we used triple-negative human breast cancer cells in which AMPK activity had been knocked down to investigate the contribution of AMPK to experimental tumor growth and core glucose metabolism. We found that AMPK supports the growth of fast-growing orthotopic tumors prepared from MDA-MB-231 and DU4475 breast cancer cells but had no effect on the proliferation or survival of these cells in culture. We used in vitro and in vivo metabolic profiling with [13C]glucose tracers to investigate the contribution of AMPK to core glucose metabolism in MDA-MB-231 cells, which have a Warburg metabolic phenotype; these experiments indicated that AMPK supports tumor glucose metabolism in part through positive regulation of glycolysis and the nonoxidative pentose phosphate cycle. We also found that AMPK activity in the MDA-MB-231 tumors could systemically perturb glucose homeostasis in sensitive normal tissues (liver and pancreas). Overall, our findings suggest that the contribution of AMPK to the growth of aggressive experimental tumors has a critical microenvironmental component that involves specific regulation of core glucose metabolism. PMID:24993821

  6. Genetic deletion of osteopontin in TRAMP mice skews prostate carcinogenesis from adenocarcinoma to aggressive human-like neuroendocrine cancers

    PubMed Central

    Mauri, Giorgio; Jachetti, Elena; Comuzzi, Barbara; Dugo, Matteo; Arioli, Ivano; Miotti, Silvia; Sangaletti, Sabina; Di Carlo, Emma; Tripodo, Claudio; Colombo, Mario P.

    2016-01-01

    Osteopontin (OPN) is a secreted glycoprotein, that belongs to the non-structural extracellular matrix (ECM), and its over expression in human prostate cancer has been associated with disease progression, androgen independence and metastatic ability. Nevertheless, the pathophysiology of OPN in prostate tumorigenesis has never been studied. We crossed TRansgenic Adenocarcinoma of the Mouse Prostate (TRAMP) mice with OPN deficient (OPN−/−) mice and followed tumor onset and progression in these double mutants. Ultrasound examination detected the early onset of a rapidly growing, homogeneous and spherical tumor in about 60% of OPN−/− TRAMP mice. Such neoplasms seldom occurred in parental TRAMP mice otherwise prone to adenocarcinomas and were characterized for being androgen receptor negative, highly proliferative and endowed with neuroendocrine (NE) features. Gene expression profiling showed up-regulation of genes involved in tumor progression, cell cycle and neuronal differentiation in OPN-deficient versus wild type TRAMP tumors. Down-regulated genes included key genes of TGFa pathway, including SMAD3 and Filamin, which were confirmed at the protein level. Furthermore, NE genes and particularly those characterizing early prostatic lesions of OPN-deficient mice were found to correlate with those of human prostate NE tumours. These data underscore a novel role of OPN in the early stages of prostate cancer growth, protecting against the development of aggressive NE tumors. PMID:26700622

  7. Phase 1 study of intratumoral Pexa-Vec (JX-594), an oncolytic and immunotherapeutic vaccinia virus, in pediatric cancer patients.

    PubMed

    Cripe, Timothy P; Ngo, Minhtran C; Geller, James I; Louis, Chrystal U; Currier, Mark A; Racadio, John M; Towbin, Alexander J; Rooney, Cliona M; Pelusio, Adina; Moon, Anne; Hwang, Tae-Ho; Burke, James M; Bell, John C; Kirn, David H; Breitbach, Caroline J

    2015-03-01

    Pexa-Vec (pexastimogene devacirepvec, JX-594) is an oncolytic and immunotherapeutic vaccinia virus designed to destroy cancer cells through viral lysis and induction of granulocyte-macrophage colony-stimulating factor (GM-CSF)-driven tumor-specific immunity. Pexa-Vec has undergone phase 1 and 2 testing alone and in combination with other therapies in adult patients, via both intratumoral and intravenous administration routes. We sought to determine the safety of intratumoral administration in pediatric patients. In a dose-escalation study using either 10(6) or 10(7) plaque-forming units per kilogram, we performed one-time injections in up to three tumor sites in five pediatric patients and two injections in one patient. Ages at study entry ranged from 4 to 21 years, and their cancer diagnoses included neuroblastoma, hepatocellular carcinoma, and Ewing sarcoma. All toxicities were ≤ grade 3. The most common side effects were sinus fever and sinus tachycardia. All three patients at the higher dose developed asymptomatic grade 1 treatment-related skin pustules that resolved within 3-4 weeks. One patient showed imaging evidence suggestive of antitumor biological activity. The two patients tested for cellular immunoreactivity to vaccinia antigens showed strong responses. Overall, our study suggests Pexa-Vec is safe to administer to pediatric patients by intratumoral administration and could be studied further in this patient population.

  8. Geminin overexpression-dependent recruitment and crosstalk with mesenchymal stem cells enhance aggressiveness in triple negative breast cancers

    PubMed Central

    Ananthula, Suryatheja; Sinha, Abhilasha; Gassim, Mohamed El; Batth, Simran; Marshall, Gailen D.; Gardner, Lauren H.; Shimizu, Yoshiko; ElShamy, Wael M.

    2016-01-01

    Resident mesenchymal stem cells (MSCs) promote cancer progression. However, pathways and mechanisms involved in recruiting MSCs into breast tumors remain largely undefined. Here we show that geminin-dependent acetylation releases HMGB1 from the chromatin to the cytoplasm and extracellular space. Extracellular acetylated HMGB1 (Ac-HMGB1) promotes geminin overexpressing (GemOE) cells survival by binding to RAGE and activating NF-κB signaling. Extracellular Ac-HMGB1 also triggers expression and activation of RAGE in the non-expressing MSCs. RAGE activation induces expression of CXCR4 in MSCs and directional migration towards SDF1 (aka CXCL12)-expressing GemOE cells in vitro and in vivo. These effects augmented by the necrotic and hypoxic environment in GemOE tumors, especially within their cores. Reciprocal interactions between newly recruited MSCs and GemOE tumor cells elevate tumor-initiating (TIC), basal and epithelial-to-mesenchymal transition (EMT) traits and enhance aggressiveness in vitro and in vivo in GemOE tumor cells. Indeed, faster, larger and more aggressive tumors develop when GemOE cells are co-injected with MSCs in orthotopic breast tumor model. Concurrently, inhibiting c-Abl (and thus geminin function), RAGE or CXCR4 prevented MSCs recruitment to GemOE cells in vitro and in vivo, and decreased the TIC, basal and EMT phenotypes in these tumor cells. Accordingly, we propose that GemOE tumor cells present within tumor cores represent metastatic precursors, and suppressing the GemOE→HMGB1/RAGE→SDF1/CXCR4 signaling circuit could be a valid target for therapies to inhibit GemOE tumors and their metastases. PMID:26989079

  9. Influence of mesna on the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.

    PubMed

    Kangarloo, Shahbal B; Gangopadhyay, Suman B; Syme, Rachel M; Wolff, Johannes E A; Glück, Stefan

    2004-01-01

    Mesna, a reactive thiol, often encounters cisplatin and carboplatin in combination protocols involving oxazaphosphorines and platinum drugs. This co-administration might be unfavorable based on the inactivation of platinum drugs by thiol groups in vitro. We investigated whether mesna influences the pharmacokinetics of platinum drugs when co-administered with cisplatin or carboplatin. The pharmacokinetics of platinum drugs were investigated in 18 pediatric patients receiving either cisplatin or carboplatin in a combination with or without mesna. In cisplatin patients, a decrease in the distribution clearance of total platinum was observed when mesna was co-administered (CLd, 2.2 +/- 0.1 mL/min.kg; n = 3), compared to cisplatin without mesna (CLd, 4.8 +/- 1.5 mL/min.kg; n = 5) (p = 0.029, t-test). This might have been caused by an influence of mesna in slowing down the protein binding of cisplatin since a trend (p = 0.057) in prolonged distribution half-life of total platinum was also observed when mesna was present (t(1/2a) 65 +/- 21 min; n = 3) compared to cisplatin without mesna (t(1/2a), 32 +/- 18 min; n = 5). However, the impact of these changes on the area under the concentration time curve (AUC), total clearance (CLt), and volume of distribution (V) for total platinum and ultrafilterable platinum species was hardly noticeable. In carboplatin patients, when mesna was co-administered: AUC (2.5 +/- 0.4 mg.min/mL.400 mg/m2; n = 5) CLt, (6.8 +/- 5.1 mL/min.kg; n = 6), and V (0.7 +/- 0.4 L/kg; n = 6) for ultrafilterable platinum species were not significantly different from when carboplatin were administered without mesna: AUC (2.3 +/- 1.3 mg.min/mL.400 mg/m2; n = 4), CLt (5.8 +/- 4.6 mL/min.kg; n = 5), and V (1.1 +/- 1.1 L/kg; n = 5). Hence, mesna does not significantly influence the pharmacokinetics of cisplatin and carboplatin in pediatric cancer patients.

  10. Are the Pathological Characteristics of Prostate Cancer More Aggressive or More Indolent Depending upon the Patient Age?

    PubMed

    Ji, Guangjie; Huang, Cong; Song, Gang; Xiong, Gengyan; Fang, Dong; Wang, He; Hao, Han; Cai, Lin; He, Qun; He, Zhisong; Zhou, Liqun

    2017-01-01

    Purpose. To identify pathological characteristics of prostate cancer according to patient age at diagnosis. Methods. A retrospective review of 2,929 men diagnosed with prostate cancer was performed. Pathological characteristics were compared across age groups: ≤55, 56-75, and >75 years. Results. The study cohort included 133 patients (4.5%), 2,033 patients (69.5%), and 763 patients (26.0%) in the three age groups, respectively. The median pathological Gleason sums in the three age groups were 8, 7, and 8, respectively. The Gleason sum, primary Gleason score, and second primary Gleason score were significantly different among the three age groups (Z = 12.975, p = 0.002; Z = 9.264, p = 0.010; Z = 6.692, p = 0.035, resp.). The percentages of Gleason pattern 5 tumors for the three age groups were 44.4%, 32.3%, and 36.8%, respectively; they were significantly different (χ(2) = 11.641, p = 0.003). The percentages of tumors with Gleason score grade groups 3-5 for the three age groups were 66.9%, 60.5%, and 66.3%, respectively; they were significantly different (χ(2) = 9.401, p = 0.009). Conclusions. The present study indicated that men aged ≤55 years or >75 years show higher levels of clinically significant prostate cancer compared to patients between the ages of 55 and 75 years. Younger and more elderly male patients are more likely to have a more aggressive disease.

  11. DUSP4/MKP2 overexpression is associated with BRAFV600E mutation and aggressive behavior of papillary thyroid cancer

    PubMed Central

    Ma, Ben; Shi, Rongliang; Yang, Shuwen; Zhou, Li; Qu, Ning; Liao, Tian; Wang, Yu; Wang, Yulong; Ji, Qinghai

    2016-01-01

    The study was performed to retrospectively analyze the correlation of dual specificity phosphatase 4 (DUSP4) expression with clinicopathological variables and BRAFV600E mutation to better characterize the potential role of DUSP4 as a biomarker in papillary thyroid cancer (PTC). Patients (n=120) who underwent surgery for PTC at Fudan University Shanghai Cancer Center (FUSCC) were enrolled in this study, and a validation cohort from The Cancer Genome Atlas (TCGA) database was identified to confirm the preliminary findings in our study. We investigated DUSP4 expression at the mRNA level in PTC tissues and adjacent normal tissues using real-time quantitative reverse transcription-polymerase chain reaction (qRT-PCR). BRAFV600E mutation analysis was also performed in PTC tissues using Sanger sequencing. Initially, we compared PTC tissues with paired normal tissues in DUSP4 expression using Student’s t-test, and then analyzed the correlation of DUSP4 with clinicopathological variables and BRAFV600E mutation in PTC using Mann–Whitney U, Kruskal–Wallis, χ2, and Fisher’s exact tests. Human-derived thyroid cell lines were also used to verify our findings. DUSP4 was significantly overexpressed in PTC tissues compared with the adjacent normal tissues (P<0.001). High DUSP4 expression showed a significant association with lymph node metastasis and extrathyroidal extension in both FUSCC and TCGA cohorts, and DUSP4 overexpression was an independent risk factor for lymph node metastasis in multivariate analysis. Additionally, DUSP4 expression was associated with BRAFV600E mutation in both the cohorts (FUSCC: P=0.002, TCGA: P<0.001) and PTC cell lines (P=0.023). In conclusion, DUSP4 was identified as a potential biomarker for aggressive behavior in PTC, and its overexpression was BRAFV600E mutation-related. PMID:27143921

  12. Are the Pathological Characteristics of Prostate Cancer More Aggressive or More Indolent Depending upon the Patient Age?

    PubMed Central

    Ji, Guangjie; Huang, Cong; Fang, Dong; Wang, He; Hao, Han; Cai, Lin; He, Qun; He, Zhisong

    2017-01-01

    Purpose. To identify pathological characteristics of prostate cancer according to patient age at diagnosis. Methods. A retrospective review of 2,929 men diagnosed with prostate cancer was performed. Pathological characteristics were compared across age groups: ≤55, 56–75, and >75 years. Results. The study cohort included 133 patients (4.5%), 2,033 patients (69.5%), and 763 patients (26.0%) in the three age groups, respectively. The median pathological Gleason sums in the three age groups were 8, 7, and 8, respectively. The Gleason sum, primary Gleason score, and second primary Gleason score were significantly different among the three age groups (Z = 12.975, p = 0.002; Z = 9.264, p = 0.010; Z = 6.692, p = 0.035, resp.). The percentages of Gleason pattern 5 tumors for the three age groups were 44.4%, 32.3%, and 36.8%, respectively; they were significantly different (χ2 = 11.641, p = 0.003). The percentages of tumors with Gleason score grade groups 3–5 for the three age groups were 66.9%, 60.5%, and 66.3%, respectively; they were significantly different (χ2 = 9.401, p = 0.009). Conclusions. The present study indicated that men aged ≤55 years or >75 years show higher levels of clinically significant prostate cancer compared to patients between the ages of 55 and 75 years. Younger and more elderly male patients are more likely to have a more aggressive disease. PMID:28265568

  13. Weight loss in cancer patients can be offset by aggressive nutritional therapy.

    PubMed

    1997-12-01

    Patients with cancer or other debilitating diseases such as AIDS and COPD often have on and off interruptions in care because of cachexia, also known as wasting syndrome. However, managing these patients with "medical foods" can and does get them on their feet faster. Find out how and why some doctors are swearing by this not so well-known management tool.

  14. Pediatric primary gastric lymphoma.

    PubMed

    Harris, G J; Laszewski, M J

    1992-04-01

    Primary gastric lymphoma in the pediatric population is rare. We have described a case of non-Hodgkin's lymphoma (Burkitt's type) manifested as a gastric mass. Despite its rarity in children, this tumor should be treated aggressively, since long-term survival has been reported.

  15. Overexpression of TMPRSS4 promotes tumor proliferation and aggressiveness in breast cancer

    PubMed Central

    Li, Xiao-Mei; Liu, Wen-Lou; Chen, Xu; Wang, Ya-Wen; Shi, Duan-Bo; Zhang, Hui; Ma, Ran-Ran; Liu, Hai-Ting; Guo, Xiang-Yu; Hou, Feng; Li, Ming; Gao, Peng

    2017-01-01

    Transmembrane protease serine 4 (TMPRSS4) is a novel type II transmembrane serine protease that is overexpressed in various types of human cancers and has an important function in cancer progression. However, there is a paucity of data available regarding the biological effects of TMPRSS4 on breast cancer (BC) cells and the underlying mechanisms. In this study, expression of TMPRSS4 in BC tissues was detected by immunohistochemistry. The relationship between TMPRSS4 expression and clinicopathological characteristics as well as prognosis was evaluated. The effects of TMPRSS4 on cell proliferation, migration and invasion were investigated in BC cell lines in vitro. Additionally, RT-qPCR and western blot analysis were used to determine the expressions of epithelial-mesenchymal transition (EMT) biomarkers and TMPRSS4 in BC cell lines. We found that TMPRSS4 was overexpressed in BC tissues and its expression level was closely correlated with tumor size, histological grade, lymph node metastasis, clinical stage as well as poor survival (all P<0.05) and could be recognized as an independent prognostic factor for BC patients. Overexpression of TMPRSS4 promoted the proliferation, migration and invasion of BC cells in vitro. Moreover, TMPRSS4 knockdown significantly enhanced the expression of E-cadherin and claudin-1 and inhibited the expression of vimentin and Slug, indicating suppression of EMT. Our results suggest that TMPRSS4 plays a crucial role in the progression of BC. Moreover, TMPRSS4 overexpression promoted the proliferation, invasion and migration of BC cells by possibly inducing EMT. To conclude, TMPRSS4 may be a potential therapeutic target for cancer treatment. PMID:28259959

  16. Expression of Stromal Caveolin- 1 May Be a Predictor for Aggressive Behaviour of Breast Cancer.

    PubMed

    Eliyatkin, Nuket; Aktas, Safiye; Diniz, Gulden; Ozgur, Halil Hakan; Ekin, Zubeyde Yildirim; Kupelioglu, Ali

    2017-02-24

    Caveolin-1 (Cav-1) is well known as a principal scaffolding protein of caveolae which are specialized plasma membrane structures. The role of Cav-1 in tumorigenesis of breast cancers is relatively less studied. The aim of the present study is to describe the biological roles of Cav-1 in breast cancers considering its contrasting dual functions as an oncogene and as a tumor suppressor. This study included 71 females with breast cancer who had been histopathologically diagnosed in Private Gunes Pathology Laboratory between the years 2007, and 2012. The mean age is 52.48 ± 12.8 years. Patients were followed up for a mean period of 47.97 ± 20.48 months. We didn't determine Cav-1 positive tumor cells. In 36 cases (50.7%), there were stromal expressions of Cav-1. In the statistical analysis, there was a statistically significant correlation between Cav-1 expression and ER (p = 0.033), metastasis (p = 0.005), lymphatic invasion (p = 0.000), nodal metastasis (p = 0,003), perinodal invasion (p = 0.003), metastasis (p = 0.005) and survival (p = 0.009). We found that Cav-1 expression is associated with tumor size, histological grade, lymph node involvement. Accordingly, we have suggested that Cav-1 may be a predictive biomarker for breast cancer.

  17. Metformin prevents aggressive ovarian cancer growth driven by high-energy diet: similarity with calorie restriction

    PubMed Central

    Al-Wahab, Zaid; Mert, Ismail; Tebbe, Calvin; Chhina, Jasdeep; Hijaz, Miriana; Morris, Robert T.; Ali-Fehmi, Rouba; Giri, Shailendra; Munkarah, Adnan R.; Rattan, Ramandeep

    2015-01-01

    Caloric restriction (CR) was recently demonstrated by us to restrict ovarian cancer growth in vivo. CR resulted in activation of energy regulating enzymes adenosine monophosphate activated kinase (AMPK) and sirtuin 1 (SIRT1) followed by downstream inhibition of Akt-mTOR. In the present study, we investigated the effects of metformin on ovarian cancer growth in mice fed a high energy diet (HED) and regular diet (RD) and compared them to those seen with CR in an immunocompetent isogeneic mouse model of ovarian cancer. Mice either on RD or HED diet bearing ovarian tumors were treated with 200 mg/kg metformin in drinking water. Metformin treatment in RD and HED mice resulted in a significant reduction in tumor burden in the peritoneum, liver, kidney, spleen and bowel accompanied by decreased levels of growth factors (IGF-1, insulin and leptin), inflammatory cytokines (MCP-1, IL-6) and VEGF in plasma and ascitic fluid, akin to the CR diet mice. Metformin resulted in activation of AMPK and SIRT1 and inhibition of pAkt and pmTOR, similar to CR. Thus metformin can closely mimic CR's tumor suppressing effects by inducing similar metabolic changes, providing further evidence of its potential not only as a therapeutic drug but also as a preventive agent. PMID:25895126

  18. The Prognostic Nutritional Index Predicts Survival and Identifies Aggressiveness of Gastric Cancer.

    PubMed

    Eo, Wan Kyu; Chang, Hye Jung; Suh, Jungho; Ahn, Jin; Shin, Jeong; Hur, Joon-Young; Kim, Gou Young; Lee, Sookyung; Park, Sora; Lee, Sanghun

    2015-01-01

    Nutritional status has been associated with long-term outcomes in cancer patients. The prognostic nutritional index (PNI) is calculated by serum albumin concentration and absolute lymphocyte count, and it may be a surrogate biomarker for nutritional status and possibly predicts overall survival (OS) of gastric cancer. We evaluated the value of the PNI as a predictor for disease-free survival (DFS) in addition to OS in a cohort of 314 gastric cancer patients who underwent curative surgical resection. There were 77 patients in PNI-low group (PNI ≤ 47.3) and 237 patients in PNI-high group (PNI > 47.3). With a median follow-up of 36.5 mo, 5-yr DFS rates in PNI-low group and PNI-high group were 63.5% and 83.6% and 5-yr OS rates in PNI-low group and PNI-high group were 63.5% and 88.4%, respectively (DFS, P < 0.0001; OS, P < 0.0001). In the multivariate analysis, the only predictors for DFS were PNI, tumor-node-metastasis (TNM) stage, and perineural invasion, whereas the only predictors for OS were PNI, age, TNM stage, and perineural invasion. In addition, the PNI was independent of various inflammatory markers. In conclusion, the PNI is an independent prognostic factor for both DFS and OS, and provides additional prognostic information beyond pathologic parameters.

  19. A novel HMGA1-CCNE2-YAP axis regulates breast cancer aggressiveness

    PubMed Central

    Ciani, Yari; Sgarra, Riccardo; Piazza, Silvano; Manfioletti, Guidalberto

    2015-01-01

    High Mobility Group A1 (HMGA1) is an architectural chromatin factor that promotes neoplastic transformation and progression. However, the mechanism by which HMGA1 exerts its oncogenic function is not fully understood. Here, we show that cyclin E2 (CCNE2) acts downstream of HMGA1 to regulate the motility and invasiveness of basal-like breast cancer cells by promoting the nuclear localization and activity of YAP, the downstream mediator of the Hippo pathway. Mechanistically, the activity of MST1/2 and LATS1/2, the core kinases of the Hippo pathway, are required for the HMGA1- and CCNE2-mediated regulation of YAP localization. In breast cancer patients, high levels of HMGA1 and CCNE2 expression are associated with the YAP/TAZ signature, supporting this connection. Moreover, we provide evidence that CDK inhibitors induce the translocation of YAP from the nucleus to the cytoplasm, resulting in a decrease in its activity. These findings reveal an association between HMGA1 and the Hippo pathway that is relevant to stem cell biology, tissue homeostasis, and cancer. PMID:26265440

  20. Decreased HoxD10 expression promotes a proliferative and aggressive phenotype in prostate cancer.

    PubMed

    Mo, R-J; Lu, J-M; Wan, Y-P; Hua, W; Liang, Y-X; Zhuo, Y-J; Kuang, Q-W; Liu, Y-L; He, H-C; Zhong, W-D

    2017-02-19

    HoxD10 gene plays a critical role in cell proliferation in the process of tumor development. However, the protein expression level and the function of HoxD10 in prostate cancer remain unknown. Using tissue microarray, we demonstrate that the protein expression of HoxD10 is commonly decreased in prostate cancer tissues (n = 92) compared to adjacent benign prostate tissues (n = 77). Functionally, knockdown of HoxD10 resulted in significant promotion of prostate cancer cell proliferation. Moreover, knockdown of HoxD10 strikingly stimulated prostate tumor growth in a mouse xenograft model. We also found a significant association between decreased immunohistochemical staining of HoxD10 expression and higher Gleason score (P = 0.031) and advanced clinical pathological stage (P = 0.011). An analysis of the Taylor database revealed that decreased HoxD10 expression predicted worse biochemical recurrence (BCR)-free survival of PCa patients (P = 0.005) and the multivariate analyses further supported that HoxD10 might be an independent predictor for BCR-free survival (P = 0.027). Collectively, our data suggest that the loss of HoxD10 function is common and may thus result in a progressive phenotype in PCa. HoxD10 may function as a biomarker that differentiates patients with BCR disease from the ones that are not after radical prostatectomy, implicating its potential as a therapeutic target.

  1. Microsatellite-stable diploid carcinoma: a biologically distinct and aggressive subset of sporadic colorectal cancer

    PubMed Central

    Hawkins, N J; Tomlinson, I; Meagher, A; Ward, R L

    2001-01-01

    Chromosomal instability and microsatellite instability represent the major pathways for colorectal cancer (CRC) progression. However, a significant percentage of CRC shows neither pattern of instability, and thus represents a potentially distinctive form of the disease. Flow cytometry was used to determine the degree of DNA aneuploidy in 46 consecutive sporadic colorectal cancers. Microsatellite status was determined by PCR amplification using standard markers, while immunostaining was used to examine the expression of p53. K- ras status was determined by restriction-mediated PCR assay. Twenty-five (54%) tumours were aneuploid, 14 (30%) were diploid and microsatellite-stable and seven (15%) were diploid and microsatellite-unstable. Tumours with microsatellite instability were more likely to be right sided, to occur in women and to be associated with an improved survival. Aneuploid tumours were significantly more common in men and were likely to be left sided. The diploid microsatellite-stable (MSS) tumours did not show a sex or site predilection, but were strongly associated with the presence of metastatic disease at the time of diagnosis. Our data suggests that diploid, MSS tumours represent a biologically and phenotypically distinct subset of colorectal carcinoma, and one that is associated with the early development of metastases. We suggest that the genetic stability that characterizes these tumours may favour the maintenance of an invasive phenotype, and thus facilitate disease progression. These findings may have important implications for treatment options in this disease subset. © 2001 Cancer Research Campaign http://www.bjcancer.com PMID:11161382

  2. Aberrant hypomethylation-mediated CD147 overexpression promotes aggressive tumor progression in human prostate cancer.

    PubMed

    Liang, Yu-Xiang; Mo, Ru-Jun; He, Hui-Chan; Chen, Jia-Hong; Zou, Jun; Han, Zhao-Dong; Lu, Jian-Ming; Cai, Chao; Zeng, Yan-Ru; Zhong, Wei-De; Wu, Chin-Lee

    2015-05-01

    Our previous study revealed the potential role of CD147 in human prostate cancer (PCa). Here, we investigated the CD147 promoter methylation status and the correlation with tumorigenicity in human PCa. CD147 mRNA and protein expression levels were both significantly higher in the 4 PCa cell lines, than in the 2 non-tumorigenic benign human prostatic epithelial cell lines (all P<0.01). We showed hypomethylation of promoter regions of CD147 in PCa cell lines with significant CD147 expression as compared to non-tumorigenic benign human prostatic epithelial cell lines slowly expressing CD147. Additionally, the treatment of methylated cell lines with 5-aza-2'-deoxycytidine increased CD147 expression significantly in low-expressing cell lines and also activated the expression of matrix metalloproteinase (MMP)-2, which may be one of the most important downstream targets of CD147. Furthermore, PCa tissues displayed decreased DNA methylation in the promoter region of CD147 compared to the corresponding non-cancerous prostate tissues, and methylation intensity correlated inversely with the CD147 mRNA levels. There was a significant negative correlation between CD147 mRNA levels and the number of methylated sites in PCa tissues (r=-0.467, P<0.01). In conclusion, our data offer convincing evidence for the first time that the DNA promoter hypomethylation of CD147 may be one of the regulatory mechanisms involved in the cancer-related overexpression of CD147 and may play a crucial role in the tumorigenesis of PCa.

  3. Interleukin 10 expression is related to aggressiveness and poor prognosis of patients with thyroid cancer.

    PubMed

    Cunha, Lucas Leite; Morari, Elaine Cristina; Nonogaki, Sueli; Marcello, Marjory Alana; Soares, Fernando Augusto; Vassallo, José; Ward, Laura Sterian

    2017-02-01

    Most patients with thyroid cancer will evolve very well with current therapies. However, 10-30% of these patients will present recurrent disease and some of them will eventually die. IL-10 is an anti-inflammatory and immunosuppressive cytokine that can contribute to the immune escape of neoplastic cells. We aimed to investigate IL-10 as a molecular marker to improve the clinical management of patients with thyroid cancer. We retrospectively studied 162 patients with follicular cell-derived thyroid cancer who attended to our institution, including 63 classic papillary thyroid carcinomas, 46 follicular variant of papillary thyroid carcinomas, 11 poorly differentiated thyroid carcinomas and 42 follicular thyroid carcinomas. Patients were treated according to current guidelines and followed-up for 1-150 months. Additionally, we studied 96 samples of non-malignant tissues. We investigated the expression of IL-10 in tumor cells by semiquantitative and quantitative methods. Malignant tissues presented higher positivity (0.773 ± 0.140) than non-malignant samples (0.623 ± 0.190; p < 0.001). Tumors with extrathyroidal invasion at diagnosis presented higher levels of positivity for IL-10 (0.802 ± 0.125) than tumors without extrathyroidal invasion (0.731 ± 0.147; p = 0.004). We observed a positive correlation between tumor size and IL-10 positivity (correlation coefficient = 0.407; p < 0.001). Patients with IL-10 positivity above the median presented lower relapse-free survival rate compared to those patients whose tumors presented IL-10 positivity below the median. We suggest that a simple IL-10 IHC analysis could help selecting patients who would benefit from a more intensive approach.

  4. Genetic Variations in Mitochondria and Prostate Cancer Aggressiveness and Progression in Caucasian and African American Men

    DTIC Science & Technology

    2013-07-01

    suggested that some inherited mtDNA variants could have an adverse effect by increasing the generation of reactive oxygen species (ROS). Besides the...500 study subjects. We have not started Aim 3 yet. 15. SUBJECT TERMS Mitochondrial DNAs prostate cancer 16. SECURITY CLASSIFICATION OF: 17...6 Conclusion…………………………………………………………………………… 6 4 Introduction The mitochondrial genome is highly

  5. Molecular apocrine breast cancers are aggressive estrogen receptor negative tumors overexpressing either HER2 or GCDFP15

    PubMed Central

    2013-01-01

    Introduction Molecular apocrine (MA) tumors are estrogen receptor (ER) negative breast cancers characterized by androgen receptor (AR) expression. We analyzed a group of 58 transcriptionally defined MA tumors and proposed a new tool to identify these tumors. Methods We performed quantitative reverse transcription PCR (qRT-PCR) for ESR1, AR, FOXA1 and AR-related genes, and immunohistochemistry (IHC) for ER, PR, Human Epidermal Growth Factor Receptor 2 (HER2), CK5/6, CK17, EGFR, Ki67, AR, FOXA1 and GCDFP15 and we analyzed clinical features. Results MA tumors were all characterized by ESR1(-) AR(+) FOXA1(+) and AR-related genes positive mRNA profile. IHC staining on these tumors showed 93% ER(-), only 58% AR(+) and 90% FOXA1(+). 67% and 57% MA tumors were HER2(3+) and GCDFP15(+), respectively. Almost all MA tumors (94%) had the IHC signature HER2(3+) or GCDFP15(+) but none of the 13 control basal-like (BL) tumors did. Clinically, MA tumors were rather aggressive, with poor prognostic factors. Conclusion MA tumors could be better defined by their qRT-PCR-AR profile than by AR IHC. In addition, we found that HER2 or GCDFP15 protein overexpression is a sensitive and specific tool to differentiate MA from BL in the context of ER negative tumors. A composite molecular and IHC signature could, therefore, help to identify MA tumors in daily practice. PMID:23663520

  6. Pediatric cancer gone viral. Part II: potential clinical application of oncolytic herpes simplex virus-1 in children.

    PubMed

    Friedman, Gregory K; Beierle, Elizabeth A; Gillespie, George Yancey; Markert, James M; Waters, Alicia M; Chen, Chun-Yu; Denton, Nicholas L; Haworth, Kellie B; Hutzen, Brian; Leddon, Jennifer L; Streby, Keri A; Wang, Pin-Yi; Cripe, Timothy P

    Oncolytic engineered herpes simplex viruses (HSVs) possess many biologic and functional attributes that support their use in clinical trials in children with solid tumors. Tumor cells, in an effort to escape regulatory mechanisms that would impair their growth and progression, have removed many mechanisms that would have protected them from virus infection and eventual virus-mediated destruction. Viruses engineered to exploit this weakness, like mutant HSV, can be safely employed as tumor cell killers, since normal cells retain these antiviral strategies. Many preclinical studies and early phase trials in adults demonstrated that oncolytic HSV can be safely used and are highly effective in killing tumor cells that comprise pediatric malignancies, without generating the toxic side effects of nondiscriminatory chemotherapy or radiation therapy. A variety of engineered viruses have been developed and tested in numerous preclinical models of pediatric cancers and initial trials in patients are underway. In Part II of this review series, we examine the preclinical evidence to support the further advancement of oncolytic HSV in the pediatric population. We discuss clinical advances made to date in this emerging era of oncolytic virotherapy.

  7. Functional interaction between acyl-CoA synthetase 4, lipooxygenases and cyclooxygenase-2 in the aggressive phenotype of breast cancer cells.

    PubMed

    Maloberti, Paula M; Duarte, Alejandra B; Orlando, Ulises D; Pasqualini, María E; Solano, Angela R; López-Otín, Carlos; Podestá, Ernesto J

    2010-11-11

    The acyl-CoA synthetase 4 (ACSL4) is increased in breast cancer, colon and hepatocellular carcinoma. ACSL4 mainly esterifies arachidonic acid (AA) into arachidonoyl-CoA, reducing free AA intracellular levels, which is in contradiction with the need for AA metabolites in tumorigenesis. Therefore, the causal role of ACSL4 is still not established. This study was undertaken to determine the role of ACSL4 in AA metabolic pathway in breast cancer cells. The first novel finding is that ACSL4 regulates the expression of cyclooxygenase-2 (COX-2) and the production of prostaglandin in MDA-MB-231 cells. We also found that ACSL4 is significantly up-regulated in the highly aggressive MDA-MB-231 breast cancer cells. In terms of its overexpression and inhibition, ACSL4 plays a causal role in the control of the aggressive phenotype. These results were confirmed by the increase in the aggressive behaviour of MCF-7 cells stably transfected with a Tet-off ACSL4 vector. Concomitantly, another significant finding was that intramitochondrial AA levels are significantly higher in the aggressive cells. Thus, the esterification of AA by ACSL4 compartmentalizes the release of AA in mitochondria, a mechanism that serves to drive the specific lipooxygenase metabolization of the fatty acid. To our knowledge, this is the first report that ACSL4 expression controls both lipooxygenase and cyclooxygenase metabolism of AA. Thus, this functional interaction represents an integrated system that regulates the proliferating and metastatic potential of cancer cells. Therefore, the development of combinatory therapies that profit from the ACSL4, lipooxygenase and COX-2 synergistic action may allow for lower medication doses and avoidance of side effects.

  8. Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior.

    PubMed

    Mobley, Aaron; Zhang, Shizhen; Bondaruk, Jolanta; Wang, Yan; Majewski, Tadeusz; Caraway, Nancy P; Huang, Li; Shoshan, Einav; Velazquez-Torres, Guermarie; Nitti, Giovanni; Lee, Sangkyou; Lee, June Goo; Fuentes-Mattei, Enrique; Willis, Daniel; Zhang, Li; Guo, Charles C; Yao, Hui; Baggerly, Keith; Lotan, Yair; Lerner, Seth P; Dinney, Colin; McConkey, David; Bar-Eli, Menashe; Czerniak, Bogdan

    2017-01-19

    The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA's effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type.

  9. Aurora Kinase A is a Biomarker for Bladder Cancer Detection and Contributes to its Aggressive Behavior

    PubMed Central

    Mobley, Aaron; Zhang, Shizhen; Bondaruk, Jolanta; Wang, Yan; Majewski, Tadeusz; Caraway, Nancy P.; Huang, Li; Shoshan, Einav; Velazquez-Torres, Guermarie; Nitti, Giovanni; Lee, Sangkyou; Lee, June Goo; Fuentes-Mattei, Enrique; Willis, Daniel; Zhang, Li; Guo, Charles C.; Yao, Hui; Baggerly, Keith; Lotan, Yair; Lerner, Seth P.; Dinney, Colin; McConkey, David; Bar-Eli, Menashe; Czerniak, Bogdan

    2017-01-01

    The effects of AURKA overexpression associated with poor clinical outcomes have been attributed to increased cell cycle progression and the development of genomic instability with aneuploidy. We used RNA interference to examine the effects of AURKA overexpression in human bladder cancer cells. Knockdown had minimal effects on cell proliferation but blocked tumor cell invasion. Whole genome mRNA expression profiling identified nicotinamide N-methyltransferase (NNMT) as a downstream target that was repressed by AURKA. Chromatin immunoprecipitation and NNMT promoter luciferase assays revealed that AURKA’s effects on NNMT were caused by PAX3-mediated transcriptional repression and overexpression of NNMT blocked tumor cell invasion in vitro. Overexpression of AURKA and activation of its downstream pathway was enriched in the basal subtype in primary human tumors and was associated with poor clinical outcomes. We also show that the FISH test for the AURKA gene copy number in urine yielded a specificity of 79.7% (95% confidence interval [CI] = 74.2% to 84.1%), and a sensitivity of 79.6% (95% CI = 74.2% to 84.1%) with an AUC of 0.901 (95% CI = 0.872 to 0.928; P < 0.001). These results implicate AURKA as an effective biomarker for bladder cancer detection as well as therapeutic target especially for its basal type. PMID:28102366

  10. Mitomycin C treatment induces resistance and enhanced migration via phosphorylated Akt in aggressive lung cancer cells

    PubMed Central

    Lai, Liang-Chuan; Chuang, Eric Y.; Tsai, Mong-Hsun

    2016-01-01

    Since 1984, mitomycin C (MMC) has been applied in the treatment of non-small-cell lung cancer (NSCLC). MMC-based chemotherapeutic regimens are still under consideration owing to the efficacy and low cost as compared with other second-line regimens in patients with advanced NSCLC. Hence, it is important to investigate whether MMC induces potential negative effects in NSCLC. Here, we found that the malignant lung cancer cells, CL1-2 and CL1-5, were more resistant to MMC than were the parental CL1-0 cells and pre-malignant CL1-1 cells. CL1-2 and CL1-5 cells consistently showed lower sub-G1 fractions post MMC treatment. DNA repair-related proteins were not induced more in CL1-5 than in CL1-0 cells, but the levels of endogenous and MMC-induced phosphorylated Akt (p-Akt) were higher in CL1-5 cells. Administering a p-Akt inhibitor reduced the MMC resistance, demonstrating that p-Akt is important in the MMC resistance of CL1-5 cells. Furthermore, we revealed that cell migration was enhanced by MMC but lowered by a p-Akt inhibitor in CL1-5 cells. This study suggests that in CL1-5 cells, the activity of p-Akt, rather than DNA repair mechanisms, may underlie the resistance to MMC and enhance the cells' migration abilities after MMC treatment. PMID:27833080

  11. A novel genomic alteration of LSAMP associates with aggressive prostate cancer in African American men

    PubMed Central

    Petrovics, Gyorgy; Li, Hua; Stümpel, Tanja; Tan, Shyh-Han; Young, Denise; Katta, Shilpa; Li, Qiyuan; Ying, Kai; Klocke, Bernward; Ravindranath, Lakshmi; Kohaar, Indu; Chen, Yongmei; Ribli, Dezső; Grote, Korbinian; Zou, Hua; Cheng, Joseph; Dalgard, Clifton L.; Zhang, Shimin; Csabai, István; Kagan, Jacob; Takeda, David; Loda, Massimo; Srivastava, Sudhir; Scherf, Matthias; Seifert, Martin; Gaiser, Timo; McLeod, David G.; Szallasi, Zoltan; Ebner, Reinhard; Werner, Thomas; Sesterhenn, Isabell A.; Freedman, Matthew; Dobi, Albert; Srivastava, Shiv

    2015-01-01

    Evaluation of cancer genomes in global context is of great interest in light of changing ethnic distribution of the world population. We focused our study on men of African ancestry because of their disproportionately higher rate of prostate cancer (CaP) incidence and mortality. We present a systematic whole genome analyses, revealing alterations that differentiate African American (AA) and Caucasian American (CA) CaP genomes. We discovered a recurrent deletion on chromosome 3q13.31 centering on the LSAMP locus that was prevalent in tumors from AA men (cumulative analyses of 435 patients: whole genome sequence, 14; FISH evaluations, 101; and SNP array, 320 patients). Notably, carriers of this deletion experienced more rapid disease progression. In contrast, PTEN and ERG common driver alterations in CaP were significantly lower in AA prostate tumors compared to prostate tumors from CA. Moreover, the frequency of inter-chromosomal rearrangements was significantly higher in AA than CA tumors. These findings reveal differentially distributed somatic mutations in CaP across ancestral groups, which have implications for precision medicine strategies. PMID:26844274

  12. Posaconazole Therapeutic Drug Monitoring in Pediatrics and Young Adults with Cancer

    PubMed Central

    Bernardo, Valeria A.; Cross, Shane J.; Crews, Kristine R.; Flynn, Patricia M.; Hoffman, James M.; Knapp, Katherine M.; Pauley, Jennifer L.; Molinelli, Alejandro R.; Greene, William L.

    2015-01-01

    BACKGROUND Limited information exists regarding the use of posaconazole for treating systemic fungal infections in children, adolescent, and young adult patients with cancer. At St. Jude Children’s Research Hospital, the recommended posaconazole dose in patients less than 34 kg is 18–24 mg/kg daily given in 4 divided doses. For patients 13 years and older or those weighing 34 kg or more, the recommended dose is 800 mg daily given orally in four divided doses. OBJECTIVE This study was conducted to determine if the current posaconazole dosing guidelines achieved target posaconazole plasma concentrations of ≥ 0.7 μg/mL. METHODS We examined data from patients who received treatment-dose posaconazole with at least one posaconazole plasma concentration measurement. RESULTS Data from 33 patients who received posaconazole for the treatment of fungal infections were analyzed. The median age of patients was 11.5 years (range 0.5–23.2 years). Twenty-one patients out of 33 (63.6%) had posaconazole concentrations of ≥ 0.7 μg/mL (median 1.4 μg/mL; range 0.7–2.98 μg/mL) at the first measurement. The median posaconazole dosage referenced to total body weight in these patients was 20 mg/kg per day. Patients with concentrations < 0.7 μg/mL (median 0.4 μg/mL; range 0.025–0.69 μg/mL) received lower posaconazole dosages when referenced to body weight (median 12.9 mg/kg per day; p = 0.02). Of the 12 patients with concentrations < 0.7 μg/mL, seven (58.3%) were 13 years of age or older. CONCLUSIONS The current dosing approach for posaconazole yielded therapeutic plasma concentrations more frequently in patients < 13 than those > 13 years of age. This difference may be related to the practice of capping adolescent and young adult doses at the suggested maximum adult daily dose. Therefore, we recommend weight-based dosing in all pediatric, adolescent and young adult cancer patients with routine therapeutic drug monitoring in all patients to ensure adequate

  13. Contrast-enhanced transrectal ultrasound for prediction of prostate cancer aggressiveness: The role of normal peripheral zone time-intensity curves

    PubMed Central

    Huang, Hui; Zhu, Zheng-Qiu; Zhou, Zheng-Guo; Chen, Ling-Shan; Zhao, Ming; Zhang, Yang; Li, Hong-Bo; Yin, Li-Ping

    2016-01-01

    To assess the role of time-intensity curves (TICs) of the normal peripheral zone (PZ) in the identification of biopsy-proven prostate nodules using contrast-enhanced transrectal ultrasound (CETRUS). This study included 132 patients with 134 prostate PZ nodules. Arrival time (AT), peak intensity (PI), mean transit time (MTT), area under the curve (AUC), time from peak to one half (TPH), wash in slope (WIS) and time to peak (TTP) were analyzed using multivariate linear logistic regression and receiver operating characteristic (ROC) curves to assess whether combining nodule TICs with normal PZ TICs improved the prediction of prostate cancer (PCa) aggressiveness. The PI, AUC (p < 0.001 for both), MTT and TPH (p = 0.011 and 0.040 respectively) values of the malignant nodules were significantly higher than those of the benign nodules. Incorporating the PI and AUC values (both, p < 0.001) of the normal PZ TIC, but not the MTT and TPH values (p = 0.076 and 0.159 respectively), significantly improved the AUC for prediction of malignancy (PI: 0.784–0.923; AUC: 0.758–0.891) and assessment of cancer aggressiveness (p < 0.001). Thus, all these findings indicate that incorporating normal PZ TICs with nodule TICs in CETRUS readings can improve the diagnostic accuracy for PCa and cancer aggressiveness assessment. PMID:27929134

  14. Aggressive Behavior

    MedlinePlus

    ... Listen Español Text Size Email Print Share Aggressive Behavior Page Content Article Body My child is sometimes very aggressive. What is the best ... once they are quiet and still reinforces this behavior, so your child learns that time out means “quiet and still.” ...

  15. Calix[6]arene bypasses human pancreatic cancer aggressiveness: downregulation of receptor tyrosine kinases and induction of cell death by reticulum stress and autophagy.

    PubMed

    Pelizzaro-Rocha, Karin Juliane; de Jesus, Marcelo Bispo; Ruela-de-Sousa, Roberta Regina; Nakamura, Celso Vataru; Reis, Fabiano Souza; de Fátima, Angelo; Ferreira-Halder, Carmen Veríssima

    2013-12-01

    Pancreatic cancer ranks fourth among cancer-related causes of death in North America. Minimal progress has been made in the diagnosis and treatment of patients with late-stage tumors. Moreover, pancreatic cancer aggressiveness is closely related to high levels of pro-survival mediators, which can ultimately lead to rapid disease progression, resistance and metastasis. The main goal of this study was to define the mechanisms by which calix[6]arene, but not other calixarenes, efficiently decreases the aggressiveness of a drug resistant human pancreas carcinoma cell line (Panc-1). Calix[6]arene was more potent in reducing Panc-1 cell viability than gemcitabine and 5-fluorouracil. In relation to the underlying mechanisms of cytotoxic effects, it led to cell cycle arrest in the G0/G1 phase through downregulation of PIM1, CDK2, CDK4 and retinoblastoma proteins. Importantly, calix[6]arene abolished signal transduction of Mer and AXL tyrosine kinase receptors, both of which are usually overexpressed in pancreatic cancer. Accordingly, inhibition of PI3K and mTOR was also observed, and these proteins are positively modulated by Mer and AXL. Despite decreasing the phosphorylation of AKT at Thr308, calix[6]arene caused an increase in phosphorylation at Ser473. These findings in conjunction with increased BiP and IRE1-α provide a molecular basis explaining the capacity of calix[6]arene to trigger endoplasmic reticulum stress and autophagic cell death. Our findings highlight calix[6]arene as a potential candidate for overcoming pancreatic cancer aggressiveness. Importantly, we provide evidence that calix[6]arene affects a broad array of key targets that are usually dysfunctional in pancreatic cancer, a highly desirable characteristic for chemotherapeutics.

  16. Signaling aggression.

    PubMed

    van Staaden, Moira J; Searcy, William A; Hanlon, Roger T

    2011-01-01

    From psychological and sociological standpoints, aggression is regarded as intentional behavior aimed at inflicting pain and manifested by hostility and attacking behaviors. In contrast, biologists define aggression as behavior associated with attack or escalation toward attack, omitting any stipulation about intentions and goals. Certain animal signals are strongly associated with escalation toward attack and have the same function as physical attack in intimidating opponents and winning contests, and ethologists therefore consider them an integral part of aggressive behavior. Aggressive signals have been molded by evolution to make them ever more effective in mediating interactions between the contestants. Early theoretical analyses of aggressive signaling suggested that signals could never be honest about fighting ability or aggressive intentions because weak individuals would exaggerate such signals whenever they were effective in influencing the behavior of opponents. More recent game theory models, however, demonstrate that given the right costs and constraints, aggressive signals are both reliable about strength and intentions and effective in influencing contest outcomes. Here, we review the role of signaling in lieu of physical violence, considering threat displays from an ethological perspective as an adaptive outcome of evolutionary selection pressures. Fighting prowess is conveyed by performance signals whose production is constrained by physical ability and thus limited to just some individuals, whereas aggressive intent is encoded in strategic signals that all signalers are able to produce. We illustrate recent advances in the study of aggressive signaling with case studies of charismatic taxa that employ a range of sensory modalities, viz. visual and chemical signaling in cephalopod behavior, and indicators of aggressive intent in the territorial calls of songbirds.

  17. IGF-IR cooperates with ERα to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules

    PubMed Central

    Afratis, Nikolaos A.; Bouris, Panagiotis; Skandalis, Spyros S.; Multhaupt, Hinke A.; Couchman, John R.; Theocharis, Achilleas D.; Karamanos, Nikos K.

    2017-01-01

    IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERα-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERα signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies. PMID:28079144

  18. IGF-IR cooperates with ERα to inhibit breast cancer cell aggressiveness by regulating the expression and localisation of ECM molecules.

    PubMed

    Afratis, Nikolaos A; Bouris, Panagiotis; Skandalis, Spyros S; Multhaupt, Hinke A; Couchman, John R; Theocharis, Achilleas D; Karamanos, Nikos K

    2017-01-12

    IGF-IR is highly associated with the behaviour of breast cancer cells. In ERα-positive breast cancer, IGF-IR is present at high levels. In clinical practice, prolonged treatment with anti-estrogen agents results in resistance to the therapy with activation of alternative signaling pathways. Receptor Tyrosine Kinases, and especially IGF-IR, have crucial roles in these processes. Here, we report a nodal role of IGF-IR in the regulation of ERα-positive breast cancer cell aggressiveness and the regulation of expression levels of several extracellular matrix molecules. In particular, activation of IGF-IR, but not EGFR, in MCF-7 breast cancer cells results in the reduction of specific matrix metalloproteinases and their inhibitors. In contrast, IGF-IR inhibition leads to the depletion by endocytosis of syndecan-4. Global important changes in cell adhesion receptors, which include integrins and syndecan-4 triggered by IGF-IR inhibition, regulate adhesion and invasion. Cell function assays that were performed in MCF-7 cells as well as their ERα-suppressed counterparts indicate that ER status is a major determinant of IGF-IR regulatory role on cell adhesion and invasion. The strong inhibitory role of IGF-IR on breast cancer cells aggressiveness for which E2-ERα signaling pathway seems to be essential, highlights IGF-IR as a major molecular target for novel therapeutic strategies.

  19. The integration of psychology in pediatric oncology research and practice: collaboration to improve care and outcomes for children and families.

    PubMed

    Kazak, Anne E; Noll, Robert B

    2015-01-01

    Childhood cancers are life-threatening diseases that are universally distressing and potentially traumatic for children and their families at diagnosis, during treatment, and beyond. Dramatic improvements in survival have occurred as a result of increasingly aggressive multimodal therapies delivered in the context of clinical research trials. Nonetheless, cancers remain a leading cause of death in children, and their treatments have short- and long-term impacts on health and well-being. For over 35 years, pediatric psychologists have partnered with pediatric oncology teams to make many contributions to our understanding of the impact of cancer and its treatment on children and families and have played prominent roles in providing an understanding of treatment-related late effects and in improving quality of life. After discussing the incidence of cancer in children, its causes, and the treatment approaches to it in pediatric oncology, we present seven key contributions of psychologists to collaborative and integrated care in pediatric cancer: managing procedural pain, nausea, and other symptoms; understanding and reducing neuropsychological effects; treating children in the context of their families and other systems (social ecology); applying a developmental perspective; identifying competence and vulnerability; integrating psychological knowledge into decision making and other clinical care issues; and facilitating the transition to palliative care and bereavement. We conclude with a discussion of the current status of integrating knowledge from psychological research into practice in pediatric cancer.

  20. Children's cancer centers

    MedlinePlus

    Pediatric cancer center; Pediatric oncology center; Comprehensive cancer center ... Treating childhood cancer is not the same as treating adult cancer. The cancers are different. So are the treatments and the ...

  1. GAD1 Upregulation Programs Aggressive Features of Cancer Cell Metabolism in the Brain Metastatic Microenvironment.

    PubMed

    Schnepp, Patricia M; Lee, Dennis D; Guldner, Ian H; O'Tighearnaigh, Treasa K; Howe, Erin N; Palakurthi, Bhavana; Eckert, Kaitlyn E; Toni, Tiffany A; Ashfeld, Brandon L; Zhang, Siyuan

    2017-04-11

    The impact of altered amino acid metabolism on cancer progression is not fully understood. We hypothesized that a metabolic transcriptome shift during metastatic evolution is crucial for brain metastasis. Here we report a powerful impact in this setting caused by epigenetic upregulation of glutamate decarboxylase 1 (GAD1), a regulator of the GABA neurotransmitter metabolic pathway. In cell-based culture and brain metastasis models, we found that downegulation of the DNA methyltransferase DNMT1 induced by the brain microenvironment-derived clusterin resulted in decreased GAD1 promoter methylation and subsequent upregulation of GAD1 expression in brain metastatic tumor cells. In a system to dynamically visualize cellular metabolic responses mediated by GAD1, we monitored the cytosolic NADH:NAD+ equilibrium in tumor cells. Reducing GAD1 in metastatic cells by primary glia cell co-culture abolished the capacity of metastatic cells to utilize extracellular glutamine, leading to cytosolic accumulation of NADH and increased oxidative status. Similarly, genetic or pharmacological disruption of the GABA metabolic pathway decreased the incidence of brain metastasis in vivo. Taken together, our results show how epigenetic changes in GAD1 expression alter local glutamate metabolism in the brain metastatic microenvironment, contributing to a metabolic adaption that facilitates metastasis outgrowth in that setting.

  2. Mechanistic Insights into Molecular Targeting and Combined Modality Therapy for Aggressive, Localized Prostate Cancer

    PubMed Central

    Dal Pra, Alan; Locke, Jennifer A.; Borst, Gerben; Supiot, Stephane; Bristow, Robert G.

    2016-01-01

    Radiation therapy (RT) is one of the mainstay treatments for prostate cancer (PCa). The potentially curative approaches can provide satisfactory results for many patients with non-metastatic PCa; however, a considerable number of individuals may present disease recurrence and die from the disease. Exploiting the rich molecular biology of PCa will provide insights into how the most resistant tumor cells can be eradicated to improve treatment outcomes. Important for this biology-driven individualized treatment is a robust selection procedure. The development of predictive biomarkers for RT efficacy is therefore of utmost importance for a clinically exploitable strategy to achieve tumor-specific radiosensitization. This review highlights the current status and possible opportunities in the modulation of four key processes to enhance radiation response in PCa by targeting the: (1) androgen signaling pathway; (2) hypoxic tumor cells and regions; (3) DNA damage response (DDR) pathway; and (4) abnormal extra-/intracell signaling pathways. In addition, we discuss how and which patients should be selected for biomarker-based clinical trials exploiting and validating these targeted treatment strategies with precision RT to improve cure rates in non-indolent, localized PCa. PMID:26909338

  3. Second cancers and late toxicities after treatment of aggressive non-Hodgkin lymphoma with the ACVBP regimen: a GELA cohort study on 2837 patients.

    PubMed

    André, Marc; Mounier, Nicolas; Leleu, Xavier; Sonet, Anne; Brice, Pauline; Henry-Amar, Michel; Tilly, Hervé; Coiffier, Bertrand; Bosly, André; Morel, Pierre; Haioun, Corinne; Gaulard, Philippe; Reyes, Felix; Gisselbrecht, Christian

    2004-02-15

    The survival of patients with aggressive non-Hodgkin lymphoma (NHL) is increasing, but the incidence of secondary cancer and late toxicity is poorly defined for those treated with cyclophosphamide-hydroxydaunomycin/doxorubicin-Oncovin-prednisone (CHOP)-like chemotherapy. From February 1984 to January 1998, 2837 patients with aggressive NHL received the control-arm chemotherapy adriamycin-cyclophosphamide-vindesine-bleomycin-prednisone (ACVBP) in 3 consecutive Groupe d'Etude des Lymphomes de l'Adulte (GELA) studies. With a median follow-up time of 74 months, the 5-year overall and event-free survival rates were 60% and 52%. Two hundred two occurrences of nonneoplastic late toxicity were reported, resulting in a 5.35% cumulative probability of incidence at 7 years. Eighty-one second tumors developed, for which the 7-year cumulative incidence rate was 2.75%; 64 were solid tumors, and 17 were hematologic malignancies. In multivariate analysis, age was the only risk factor for the second development of cancer. Epidemiologic analysis allowed a comparison of this NHL group with the general population. Considering all tumors, no excess of second cancer was observed. In the male population, however, there was an excess of lung cancer (standardized incidence ratio [SIR], 2.45; P <.001) and myelodysplastic syndrome/acute myelocytic leukemia (MDS/AML) (SIR, 5.65; P =.006), and in the female population there was an excess of MDS/AML (SIR, 19.9; P <.001). With a long follow-up, the ACVBP regimen was highly effective for the treatment of aggressive NHL. Increases occurred in secondary MDS/AML and in lung cancer among men.

  4. Hypoxia-inducible factor 1 alpha is required for the tumourigenic and aggressive phenotype associated with Rab25 expression in ovarian cancer

    PubMed Central

    Gomez-Roman, Natividad; Sahasrabudhe, Neha Mohan; McGregor, Fiona; Chalmers, Anthony J.; Cassidy, Jim; Plumb, Jane

    2016-01-01

    The small GTPase Rab25 has been functionally linked to tumour progression and aggressiveness in ovarian cancer and promotes invasion in three-dimensional environments. This type of migration has been shown to require the expression of the hypoxia-inducible factor 1 alpha (HIF-1α). In this report we demonstrate that Rab25 regulates HIF-1α protein expression in an oxygen independent manner in a panel of cancer cell lines. Regulation of HIF-1α protein expression by Rab25 did not require transcriptional upregulation, but was dependent on de novo protein synthesis through the Erbb2/ERK1/2 and p70S6K/mTOR pathways. Rab25 expression induced HIF-1 transcriptional activity, increased cisplatin resistance, and conferred intraperitoneal growth to the A2780 cell line in immunocompromised mice. Targeting HIF1 activity by silencing HIF-1β re-sensitised cells to cisplatin in vitro and reduced tumour formation of A2780-Rab25 expressing cells in vivo in a mouse ovarian peritoneal carcinomatosis model. Similar effects on cisplatin resistance in vitro and intraperitoneal tumourigenesis in vivo were obtained after HIF1b knockdown in the ovarian cancer cell line SKOV3, which expresses endogenous Rab25 and HIF-1α at atmospheric oxygen concentrations. Our results suggest that Rab25 tumourigenic potential and chemoresistance relies on HIF1 activity in aggressive and metastatic ovarian cancer. Targeting HIF-1 activity may potentially be effective either alone or in combination with standard chemotherapy for aggressive metastatic ovarian cancer. PMID:26967059

  5. Association between Prostinogen (KLK15) Genetic Variants and Prostate Cancer Risk and Aggressiveness in Australia and a Meta-Analysis of GWAS Data

    PubMed Central

    Batra, Jyotsna; Lose, Felicity; O'Mara, Tracy; Marquart, Louise; Stephens, Carson; Alexander, Kimberly; Srinivasan, Srilakshmi; Eeles, Rosalind A.; Easton, Douglas F.; Olama, Ali Amin Al; Kote-Jarai, Zsofia; Guy, Michelle; Muir, Kenneth; Lophatananon, Artitaya; Rahman, Aneela A.; Neal, David E.; Hamdy, Freddie C.; Donovan, Jenny L.; Chambers, Suzanne; Gardiner, Robert A.; Aitken, Joanne; Yaxley, John; Kedda, Mary-Anne

    2011-01-01

    Background Kallikrein 15 (KLK15)/Prostinogen is a plausible candidate for prostate cancer susceptibility. Elevated KLK15 expression has been reported in prostate cancer and it has been described as an unfavorable prognostic marker for the disease. Objectives We performed a comprehensive analysis of association of variants in the KLK15 gene with prostate cancer risk and aggressiveness by genotyping tagSNPs, as well as putative functional SNPs identified by extensive bioinformatics analysis. Methods and Data Sources Twelve out of 22 SNPs, selected on the basis of linkage disequilibrium pattern, were analyzed in an Australian sample of 1,011 histologically verified prostate cancer cases and 1,405 ethnically matched controls. Replication was sought from two existing genome wide association studies (GWAS): the Cancer Genetic Markers of Susceptibility (CGEMS) project and a UK GWAS study. Results Two KLK15 SNPs, rs2659053 and rs3745522, showed evidence of association (p<0.05) but were not present on the GWAS platforms. KLK15 SNP rs2659056 was found to be associated with prostate cancer aggressiveness and showed evidence of association in a replication cohort of 5,051 patients from the UK, Australia, and the CGEMS dataset of US samples. A highly significant association with Gleason score was observed when the data was combined from these three studies with an Odds Ratio (OR) of 0.85 (95% CI = 0.77–0.93; p = 2.7×10−4). The rs2659056 SNP is predicted to alter binding of the RORalpha transcription factor, which has a role in the control of cell growth and differentiation and has been suggested to control the metastatic behavior of prostate cancer cells. Conclusions Our findings suggest a role for KLK15 genetic variation in the etiology of prostate cancer among men of European ancestry, although further studies in very large sample sets are necessary to confirm effect sizes. PMID:22132073

  6. Pediatric oncology in Turkey.

    PubMed

    Kebudi, Rejin

    2012-03-01

    The survival of children with cancer has increased dramatically in the last decades, as a result of advances in diagnosis, treatment and supportive care. Each year in Turkey, 2500-3000 new childhood cancer cases are expected. According to the Turkish Pediatric Oncology Group and Turkish Pediatric Hematology Societies Registry, about 2000 new pediatric cancer cases are reported each year. The population in Turkey is relatively young. One fourth of the population is younger than 15 years of age. According to childhood mortality, cancer is the fourth cause of death (7.2%) after infections, cardiac deaths and accidents. The major cancers in children in Turkey are leukemia (31%), lymphoma (19%), central nervous system (CNS) neoplasms (13%), neuroblastomas (7%), bone tumors (6.1%), soft tissue sarcomas (6%), followed by renal tumors, germ cell tumors, retinoblastoma, carcinomas-epithelial neoplasms, hepatic tumors and others. Lymphomas rank second in frequency as in many developing countries in contrast to West Europe or USA, where CNS neoplasms rank second in frequency. The seven-year survival rate in children with malignancies in Turkey is 65.8%. The history of modern Pediatric Oncology in Turkey dates back to the 1970's. Pediatric Oncology has been accepted as a subspecialty in Turkey since 1983. Pediatric Oncologists are all well trained and dedicated. All costs for the diagnosis and treatment of children with cancer is covered by the government. Education and infrastructure for palliative care needs improvement.

  7. CD147 and MCT1-potential partners in bladder cancer aggressiveness and cisplatin resistance.

    PubMed

    Afonso, Julieta; Santos, Lúcio L; Miranda-Gonçalves, Vera; Morais, António; Amaro, Teresina; Longatto-Filho, Adhemar; Baltazar, Fátima

    2015-11-01

    The relapsing and progressive nature of bladder tumors, and the heterogeneity in the response to cisplatin-containing regimens, are the major concerns in the care of urothelial bladder carcinoma (UBC) patients. The metabolic adaptations that alter the tumor microenvironment and thus contribute to chemoresistance have been poorly explored in UBC setting. We found significant associations between the immunoexpressions of the microenvironment-related molecules CD147, monocarboxylate transporters (MCTs) 1 and 4, CD44 and CAIX in tumor tissue sections from 114 UBC patients. The presence of MCT1 and/or MCT4 expressions was significantly associated with unfavorable clinicopathological parameters. The incidence of CD147 positive staining significantly increased with advancing stage, grade and type of lesion, and occurrence of lymphovascular invasion. Similar associations were observed when considering the concurrent expression of CD147 and MCT1. This expression profile lowered significantly the 5-year disease-free and overall survival rates. Moreover, when selecting patients who received platinum-based chemotherapy, the prognosis was significantly worse for those with MCT1 and CD147 positive tumors. CD147 specific silencing by small interfering RNAs (siRNAs) in UBC cells was accompanied by a decrease in MCT1 and MCT4 expressions and, importantly, an increase in chemosensitivity to cisplatin. Our results provide novel insights for the involvement of CD147 and MCTs in bladder cancer progression and resistance to cisplatin-based chemotherapy. We consider that the possible cooperative role of CD147 and MCT1 in determining cisplatin resistance should be further explored as a potential theranostics biomarker.

  8. Stray radiation dose and second cancer risk for a pediatric patient receiving craniospinal irradiation with proton beams

    NASA Astrophysics Data System (ADS)

    Taddei, Phillip J.; Mirkovic, Dragan; Fontenot, Jonas D.; Giebeler, Annelise; Zheng, Yuanshui; Kornguth, David; Mohan, Radhe; Newhauser, Wayne D.

    2009-04-01

    Proton beam radiotherapy unavoidably exposes healthy tissue to stray radiation emanating from the treatment unit and secondary radiation produced within the patient. These exposures provide no known benefit and may increase a patient's risk of developing a radiogenic cancer. The aims of this study were to calculate doses to major organs and tissues and to estimate second cancer risk from stray radiation following craniospinal irradiation (CSI) with proton therapy. This was accomplished using detailed Monte Carlo simulations of a passive-scattering proton treatment unit and a voxelized phantom to represent the patient. Equivalent doses, effective dose and corresponding risk for developing a fatal second cancer were calculated for a 10-year-old boy who received proton therapy. The proton treatment comprised CSI at 30.6 Gy plus a boost of 23.4 Gy to the clinical target volume. The predicted effective dose from stray radiation was 418 mSv, of which 344 mSv was from neutrons originating outside the patient; the remaining 74 mSv was caused by neutrons originating within the patient. This effective dose corresponds to an attributable lifetime risk of a fatal second cancer of 3.4%. The equivalent doses that predominated the effective dose from stray radiation were in the lungs, stomach and colon. These results establish a baseline estimate of the stray radiation dose and corresponding risk for a pediatric patient undergoing proton CSI and support the suitability of passively-scattered proton beams for the treatment of central nervous system tumors in pediatric patients.

  9. Carotenoid Intake and Adipose Tissue Carotenoid Levels in Relation to Prostate Cancer Aggressiveness among African-American and European-American Men in the North Carolina-Louisiana Prostate Cancer Project (PCaP)

    PubMed Central

    Antwi, Samuel O.; Steck, Susan E.; Su, L. Joseph; Hebert, James R.; Zhang, Hongmei; Craft, Neal E.; Fontham, Elizabeth T. H.; Smith, Gary J.; Bensen, Jeannette T.; Mohler, James L.; Arab, Lenore

    2016-01-01

    Background Associations between carotenoid intake and prostate cancer (CaP) incidence have varied across studies. This may be due to combining indolent with aggressive disease in most studies. This study examined whether carotenoid intake and adipose tissue carotenoid levels were inversely associated with CaP aggressiveness. Methods Data on African-American (AA, n=1,023) and European-American (EA, n=1,079) men with incident CaP from North Carolina and Louisiana were analyzed. Dietary carotenoid intake was assessed using a detailed food frequency questionnaire, and abdominal adipose tissue samples were analyzed for carotenoid concentrations using high-performance liquid chromatography. Multivariable logistic regression was used in race-stratified analysis to calculate odds ratios (ORs) and 95% confidence intervals (95%CI) comparing high aggressive CaP with low/intermediate aggressive CaP. Results Carotenoid intake differed significantly between AAs and EAs, which included higher intake of lycopene among EAs and higher β–cryptoxanthin intake among AAs. Comparing the highest and lowest tertiles, dietary lycopene was associated inversely with high aggressive CaP among EAs (OR=0.55, 95%CI: 0.34–0.89, Ptrend=0.02), while an inverse association was observed between dietary β–cryptoxanthin intake and high aggressive CaP among AAs (OR=0.56, 95%CI: 0.36–0.87, Ptrend=0.01). Adipose tissue α–carotene and lycopene (cis + trans) concentrations were higher among EAs than AAs, and marginally significant inverse linear trends were observed for adipose α–carotene (Ptrend=0.07) and lycopene (Ptrend=0.11), and CaP aggressiveness among EAs only. Conclusions These results suggest that diets high in lycopene and β–cryptoxanthin may protect against aggressive CaP among EAs and AAs, respectively. Differences in dietary behaviors may explain the racial differences in associations. PMID:27271547

  10. Toward the Cure of All Children With Cancer Through Collaborative Efforts: Pediatric Oncology As a Global Challenge.

    PubMed

    Rodriguez-Galindo, Carlos; Friedrich, Paola; Alcasabas, Patricia; Antillon, Federico; Banavali, Shripad; Castillo, Luis; Israels, Trijn; Jeha, Sima; Harif, Mhammed; Sullivan, Michael J; Quah, Thuan Chong; Patte, Catherine; Pui, Ching-Hon; Barr, Ronald; Gross, Thomas

    2015-09-20

    Advances in the treatment of childhood cancers have resulted in part from the development of national and international collaborative initiatives that have defined biologic determinants and generated risk-adapted therapies that maximize cure while minimizing acute and long-term effects. Currently, more than 80% of children with cancer who are treated with modern multidisciplinary treatments in developed countries are cured; however, of the approximately 160,000 children and adolescents who are diagnosed with cancer every year worldwide, 80% live in low- and middle-income countries (LMICs), where access to quality care is limited and chances of cure are low. In addition, the disease burden is not fully known because of the lack of population-based cancer registries in low-resource countries. Regional and ethnic variations in the incidence of the different childhood cancers suggest unique interactions between genetic and environmental factors that could provide opportunities for etiologic research. Regional collaborative initiatives have been developed in Central and South America and the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives integrate regional capacity building, education of health care providers, implementation of intensity-graduated treatments, and establishment of research programs that are adjusted to local capacity and local needs. Together, the existing consortia and regional networks operating in LMICs have the potential to reach out to almost 60% of all children with cancer worldwide. In summary, childhood cancer burden has been shifted toward LMICs and, for that reason, global initiatives directed at pediatric cancer care and control are needed. Regional networks aiming to build capacity while incorporating research on epidemiology, health services, and outcomes should be supported.

  11. Toward the Cure of All Children With Cancer Through Collaborative Efforts: Pediatric Oncology As a Global Challenge

    PubMed Central

    Rodriguez-Galindo, Carlos; Friedrich, Paola; Alcasabas, Patricia; Antillon, Federico; Banavali, Shripad; Castillo, Luis; Israels, Trijn; Jeha, Sima; Harif, Mhammed; Sullivan, Michael J.; Quah, Thuan Chong; Patte, Catherine; Pui, Ching-Hon; Barr, Ronald; Gross, Thomas

    2015-01-01

    Advances in the treatment of childhood cancers have resulted in part from the development of national and international collaborative initiatives that have defined biologic determinants and generated risk-adapted therapies that maximize cure while minimizing acute and long-term effects. Currently, more than 80% of children with cancer who are treated with modern multidisciplinary treatments in developed countries are cured; however, of the approximately 160,000 children and adolescents who are diagnosed with cancer every year worldwide, 80% live in low- and middle-income countries (LMICs), where access to quality care is limited and chances of cure are low. In addition, the disease burden is not fully known because of the lack of population-based cancer registries in low-resource countries. Regional and ethnic variations in the incidence of the different childhood cancers suggest unique interactions between genetic and environmental factors that could provide opportunities for etiologic research. Regional collaborative initiatives have been developed in Central and South America and the Caribbean, Africa, the Middle East, Asia, and Oceania. These initiatives integrate regional capacity building, education of health care providers, implementation of intensity-graduated treatments, and establishment of research programs that are adjusted to local capacity and local needs. Together, the existing consortia and regional networks operating in LMICs have the potential to reach out to almost 60% of all children with cancer worldwide. In summary, childhood cancer burden has been shifted toward LMICs and, for that reason, global initiatives directed at pediatric cancer care and control are needed. Regional networks aiming to build capacity while incorporating research on epidemiology, health services, and outcomes should be supported. PMID:26304881

  12. Chemotherapy-induced neutropenia among pediatric cancer patients in Egypt: Risks and consequences

    PubMed Central

    Badr, Mohamed; Hassan, Tamer; Sakr, Hanan; Karam, Nehad; Rahman, Doaa Abdel; Shahbah, Doaa; Zakaria, Marwa; Fehr, Sahbaa

    2016-01-01

    Chemotherapy-induced neutropenia (CIN) is the major dose-limiting toxicity of systemic chemotherapy and it is associated with significant morbidity, mortality and treatment cost. The aim of the present study was to identify the risk factors that may predispose pediatric cancer patients who receive myelosuppressive chemotherapy to CIN and associated sequelae. A total of 113 neutropenia episodes were analyzed and the risk factors for CIN were classified as patient-specific, disease-specific and regimen-specific, while the consequences of CIN were divided into infectious and dose-modifying sequelae. The risks and consequences were analyzed to target high-risk patients with appropriate preventive strategies. Among our patients, 28% presented with a single neutropenia attack, while 72% experienced recurrent attacks during their treatment cycles. The mean absolute neutrophil count was 225.5±128.5 ×109/l (range, 10–497 ×109/l), starting 14.2±16.3 days (range, 2–100 days) after the onset of chemotherapy and resolving within 11.2±7.3 days, either with (45.1%) or without (54.9%) granulocyte colony-stimulating factor (G-CSF). No significant association was observed between any patient characteristics or disease stage and the risk for CIN. However, certain malignancies, such as acute lymphocytic leukemia (ALL), neuroblastoma and Burkitt's lymphoma, and certain regimens, such as induction block for ALL and acute myelocytic leukemia, exerted the most potent myelotoxic effect, with severe and prolonged episodes of neutropenia. G-CSF significantly shortened the duration of the episodes and enhanced bone marrow recovery. Febrile neutropenia was the leading complication among our cases (73.5%) and was associated with several documented infections, particularly mucositis (54.9%), respiratory (45.1%), gastrointestinal tract (38.9%) and skin (23.9%) infections. A total of 6% of our patients succumbed to infection-related complications. Neutropenia was responsible for treatment

  13. Nuclear maspin expression correlates with the CpG island methylator phenotype and tumor aggressiveness in colorectal cancer.

    PubMed

    Kim, Jung Ho; Cho, Nam-Yun; Bae, Jeong Mo; Kim, Kyung-Ju; Rhee, Ye-Young; Lee, Hye Seung; Kang, Gyeong Hoon

    2015-01-01

    It has been suggested that nuclear expression of maspin (mammary serine protease inhibitor; also known as SERPINB5) in colorectal cancer (CRC) is associated with proximal colonic tumor location, mucinous and poorly differentiated histology, microsatellite instability-high (MSI-H), and poor prognosis. Based on these findings, there may be a potential association between nuclear maspin expression and the CpG island methylator phenotype (CIMP) in CRC, but no study has elucidated this issue. Here, we evaluated maspin protein expression status by immunohistochemistry in 216 MSI-H CRCs. CIMP status was also determined by methylation-specific quantitative PCR method (MethyLight) using eight CIMP markers (MLH1, NEUROG1, CRABP1, CACNA1G, CDKN2A (p16), IGF2, SOCS1, and RUNX3) in 216 MSI-H CRCs. Associations between maspin expression status and various pathological, molecular, and survival data were statistically analyzed. Among the 216 MSI-H CRCs, 111 (51%) cases presented nuclear maspin-positive tumors. Nuclear maspin-positive MSI-H CRCs were significantly associated with proximal tumor location (P = 0.003), tumor budding (P < 0.001), lymphovascular invasion (P = 0.001), perineural invasion (P = 0.008), absence of peritumoral lymphoid reaction (P = 0.045), lymph node metastasis (P = 0.003), distant metastasis (P = 0.005), advanced AJCC/UICC stage (stage III/IV) (P = 0.001), and CIMP-high (CIMP-H) status (P < 0.001). Patients with nuclear maspin-positive tumors showed worse disease-free survival than patients with nuclear maspin-negative tumors (log-rank P = 0.025). In conclusion, nuclear maspin expression is molecularly associated with CIMP-H rather than MSI-H, and clinicopathologically correlates with tumor aggressiveness in CRC.

  14. The pattern of epidermal growth factor receptor variation with disease progression and aggressiveness in colorectal cancer depends on tumor location

    PubMed Central

    PAPAGIORGIS, PETROS C.; ZIZI, ADAMANTIA E.; TSELENI, SOPHIA; OIKONOMAKIS, IOANNIS N.; NIKITEAS, NIKOLAOS I.

    2012-01-01

    The role of epidermal growth factor receptor (EGFR) in colorectal cancer (CRC) prognosis remains unclear despite the recent development of anti-EGFR treatments for metastatic disease. The heterogeneity of CRC may account for this discrepancy; proximal and distal CRC has been found to be genetically and clinicopathologically different. The aim of this study was to investigate the effect of tumor location on the association of EGFR with the conventional prognostic indicators (stage and grade) in CRC. Immunohistochemical assessment of EGFR was retrospectively performed in 119 primary CRC specimens and data were correlated with tumor stage and grade in the proximal and distal tumor subset. The molecular combination of EGFR with p53 (previously assessed in this sample) was similarly analyzed. EGFR positivity was detected in 34, 30 and 35% of the entire cohort, proximal and distal tumors, respectively. The pattern of EGFR clinicopathological correlation was found to differ by site. A reduction in the frequency of EGFR(+) with progression of stage and/or worsening of grade was observed proximally, whereas an opposite trend was recorded distally. Proximal tumors with stage I or with indolent features (stage I, well-differentiated) exhibited a significantly higher proportion of EGFR positivity than other tumors of this location (p=0.023 and p=0.022, respectively) or corresponding distal tumors (p=0.018 and p=0.035, respectively). Moreover, the co-existence of EGFR and high p53 staining (accounting for 11% of cases) was found in a significantly higher proportion of stage IV tumors compared to other stages (p=0.004), although only for the distal subset. Proximal and distal tumors showed various patterns of EGFR variation with disease progression and aggressiveness. This disparity provides further support to the hypothesis that these particular subsets of CRC are distinct tumor entities. It may also be suggestive of a potentially different therapeutic approach according to

  15. Cyr61 Is Regulated by cAMP-Dependent Protein Kinase With Serum Levels Correlating With Prostate Cancer Aggressiveness

    PubMed Central

    Terada, Naoki; Shiraishi, Takumi; Zeng, Yu; Mooney, Steven M.; Yeater, David B.; Mangold, Leslie A.; Partin, Alan W.; Kulkarni, Prakash; Getzenberg, Robert H.

    2012-01-01

    BACKGROUND Cysteine-rich angiogenic inducer 61 (Cyr61) is an extracellular matrix protein involved in the transduction of growth factor and hormone signaling. Previously, we demonstrated that Cyr61 was highly expressed in prostate cancer (PCa) but that the expression levels were associated with a lower risk of PCa recurrence. In the present study, we demonstrate that serum Cyr61 is a potential biomarker that correlates with PCa aggressiveness. Furthermore, we also explore the potential mechanism underlying the changes in Cyr61 expression during PCa progression. METHODS Cyr61 concentrations in the medium from PCa cell lines and in serum samples obtained from PCa patients were measured by sandwich ELISA. Serum Cyr61 levels were correlated with disease characteristics and the association between Cyr61 expression changes by several types of stimulation or stress and cAMP/cAMP-dependent protein kinase (PKA) pathway were examined. RESULTS There was a positive correlation between Cyr61 levels in cell supernatants and mRNA expression in these cell lines. Serum Cyr61 levels were significantly higher in non-organ-confined PCa patients (116.3 ± 140.2 ng/ml) than in organ-confined PCa patients (79.7 ± 56.1 ng/ml) (P = 0.031). Cyr61 expression was up-regulated in response to both lysophosphatidic acid and androgen treatments which promoted PCa cell invasion. Serum starvation and phosphoinositide-3-kinase inhibition also resulted in Cyr61 up-regulation; however, they suppressed cell proliferation. Cyr61 up-regulation was correlated with an increase in cAMP and suppressed by PKA inhibition. CONCLUSIONS These findings suggest that Cyr61 expression in PCa is regulated by the cAMP/PKA pathway and that circulating Cyr61 levels are a potential serum-based biomarker for characterizing PCa. PMID:22025384

  16. MiR-205 and MiR-373 Are Associated with Aggressive Human Mucinous Colorectal Cancer

    PubMed Central

    Eyking, Annette; Reis, Henning; Frank, Magdalena; Gerken, Guido; Schmid, Kurt W.; Cario, Elke

    2016-01-01

    Mucinous adenocarcinoma (MAC) represents a distinct histopathological entity of colorectal cancer (CRC), which is associated with disease progression and poor prognosis. Here, we found that expression levels of miR-205 and miR-373 were specifically upregulated only in patients with mucinous colon cancers, but not in CRC that lack mucinous components. To investigate the effects of miR-205 and miR-373 on intestinal epithelial cell (IEC) biology by gain- and loss-of-function experiments in a proof-of-concept approach, we chose previously established in-vitro human Caco-2-based models of differentiated, non-invasive (expressing TLR4 wild-type; termed Caco-2[WT]) versus undifferentiated, invasive (expressing TLR4 mutant D299G; termed Caco-2[D299G]) IEC. Enterocyte-like Caco-2[WT] showed low levels of miR-205 and miR-373 expression, while both miRNAs were significantly upregulated in colorectal carcinoma-like Caco-2[D299G], thus resembling the miRNA expression pattern of paired normal versus tumor samples from MAC patients. Using stable transfection, we generated miR-205- or miR-373-expressing and miR-205- or miR-373-inhibiting subclones of these IEC lines. We found that introduction of miR-205 into Caco-2[WT] led to expansion of mucus-secreting goblet cell-like cells, which was associated with induction of KLF4, MUC2 and TGFβ1 expression. Activation of miR-205 in Caco-2[WT] induced chemoresistance, while inhibition of miR-205 in Caco-2[D299G] promoted chemosensitivity. Caco-2[WT] overexpressing miR-373 showed mitotic abnormalities and underwent morphologic changes (loss of epithelial polarity, cytoskeletal reorganization, and junctional disruption) associated with epithelial-mesenchymal transition and progression to inflammation-associated colonic carcinoma, which correlated with induction of phosphorylated STAT3 and N-CADHERIN expression. Functionally, introduction of miR-373 into Caco-2[WT] mediated loss of cell-cell adhesion and increased proliferation and invasion

  17. Association between Plasma 25-Hydroxyvitamin D, Ancestry and Aggressive Prostate Cancer among African Americans and European Americans in PCaP

    PubMed Central

    Steck, Susan E.; Arab, Lenore; Zhang, Hongmei; Bensen, Jeannette T.; Fontham, Elizabeth T. H.; Johnson, Candace S.; Mohler, James L.; Smith, Gary J.; Su, Joseph L.; Trump, Donald L.; Woloszynska-Read, Anna

    2015-01-01

    Background African Americans (AAs) have lower circulating 25-hydroxyvitamin D3 [25(OH)D3] concentrations and higher prostate cancer (CaP) aggressiveness than other racial/ethnic groups. The purpose of the current study was to examine the relationship between plasma 25(OH)D3, African ancestry and CaP aggressiveness among AAs and European Americans (EAs). Methods Plasma 25(OH)D3 was measured using LC-MS/MS (Liquid Chromatography Tandem Mass Spectrometry) in 537 AA and 663 EA newly-diagnosed CaP patients from the North Carolina-Louisiana Prostate Cancer Project (PCaP) classified as having either ‘high’ or ‘low’ aggressive disease based on clinical stage, Gleason grade and prostate specific antigen at diagnosis. Mean plasma 25(OH)D3 concentrations were compared by proportion of African ancestry. Logistic regression was used to calculate multivariable adjusted odds ratios (OR) and 95% confidence intervals (95%CI) for high aggressive CaP by tertile of plasma 25(OH)D3. Results AAs with highest percent African ancestry (>95%) had the lowest mean plasma 25(OH)D3 concentrations. Overall, plasma 25(OH)D3 was associated positively with aggressiveness among AA men, an association that was modified by calcium intake (ORT3vs.T1: 2.23, 95%CI: 1.26–3.95 among men with low calcium intake, and ORT3vs.T1: 0.19, 95%CI: 0.05–0.70 among men with high calcium intake). Among EAs, the point estimates of the ORs were <1.0 for the upper tertiles with CIs that included the null. Conclusions Among AAs, plasma 25(OH)D3 was associated positively with CaP aggressiveness among men with low calcium intake and inversely among men with high calcium intake. The clinical significance of circulating concentrations of 25(OH)D3 and interactions with calcium intake in the AA population warrants further study. PMID:25919866

  18. Inhibition of Pediatric Glioblastoma Tumor Growth by the Anti-Cancer Agent OKN-007 in Orthotopic Mouse Xenografts

    PubMed Central

    Coutinho de Souza, Patricia; Mallory, Samantha; Smith, Nataliya; Saunders, Debra; Li, Xiao-Nan; McNall-Knapp, Rene Y.; Fung, Kar-Ming; Towner, Rheal A.

    2015-01-01

    Pediatric glioblastomas (pGBM), although rare, are one of the leading causes of cancer-related deaths in children, with tumors essentially refractory to existing treatments. Here, we describe the use of conventional and advanced in vivo magnetic resonance imaging (MRI) techniques to assess a novel orthotopic xenograft pGBM mouse (IC-3752GBM patient-derived culture) model, and to monitor the effects of the anti-cancer agent OKN-007 as an inhibitor of pGBM tumor growth. Immunohistochemistry support data is also presented for cell proliferation and tumor growth signaling. OKN-007 was found to significantly decrease tumor volumes (p<0.05) and increase animal survival (p<0.05) in all OKN-007-treated mice compared to untreated animals. In a responsive cohort of treated animals, OKN-007 was able to significantly decrease tumor volumes (p<0.0001), increase survival (p<0.001), and increase diffusion (p<0.01) and perfusion rates (p<0.05). OKN-007 also significantly reduced lipid tumor metabolism in responsive animals [(Lip1.3 and Lip0.9)-to-creatine ratio (p<0.05)], as well as significantly decrease tumor cell proliferation (p<0.05) and microvessel density (p<0.05). Furthermore, in relationship to the PDGFRα pathway, OKN-007 was able to significantly decrease SULF2 (p<0.05) and PDGFR-α (platelet-derived growth factor receptor-α) (p<0.05) immunoexpression, and significantly increase decorin expression (p<0.05) in responsive mice. This study indicates that OKN-007 may be an effective anti-cancer agent for some patients with pGBMs by inhibiting cell proliferation and angiogenesis, possibly via the PDGFRα pathway, and could be considered as an additional therapy for pediatric brain tumor patients. PMID:26248280

  19. The Quantitative Criteria Based on the Fractal Dimensions, Entropy, and Lacunarity for the Spatial Distribution of Cancer Cell Nuclei Enable Identification of Low or High Aggressive Prostate Carcinomas

    PubMed Central

    Waliszewski, Przemyslaw

    2016-01-01

    Background: Tumor grading, PSA concentration, and stage determine a risk of prostate cancer patients with accuracy of about 70%. An approach based on the fractal geometrical model was proposed to eliminate subjectivity from the evaluation of tumor aggressiveness and to improve the prediction. This study was undertaken to validate classes of equivalence for the spatial distribution of cancer cell nuclei in a larger, independent set of prostate carcinomas. Methods: The global fractal capacity D0, information D1 and correlation D2 dimension, the local fractal dimension (LFD) and the local connected fractal dimension (LCFD), Shannon entropy H and lacunarity λ were measured using computer algorithms in digitalized images of both the reference set (n = 60) and the test set (n = 208) of prostate carcinomas. Results: Prostate carcinomas were re-stratified into seven classes of equivalence. The cut-off D0-values 1.5450, 1.5820, 1.6270, 1.6490, 1.6980, 1.7640 defined the classes from C1 to C7, respectively. The other measures but the D1 failed to define the same classes of equivalence. The pairs (D0, LFD), (D0, H), (D0, λ), (D1, LFD), (D1, H), (D1, λ) characterized the spatial distribution of cancer cell nuclei in each class. The co-application of those measures enabled the subordination of prostate carcinomas to one out of three clusters associated with different tumor aggressiveness. For D0 < 1.5820, LFD < 1.3, LCFD > 1.5, H < 0.7, and λ > 0.8, the class C1 or C2 contains low complexity low aggressive carcinomas exclusively. For D0 > 1.6980, LFD > 1.7644, LCFD > 1.7051, H > 0.9, and λ < 0.7, the class C6 or C7 contains high complexity high aggressive carcinomas. Conclusions: The cut-off D0-values defining the classes of equivalence were validated in this study. The cluster analysis suggested that the number of the subjective Gleason grades and the number of the objective classes of equivalence could be decreased from seven to three without a loss of clinically

  20. Overexpression of the A Disintegrin and Metalloproteinase ADAM15 is linked to a Small but Highly Aggressive Subset of Prostate Cancers.

    PubMed

    Burdelski, Christoph; Fitzner, Michael; Hube-Magg, Claudia; Kluth, Martina; Heumann, Asmus; Simon, Ronald; Krech, Till; Clauditz, Till; Büscheck, Franziska; Steurer, Stefan; Wittmer, Corinna; Hinsch, Andrea; Luebke, Andreas M; Jacobsen, Frank; Minner, Sarah; Tsourlakis, Maria Christina; Beyer, Burkhard; Steuber, Thomas; Thederan, Imke; Sauter, Guido; Izbicki, Jakob; Schlomm, Thorsten; Wilczak, Waldemar

    2017-04-01

    The A Disintegrin and Metalloproteinase (ADAM) family of endopeptidases plays a role in many solid cancers and includes promising targets for anticancer therapies. Deregulation of ADAM15 has been linked to tumor aggressiveness and cell line studies suggest that ADAM15 overexpression may also be implicated in prostate cancer. To evaluate the impact of ADAM15 expression and its relationship with key genomic alterations, a tissue microarray containing 12,427 prostate cancers was analyzed by immunohistochemistry. ADAM15 expression was compared to phenotype, prognosis and molecular features including TMPRSS2:ERG fusion and frequent deletions involving PTEN, 3p, 5q and 6q. Normal prostate epithelium did not show ADAM15 staining. In prostate cancers, negative, weak, moderate, and strong ADAM15 staining was found in 87.7%, 3.7%, 5.6%, and 3.0% of 9826 interpretable tumors. Strong ADAM15 staining was linked to high Gleason grade, advanced pathological tumor stage, positive nodal stage and resection margin. ADAM15 overexpression was also associated with TMPRSS2:ERG fusions and PTEN deletions (P<.0001) but unrelated to deletions of 3p, 5q and 6q. In univariate analysis, high ADAM15 expression was strongly linked to PSA recurrence (P<.0001). However, in multivariate analyses this association was only maintained if the analysis was limited to preoperatively available parameters in ERG-negative cancers. The results of our study demonstrate that ADAM15 is strongly up regulated in a small but highly aggressive fraction of prostate cancers. In these tumors, ADAM15 may represent a suitable drug target. In a preoperative scenario, ADAM15 expression measurement may assist prognosis assessment, either alone or in combination with other markers.

  1. Region 2 of 8q24 is associated with the risk of aggressive prostate cancer in Caribbean men of African descent from Guadeloupe (French West Indies).

    PubMed

    Cancel-Tassin, Geraldine; Romana, Marc; Gaffory, Cecile; Blanchet, Pascal; Cussenot, Olivier; Multigner, Luc

    2015-01-01

    Multiple regions of the genome have been associated with the risk of prostate cancer in Caucasians, particularly including several polymorphisms located at 8q24. Region 2 of 8q24 has been repeatedly found to be associated with the risk of prostate cancer among men of African descent, although one study performed in the Caribbean island of Jamaica did not report this finding. In this study, the single nucleotide polymorphism rs16901979, located in region 2 of 8q24, was genotyped in 498 cases of histologically confirmed prostate cancer and 541 controls from the French Caribbean islands of Guadeloupe, where the population is largely of African descent. The AA genotype and the A allele at rs16901979 were associated with elevated risks of prostate cancer (odds ratios [ORs] = 1.84, 95% confidence interval [95% CI] = 1.26-2.69, P = 0.002 and OR = 1.36, 95% CI = 1.13-1.64, P = 0.001, respectively). Following stratification of the patients by disease aggressiveness, as defined by the Gleason score, the pooled genotypes AC + AA were associated with a higher risk of a Gleason score ≥7 at diagnosis (OR = 1.79, 95% CI = 1.17-2.73, P = 0.007). In summary, the A allele at rs16901979 was associated with the risk of prostate cancer in the Caribbean population of Guadeloupe, confirming its involvement in populations of African descent. Moreover, our study provides the first evidence of an association between this variant and the risk of aggressive prostate cancer.

  2. Pediatric Mental Health Emergencies and Special Health Care Needs

    PubMed Central

    Chun, Thomas H.; Katz, Emily R.; Duffy, Susan J.

    2013-01-01

    SYNOPSIS Children with mental health problems are increasingly being evaluated and treated by both pediatric primary care and pediatric emergency physicians. This article focuses on the epidemiology, evaluation, and management of the two most common pediatric mental health emergencies, suicidal and homicidal/aggressive patients, as well as the equally challenging population of children with autism or other developmental disabilities. PMID:24093903

  3. CREB1 directly activates the transcription of ribonucleotide reductase small subunit M2 and promotes the aggressiveness of human colorectal cancer

    PubMed Central

    Fang, Zejun; Lin, Aifen; Chen, Jiaoe; Zhang, Xiaomin; Liu, Hong; Li, Hongzhang; Hu, Yanyan; Zhang, Xia; Zhang, Jiangang; Qiu, Lanlan; Mei, Lingming; Shao, Jimin; Chen, Xiang

    2016-01-01

    As the small subunit of Ribonucleotide reductase (RR), RRM2 displays a very important role in various critical cellular processes such as cell proliferation, DNA repair, and senescence, etc. Importantly, RRM2 functions like a tumor driver in most types of cancer but little is known about the regulatory mechanism of RRM2 in cancer development. In this study, we found that the cAMP responsive element binding protein 1 (CREB1) acted as a transcription factor of RRM2 gene in human colorectal cancer (CRC). CREB1 directly bound to the promoter of RRM2 gene and induced its transcriptional activation. Knockdown of CREB1 decreased the expression of RRM2 at both mRNA and protein levels. Moreover, knockdown of RRM2 attenuated CREB1-induced aggressive phenotypes of CRC cells in vitro and in vivo. Analysis of the data from TCGA database and clinical CRC specimens with immunohistochemical staining also demonstrated a strong correlation between the co-expression of CREB1 and RRM2. Decreased disease survivals were observed in CRC patients with high expression levels of CREB1 or RRM2. Our results indicate CREB1 as a critical transcription factor of RRM2 which promotes tumor aggressiveness, and imply a significant correlation between CREB1 and RRM2 in CRC specimens. These may provide the possibility that CREB1 and RRM2 could be used as biomarkers or targets for CRC diagnosis and treatment. PMID:27801665

  4. Preclinical Development of Novel Rac1-GEF Signaling Inhibitors using a Rational Design Approach in Highly Aggressive Breast Cancer Cell Lines

    PubMed Central

    Cardama, Georgina A; Comin, Maria J; Hornos, Leandro; Gonzalez, Nazareno; Defelipe, Lucas; Turjanski, Adrian G; Alonso, Daniel F; Gomez, Daniel E; Menna, Pablo Lorenzano

    2014-01-01

    Rho GTPases play a key role in the regulation of multiple essential cellular processes, including actin dynamics, gene transcription and cell cycle progression. Aberrant activation of Rac1, a member of Rho family of small GTPases, is associated with tumorigenesis, cancer progression, invasion and metastasis. Particularly, Rac1 is overexpressed and hyperactivated in highly aggressive breast cancer. Thus, Rac1 appears to be a promising and relevant target for the development of novel anticancer drugs. We identified the novel Rac1 inhibitor ZINC69391 through a docking-based virtual library screening targeting Rac1 activation by GEFs. This compound was able to block Rac1 interaction with its GEF Tiam1, prevented EGF-induced Rac1 activation and inhibited cell proliferation, cell migration and cell cycle progression in highly aggressive breast cancer cell lines. Moreover, ZINC69391 showed an in vivo antimetastatic effect in a syngeneic animal model. We further developed the novel analog 1A-116 by rational design and showed to be specific and more potent than the parental compound in vitro and interfered Rac1-P-Rex1 interaction. We also showed an enhanced in vivo potency of 1A-116 analog. These results show that we have developed novel Rac1 inhibitors that may be used as a novel anticancer therapy. PMID:24066799

  5. DLX1 acts as a crucial target of FOXM1 to promote ovarian cancer aggressiveness by enhancing TGF-β/SMAD4 signaling

    PubMed Central

    Chan, D W; Hui, W W Y; Wang, J J; Yung, M M H; Hui, L M N; Qin, Y; Liang, R R; Leung, T H Y; Xu, D; Chan, K K L; Yao, K-M; Tsang, B K; Ngan, H Y S

    2017-01-01

    Recent evidence from a comprehensive genome analysis and functional studies have revealed that FOXM1 is a crucial metastatic regulator that drives cancer progression. However, the regulatory mechanism by which FOXM1 exerts its metastatic functions in cancer cells remains obscure. Here, we report that DLX1 acts as a FOXM1 downstream target, exerting pro-metastatic function in ovarian cancers. Both FOXM1 isoforms (FOXM1B or FOXM1C) could transcriptionally upregulate DLX1 through two conserved binding sites, located at +61 to +69bp downstream (TFBS1) and −675 to −667bp upstream (TFBS2) of the DLX1 promoter, respectively. This regulation was further accentuated by the significant correlation between the nuclear expression of FOXM1 and DLX1 in high-grade serous ovarian cancers. Functionally, the ectopic expression of DLX1 promoted ovarian cancer cell growth, cell migration/invasion and intraperitoneal dissemination of ovarian cancer in mice, whereas small interfering RNA-mediated DLX1 knockdown in FOXM1-overexpressing ovarian cancer cells abrogated these oncogenic capacities. In contrast, depletion of FOXM1 by shRNAi only partially attenuated tumor growth and exerted almost no effect on cell migration/invasion and the intraperitoneal dissemination of DLX1-overexpressing ovarian cancer cells. Furthermore, the mechanistic studies showed that DLX1 positively modulates transforming growth factor-β (TGF-β) signaling by upregulating PAI-1 and JUNB through direct interaction with SMAD4 in the nucleus upon TGF-β1 induction. Taken together, these data strongly suggest that DLX1 has a pivotal role in FOXM1 signaling to promote cancer aggressiveness through intensifying TGF-β/SMAD4 signaling in high-grade serous ovarian cancer cells. PMID:27593933

  6. Simulation of Post-Thyroidectomy Treatment Alternatives for Triiodothyronine or Thyroxine Replacement in Pediatric Thyroid Cancer Patients

    PubMed Central

    Ben-Shachar, Rotem; Huang, Stephen A.; DiStefano, Joseph J.

    2012-01-01

    Background As in adults, thyroidectomy in pediatric patients with differentiated thyroid cancer is often followed by 131I remnant ablation. A standard protocol is to give normalizing oral thyroxine (T4) or triiodothyronine (T3) after surgery and then withdraw it for 2 to 6 weeks. Thyroid remnants or metastases are treated most effectively when serum thyrotropin (TSH) is high, but prolonged withdrawals should be avoided to minimize hypothyroid morbidity. Methods A published feedback control system model of adult human thyroid hormone regulation was modified for children using pediatric T4 kinetic data. The child model was developed from data for patients ranging from 3 to 9 years old. We simulated a range of T4 and T3 replacement protocols for children, exploring alternative regimens for minimizing the withdrawal period, while maintaining normal or suppressed TSH during replacement. The results are presented with the intent of providing a quantitative basis to guide further studies of pediatric treatment options. Replacement was simulated for up to 3 weeks post-thyroidectomy, followed by various withdrawal periods. T4 vs. T3 replacement, remnant size, dose size, and dose frequency were tested for effects on the time for TSH to reach 25 mU/L (withdrawal period). Results For both T3 and T4 replacement, higher doses were associated with longer withdrawal periods. T3 replacement yielded shorter withdrawal periods than T4 replacement (up to 3.5 days versus 7–10 days). Higher than normal serum T3 concentrations were required to normalize or suppress TSH during T3 monotherapy, but not T4 monotherapy. Larger remnant sizes resulted in longer withdrawal periods if T4 replacement was used, but had little effect for T3 replacement. Conclusions T3 replacement yielded withdrawal periods about half those for T4 replacement. Higher than normal hormone levels under T3 monotherapy can be partially alleviated by more frequent, smaller doses (e.g., twice a day). LT4 may be the

  7. The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease

    PubMed Central

    Jeong, Phildu; Kim, Seon-Kyu; Kim, Seon-Young; Yan, Chunri; Seo, Sung Phil; Lee, Sang Keun; Kim, Jayoung; Kim, Wun-Jae

    2015-01-01

    Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients. PMID:26225770

  8. The c-MET Network as Novel Prognostic Marker for Predicting Bladder Cancer Patients with an Increased Risk of Developing Aggressive Disease.

    PubMed

    Kim, Young-Won; Yun, Seok Joong; Jeong, Phildu; Kim, Seon-Kyu; Kim, Seon-Young; Yan, Chunri; Seo, Sung Phil; Lee, Sang Keun; Kim, Jayoung; Kim, Wun-Jae

    2015-01-01

    Previous studies have shown that c-MET is overexpressed in cases of aggressive bladder cancer (BCa). Identification of crosstalk between c-MET and other RTKs such as AXL and PDGFR suggest that c-MET network genes (c-MET-AXL-PDGFR) may be clinically relevant to BCa. Here, we examine whether expression of c-MET network genes can be used to identify BCa patients at increased risk of developing aggressive disease. In vitro analysis, c-MET knockdown suppressed cell proliferation, invasion, and migration, and increased sensitivity to cisplatin-induced apoptosis. In addition, c-MET network gene (c-MET, AXL, and PDGFR) expression allowed discrimination of BCa tissues from normal control tissues and appeared to predict poor disease progression in non-muscle invasive BCa patients and poor overall survival in muscle invasive BCa patients. These results suggest that c-MET network gene expression is a novel prognostic marker for predicting which BCa patients have an increased risk of developing aggressive disease. These genes might be a useful marker for co-targeting therapy, and are expected to play an important role in improving both response to treatment and survival of BCa patients.

  9. Taurolidine-citrate lock solution (TauroLock) significantly reduces CVAD-associated grampositive infections in pediatric cancer patients

    PubMed Central

    Simon, Arne; Ammann, Roland A; Wiszniewsky, Gertrud; Bode, Udo; Fleischhack, Gudrun; Besuden, Mette M

    2008-01-01

    Background Taurolidin/Citrate (TauroLock™), a lock solution with broad spectrum antimicrobial activity, may prevent bloodstream infection (BSI) due to coagulase-negative staphylococci (CoNS or 'MRSE' in case of methicillin-resistant isolates) in pediatric cancer patients with a long term central venous access device (CVAD, Port- or/Broviac-/Hickman-catheter type). Methods In a single center prospective 48-months cohort study we compared all patients receiving anticancer chemotherapy from April 2003 to March 2005 (group 1, heparin lock with 200 IU/ml sterile normal saline 0.9%; Canusal® Wockhardt UK Ltd, Wrexham, Wales) and all patients from April 2005 to March 2007 (group 2; taurolidine 1.35%/Sodium Citrate 4%; TauroLock™, Tauropharm, Waldbüttelbrunn, Germany). Results In group 1 (heparin), 90 patients had 98 CVAD in use during the surveillance period. 14 of 30 (47%) BSI were 'primary Gram positive BSI due to CoNS (n = 4) or MRSE (n = 10)' [incidence density (ID); 2.30 per 1000 inpatient CVAD-utilization days]. In group 2 (TauroLock™), 89 patients had 95 CVAD in use during the surveillance period. 3 of 25 (12%) BSI were caused by CoNS. (ID, 0.45). The difference in the ID between the two groups was statistically significant (P = 0.004). Conclusion The use of Taurolidin/Citrate (TauroLock™) significantly reduced the number and incidence density of primary catheter-associated BSI due to CoNS and MRSE in pediatric cancer patients. PMID:18664278

  10. A feasibility study for enrichment of highly-aggressive cancer subpopulations by their biophysical properties via dielectrophoresis enhanced with synergistic fluid flow.

    PubMed

    Douglas, Temple Anne; Cemazar, Jaka; Balani, Nikita; Sweeney, Daniel C; Schmelz, Eva M; Davalos, Rafael V

    2017-03-25

    A common problem with cancer treatment is the development of treatment resistance and tumor recurrence that result from treatments that kill most tumor cells yet leave behind aggressive cells to repopulate. Presented here is a microfluidic device that can be used to isolate tumor subpopulations to optimize treatment selection. Dielectrophoresis (DEP) is a phenomenon where particles are polarized by an electric field and move along the electric field gradient. Different cell subpopulations have different DEP responses depending on their bioelectrical phenotype, which, we hypothesize, correlate with aggressiveness. We have designed a microfluidic device in which a region containing posts locally distorts channel of the electric field created by an AC voltage across a microfluidic channel and which forces cells toward the posts through DEP. This force is balanced with a simultaneous drag force from fluid motion that pulls cells away from the posts. We have shown that by adjusting the drag force, cells with aggressive phenotypes are influenced more by the DEP force and trap on posts while others flow through the chip unaffected. Utilizing single-cell trapping on cell-sized posts by a drag-DEP force balance, we show that separation of very similar cell subpopulations may be achieved, a result that was previously impossible with DEP alone. Separated subpopulations maintain high viability downstream, and remain in a native state, without fluorescent labeling. These cells can then be cultured to help select a therapy that kills aggressive subpopulations equally or better than the bulk of the tumor, mitigating resistance and recurrence. This article is protected by copyright. All rights reserved.

  11. Dietary, Supplement, and Adipose Tissue Tocopherols Levels in Relation to Prostate Cancer Aggressiveness Among African and European Americans: The North Carolina-Louisiana Prostate Cancer Project (PCaP)

    PubMed Central

    Antwi, Samuel; Steck, Susan E.; Su, L. Joseph; Hebert, James R.; Zhang, Hongmei; Fontham, Elizabeth T. H.; Smith, Gary; Bensen, Jeannette T.; Mohler, James L.; Arab, Lenore

    2016-01-01

    Background Controversies remain over the safety and efficacy of vitamin E (i.e., α–tocopherol) supplementation use for the prevention of prostate cancer (CaP); however, associations of different tocopherol forms and CaP aggressiveness have yet to be examined. Methods This study examined whether food intake of tocopherols, vitamin E supplement use, and adipose tissue biomarkers of tocopherol were associated with CaP aggressiveness among African-American (AA, n=1,023) and European-American (EA, n=1,079) men diagnosed with incident CaP. Dietary tocopherols were estimated from a food frequency questionnaire, supplement use from questionnaire/inventory, and biomarkers from abdominal adipose samples measured using high-performance liquid chromatography. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were estimated from logistic regression comparing high aggressive CaP to low/intermediate aggressive CaP, adjusting for covariates. Results Dietary intakes of α-and δ-tocopherol were related inversely to CaP aggressiveness among EAs [OR (95% CI), highest versus lowest quartile: α-tocopherol, 0.34 (0.17–0.69), Ptrend = 0.006; δ-tocopherol, 0.45 (0.21–0.95) Ptrend = 0.007]. Inverse associations between dietary and supplemental α-tocopherol and CaP aggressiveness were observed among AAs, though these did not reach statistical significance [OR (95% CI), highest versus lowest quartile: dietary α-tocopherol, 0.58 (0.28–1.19), Ptrend = 0.20; supplemental α-tocopherol, 0.64 (0.31–1.21) Ptrend = 0.15]. No significant association was observed between adipose tocopherol levels and CaP aggressiveness [OR (95% CI), highest versus lowest quartiles of α-tocopherol for EAs 1.43 (0.66–3.11) and AAs 0.66 (0.27–1.62)]. Conclusions The inverse associations observed between dietary sources of tocopherols and CaP aggressiveness suggests a beneficial role of food sources of these tocopherols in CaP aggressiveness. PMID:26053590

  12. Inherited Disorders as a Risk Factor and Predictor of Neurodevelopmental Outcome in Pediatric Cancer

    ERIC Educational Resources Information Center

    Ullrich, Nicole J.

    2008-01-01

    Each year in the United States, an average of one to two children per 10,000 develop cancer. The etiology of most childhood cancer remains largely unknown but is likely attributable to random or induced genetic aberrations in somatic tissue. However, a subset of children develops cancer in the setting of an underlying inheritable condition…

  13. Breast Cancer Cell-Derived GM-CSF Licenses Regulatory Th2 Induction by Plasmacytoid Predendritic Cells in Aggressive Disease Subtypes.

    PubMed

    Ghirelli, Cristina; Reyal, Fabien; Jeanmougin, Marine; Zollinger, Raphaël; Sirven, Philémon; Michea, Paula; Caux, Christophe; Bendriss-Vermare, Nathalie; Donnadieu, Marie-Hélène; Caly, Martial; Fourchotte, Virginie; Vincent-Salomon, Anne; Sigal-Zafrani, Brigitte; Sastre-Garau, Xavier; Soumelis, Vassili

    2015-07-15

    Reciprocal interactions between tumor cells and their microenvironment vitally impact tumor progression. In this study, we show that GM-CSF produced by primary breast tumor cells induced the activation of plasmacytoid predendritic cells (pDC), a cell type critical to anti-viral immunity. pDC that expressed the GM-CSF receptor were increased in breast tumors compared with noninvolved adjacent breast tissue. Tumor-activated pDC acquired naïve CD4(+) T-cell stimulatory capacity and promoted a regulatory Th2 response. Finally, the concomitant increase of GM-CSF and pDC was significantly associated with relatively more aggressive breast cancer subtypes. Our results characterize the first tumor-derived factor that can activate pDC to promote a regulatory Th2 response, with implications for therapeutic targeting of a tumor-immune axis of growing recognition in its significance to cancer.

  14. Divergent in vitro/in vivo responses to drug treatments of highly aggressive NIH-Ras cancer cells: a PET imaging and metabolomics-mass-spectrometry study

    PubMed Central

    Gaglio, Daniela; Valtorta, Silvia; Ripamonti, Marilena; Bonanomi, Marcella; Damiani, Chiara; Todde, Sergio; Negri, Alfredo Simone; Sanvito, Francesca; Mastroianni, Fabrizia; Campli, Antonella Di; Turacchio, Gabriele; Di Grigoli, Giuseppe; Belloli, Sara; Luini, Alberto; Gilardi, Maria Carla; Colangelo, Anna Maria

    2016-01-01

    Oncogenic K-ras is capable to control tumor growth and progression by rewiring cancer metabolism. In vitro NIH-Ras cells convert glucose to lactate and use glutamine to sustain anabolic processes, but their in vivo environmental adaptation and multiple metabolic pathways activation ability is poorly understood. Here, we show that NIH-Ras cancer cells and tumors are able to coordinate nutrient utilization to support aggressive cell proliferation and survival. Using PET imaging and metabolomics-mass spectrometry, we identified the activation of multiple metabolic pathways such as: glycolysis, autophagy recycling mechanism, glutamine and serine/glycine metabolism, both under physiological and under stress conditions. Finally, differential responses between in vitro and in vivo systems emphasize the advantageous and uncontrolled nature of the in vivo environment, which has a pivotal role in controlling the responses to therapy. PMID:27409831

  15. Meta-analysis of gene expression studies in endometrial cancer identifies gene expression profiles associated with aggressive disease and patient outcome

    PubMed Central

    O’Mara, Tracy A.; Zhao, Min; Spurdle, Amanda B.

    2016-01-01

    Although endometrioid endometrial cancer (EEC; comprising ~80% of all endometrial cancers diagnosed) is typically associated with favourable patient outcome, a significant portion (~20%) of women with this subtype will relapse. We hypothesised that gene expression predictors of the more aggressive non-endometrioid endometrial cancers (NEEC) could be used to predict EEC patients with poor prognosis. To explore this hypothesis, we performed meta-analysis of 12 gene expression microarray studies followed by validation using RNA-Seq data from The Cancer Genome Atlas (TCGA) and identified 1,253 genes differentially expressed between EEC and NEEC. Analysis found 121 genes were associated with poor outcome among EEC patients. Forward selection likelihood-based modelling identified a 9-gene signature associated with EEC outcome in our discovery RNA-Seq dataset which remained significant after adjustment for clinical covariates, but was not significant in a smaller RNA-Seq dataset. Our study demonstrates the value of employing meta-analysis to improve the power of gene expression microarray data, and highlight genes and molecular pathways of importance for endometrial cancer therapy. PMID:27830726

  16. Expression and/or activity of the SVCT2 ascorbate transporter may be decreased in many aggressive cancers, suggesting potential utility for sodium bicarbonate and dehydroascorbic acid in cancer therapy.

    PubMed

    McCarty, Mark F

    2013-10-01

    Hypoxia-inducible factor-1 (HIF-1) is a heterodimer transcription factor whose elevated activity in many cancers helps them to survive under hypoxic conditions and enhances their capacity to grow invasively, establish metastases, and survive chemo- or radiotherapy. Optimal intracellular levels of ascorbate suppress the level and transcriptional activity of HIF-1under normoxic or mildly hypoxic conditions by supporting the activity of proly and asparagyl hydroxylases that target HIF-1alpha. High intracellular ascorbate can also work in various ways to down-regulate activation of NF-kappaB which, like HIF-1 is constitutively active in many cancers and promotes aggressive behavior - in part by promoting transcription of HIF-1alpha. Yet recent evidence suggests that, even in the context of adequate ascorbate nutrition, the intracellular ascorbate content of many aggressive cancers may be supoptimal for effective HIF-1 control. This likely reflects low expression or activity of the SVCT2 ascorbate transporter. The expression of SVCT2 in cancers has so far received little study; but the extracellular acidity characteristic of many tumors would be expected to reduce the activity of this transporter, which has a mildly alkaline pH optimum. Unfortunately, since SVCT2 has a high affinity for ascorbate, and its activity is nearly saturated at normal healthy serum levels of this vitamin, increased oral administration of ascorbate would be unlikely to have much impact on the intracellular ascorbate content of tumors. However, cancers in which HIF-1 is active express high levels of glucose transporters such as GLUT-1, and these transporters can promote influx of dehydroascorbic acid (DHA) via facilitated diffusion; once inside the cell, DHA is rapidly reduced to ascorbate, which effectively is "trapped" within the cell. Hence, episodic intravenous infusions of modest doses of DHA may have potential for optimizing the intracellular ascorbate content of cancers, potentially

  17. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation.

    PubMed

    Deshmukh, Sachin K; Srivastava, Sanjeev K; Bhardwaj, Arun; Singh, Ajay P; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L; Dal Zotto, Valeria; Carter, James E; Singh, Seema

    2015-05-10

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity.

  18. Resistin and interleukin-6 exhibit racially-disparate expression in breast cancer patients, display molecular association and promote growth and aggressiveness of tumor cells through STAT3 activation

    PubMed Central

    Bhardwaj, Arun; Singh, Ajay P.; Tyagi, Nikhil; Marimuthu, Saravanakumar; Dyess, Donna L.; Zotto, Valeria Dal; Carter, James E.; Singh, Seema

    2015-01-01

    African-American (AA) women with breast cancer (BC) are diagnosed with more aggressive disease, have higher risk of recurrence and poorer prognosis as compared to Caucasian American (CA) women. Therefore, it is imperative to define the factors associated with such disparities to reduce the unequal burden of cancer. Emerging data suggest that inherent differences exist in the tumor microenvironment of AA and CA BC patients, however, its molecular bases and functional impact have remained poorly understood. Here, we conducted cytokine profiling in serum samples from AA and CA BC patients and identified resistin and IL-6 to be the most differentially-expressed cytokines with relative greater expression in AA patients. Resistin and IL-6 exhibited positive correlation in serum levels and treatment of BC cells with resistin led to enhanced production of IL-6. Moreover, resistin also enhanced the expression and phosphorylation of STAT3, and treatment of BC cells with IL-6-neutralizing antibody prior to resistin stimulation abolished STAT3 phosphorylation. In addition, resistin promoted growth and aggressiveness of BC cells, and these effects were mediated through STAT3 activation. Together, these findings suggest a crucial role of resistin, IL-6 and STAT3 in BC racial disparity. PMID:25868978

  19. Gankyrin sustains PI3K/GSK-3β/β-catenin signal activation and promotes colorectal cancer aggressiveness and progression

    PubMed Central

    Wu, Qianlong; Zhang, Tong; Wang, Chengxing; Wei, Jianchang; Chen, Zhuanpeng; Hu, He; Li, Wanglin; Cao, Jie

    2016-01-01

    High levels of angiogenesis, metastasis and chemoresistance are major clinical features of colorectal cancer (CRC), a lethal disease with a high incidence worldwide. Aberrant activation of Wnt/β-catenin pathway contributes to CRC progression. However, little is known about regulatory mechanisms of the β-catenin activity in cancer progression. Here we report that Gankyrin was markedly upregulated in primary tumor tissues from CRC patients and was associated with poor survival. Moreover, we demonstrated that overexpressing Gankyrin promoted, while knockdown of Gankyrin impaired, the aggressive phenotype of proliferation, angiogenesis, chemoresistance and metastasis of CRC cells both in vitro and in vivo. Importantly, we found a unique molecular mechanism of Gankyrin in CRC cells signaling transduction, that regulated the cross-talk between PI3K/Akt and Wnt/β-catenin signaling pathways, sustaining PI3K/GSK-3β/β-catenin signal activation in CRC. Therefore, these findings not only reveal a mechanism that promotes aggressiveness and progression in CRC, but also provide insight into novel molecular targets for antitumor therapy in CRCs. PMID:27835604

  20. Brief Report: Children's Response to Serious Illness: Perceptions of Benefit and Burden in a Pediatric Cancer Population

    PubMed Central

    Currier, Joseph M.; Hermes, Susan

    2009-01-01

    Objective To examine a revised measure of benefit finding for children, in relation to perceptions of illness-related burden, and other measures of child psychological functioning. Methods A sample of 78 children with cancer completed the newly revised Benefit/Burden Scale for Children (BBSC) and measures of optimism/pessimism, positive/negative affect, anxiety and defensiveness. Results Factor analysis of the BBSC revealed a clear two-factor solution, with benefit finding and illness-related burden representing orthogonal factors. Both scales were internally consistent and demonstrated different patterns of correlation with the other measures assessed in the study. Conclusion The BBSC is internally reliable and preliminary data supports the validity of separate benefit and burden constructs. Children report positive and negative aspects of their illness simultaneously, and perceptions of benefit and burden function as independent constructs. The BBSC is a useful measure for pediatric cancer patients that could be applied to children experiencing other significant life events. PMID:19342537

  1. Vitamin D, Vitamin D Receptor Polymorphisms and Breast Cancer Aggressiveness in African American and European American Women

    DTIC Science & Technology

    2011-05-01

    successfully funded by NCI (P01 CA151135, PIs: Ambrosone, Palmer, Millikan ). CONCLUSION To conclude, we found premenopausal women with cancer of...e1000279. 15. Millikan RC, Newman B, Tse CK, Moorman PG, Conway K, et al. (2008) Epidemiology of basal-like breast cancer. Breast Cancer Res Treat

  2. Genetic variants in ATP6 and ND3 mitochondrial genes are not associated with aggressive prostate cancer in Mexican-Mestizo men with overweight or obesity.

    PubMed

    Canto, Patricia; Benítez Granados, Jesús; Martínez Ramírez, Mónica Adriana; Reyes, Edgardo; Feria-Bernal, Guillermo; García-García, Eduardo; Tejeda, María Elena; Zavala, Esperanza; Tapia, André; Rojano-Mejía, David; Méndez, Juan Pablo

    2016-09-01

    Mitochondrial defects have been related to obesity and prostate cancer. We investigated if Mexican-Mestizo men presenting this type of cancer, exhibited somatic mutations of ATP6 and/or ND3.Body mass index (BMI) was determined; the degree of prostate cancer aggressiveness was demarcated by the Gleason score. DNA from tumor tissue and from blood leukocytes was amplified by the polymerase chain reaction and ATP6 and ND3 were sequenced. We included 77 men: 20 had normal BMI, 38 were overweight and 19 had obesity; ages ranged from 52 to 83. After sequencing ATP6 and ND3, from DNA obtained from leukocytes and tumor tissue, we did not find any somatic mutations. All changes observed, in both genes, were polymorphisms. In ATP6 we identified, in six patients, two non-synonymous nucleotide changes and in ND3 we observed that twelve patients presented non-synonymous polymorphisms. To our knowledge, this constitutes the first report where the complete sequences of the ATP6 and ND3 have been analyzed in Mexican-Mestizo men with prostate cancer and diverse BMI. Our results differ with those reported in Caucasian populations, possibly due to ethnic differences.

  3. Biochemical and Genetic Markers in Aggressiveness and Recurrence of Prostate Cancer: Race-Specific Links to Inflammation and Insulin Resistance

    DTIC Science & Technology

    2013-07-01

    which are also risk factors for PCa in this racial group [9, 10]. The proposed studies will test the hypothesis that specific biochemical and genetic ...on the hypothesis that specific biochemical and genetic factors contribute to racial/ethnic disparity in aggressiveness and recurrence of PCa. Our... determine if there are differences in single nucleotide polymorphisms (SNPs) in selected candidate genes implicated in metabolic syndrome, obesity, chronic

  4. Effects of Honey on Oral Mucositis among Pediatric Cancer Patients Undergoing Chemo/Radiotherapy Treatment at King Abdulaziz University Hospital in Jeddah, Kingdom of Saudi Arabia

    PubMed Central

    Al Jaouni, Soad K.; Al Muhayawi, Mohammad S.; Hussein, Abear; Elfiki, Iman; Al-Raddadi, Rajaa; Al Muhayawi, Saad M.; Almasaudi, Saad

    2017-01-01

    One of the most common complications of cancer chemotherapy is oral mucositis. This study evaluates the therapeutic effects of honey with the focus on grade III and IV oral mucositis, reduction of bacterial and fungal infections, duration of episodes of oral mucositis, and body weight in pediatric leukemic patients undergoing chemo/radiotherapy. This is an open labeled randomized controlled study conducted at our hospital on 40 pediatric cancer patients undergoing chemo/radiotherapy. All the 40 patients included in this study experienced a sum total of 390 episodes of fever and neutropenia associated with oral mucositis. A significant reduction of oral mucositis, associated Candida, and aerobic pathogenic bacterial infections was noted in patients in the honey treatment group. Also, there is a significant decrease in the duration of hospitalization for all those in the treatment group combined with a significant increase of body weight, delayed onset, and decreased severity of pain related to oral mucositis. Complications of oral mucositis can be tremendously reduced by the topical application of local Saudi honey and honey should be used as an integrative approach in prophylaxis and treatment of chemo/radiotherapy-induced oral mucositis in pediatric cancer patients. Further research is needed to elucidate and better understand the underlying mechanism. PMID:28270852

  5. Cholesteryl Ester Accumulation Induced by PTEN Loss and PI3K/AKT Activation Underlies Human Prostate Cancer Aggressiveness

    PubMed Central

    Yue, Shuhua; Li, Junjie; Lee, Seung-Young; Lee, Hyeon Jeong; Shao, Tian; Song, Bing; Cheng, Liang; Masterson, Timothy A.; Liu, Xiaoqi; Ratliff, Timothy L.; Cheng, Ji-Xin

    2014-01-01

    Summary Altered lipid metabolism is increasingly recognized as a signature of cancer cells. Enabled by label-free Raman spectromicroscopy, we performed quantitative analysis of lipogenesis at single cell level in human patient cancerous tissues. Our imaging data revealed an unexpected, aberrant accumulation of esterified cholesterol in lipid droplets of high-grade prostate cancer and metastases. Biochemical study showed that such cholesteryl ester accumulation was a consequence of loss of tumor suppressor PTEN and subsequent activation of PI3K/AKT pathway in prostate cancer cells. Furthermore, we found that such accumulation arose from significantly enhanced uptake of exogenous lipoproteins and required cholesterol esterification. Depletion of cholesteryl ester storage significantly reduced cancer proliferation, impaired cancer invasion capability, and suppressed tumor growth in mouse xenograft models with negligible toxicity. These findings open opportunities for diagnosing and treating prostate cancer by targeting the altered cholesterol metabolism. PMID:24606897

  6. The in vitro and vivo effects of nuclear and cytosolic parafibromin expression on the aggressive phenotypes of colorectal cancer cells: a search of potential gene therapy target.

    PubMed

    Zheng, Hua-Chuan; Liu, Jia-Jie; Li, Jing; Wu, Ji-Cheng; Yang, Lei; Zhao, Gui-Feng; Zhao, Xin; Jiang, Hua-Mao; Huang, Ke-Qiang; Li, Zhi-Jie

    2017-02-16

    Down-regulated parafibromin is positively linked to the pathogenesis of parathyroid, lung, breast, ovarian, gastric and colorectal cancers. Here, we found that wild-type (WT) parafibromin overexpression suppressed proliferation, tumor growth, induced cell cycle arrest and apoptosis in colorectal cancer cells (p<0.05), but it was the converse for mutant-type (MT, mutation in nucleus localization sequence) parafibromin (p<0.05). Both WT and MT transfectants inhibited migration and invasion, and caused better differentiation (p<0.05) of cancer cells. WT parafibromin transfectants showed the overexpression of Cyclin B1, Cyclin D1, Cyclin E, p38, p53, and AIF in HCT-15 and HCT-116 cells, while MT parafibromin only up-regulated p38 expression. There was lower mRNA expression of bcl-2 in parafibromin transfectants than the control and mock, while higher expression of c-myc, Cyclin D1, mTOR, and Raptor. According to transcriptomic analysis, WT parafibromin suppressed PI3K-Akt and FoxO signaling pathways, while MT one promoted PI3K-Akt pathway, focal adhesion, and regulation of actin cytoskeleton. Parafibromin was less expressed in colorectal cancer than paired mucosa (p<0.05), and inversely correlated with its differentiation at both mRNA and protein levels (p<0.05). These findings indicated that WT parafibromin might reverse the aggressive phenotypes of colorectal cancer cells and be employed as a target for gene therapy. Down-regulated parafibromin expression might be closely linked to colorectal carcinogenesis and cancer differentiation.

  7. Adolescents with Cancer in Italy: Improving Access to National Cooperative Pediatric Oncology Group (AIEOP) Centers.

    PubMed

    Ferrari, Andrea; Rondelli, Roberto; Pession, Andrea; Mascarin, Maurizio; Buzzoni, Carlotta; Mosso, Maria Luisa; Maule, Milena; Barisone, Elena; Bertolotti, Marina; Clerici, Carlo Alfredo; Jankovic, Momcilo; Fagioli, Franca; Biondi, Andrea

    2016-06-01

    This analysis compared the numbers of patients treated at Italian pediatric oncology group (Associazione Italiana Ematologia Oncologia Pediatrica [AIEOP]) centers with the numbers of cases predicted according to the population-based registry. It considered 32,431 patients registered in the AIEOP database (1989-2012). The ratio of observed (O) to expected (E) cases was 0.79 for children (0-14 years old) and 0.15 for adolescents (15-19 years old). The proportion of adolescents increased significantly over the years, however, from 0.05 in the earliest period to 0.10, 0.18, and then 0.28 in the latest period of observation, suggesting a greater efficacy of local/national programs dedicated to adolescents.

  8. Pediatric sedation.

    PubMed

    Daud, Yasmeen N; Carlson, Douglas W

    2014-08-01

    Pediatric sedation is an evolving field performed by an extensive list of specialties. Well-defined sedation systems within pediatric facilities are paramount to providing consistent, safe sedation. Pediatric sedation providers should be trained in the principles and practice of sedation, which include patient selection, pre-sedation assessment to determine risks during sedation, selection of optimal sedation medication, monitoring requirements, and post-sedation care. Training, credentialing, and continuing sedation education must be incorporated into sedation systems to verify and monitor the practice of safe sedation. Pediatric hospitalists represent a group of providers with extensive pediatric knowledge and skills who can safely provide pediatric sedation.

  9. [Therapeutic Aggressiveness and Liquid Oncology].

    PubMed

    Barón Duarte, F J; Rodríguez Calvo, M S; Amor Pan, J R

    2017-01-01

    Aggressiveness criteria proposed in the scientific literature a decade ago provide a quality judgment and are a reference in the care of patients with advanced cancer, but their use is not generalized in the evaluation of Oncology Services. In this paper we analyze the therapeutic aggressiveness, according to standard criteria, in 1.001 patients with advanced cancer who died in our Institution between 2010 and 2013. The results seem to show that aggressiveness at the end of life is present more frequently than experts recommend. About 25% of patients fulfill at least one criterion of aggressiveness. This result could be explained by a liquid Oncology which does not prioritize the patient as a moral subject in the clinical appointment. Medical care is oriented to necessities and must be articulated in a model focused on dignity and communication. Its implementation through Advanced Care Planning, consideration of patient's values and preferences, and Limitation of therapeutic effort are ways to reduce aggressiveness and improve clinical practice at the end of life. We need to encourage synergic and proactive attitudes, adding the best of cancer research with the best clinical care for the benefit of human being, moral subject and main goal of Medicine.

  10. Experts' Recommendations for Treating Maladaptive Aggression in Youth

    PubMed Central

    Pappadopulos, Elizabeth; Rosato, Nancy Scotto; Correll, Christoph U.; Findling, Robert L.; Lucas, Judith; Crystal, Stephen

    2011-01-01

    Abstract Background Psychiatric treatment for children and adolescents with clinically significant aggression is common and often involves the use of antipsychotic medications. Increasingly, pediatricians are initiating or managing such treatments despite limited evidence on optimal diagnostic, psychosocial, and medication approaches for pediatric aggression. Aims The objective of this study was to gather clinicians' and researchers' expertise concerning the treatment of maladaptive aggression, using expert consensus survey methods to aid the development of guidelines for pediatricians and psychiatrists on the outpatient treatment of maladaptive aggression in youth (T-MAY). Methods Forty-six experts (psychiatrists, pediatricians, and researchers) with >10 years of clinical and/or research experience in the treatment of pediatric aggression completed a 27-item survey (>400 treatment alternatives) about optimal diagnostic, psychosocial, and medication treatments. Data were analyzed using descriptive statistics and confidence intervals. Results Expert consensus methodology clearly differentiated optimal versus nonoptimal treatment strategies for maladaptive aggression. In contrast to current practice trends, results indicated that experts support the use of psychosocial interventions and parent education and training before the use of medication for maladaptive aggression at every stage of medication treatment, from diagnosis to maintenance to medication discontinuation. Conclusion Overall findings indicate that evidence-informed strategies for outpatient treatment of pediatric maladaptive aggression, guided by systematically derived expert opinions, are attainable. In light of the gap between the research literature and clinical practice, expert consensus opinion supports specific practices for optimal outpatient management in children and adolescents with severe and persistent behavioral difficulties. PMID:22196314

  11. miRNA expression profiling of inflammatory breast cancer identifies a 5-miRNA signature predictive of breast tumor aggressiveness.

    PubMed

    Lerebours, Florence; Cizeron-Clairac, Geraldine; Susini, Aurelie; Vacher, Sophie; Mouret-Fourme, Emmanuelle; Belichard, Catherine; Brain, Etienne; Alberini, Jean-Louis; Spyratos, Frédérique; Lidereau, Rosette; Bieche, Ivan

    2013-10-01

    IBC (inflammatory breast cancer) is a rare but very aggressive form of breast cancer with a particular phenotype. The molecular mechanisms responsible for IBC remain largely unknown. In particular, genetic and epigenetic alterations specific to IBC remain to be identified. MicroRNAs, a class of small noncoding RNAs able to regulate gene expression, are deregulated in breast cancer and may therefore serve as tools for diagnosis and prediction. This study was designed to determine miRNA expression profiling (microRNAome) in IBC. Quantitative RT-PCR was used to determine expression levels of 804 miRNAs in a screening series of 12 IBC compared to 31 non-stage-matched non-IBC and 8 normal breast samples. The differentially expressed miRNAs were then validated in a series of 65 IBC and 95 non-IBC. From a set of 18 miRNAs of interest selected from the screening series, 13 were differentially expressed with statistical significance in the validation series of IBC compared to non-IBC. Among these, a 5-miRNA signature comprising miR-421, miR-486, miR-503, miR-720 and miR-1303 was shown to be predictive for IBC phenotype with an overall accuracy of 89%. Moreover, multivariate analysis showed that this signature was an independent predictor of poor Metastasis-Free Survival in non-IBC patients.

  12. Evidence-Based Recommendations for Fertility Preservation Options for Inclusion in Treatment Protocols for Pediatric and Adolescent Patients Diagnosed With Cancer.

    PubMed

    Fernbach, Alison; Lockart, Barbara; Armus, Cheryl L; Bashore, Lisa M; Levine, Jennifer; Kroon, Leah; Sylvain, Genevieve; Rodgers, Cheryl

    2014-07-01

    As survival rates improve for pediatric cancers, increased attention has been paid to late effects of cancer therapy, in particular, infertility. Fertility preservation options are available for pre- and postpubertal cancer patients; however, many providers lack knowledge regarding options. The aim of this article is to provide a comprehensive synthesis of current evidence and recommendations regarding fertility preservation options for children, adolescents, and young adults undergoing cancer treatment. A systematic search was performed to identify fertility preservation evidence. Fifty-three studies and 4 clinical guidelines were used for the review. Final recommendations consisted of 2 strong and 1 weak recommendation for both female and male fertility preservation options. The treatment team should be knowledgeable about fertility preservation so that they can educate patients and families about available fertility preservation options. It is important to consider and discuss all available fertility options with patients at the time of diagnosis.

  13. Association Between Parent and Child Distress and the Moderating Effects of Life Events in Families With and Without a History of Pediatric Cancer

    PubMed Central

    Okado, Yuko; Long, Alanna M.

    2014-01-01

    Objective Examined the associations between parental and child distress, and moderating effects of child exposure to life events, in families with and without a history of pediatric cancer. Methods Children with cancer and their parents (N = 255) and healthy comparison dyads (N = 142) completed self-report measures of depression, anxiety, and posttraumatic stress symptoms. Children reported on the total number of stressful life events they had experienced. Correlations between parental and child symptoms were examined. Moderating effects of child exposure to life events were tested using multiple regression. Results Parent and child symptoms were significantly related only in the cancer group. Child exposure to life events attenuated this relationship. Moderation effects were significant at or below average levels of life stress. Conclusions The experience of childhood cancer may strengthen the link between parent and child psychological functioning. However, child exposure to other life events may weaken this link. PMID:25064801

  14. PDGF-D promotes cell growth, aggressiveness, angiogenesis and EMT transformation of colorectal cancer by activation of Notch1/Twist1 pathway.

    PubMed

    Chen, Jinhuang; Yuan, Wenzheng; Wu, Liang; Tang, Qiang; Xia, Qinghua; Ji, Jintong; Liu, Zhengyi; Ma, Zhijun; Zhou, Zili; Cheng, Yifeng; Shu, Xiaogang

    2017-02-07

    Platelet-derived growth factor-D (PDGF-D) plays a crucial role in the progression of several cancers. However, its role in colorectal cancer (CRC) remains unclear. Our study showed that PDGF-D was highly expressed in CRC tissues and was positively associated with the clinicopathological features. Down-regulation of PDGF-D inhibited the tumor growth, migration and angiogenesis of SW480 cells in vitro and in vivo. Whereas up-regulation of PDGF-D promoted the malignant behaviors of HCT116 cells. Moreover, PDGF-D up-regulated the expression of Notch1 and Twist1 in CRC cells. In addition, PDGF-D expression promoted Epithelial to mesenchymal transition (EMT), which was accompanied with decreased E-cadherin and increased Vimentin expression. Consistently, PDGF-D, Notch1, and Twist1 are obviously up-regulated in transforming growth factor-beta 1 (TGF-β1) treated HCT116 cells. Since Notch1 and Twist1 play an important role in EMT and tumor progression, we examined whether there is a correlation between Notch1 and Twist1 in EMT status. Our results showed that up-regulation of Notch1 was able to rescue the effects of PDGF-D down-regulation on Twist1 expression in SW480 cells, whereas down-regulation of Notch1 reduced Twist1 expression in HCT116 cells. Furthermore, we found that Twist1 promoted EMT and aggressiveness of CRC cells. These results suggest that PDGF-D promotes tumor growth and aggressiveness of CRC, moreover, down-regulation of PDGF-D inactivates Notch1/Twist1 axis, which could reverse EMT and prevent CRC progression.

  15. Pediatric MS

    MedlinePlus

    ... with Others on MSconnection.org Join a Local Support Group Ask an MS Navigator Edward M. Dowd Personal ... navigate the school system through the Pediatric MS Support Group . Treating pediatric MS Studies have shown that the ...

  16. Pediatric Injury

    MedlinePlus

    ... Control and Prevention’s Safe Child website . What is pediatric critical care? Children who have severe or life-threatening injuries ... are staffed by physicians with specialized training in pediatric critical care medicine ("pediatric intensivists"). Because children can experience a ...

  17. Microwave beamforming for non-invasive patient-specific hyperthermia treatment of pediatric brain cancer

    NASA Astrophysics Data System (ADS)

    Burfeindt, Matthew J.; Zastrow, Earl; Hagness, Susan C.; Van Veen, Barry D.; Medow, Joshua E.

    2011-05-01

    We present a numerical study of an array-based microwave beamforming approach for non-invasive hyperthermia treatment of pediatric brain tumors. The transmit beamformer is designed to achieve localized heating—that is, to achieve constructive interference and selective absorption of the transmitted electromagnetic waves at the desired focus location in the brain while achieving destructive interference elsewhere. The design process takes into account patient-specific and target-specific propagation characteristics at 1 GHz. We evaluate the effectiveness of the beamforming approach using finite-difference time-domain simulations of two MRI-derived child head models from the Virtual Family (IT'IS Foundation). Microwave power deposition and the resulting steady-state thermal distribution are calculated for each of several randomly chosen focus locations. We also explore the robustness of the design to mismatch between the assumed and actual dielectric properties of the patient. Lastly, we demonstrate the ability of the beamformer to suppress hot spots caused by pockets of cerebrospinal fluid (CSF) in the brain. Our results show that microwave beamforming has the potential to create localized heating zones in the head models for focus locations that are not surrounded by large amounts of CSF. These promising results suggest that the technique warrants further investigation and development.

  18. Hyperpolarized 13C MR Markers of Renal Tumor Aggressiveness

    DTIC Science & Technology

    2013-10-01

    reliably distinguish renal cancer aggressiveness for optimal triage of therapies . Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI...reliably distinguish renal cancer aggressiveness for optimal triage of therapies . Hyperpolarized (HP) 13C magnetic resonance spectroscopic imaging (MRSI) is... cancer and normal tissues were obtained from nephrectomy specimens and sliced using Krumdieck slicer. With a precision gauge micrometer, the slice

  19. Psychoeducational Interventions with Pediatric Cancer Patients: Part I. Patient Information and Knowledge

    ERIC Educational Resources Information Center

    Bradlyn, Andrew S.; Beale, Ivan L.; Kato, Pamela M.

    2003-01-01

    We present a systematic review of published research on psychoeducational interventions for children with cancer. The current lack of an organizational model for this literature makes it difficult to form a coherent picture of the scattered literature and draw nomothetic conclusions. A model is described that is based on functional concepts from…

  20. Imaging primary prostate cancer with 11C-Choline PET/CT: relation to tumour stage, Gleason score and biomarkers of biologic aggressiveness

    PubMed Central

    Chen, Ji; Zhao, Yong; Li, Xin; Sun, Peng; Wang, Muwen; Wang, Ridong; Jin, Xunbo

    2012-01-01

    Background As a significant overlap of 11C-Choline standardized uptake value (SUV) between prostate cancer and benign prostate hyperplasia (BPH) tissue, controversy exists regarding the clinical value of 11C-Choline PET/CT scan in primary prostate cancer. In this study, the SUVmax of the prostate lesions and the pelvic muscles were measured and their ratios (SUVmax-P/M ratio) were calculated. Then we evaluated whether the tracer 11C-Choline uptake, quantified as SUVmax-P/M ratio, correlated with tumour stage, Gleason score, and expression levels of several biomarkers of aggressiveness. Methods Twenty-six patients with primary prostate cancer underwent 11C-Choline PET/CT. Tumour specimens from these patients were graded histopathologically, and immunnohistochemistry for Ki-67, CD31, androgen receptor (AR), Her-2/neu, Bcl-2, and PTEN were performed. Results Both SUVmax and SUVmax-P/M ratio showed no significant difference between patients with tumour stage II and III, but significantly elevated in patients with tumour stage IV. SUVmax-P/M ratio was also significantly higher in lesions with Gleason score of 4+3 or higher versus less than or equal to 3+4. SUVmax-P/M ratio was found significantly correlated with expression levels of Ki-67 and CD31. In addition, a higher SUVmax-P/M ratio was demonstrated in Her-2/neu positive subgroup than negative subgroup. At the same time, Gleason score and expression levels of these biomarkers showed no significant association with SUVmax. Conclusions Using the parameter SUVmax-P/M ratio, 11C-Choline PET/CT may be a valuable non-invasive imaging technology in the diagnosis of primary prostate cancer. PMID:23077456

  1. Homeobox A9 directly targeted by miR-196b regulates aggressiveness through nuclear Factor-kappa B activity in non-small cell lung cancer cells.

    PubMed

    Yu, Seong-Lan; Lee, Dong Chul; Sohn, Hyun Ahm; Lee, Soo Young; Jeon, Hyo Sung; Lee, Joon H; Park, Chang Gyo; Lee, Hoi Young; Yeom, Young Il; Son, Ji Woong; Yoon, Yoo Sang; Kang, Jaeku

    2016-12-01

    MicroRNAs (miRNAs) are recognized as crucial posttranscriptional regulators of gene expression, and play critical roles as oncogenes or tumor suppressors in various cancers. Here, we show that miR-196b is upregulated in mesenchymal-like-state non-small cell lung cancer (NSCLC) cells and lung cancer tissues. Moreover, miR-196b upregulation stimulates cell invasion and a change in cell morphology to a spindle shape via loss of cell-to-cell contacts. We identified homeobox A9 (HOXA9) as a target gene of miR-196b by using public databases such as TargetScan, miRDB, and microRNA.org. HOXA9 expression is inversely correlated with miR-196b levels in clinical NSCLC samples as compared to that in corresponding control samples, and with the migration and invasion of NSCLC cells. Ectopic expression of HOXA9 resulted in a suppression of miR-196b-induced cell invasion, and HOXA9 reexpression increased E-cadherin expression. Furthermore, HOXA9 potently attenuated the expression of snail family zinc finger 2 (SNAI2/SLUG) and matrix metallopeptidase 9 (MMP9) by controlling the binding of nuclear factor-kappa B to the promoter of SLUG and MMP9 genes, respectively. Therefore, we suggest that HOXA9 plays a central role in controlling the aggressive behavior of lung cancer cells and that miR-196b can serve as a potential target for developing anticancer agents. © 2015 Wiley Periodicals, Inc.

  2. Giant pediatric intraventricular meningioma: Case report and review of literature

    PubMed Central

    Munjal, Satyashiva; Vats, Atul; Kumar, Jitendra; Srivastava, Amit; Mehta, Veer Singh

    2016-01-01

    Intraventricular meningiomas are rare in the pediatric population. These tumors are often large in size and aggressive in behavior when they occur in children. The management of these tumors is a surgical challenge. PMID:27857790

  3. Engineering functionalized multi-phased silicon/silicon oxide nano-biomaterials to passivate the aggressive proliferation of cancer.

    PubMed

    Premnath, P; Tan, B; Venkatakrishnan, K

    2015-07-20

    Currently, the use of nano silicon in cancer therapy is limited as drug delivery vehicles and markers in imaging, not as manipulative/controlling agents. This is due to limited properties that native states of nano silicon and silicon oxides offers. We introduce nano-functionalized multi-phased silicon/silicon oxide biomaterials synthesized via ultrashort pulsed laser synthesis, with tunable properties that possess inherent cancer controlling properties that can passivate the progression of cancer. This nanostructured biomaterial is composed of individual functionalized nanoparticles made of a homogenous hybrid of multiple phases of silicon and silicon oxide in increasing concentration outwards from the core. The chemical properties of the proposed nanostructure such as number of phases, composition of phases and crystal orientation of each functionalized nanoparticle in the three dimensional nanostructure is defined based on precisely tuned ultrashort pulsed laser-material interaction mechanisms. The amorphous rich phased biomaterial shows a 30 fold (95%) reduction in number of cancer cells compared to bulk silicon in 48 hours. Further, the size of the cancer cells reduces by 76% from 24 to 48 hours. This method exposes untapped properties of combination of multiple phases of silicon oxides and its applications in cancer therapy.

  4. Complex interaction between serum folate levels and genetic polymorphisms in folate pathway genes: biomarkers of prostate cancer aggressiveness.

    PubMed

    Jackson, Maria D; Tulloch-Reid, Marshall K; McFarlane-Anderson, Norma; Watson, Alexis; Seers, Vestra; Bennett, Franklyn I; Egleston, Brian; Ragin, Camille

    2013-03-01

    Little is known about the role of folate and polymorphisms associated with folate metabolism on prostate cancer risk in populations of African origin. We examined the relationship between serum folate and prostate cancer and whether any association was modified by genetic polymorphisms for folate metabolism. The study was case-control in design and consisted of 218 men 40-80 years old with newly diagnosed, histologically confirmed prostate cancer and 236 cancer-free men attending the same urology clinics in Jamaica, March 2005-July 2007. Serum folate was measured by an immunoassay method and genomic DNA evaluated for MTHR (C677T and A1298C), MTRR A66G, and MTR A2756G polymorphisms. Mean serum folate concentration was higher among cases (12.3 ± 4.1 nmol/L) than controls (9.7 ± 4.2 nmol/L). Serum folate concentration showed a positive association with prostate cancer (OR, 4.41; CI, 2.52-7.72 per 10 nmol/L) regardless of grade. No interactions were observed between genotype and folate concentration, but a weak gene effect was observed for MTHFR A1298C and low-grade prostate cancer. Larger studies to investigate the role of gene-gene/gene-diet interactions in Black men are needed.

  5. Pediatric head injury.

    PubMed

    Tulipan, N

    1998-01-01

    Pediatric head injury is a public health problem that exacts a high price from patients, their families and society alike. While much of the brain damage in head-injured patients occurs at the moment of impact, secondary injuries can be prevented by aggressive medical and surgical intervention. Modern imaging devices have simplified the task of diagnosing intracranial injuries. Recent advances in monitoring technology have made it easier to assess the effectiveness of medical therapy. These include intracranial pressure monitoring devices that are accurate and safe, and jugular bulb monitoring which provides a continuous, qualitative measure of cerebral blood flow. The cornerstones of treatment remain hyperventilation and osmotherapy. Despite maximal treatment, however, the mortality and morbidity associated with pediatric head injury remains high. Reduction of this mortality and morbidity will likely depend upon prevention rather than treatment.

  6. [Pediatric adamantinoma. Case report].

    PubMed

    Cafferata, Constanza; Galluzzo, Laura; Cacciavillano, Walter; Innocenti, Sergio

    2015-01-01

    Adamantinoma is a primary tumor of long bones, which affects mainly the shaft of the tibia, and is extremely rare in pediatrics. It frequently presents during the second decade of life, with a slight predominance in males. It is a low grade tumor, with local aggressiveness and low rate of metastasis and recurrence once it is completely removed. Its diagnosis is difficult, not only because it is a rare disease in children, but also because of the difficulty in the differential diagnosis with other benign lesions. We report the case of a 15-year-old patient with a painless swelling of the distal tibia, whose diagnosis was confirmed with the piece of amputation, as imaging features and both initial biopsies were not enough to achieve diagnosis. Though most of the literature consists of case reports, and very few in pediatric patients, they all agree on the difficulty in achieving the diagnosis of adamantinoma.

  7. Abundant NDRG2 Expression Is Associated with Aggressiveness and Unfavorable Patients’ Outcome in Basal-Like Breast Cancer

    PubMed Central

    Gasthaus, Janina; Tiedemann, Janina; Mijnes, Jolein; Heide, Timon; Braunschweig, Till; Knüchel, Ruth; Dahl, Edgar

    2016-01-01

    NDRG2, a member of the N-myc downstream-regulated gene family, is thought to be a putative tumor suppressor gene with promising clinical impact in breast cancer. Since breast cancer comprises heterogeneous intrinsic subtypes with distinct clinical outcomes we investigated the pivotal role of NDRG2 in basal-type breast cancers. Based on subtype classified tumor (n = 45) and adjacent normal tissues (n = 17) we examined NDRG2 mRNA expression and CpG-hypermethylation, whose significance was further validated by independent data sets from The Cancer Genome Atlas (TCGA). In addition, NDRG2 protein expression was evaluated immunohistochemically using a tissue micro array (TMA, n = 211). In vitro, we investigated phenotypic effects caused by NDRG2 silencing in the basal A-like HCC1806 as well as NDRG2 over-expression in basal A-like BT20 compared to luminal-type MCF7 breast cancer cells. Our tissue collections demonstrated an overall low NDRG2 mRNA expression in breast cancer subtypes compared to normal breast tissue in line with an increased CpG-hypermethylation in breast cancer tissue. Independent TCGA data sets verified a significant (P<0.001) expression loss of NDRG2 in breast tumors. Of interest, basal-like tumors more frequently retained abundant NDRG2 expression concordant with a lower CpG-hypermethylation. Unexpectedly, basal-like breast cancer revealed an association of NDRG2 expression with unfavorable patients’ outcome. In line with this observation, in vitro experiments demonstrated reduced proliferation and migration rates (~20%) in HCC1806 cells following NDRG2 silencing. In contrast, NDRG2 over-expressing luminal-type MCF7 cells demonstrated a 26% decreased proliferation rate. Until now, this is the first study investigating the putative role of NDRG2 in depth in basal-type breast cancer. Our data indicate that the described putative tumor suppressive function of NDRG2 may be confined to luminal- and basal B-type breast cancers. PMID:27400234

  8. What Is Thyroid Cancer?

    MedlinePlus

    ... Treatment? Thyroid Cancer About Thyroid Cancer What Is Thyroid Cancer? Cancer starts when cells in the body begin ... cell) Medullary Anaplastic (an aggressive undifferentiated tumor) Differentiated thyroid cancers Most thyroid cancers are differentiated cancers. The cells ...

  9. Retraction: "Activated K-Ras and INK4a/Arf Deficiency Promote Aggressiveness of Pancreatic Cancer by Induction of EMT Consistent With Cancer Stem Cell Phenotype" by Wang et al.

    PubMed

    2016-10-01

    The above article, published online on November 23, 2012 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor in Chief, Gary S. Stein, and Wiley Periodicals, Inc. The retraction has been agreed following an investigation from Wayne State University involving the first author and the corresponding author that found Figure 4B and C to be inappropriately manipulated and re-labeled. Literature Cited Wang Z, Ali S, Banerjee S, Bao B, Li Y, Azmi AS, Korc M, Sarkar FH. 2013. Activated K-Ras and INK4a/Arf deficiency promote aggressiveness of pancreatic cancer by induction of EMT consistent with cancer stem cell phenotype. J Cell Physiol 228:556-562; doi: 10.1002/jcp.24162.

  10. Novel Nomogram That Predicts Aggressive Disease and Treatment Failure Among African-American Men with Prostate Cancer

    DTIC Science & Technology

    2014-10-01

    and Caucasian (CS) men with low-grade prostate cancer and similar cancer of the prostate risk assessment—postsurgery ( CAPRA -S) features following...grade disease and similar CAPRA -S scores. Results: With a median follow-up time of 27 months, the overall 7-year FFbF rate was 86% vs. 79% in CS and AA...0.35) or CAPRA -S score (P ¼ 0.28). In the subset analysis of patients with low-grade disease, AA race was associated with worse FFbF outcomes (P

  11. Barriers to cure for children with cancer in India and strategies to improve outcomes: a report by the Indian Pediatric Hematology Oncology Group.

    PubMed

    Yadav, Satya Prakash; Rastogi, Neha; Kharya, Gaurav; Misra, Ruchira; Ramzan, Mohammed; Katewa, Satyendra; Dua, Vikas; Bhat, Sunil; Kellie, Stewart J; Howard, Scott C

    2014-04-01

    The survival of children with cancer in India is inferior to that of children in high-income countries. The Indian Pediatric Hematology Oncology Group (IPHOG) held a series of online meetings via www.Cure4kids.org to identify barriers to cure and develop strategies to improve outcomes. Five major hurdles were identified: delayed diagnosis, abandonment, sepsis, lack of co-operative groups, and relapse. Development of regional networks like IPHOG has allowed rapid identification of local causes of treatment failure for children with cancer in India and identification of strategies likely to improve care and outcomes in the participating centers. Next steps will include interventions to raise community awareness of childhood cancer, promote early diagnosis and referral, and reduce abandonment and toxic death at each center. Starting of fellowship programs in pediatric hemato-oncology, short training programs for pediatricians, publishing outcome data, formation of parent and patient support groups, choosing the right and effective treatment protocol, and setting up of bone marrow transplant services are some of the effective steps taken in the last decade, which needs to be supported further.

  12. Immunotherapeutics for Pediatric Solid Tumors | NCI Technology Transfer Center | TTC

    Cancer.gov

    The National Cancer Institute’s Pediatric Oncology Branch seeks partners interested in licensing or collaborative research to co-develop new immunotherapeutic agents based on chimeric antigen receptor (CARs) for the treatment of pediatric solid tumors.

  13. Epigenetic silencing of miR-490-3p promotes development of an aggressive colorectal cancer phenotype through activation of the Wnt/β-catenin signaling pathway.

    PubMed

    Zheng, Kehong; Zhou, Xinying; Yu, Jinlong; Li, Qiang; Wang, Hui; Li, Mingyi; Shao, Ziyun; Zhang, Feifei; Luo, Yuhao; Shen, Zetao; Chen, Fei; Shi, Fujun; Cui, Chunhui; Zhao, Dachuan; Lin, Zhiqun; Zheng, Wei; Zou, Zhaowei; Huang, Zonghai; Zhao, Liang

    2016-06-28

    The Wnt/β-catenin pathway is known to contribute to colorectal cancer (CRC) progression, although little is known about the contribution of β-catenin on this process. We investigated the role of miR-490-3p, which was recently reported to suppress tumorigenesis through its effect on Wnt/β-catenin signaling. We found that hypermethylation of the miR-490-3p promoter down-regulates miR-490-3p expression in CRC tissue. Gain- and loss-of-function assays in vitro and in vivo reveal that miR-490-3p suppresses cancer cell proliferation by inducing apoptosis and inhibits cell invasiveness by repressing the initiation of epithelial-to-mesenchymal transition (EMT), a key mechanism in cancer cell invasiveness and metastasis. The frequently rearranged in advanced T-cell lymphomas (FRAT1) protein was identified as a direct target of miR-490-3p and contributes to its tumor-suppressing effects. miR-490-3p appears to have an inhibitory effect on β-catenin expression in nuclear fractions of CRC cells, whereas FRAT1 expression is associated with the accumulation of β-catenin in the nucleus of cells, which could be weakened by transfection with miR-490-3p. Our findings suggest that the miR-490-3p/FRAT1/β-catenin axis is important in CRC progression and provides new insight into the molecular mechanisms underlying CRC. They may help to confirm the pathway driving CRC aggressiveness and serve for the development of a novel miRNA-targeting anticancer therapy.

  14. The TORC1/TORC2 inhibitor, Palomid 529, reduces tumor growth and sensitizes to docetaxel and cisplatin in aggressive and hormone-refractory prostate cancer cells.

    PubMed

    Gravina, Giovanni Luca; Marampon, Francesco; Petini, Foteini; Biordi, Leda; Sherris, David; Jannini, Emmanuele A; Tombolini, Vincenzo; Festuccia, Claudio

    2011-08-01

    One of the major obstacles in the treatment of hormone-refractory prostate cancer (HRPC) is the development of chemo-resistant tumors. The aim of this study is to evaluate the role of Palomid 529 (P529), a novel TORC1/TORC2 inhibitor, in association with docetaxel (DTX) and cisplatin (CP). This work utilizes a wide panel of prostatic cancer cell lines with or without basal activation of Akt as well as two in vivo models of aggressive HRPC. The blockade of Akt/mTOR activity was associated to reduced cell proliferation and induction of apoptosis. Comparison of IC50 values calculated for PTEN-positive and PTEN-negative cell lines as well as the PTEN transfection in PC3 cells or PTEN silencing in DU145 cells revealed that absence of PTEN was indicative for a better activity of the drug. In addition, P529 synergized with DTX and CP. The strongest synergism was achieved when prostate cancer (PCa) cells were sequentially exposed to CP or DTX followed by treatment with P529. Treatment with P529 before the exposure to chemotherapeutic drugs resulted in a moderate synergism, whereas intermediated values of combination index were found when drugs were administered simultaneously. In vivo treatment of a combination of P529 with DTX or CP increased the percentage of complete responses and reduced the number of mice with tumor progression. Our results provide a rationale for combinatorial treatment using conventional chemotherapy and a Akt/mTOR inhibitor as promising therapeutic approach for the treatment of HRPC, a disease largely resistant to conventional therapies.

  15. The mitotic checkpoint regulator RAE1 induces aggressive breast cancer cell phenotypes by mediating epithelial-mesenchymal transition

    PubMed Central

    Oh, Ji Hoon; Hur, Ho; Lee, Ji-Yeon; Kim, Yeejeong; Seo, Younsoo; Kim, Myoung Hee

    2017-01-01

    The gene RAE1 encodes ribonucleic acid export 1 (RAE1), which is involved in mRNA export and is known to serve as a mitotic checkpoint regulator. In addition, RAE1 haplo-insufficiency leads to chromosome missegregation and early aging-associated phenotypes. In humans, a positive correlation has been found between RAE1 copy number abnormalities and gene amplification in breast cancer cells. However, the precise functional role of RAE1 in breast cancer remains to be determined. An in silico analysis of data retrieved from GENT and cBio-Portal identified RAE1 upregulation in breast cancer tissues relative to normal breast cells. Functional studies of various cell lines showed that RAE1 induced invasive and migratory abilities by regulating epithelial-mesenchymal transition signals. A tissue microarray was constructed to demonstrate the interrelationship between clinicopathological features and RAE1 expression. Immunohistochemistry revealed a positive correlation between RAE1 expression and a high histologic grade. Furthermore, RAE1 overexpression was associated with considerably poorer disease-free survival and distant metastasis-free survival, especially in patients with oestrogen receptor-positive tumours. In summary, RAE1 may be a prognostic marker and therapeutic intervention target in malignant breast cancers. PMID:28181567

  16. The mitotic checkpoint regulator RAE1 induces aggressive breast cancer cell phenotypes by mediating epithelial-mesenchymal transition.

    PubMed

    Oh, Ji Hoon; Hur, Ho; Lee, Ji-Yeon; Kim, Yeejeong; Seo, Younsoo; Kim, Myoung Hee

    2017-02-09

    The gene RAE1 encodes ribonucleic acid export 1 (RAE1), which is involved in mRNA export and is known to serve as a mitotic checkpoint regulator. In addition, RAE1 haplo-insufficiency leads to chromosome missegregation and early aging-associated phenotypes. In humans, a positive correlation has been found between RAE1 copy number abnormalities and gene amplification in breast cancer cells. However, the precise functional role of RAE1 in breast cancer remains to be determined. An in silico analysis of data retrieved from GENT and cBio-Portal identified RAE1 upregulation in breast cancer tissues relative to normal breast cells. Functional studies of various cell lines showed that RAE1 induced invasive and migratory abilities by regulating epithelial-mesenchymal transition signals. A tissue microarray was constructed to demonstrate the interrelationship between clinicopathological features and RAE1 expression. Immunohistochemistry revealed a positive correlation between RAE1 expression and a high histologic grade. Furthermore, RAE1 overexpression was associated with considerably poorer disease-free survival and distant metastasis-free survival, especially in patients with oestrogen receptor-positive tumours. In summary, RAE1 may be a prognostic marker and therapeutic intervention target in malignant breast cancers.

  17. Parent caregiver self-efficacy and child reactions to pediatric cancer treatment procedures.

    PubMed

    Peterson, Amy M; Harper, Felicity W K; Albrecht, Terrance L; Taub, Jeffrey W; Orom, Heather; Phipps, Sean; Penner, Louis A

    2014-01-01

    This study examined how parents' sense of self-efficacy specific to caregiving for their child during cancer treatment procedures affected children's distress and cooperation during procedures. Potential correlates of caregiver self-efficacy (ie, demographics, child clinical characteristics, parent dispositional attributes, and social support) were also examined. Participants were 119 children undergoing cancer treatment procedures and their parents. Parents' self-efficacy about 6 procedure-specific caregiver tasks was measured. Parents, children, nurses, and observers rated child distress and parents, nurses and observers rated child cooperation during procedures. Higher parent self-efficacy about keeping children calm during procedures predicted lower child distress and higher child cooperation during procedures. Parent dispositional attributes (eg, enduring positive mood, empathy) and social support predicted self-efficacy. Parent caregiver self-efficacy influences child distress and cooperation during procedures and is associated with certain parent attributes. Findings suggest the utility of identifying parents who would benefit from targeted interventions to increase self-efficacy about caregiving during treatment procedures.

  18. Aggressive Prostate Cancer Is Prevented in ERαKO Mice and Stimulated in ERβKO TRAMP Mice

    PubMed Central

    Ślusarz, Anna; Jackson, Glenn A.; Day, J. Kevin; Shenouda, Nader S.; Bogener, Jennifer L.; Browning, Jim D.; Fritsche, Kevin L.; MacDonald, Ruth S.; Besch-Williford, Cynthia L.

    2012-01-01

    Previous evidence suggests soy genistein may be protective against prostate cancer, but whether this protection involves an estrogen receptor (ER)-dependent mechanism is unknown. To test the hypothesis that phytoestrogens may act through ERα or ERβ to play a protective role against prostate cancer, we bred transgenic mice lacking functional ERα or ERβ with transgenic adenocarcinoma of mouse prostate (TRAMP) mice. Dietary genistein reduced the incidence of cancer in ER wild-type (WT)/transgenic adenocarcinoma of mouse prostate mice but not in ERα knockout (KO) or ERβKO mice. Cancer incidence was 70% in ERWT mice fed the control diet compared with 47% in ERWT mice fed low-dose genistein (300 mg/kg) and 32% on the high-dose genistein (750 mg/kg). Surprisingly, genistein only affected the well differentiated carcinoma (WDC) incidence but had no effect on poorly differentiated carcinoma (PDC). No dietary effects have been observed in either of the ERKO animals. We observed a very strong genotypic influence on PDC incidence, a protective effect in ERαKO (only 5% developed PDC), compared with 19% in the ERWT, and an increase in the incidence of PDC in ERβKO mice to 41%. Interestingly, immunohistochemical analysis showed ERα expression changing from nonnuclear in WDC to nuclear in PDC, with little change in ERβ location or expression. In conclusion, genistein is able to inhibit WDC in the presence of both ERs, but the effect of estrogen signaling on PDC is dominant over any dietary treatment, suggesting that improved differential targeting of ERα vs. ERβ would result in prevention of advanced prostate cancer. PMID:22753646

  19. Pediatric Sepsis.

    PubMed

    Prusakowski, Melanie K; Chen, Audrey P

    2017-02-01

    Pediatric sepsis is distinct from adult sepsis in its definitions, clinical presentations, and management. Recognition of pediatric sepsis is complicated by the various pediatric-specific comorbidities that contribute to its mortality and the age- and development-specific vital sign and clinical parameters that obscure its recognition. This article outlines the clinical presentation and management of sepsis in neonates, infants, and children, and highlights some key populations who require specialized care.

  20. Pediatric Cervicofacial Necrotizing Fasciitis

    PubMed Central

    King, Ericka; Chun, Robert; Sulman, Cecille

    2015-01-01

    Objective To present a case of a pediatric cervicofacial necrotizing fasciitis (NF), a rapidly progressive infection, and a review of a 10-year pediatric inpatient database. Design Case report and review. Setting Pediatric intensive care unit. Patients A healthy 5-year-old male who developed NF of the lower lip 36 hours following minor trauma. International Classification of Diseases, Ninth Revision, code 728.86 (NF), was the inclusion criteria for the Kids’ Inpatient Database (KID) in 1997 and 2006. Results A pediatric case is presented with a thorough photographic record demonstrating the need for rapid diagnosis and treatment. In a review of the KID from 1997 and 2006, the relative risk of being discharged with NF in 2006 vs 1997 was 1.4 (95% CI, 9.95-2.28). Age at diagnosis of NF was older in 2006 compared with 1997 (11.5 years vs 8.05 years; P<.001). Deaths with a diagnosis of NF increased from 1997 compared with 2006: from 3.9% to 5.4%. In 2006, the odds of death were 15.1 times higher in pediatric discharges with a diagnosis of NF compared with discharges without a diagnosis of NF (P<.001; 95% CI, 9.3-23.1). Conclusions Even with the advent of new treatments and antibiotics, the incidence and death rates of NF have changed little over the past 10 years. While it is still a rare diagnosis, knowledge and awareness of necrotizing fasciitis with aggressive medical and surgical treatment are still the foundation in disease survival. PMID:22508620

  1. Vitamin D, Vitamin D Receptor Polymorphisms and Breast Cancer Aggressiveness in African American and European American Women

    DTIC Science & Technology

    2010-05-01

    stratified by menopausal status, vitamin D levels were lower in women with invasive breast cancer than in controls, regardless of menopausal status (Table 6...mean ± SD (year) 55.8 ± 12.5 53.8 ± 13.8 Menopause , n (%) Premenopausal 245 (42.3) 245 (42.7) Postmenopausal 334 (57.7) 329 (57.3) BMI...10 | P a g e Table 6. Serum 25-OHD levels by tumor characteristics and menopausal status Premenopausal

  2. Vitamin D, Vitamin D Receptor Polymorphisms, and Breast Cancer Aggressiveness in African American and European American Women

    DTIC Science & Technology

    2009-05-01

    have finished all the required didactic course work and exams. I have been attending a series of meetings that are specifically in or highly correlated...of the patients were postmenopausal (65.4%), and had education more than high school (65.6%). Among the patients, 14.3% had cancer at in situ stage...Menopausal status, n (%) Premenopause 176 (34.6) Postmenopause 333 (65.4) Education , n (%) Less than high school 28 (6.6

  3. Enhancement of the Efficacy of Conventional Anticancer Compounds Through the Repression of SNAI Proteins in Aggressive Breast Cancer Cells

    DTIC Science & Technology

    2014-04-01

    67] Ooi, L. L., Zhou, H., Kalak, R., Zheng, Y., Conigrave, A. D., Seibel, M. J., and Dunstan, C. R. (2010) Vitamin D deficiency promotes human breast...agents such as vitamin D and anti-estrogens. Specific Aims: (1) To evaluate the levels of SNAI proteins in relation to the levels of the proteins...that impart resistance against vitamin D and anti-estrogens in human breast cancer tissues; (2) To determine the effects of alterations of the levels

  4. Pediatric brain tumor cell lines.

    PubMed

    Xu, Jingying; Margol, Ashley; Asgharzadeh, Shahab; Erdreich-Epstein, Anat

    2015-02-01

    Pediatric brain tumors as a group, including medulloblastomas, gliomas, and atypical teratoid rhabdoid tumors (ATRT) are the most common solid tumors in children and the leading cause of death from childhood cancer. Brain tumor-derived cell lines are critical for studying the biology of pediatric brain tumors and can be useful for initial screening of new therapies. Use of appropriate brain tumor cell lines for experiments is important, as results may differ depending on tumor properties, and can thus affect the conclusions and applicability of the model. Despite reports in the literature of over 60 pediatric brain tumor cell lines, the majority of published papers utilize only a small number of these cell lines. Here we list the approximately 60 currently-published pediatric brain tumor cell lines and summarize some of their central features as a resource for scientists seeking pediatric brain tumor cell lines for their research.

  5. Patient Involvement in Informed Consent for Pediatric Phase I Cancer Research

    PubMed Central

    Miller, Victoria A.; Baker, Justin N.; Leek, Angela C.; Drotar, Dennis; Kodish, Eric

    2014-01-01

    Objective To examine children’s and adolescents’ involvement in the informed consent conference for phase I cancer trials and test associations with patient age, ease of understanding, and pressure to participate. Procedure Participants included 61 patients ages 7 through 21 years who were offered participation in a phase I trial. Consent conferences were audiotaped, transcribed, and coded for communication between patients and physicians and between patients and parents. Results Based on word counts, the mean proportion of the consent conference in which the physician was talking to the patient was 36%; the vast majority (73%) of this communication consisted of giving information. Physician-patient communication increased with age, but overall levels of patient-to-physician communication were low (3%). After controlling for patient age, greater physician-to-patient communication was associated with greater ease of understanding. Conclusions The focus on providing information in the context of informed consent may come at the expense of other communication exchanges that are important to patients, especially in the context of end of life decisions. Children and adolescents may benefit from the assent process when physicians direct more of their communication to them. Future research should identify the reasons for low patient communication during the consent conference and strategies to enhance their participation in decision making about phase I trial enrollment. PMID:24487916

  6. Pterostilbene Decreases the Antioxidant Defenses of Aggressive Cancer Cells In Vivo: A Physiological Glucocorticoids- and Nrf2-Dependent Mechanism

    PubMed Central

    Benlloch, María; Obrador, Elena; Valles, Soraya L.; Rodriguez, María L.; Sirerol, J. Antoni; Alcácer, Javier; Pellicer, José A.; Salvador, Rosario; Cerdá, Concha; Sáez, Guillermo T.

    2016-01-01

    Abstract Aims: Polyphenolic phytochemicals have anticancer properties. However, in mechanistic studies, lack of correlation with the bioavailable concentrations is a critical issue. Some reports had suggested that these molecules downregulate the stress response, which may affect growth and the antioxidant protection of malignant cells. Initially, we studied this potential underlying mechanism using different human melanomas (with genetic backgrounds correlating with most melanomas), growing in nude mice as xenografts, and pterostilbene (Pter, a natural dimethoxylated analog of resveratrol). Results: Intravenous administration of Pter decreased human melanoma growth in vivo. However, Pter, at levels measured within the tumors, did not affect melanoma growth in vitro. Pter inhibited pituitary production of the adrenocorticotropin hormone (ACTH), decreased plasma levels of corticosterone, and thereby downregulated the glucocorticoid receptor- and nuclear factor (erythroid-derived 2)-like 2 (Nrf2)-dependent antioxidant defense system in growing melanomas. Exogenous corticosterone or genetically induced Nrf2 overexpression in melanoma cells prevented the inhibition of tumor growth and decreased antioxidant defenses in these malignant cells. These effects and mechanisms were also found in mice bearing different human pancreatic cancers. Glutathione depletion (selected as an antimelanoma strategy) facilitated the complete elimination by chemotherapy of melanoma cells isolated from mice treated with Pter. Innovation: Although bioavailability-related limitations may preclude direct anticancer effects in vivo, natural polyphenols may also interfere with the growth and defense of cancer cells by downregulating the pituitary gland-dependent ACTH synthesis. Conclusions: Pter downregulates glucocorticoid production, thus decreasing the glucocorticoid receptor and Nrf2-dependent signaling/transcription and the antioxidant protection of melanoma and pancreatic cancer cells

  7. Association of RNASEL and 8q24 variants with the presence and aggressiveness of hereditary and sporadic prostate cancer in a hispanic population

    PubMed Central

    San Francisco, Ignacio F; Rojas, Pablo A; Torres-Estay, Verónica; Smalley, Susan; Cerda-Infante, Javier; Montecinos, Viviana P; Hurtado, Claudia; Godoy, Alejandro S

    2014-01-01

    To study the association between the polymorphisms Arg462Gln and Asp541Glu from the RNASEL gene (1q25), and the polymorphisms rs620861, rs1447295, rs6983267, rs7837328 from the chromosome 8q24 with the risk of presenting prostate cancer (PCa) and its clinical characteristics in a Hispanic (Chilean) population. The study was performed on 21 control patients and 83 patients diagnosed with PCa. Polymorphisms were analysed from blood samples through real-time PCR by using TaqMan probes, and the genetic analysis was performed with the SNPStats program. Also, a comparison was performed between clinical characteristics of PCa and the presence of the different polymorphism genotypes by using the Minitab software. There was a significant association between the genotype G/G from the polymorphism rs6983267 with an overall increased risk of PCa, in patients both with or without family history of PCa (OR = 4.47, 95% CI = 1.05–18.94, P = 0.034 and OR = 3.57, 95% CI = 0.96–13.35, P = 0.037, respectively). Regarding clinical parameters, patients carrying the genotype C/C from the polymorphism Asp541Glu had significantly higher prostate-specific antigen (PSA) levels than patients carrying the other genotypes (P = 0.034). Moreover, patients with the genotype G/G of rs6983267 had higher PSA levels (P = 0.024). The polymorphism rs6983267 from region 3 of the chromosome 8q24 appears to be a prominent risk factor for PCa and a biomarker for cancer aggressiveness in the group of patients who presented higher levels of PSA at the time of diagnosis. PMID:24224612

  8. CLDN3 inhibits cancer aggressiveness via Wnt-EMT signaling and is a potential prognostic biomarker for hepatocellular carcinoma.

    PubMed

    Jiang, Lei; Yang, Yi-Dong; Fu, Li; Xu, Weiqi; Liu, Dabin; Liang, Qiaoyi; Zhang, Xiang; Xu, Lixia; Guan, Xin-Yuan; Wu, Bin; Sung, Joseph J Y; Yu, Jun

    2014-09-15

    Hepatocellular carcinoma (HCC) is one of the most common fatal malignancies but the molecular genetic basis of this disease remains unclear. By using genome-wide methylation profiling analysis, we identified CLDN3 as an epigenetically regulated gene in cancer. Here, we investigated its function and clinical relevance in human HCC. CLDN3 downregulation occurred in 87/114 (76.3%) of primary HCCs, where it was correlated significantly with shorter survival of HCC patients (P=0.021). Moreover, multivariate cyclooxygenase regression analysis showed that CLDN3 was an independent prognostic factor for overall survival (P=0.014). Absent expression of CLDN3 was also detected in 67% of HCC cell lines, which was significantly associated with its promoter hypermethylation. Ectopic expression of CLDN3 in HCC cells could inhibit cell motility, cell invasiveness, and tumor formation in nude mice. Mechanistic investigations suggested through downregulation of GSK3B, CTNNB1, SNAI2, and CDH2, CLDN3 could significantly suppress metastasis by inactivating the Wnt/β-catenin-epithelial mesenchymal transition (EMT) axis in HCC cells. Collectively, our findings demonstrated that CLDN3 is an epigenetically silenced metastasis suppressor gene in HCC. A better understanding of the molecular mechanism of CLDN3 in inhibiting liver cancer cell metastasis may lead to a more effective management of HCC patients with the inactivation of CLDN3.

  9. Taking Time: Support for People with Cancer

    MedlinePlus

    ... Education Publications PDQ® Cancer Information Summaries Adult Treatment Pediatric Treatment Supportive & Palliative Care Cancer Screening Cancer Prevention Cancer Genetics Integrative Therapies ...

  10. E2F1 promote the aggressiveness of human colorectal cancer by activating the ribonucleotide reductase small subunit M2

    SciTech Connect

    Fang, Zejun; Gong, Chaoju; Liu, Hong; Zhang, Xiaomin; Mei, Lingming; Song, Mintao; Qiu, Lanlan; Luo, Shuchai; Zhu, Zhihua; Zhang, Ronghui; Gu, Hongqian; Chen, Xiang

    2015-08-21

    As the ribonucleotide reductase small subunit, the high expression of ribonucleotide reductase small subunit M2 (RRM2) induces cancer and contributes to tumor growth and invasion. In several colorectal cancer (CRC) cell lines, we found that the expression levels of RRM2 were closely related to the transcription factor E2F1. Mechanistic studies were conducted to determine the molecular basis. Ectopic overexpression of E2F1 promoted RRM2 transactivation while knockdown of E2F1 reduced the levels of RRM2 mRNA and protein. To further investigate the roles of RRM2 which was activated by E2F1 in CRC, CCK-8 assay and EdU incorporation assay were performed. Overexpression of E2F1 promoted cell proliferation in CRC cells, which was blocked by RRM2 knockdown attenuation. In the migration and invasion tests, overexpression of E2F1 enhanced the migration and invasion of CRC cells which was abrogated by silencing RRM2. Besides, overexpression of RRM2 reversed the effects of E2F1 knockdown partially in CRC cells. Examination of clinical CRC specimens demonstrated that both RRM2 and E2F1 were elevated in most cancer tissues compared to the paired normal tissues. Further analysis showed that the protein expression levels of E2F1 and RRM2 were parallel with each other and positively correlated with lymph node metastasis (LNM), TNM stage and distant metastasis. Consistently, the patients with low E2F1 and RRM2 levels have a better prognosis than those with high levels. Therefore, we suggest that E2F1 can promote CRC proliferation, migration, invasion and metastasis by regulating RRM2 transactivation. Understanding the role of E2F1 in activating RRM2 transcription will help to explain the relationship between E2F1 and RRM2 in CRC and provide a novel predictive marker for diagnosis and prognosis of the disease. - Highlights: • E2F1 promotes RRM2 transactivation in CRC cells. • E2F1 promotes the proliferation of CRC cells by activating RRM2. • E2F1 promotes the migration and

  11. Parametric PET/MR Fusion Imaging to Differentiate Aggressive from Indolent Primary Prostate Cancer with Application for Image-Guided Prostate Cancer Biopsies

    DTIC Science & Technology

    2014-10-01

    Unlimited 13. SUPPLEMENTARY NOTES 14. ABSTRACT The study investigates whether fusion PET/ MRI imaging with 18F-choline PET/CT and...diffusion-weighted MRI can be successfully applied to target prostate cancer using image-guided prostate biopsies. The study further aims to establish...whether fusion PET/ MRI -derived parametric imaging parameters identify significant prostate cancer better than standard prostate biopsies. In order to

  12. Virtual Pediatric Hospital

    MedlinePlus

    ... Thoracopaedia - An Imaging Encyclopedia of Pediatric Thoracic Disease Virtual Pediatric Hospital is the Apprentice's Assistant™ Last revised ... pediatric resources: GeneralPediatrics.com | PediatricEducation.org | SearchingPediatrics.com Virtual Pediatric Hospital is curated by Donna M. D' ...

  13. Suppression of iASPP-dependent aggressiveness in cervical cancer through reversal of methylation silencing of microRNA-124

    PubMed Central

    Dong, Peixin; Xiong, Ying; Watari, Hidemichi; Hanley, Sharon JB; Konno, Yosuke; Ihira, Kei; Suzuki, Fumihiko; Yamada, Takahiro; Kudo, Masataka; Yue, Junming; Sakuragi, Noriaki

    2016-01-01

    Derepression of wild-type p53 by suppressing its negative inhibitor iASPP (Inhibitor of apoptosis-stimulating protein of p53) represents a potential therapeutic option for cervical cancer (CC). Here, we reported a novel functional significance of iASPP upregulation in cervical tumorigenesis: iASPP acts as a key promoter of CC cell proliferation, epithelial-mesenchymal transition, invasion and cancer stemness, by interacting with p53 to suppress p53-mediated transcription of target genes and reducing p53-responsive microRNA-34a levels. Moreover, we demonstrate that miR-124, directly targeting iASPP, reduces expression of iASPP and attenuates CC cell growth and invasiveness. Low miR-124 expression is inversely correlated with increased expression of iASPP mRNA in CC tissues. In a cohort of 40 patients with CC, the low miR-124 expression was correlated with poor 5-year overall survival (P = 0.0002) and shorter disease-free survival 5-year (P = 0006). Treatment with the DNA methyltransferase inhibitor Zebularine increases miR-124 expression and retards CC cell growth and invasion with minimal toxicity to normal cells. Even at a non-toxic concentration, Zebularine was effective in suppressing CC cell invasion and migration. Altogether, the restoration of miR-124 reduces iASPP expression and leads to p53-dependent tumor suppression, suggesting a therapeutic strategy to treat iASPP-associated CC. PMID:27765948

  14. Immune Adjuvant Activity of Pre-Resectional Radiofrequency Ablation Protects against Local and Systemic Recurrence in Aggressive Murine Colorectal Cancer

    PubMed Central

    Ito, Fumito; Ku, Amy W.; Bucsek, Mark J.; Muhitch, Jason B.; Vardam-Kaur, Trupti; Kim, Minhyung; Fisher, Daniel T.; Camoriano, Marta; Khoury, Thaer; Skitzki, Joseph J.; Gollnick, Sandra O.; Evans, Sharon S.

    2015-01-01

    Purpose While surgical resection is a cornerstone of cancer treatment, local and distant recurrences continue to adversely affect outcome in a significant proportion of patients. Evidence that an alternative debulking strategy involving radiofrequency ablation (RFA) induces antitumor immunity prompted the current investigation of the efficacy of performing RFA prior to surgical resection (pre-resectional RFA) in a preclinical mouse model. Experimental Design Therapeutic efficacy and systemic immune responses were assessed following pre-resectional RFA treatment of murine CT26 colon adenocarcinoma. Results Treatment with pre-resectional RFA significantly delayed tumor growth and improved overall survival compared to sham surgery, RFA, or resection alone. Mice in the pre-resectional RFA group that achieved a complete response demonstrated durable antitumor immunity upon tumor re-challenge. Failure to achieve a therapeutic benefit in immunodeficient mice confirmed that tumor control by pre-resectional RFA depends on an intact adaptive immune response rather than changes in physical parameters that make ablated tumors more amenable to a complete surgical excision. RFA causes a marked increase in intratumoral CD8+ T lymphocyte infiltration, thus substantially enhancing the ratio of CD8+ effector T cells: FoxP3+ regulatory T cells. Importantly, pre-resectional RFA significantly increases the number of antigen-specific CD8+ T cells within the tumor microenvironment and tumor-draining lymph node but had no impact on infiltration by myeloid-derived suppressor cells, M1 macrophages or M2 macrophages at tumor sites or in peripheral lymphoid organs (i.e., spleen). Finally, pre-resectional RFA of primary tumors delayed growth of distant tumors through a mechanism that depends on systemic CD8+ T cell-mediated antitumor immunity. Conclusion Improved survival and antitumor systemic immunity elicited by pre-resectional RFA support the translational potential of this neoadjuvant

  15. Lowering Whole-Body Radiation Doses in Pediatric Intensity-Modulated Radiotherapy Through the Use of Unflattened Photon Beams;Flattening filter; Pediatric; Intensity-modulated radiotherapy; Second cancers; Radiation-induced malignancies

    SciTech Connect

    Cashmore, Jason; Ramtohul, Mark; Ford, Dan

    2011-07-15

    Purpose: Intensity modulated radiotherapy (IMRT) has been linked with an increased risk of secondary cancer induction due to the extra leakage radiation associated with delivery of these techniques. Removal of the flattening filter offers a simple way of reducing head leakage, and it may be possible to generate equivalent IMRT plans and to deliver these on a standard linear accelerator operating in unflattened mode. Methods and Materials: An Elekta Precise linear accelerator has been commissioned to operate in both conventional and unflattened modes (energy matched at 6 MV) and a direct comparison made between the treatment planning and delivery of pediatric intracranial treatments using both approaches. These plans have been evaluated and delivered to an anthropomorphic phantom. Results: Plans generated in unflattened mode are clinically identical to those for conventional IMRT but can be delivered with greatly reduced leakage radiation. Measurements in an anthropomorphic phantom at clinically relevant positions including the thyroid, lung, ovaries, and testes show an average reduction in peripheral doses of 23.7%, 29.9%, 64.9%, and 70.0%, respectively, for identical plan delivery compared to conventional IMRT. Conclusions: IMRT delivery in unflattened mode removes an unwanted and unnecessary source of scatter from the treatment head and lowers leakage doses by up to 70%, thereby reducing the risk of radiation-induced second cancers. Removal of the flattening filter is recommended for IMRT treatments.

  16. The need for evidence based nutritional guidelines for pediatric acute lymphoblastic leukemia patients: acute and long-term following treatment.

    PubMed

    Owens, Joyce L; Hanson, Sheila J; McArthur, Jennifer A; Mikhailov, Theresa A

    2013-10-31

    High survival rates for pediatric leukemia are very promising. With regard to treatment, children tend to be able to withstand a more aggressive treatment protocol than adults. The differences in both treatment modalities and outcomes between children and adults make extrapolation of adult studies to children inappropriate. The higher success is associated with a significant number of children experiencing nutrition-related adverse effects both in the short and long term after treatment. Specific treatment protocols have been shown to deplete nutrient levels, in particular antioxidants. The optimal nutrition prescription during, after and long-term following cancer treatment is unknown. This review article will provide an overview of the known physiologic processes of pediatric leukemia and how they contribute to the complexity of performing nutritional assessment in this population. It will also discuss known nutrition-related consequences, both short and long term in pediatric leukemia patients. Since specific antioxidants have been shown to be depleted as a consequence of therapy, the role of oxidative stress in the pediatric leukemia population will also be explored. More pediatric studies are needed to develop evidence based therapeutic interventions for nutritional complications of leukemia and its treatment.

  17. Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning

    NASA Astrophysics Data System (ADS)

    Geng, Changran; Moteabbed, Maryam; Xie, Yunhe; Schuemann, Jan; Yock, Torunn; Paganetti, Harald

    2016-01-01

    The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of ~17 mm and ~8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from  -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains

  18. Assessing the radiation-induced second cancer risk in proton therapy for pediatric brain tumors: the impact of employing a patient-specific aperture in pencil beam scanning.

    PubMed

    Geng, Changran; Moteabbed, Maryam; Xie, Yunhe; Schuemann, Jan; Yock, Torunn; Paganetti, Harald

    2016-01-07

    The purpose of this study was to compare the radiation-induced second cancer risks for in-field and out-of-field organs and tissues for pencil beam scanning (PBS) and passive scattering proton therapy (PPT) and assess the impact of adding patient-specific apertures to sharpen the penumbra in pencil beam scanning for pediatric brain tumor patients. Five proton therapy plans were created for each of three pediatric patients using PPT as well as PBS with two spot sizes (average sigma of ~17 mm and ~8 mm at isocenter) and choice of patient-specific apertures. The lifetime attributable second malignancy risks for both in-field and out-of-field tissues and organs were compared among five delivery techniques. The risk for in-field tissues was calculated using the organ equivalent dose, which is determined by the dose volume histogram. For out-of-field organs, the organ-specific dose equivalent from secondary neutrons was calculated using Monte Carlo and anthropomorphic pediatric phantoms. We find that either for small spot size PBS or for large spot size PBS, a patient-specific aperture reduces the in-field cancer risk to values lower than that for PPT. The reduction for large spot sizes (on average 43%) is larger than for small spot sizes (on average 21%). For out-of-field organs, the risk varies only marginally by employing a patient-specific aperture (on average from  -2% to 16% with increasing distance from the tumor), but is still one to two orders of magnitude lower than that for PPT. In conclusion, when pencil beam spot sizes are large, the addition of apertures to sharpen the penumbra decreases the in-field radiation-induced secondary cancer risk. There is a slight increase in out-of-field cancer risk as a result of neutron scatter from the aperture, but this risk is by far outweighed by the in-field risk benefit from using an aperture with a large PBS spot size. In general, the risk for developing a second malignancy in out-of-field organs for PBS remains

  19. mRNA and methylation profiling of radioresistant esophageal cancer cells: the involvement of Sall2 in acquired aggressive phenotypes

    PubMed Central

    Luo, Judong; Wang, Wenjie; Tang, Yiting; Zhou, Dandan; Gao, Yi; Zhang, Qi; Zhou, Xifa; Zhu, Hui; Xing, Ligang; Yu, Jinming

    2017-01-01

    Esophageal squamous cell carcinoma (ESCC) is one of the deadliest malignancies worldwide. Radiotherapy plays a critical role in the curative management of inoperable ESCC patients. However, radioresistance restricts the efficacy of radiotherapy for ESCC patients. The molecules involved in radioresistance remain largely unknown, and new approaches to sensitize cells to irradiation are in demand. Technical advances in analysis of mRNA and methylation have enabled the exploration of the etiology of diseases and have the potential to broaden our understanding of the molecular pathways of ESCC radioresistance. In this study, we constructed radioresistant TE-1 and Eca-109 cell lines (TE-1/R and Eca-109/R, respectively). The radioresistant cells showed an increased migration ability but reduced apoptosis and cisplatin sensitivity compared with their parent cells. mRNA and methylation profiling by microarray revealed 1192 preferentially expressed mRNAs and 8841 aberrantly methylated regions between TE-1/R and TE-1 cells. By integrating the mRNA and methylation profiles, we related the decreased expression of transcription factor Sall2 with a corresponding increase in its methylation in TE-1/R cells, indicating its involvement in radioresistance. Upregulation of Sall2 decreased the growth and migration advantage of radioresistant ESCC cells. Taken together, our present findings illustrate the mRNA and DNA methylation changes during the radioresistance of ESCC and the important role of Sall2 in esophageal cancer malignancy. PMID:28367244

  20. siRNA Knockdown of Ribosomal Protein Gene RPL19 Abrogates the Aggressive Phenotype of Human Prostate Cancer

    PubMed Central

    Bee, Alix; Brewer, Daniel; Beesley, Carol; Dodson, Andrew; Forootan, Shiva; Dickinson, Timothy; Gerard, Patricia; Lane, Brian; Yao, Sheng; Cooper, Colin S.; Djamgoz, Mustafa B. A.; Gosden, Christine M.; Ke, Youqiang; Foster, Christopher S.

    2011-01-01

    We provide novel functional data that posttranscriptional silencing of gene RPL19 using RNAi not only abrogates the malignant phenotype of PC-3M prostate cancer cells but is selective with respect to transcription and translation of other genes. Reducing RPL19 transcription modulates a subset of genes, evidenced by gene expression array analysis and Western blotting, but does not compromise cell proliferation or apoptosis in-vitro. However, growth of xenografted tumors containing the knocked-down RPL19 in-vivo is significantly reduced. Analysis of the modulated genes reveals induction of the non-malignant phenotype principally to involve perturbation of networks of transcription factors and cellular adhesion genes. The data provide evidence that extra-ribosomal regulatory functions of RPL19, beyond protein synthesis, are critical regulators of cellular phenotype. Targeting key members of affected networks identified by gene expression analysis raises the possibility of therapeutically stabilizing a benign phenotype generated by modulating the expression of an individual gene and thereafter constraining a malignant phenotype while leaving non-malignant tissues unaffected. PMID:21799931

  1. Introduction to pediatric oncology

    SciTech Connect

    McWhirter, W.R.; Masel, J.P.

    1987-01-01

    This book covers the varied and complex aspects of management in pediatric oncology. Emphasis is placed on a team approach and on establishing and maintaining an individualized, humanistic relationships with the patient. Numerous illustrations show modern imaging techniques that are proving most valuable in the investigation of suspected or confirmed childhood cancer. Physical and psychological side effects of short-term and long-term treatment are also discussed.

  2. Mutation of genes of the PI3K/AKT pathway in breast cancer supports their potential importance as biomarker for breast cancer aggressiveness.

    PubMed

    Tserga, Aggeliki; Chatziandreou, Ilenia; Michalopoulos, Nicolaos V; Patsouris, Efstratios; Saetta, Angelica A

    2016-07-01

    Deregulation of phosphatidylinositol 3-kinase (PI3K)/AKT signaling pathway is closely associated with cancer development and cancer progression. PIK3CA, AKT1, and PTEN are the fundamental molecules of the PI3K/AKT pathway with increased mutation rates in cancer cases leading to aberrant regulation of the pathway. Even though molecular alterations of the PI3K/AKT pathway have been studied in breast cancer, correlations between specific molecular alterations and clinicopathological features remain contradictory. In this study, we examined mutations of the PI3K/AKT pathway in 75 breast carcinomas using high-resolution melting analysis and pyrosequencing, in parallel with analysis of relative expression of PIK3CA and AKT2 genes. Mutations of PIK3CA were found in our cohort in 21 cases (28 %), 10 (13 %) in exon 9 and 11(15 %) in exon 20. Mutation frequency of AKT1 and PTEN genes was 4 and 3 %, respectively. Overall, alterations in the PI3K/AKT signaling cascade were detected in 35 % of the cases. Furthermore, comparison of 50 breast carcinomas with adjacent normal tissues showed elevated PIK3CA messenger RNA (mRNA) levels in 18 % of tumor cases and elevated AKT2 mRNA levels in 14 %. Our findings, along with those of previous studies, underline the importance of the PI3K/AKT pathway components as potential biomarkers for breast carcinogenesis.

  3. SU-E-T-628: Predicted Risk of Post-Irradiation Cerebral Necrosis in Pediatric Brain Cancer Patients: A Treatment Planning Comparison of Proton Vs. Photon Therapy

    SciTech Connect

    Freund, D; Zhang, R; Sanders, M; Newhauser, W

    2015-06-15

    Purpose: Post-irradiation cerebral necrosis (PICN) is a severe late effect that can Result from brain cancers treatment using radiation therapy. The purpose of this study was to compare the treatment plans and predicted risk of PICN after volumetric modulated arc therapy (VMAT) to the risk after passively scattered proton therapy (PSPT) and intensity modulated proton therapy (IMPT) in a cohort of pediatric patients. Methods: Thirteen pediatric patients with varying age and sex were selected for this study. A clinical treatment volume (CTV) was constructed for 8 glioma patients and 5 ependymoma patients. Prescribed dose was 54 Gy over 30 fractions to the planning volume. Dosimetric endpoints were compared between VMAT and proton plans. The normal tissue complication probability (NTCP) following VMAT and proton therapy planning was also calculated using PICN as the biological endpoint. Sensitivity tests were performed to determine if predicted risk of PICN was sensitive to positional errors, proton range errors and selection of risk models. Results: Both PSPT and IMPT plans resulted in a significant increase in the maximum dose and reduction in the total brain volume irradiated to low doses compared with the VMAT plans. The average ratios of NTCP between PSPT and VMAT were 0.56 and 0.38 for glioma and ependymoma patients respectively and the average ratios of NTCP between IMPT and VMAT were 0.67 and 0.68 for glioma and ependymoma plans respectively. Sensitivity test revealed that predicted ratios of risk were insensitive to range and positional errors but varied with risk model selection. Conclusion: Both PSPT and IMPT plans resulted in a decrease in the predictive risk of necrosis for the pediatric plans studied in this work. Sensitivity analysis upheld the qualitative findings of the risk models used in this study, however more accurate models that take into account dose and volume are needed.

  4. Alcohol and Aggression.

    ERIC Educational Resources Information Center

    Gustafson, Roland

    1994-01-01

    Reviews the acute effects of alcohol on aggressive responding. From experimental studies that use human subjects, it is concluded that a moderate dose of alcohol does not increase aggression if subjects are unprovoked. Under provocative situations, aggression is increased as a function of alcohol intoxication, provided that subjects are restricted…

  5. Should aggressive thoracic therapy be performed in patients with synchronous oligometastatic non-small cell lung cancer? A meta-analysis

    PubMed Central

    Li, Dianhe; Wang, Haofei; Qiu, Min; Li, Na

    2017-01-01

    Background We performed a meta-analysis to compare overall survival (OS) outcomes in patients with synchronous oligometastatic non-small cell lung cancer (NSCLC) who underwent aggressive thoracic therapy (ATT) with those who did not. Methods A systematic review of controlled trials of ATT on survival in synchronous oligometastatic NSCLC was conducted. Hazard ratio (HR) for the main endpoint OS was pooled using a fixed-effects model. Subgroup analysis was performed in patients with single organ metastases, or with different numbers of brain metastases, or with different stages of thoracic disease. Pooled survival curves of OS were constructed. Results Seven eligible retrospective observational cohort studies were identified including 668 synchronous oligometastatic NSCLC patients, of whom 227 (34.0%) received ATT. For patients with synchronous oligometastatic NSCLC, ATT was associated with a significant improvement of OS (HR, 0.48; 95% CI, 0.39–0.60; P<0.00001). In subgroup analysis, the association with OS was similar or even strengthened, with a HR of 0.42 (95% CI, 0.31–0.56) in single organ metastases group, 0.49 (95% CI, 0.31–0.75) in solitary brain metastasis group, and 0.38 (95% CI, 0.20–0.73) in thoracic stage I–II group, respectively. The pooled cumulative survival rates for patients received ATT were 74.9% at 1 year, 52.1% at 2 years, 23.0% at 3 years, and 12.6% at 4 years. The corresponding pooled survival for patients who did not receive ATT were 32.3%, 13.7%, 3.7%, and 2.0%, respectively. Conclusions Survival benefit from ATT is common in synchronous oligometastatic patients. Selected patients with synchronous oligometastatic NSCLC could also achieve long-term survival with ATT. PMID:28275479

  6. Regional Deprivation and Non-Cancer Related Computed Tomography Use in Pediatric Patients in Germany: Cross-Sectional Analysis of Cohort Data

    PubMed Central

    Dreger, Steffen; Krille, Lucian; Maier, Werner; Pokora, Roman; Blettner, Maria; Zeeb, Hajo

    2016-01-01

    Background Conflicting findings were observed in recent studies assessing the association between patients’ area-level socio-economic status and the received number of computed tomography (CT) examinations in children. The aim was to investigate the association between area-level socio-economic status and variation in CT examination practice for pediatric patients in Germany. Methods Data from Radiology Information Systems for children aged 0 to < 15 years without cancer who had at least one CT examination between 2001 and 2010 were extracted in 20 hospitals across Germany. The small-area German Index of Multiple Deprivation (GIMD) was used to assess regional deprivation. The GIMD scores were classified into least, medium and most deprived areas and linked with the patient’s last known postal code. A multinomial logistic regression model was used to assess the association between patients’ CT numbers and regional deprivation adjusting for age, sex, and location of residence (urban/rural). Results A total of 37,810 pediatric patients received 59,571 CT scans during the study period. 27,287 (72%) children received only one CT, while n = 885 (2.3%) received six or more. Increasing numbers of CT examinations in non-cancer patients were significantly associated with higher regional deprivation, which increased, although CI overlap, for higher CT categories: ‘2–3 CT’ odds ratio (OR) = 1.45, 95%CI: 1.40–1.50; ‘4–5 CT’ OR = 1.48, 95%CI: 1.38–1.59; ‘6+CT’ OR = 1.54, 95%CI: 1.41–1.69. In addition, male sex, higher age categories, and specific body regions were positively associated with increased numbers of CT examinations. Conclusion We observed a positive association between regional deprivation and CT numbers in non-cancer pediatric patients. Limitations of the ecological approach and the lack of differentiation of CT details have to be acknowledged. More information on CT indications is necessary for a full assessment of this finding. In

  7. MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

    PubMed Central

    Chimal-Ramírez, G. K.; Espinoza-Sánchez, N. A.; Utrera-Barillas, D.; Benítez-Bribiesca, L.; Velázquez, J. R.; Arriaga-Pizano, L. A.; Monroy-García, A.; Reyes-Maldonado, E.; Domínguez-López, M. L.; Piña-Sánchez, Patricia; Fuentes-Pananá, E. M.

    2013-01-01

    Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets. PMID:23762835

  8. Pediatric Terminology

    Cancer.gov

    The National Institute of Child Health and Human Development (NICHD) is working with NCI Enterprise Vocabulary Services (EVS) to provide standardized terminology for coding pediatric clinical trials and other resea

  9. Pediatric Specialists

    MedlinePlus

    ... Family Life Family Life Family Life Medical Home Family Dynamics Media Work & Play Getting Involved in Your Community ... Family Life Medical Home Health Insurance Pediatric Specialists Family Dynamics Media Work & Play Getting Involved in Your Community ...

  10. Preclinical Testing of a New MR Imaging Approach to Distinguish Aggressive from Indolent Disease

    DTIC Science & Technology

    2014-06-01

    aggressiveness including histologic analysis, Ki-67 proliferative assays, lactate dehydrogenase (LDH) activity, LDH-A expression, cellularity, and micro...assay determinations of cancer aggressiveness including histologic analysis, Ki-67 proliferative assays, lactate dehydrogenase (LDH) activity, LDH-A...distinguish aggressive prostate cancers from indolent disease based on up- regulated lactate - dehydrogenase (LDH) conversion of HP-pyruvate to lactate and

  11. Pediatric Anthropometry

    NASA Astrophysics Data System (ADS)

    Klinich, Kathleen D.; Reed, Matthew P.

    Anthropometry is the measurement of human size, shape, and physical capabilities. Most pediatric anthropometry data are gathered to describe child growth patterns, but data on body size, mass distribution, range of motion, and posture are used to develop crash test dummies and computational models of child occupants. Pediatric anthropometry data are also used to determine child restraint dimensions, so they will accommodate the applicable population of child occupants.

  12. Survivin Expression and Prognostic Significance in Pediatric Malignant Peripheral Nerve Sheath Tumors (MPNST)

    PubMed Central

    Boldrin, Daniela; Merlo, Anna; Gambini, Claudio; Ferrari, Andrea; Dall'Igna, Patrizia; Coffin, Cheryl M.; Martines, Annalisa; Bonaldi, Laura; De Salvo, Gian Luca; Zanovello, Paola; Rosato, Antonio

    2013-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are very aggressive malignancies comprising approximately 5–10% of all soft tissue sarcomas. In this study, we focused on pediatric MPNST arising in the first 2 decades of life, as they represent one the most frequent non-rhabdomyosarcomatous soft tissue sarcomas in children. In MPNST, several genetic alterations affect the chromosomal region 17q encompassing the BIRC5/SURVIVIN gene. As cancer-specific expression of survivin has been found to be an effective marker for cancer detection and outcome prediction, we analyzed survivin expression in 35 tumor samples derived from young patients affected by sporadic and neurofibromatosis type 1-associated MPNST. Survivin mRNA and protein expression were assessed by Real-Time PCR and immunohistochemical staining, respectively, while gene amplification was analyzed by FISH. Data were correlated with the clinicopathological characteristics of patients. Survivin mRNA was overexpressed in pediatric MPNST and associated to a copy number gain of BIRC5; furthermore, increased levels of transcripts correlated with a higher FNCLCC tumor grade (grade 1 and 2 vs. 3, p = 0.0067), and with a lower survival probability (Log-rank test, p = 0.0038). Overall, these data support the concept that survivin can be regarded as a useful prognostic marker for pediatric MPNST and a promising target for therapeutic interventions. PMID:24303016

  13. Survivin expression and prognostic significance in pediatric malignant peripheral nerve sheath tumors (MPNST).

    PubMed

    Alaggio, Rita; Turrini, Riccardo; Boldrin, Daniela; Merlo, Anna; Gambini, Claudio; Ferrari, Andrea; Dall'igna, Patrizia; Coffin, Cheryl M; Martines, Annalisa; Bonaldi, Laura; De Salvo, Gian Luca; Zanovello, Paola; Rosato, Antonio

    2013-01-01

    Malignant peripheral nerve sheath tumors (MPNST) are very aggressive malignancies comprising approximately 5-10% of all soft tissue sarcomas. In this study, we focused on pediatric MPNST arising in the first 2 decades of life, as they represent one the most frequent non-rhabdomyosarcomatous soft tissue sarcomas in children. In MPNST, several genetic alterations affect the chromosomal region 17q encompassing the BIRC5/SURVIVIN gene. As cancer-specific expression of survivin has been found to be an effective marker for cancer detection and outcome prediction, we analyzed survivin expression in 35 tumor samples derived from young patients affected by sporadic and neurofibromatosis type 1-associated MPNST. Survivin mRNA and protein expression were assessed by Real-Time PCR and immunohistochemical staining, respectively, while gene amplification was analyzed by FISH. Data were correlated with the clinicopathological characteristics of patients. Survivin mRNA was overexpressed in pediatric MPNST and associated to a copy number gain of BIRC5; furthermore, increased levels of transcripts correlated with a higher FNCLCC tumor grade (grade 1 and 2 vs. 3, p = 0.0067), and with a lower survival probability (Log-rank test, p = 0.0038). Overall, these data support the concept that survivin can be regarded as a useful prognostic marker for pediatric MPNST and a promising target for therapeutic interventions.

  14. Hearing regulates Drosophila aggression.

    PubMed

    Versteven, Marijke; Vanden Broeck, Lies; Geurten, Bart; Zwarts, Liesbeth; Decraecker, Lisse; Beelen, Melissa; Göpfert, Martin C; Heinrich, Ralf; Callaerts, Patrick

    2017-02-21

    Aggression is a universal social behavior important for the acquisition of food, mates, territory, and social status. Aggression in Drosophila is context-dependent and can thus be expected to involve inputs from multiple sensory modalities. Here, we use mechanical disruption and genetic approaches in Drosophila melanogaster to identify hearing as an important sensory modality in the context of intermale aggressive behavior. We demonstrate that neuronal silencing and targeted knockdown of hearing genes in the fly's auditory organ elicit abnormal aggression. Further, we show that exposure to courtship or aggression song has opposite effects on aggression. Our data define the importance of hearing in the control of Drosophila intermale aggression and open perspectives to decipher how hearing and other sensory modalities are integrated at the neural circuit level.

  15. Ovatodiolide sensitizes aggressive breast cancer cells to doxorubicin, eliminates their cancer stem cell-like phenotype, and reduces doxorubicin-associated toxicity.

    PubMed

    Bamodu, Oluwaseun Adebayo; Huang, Wen-Chien; Tzeng, David T W; Wu, Alexander; Wang, Liang Shun; Yeh, Chi-Tai; Chao, Tsu-Yi

    2015-08-10

    Triple-negative breast cancer (TNBC) is chemotherapy-refractory and associated with poor clinical prognosis. Doxorubicin (Doxo), a class I anthracycline and first-line anticancer agent, effective against a wide spectrum of neoplasms including breast carcinoma, is associated with several cumulative dose-dependent adverse effects, including cardiomyopathy, typhilitis, and acute myelotoxicity. This study evaluated the usability of Ovatodiolide (Ova) in sensitizing TNBC cells to Doxo cytotoxicity, so as to reduce Doxo effective dose and consequently its adverse effects. TNBC cell lines MDA-MB-231 and HS578T were used. Pre-treatment of the TNBC cells with 10 µM Ova 24 h before Doxo administration increased the Doxo anticancer effect (IC50 1.4 µM) compared to simultaneous treatment with Doxo ( IC50 1.8 µM), or Doxo alone (IC50 9.2 µM). Intracellular accumulation of Doxo was lowest in Ova pre-treated cells at all Doxo concentrations, when compared with Doxo or simultaneously treated cells. In comparison to the Doxo-only group, cell cycle analysis of MDA-MB-231 cells treated concurrently with 2.5 µM Ova and 1.25 µM Doxo showed increased percentage of cells arrested at G0/G1; however, pre-treatment with the same concentration of Ova 24 h before Doxo showed greater tumor growth inhibition, with a 2.4-fold increased percentage of cells in G0/G1 arrest, greater Doxo-induced apoptosis, and significantly reduced intracellular Doxo accumulation. Additionally, Ova-sensitized TNBC cells also lost their cancer stem cell-like phenotype evidenced by significant dissolution, necrosis of formed mammospheres. Taken together, these findings indicate that Ova sensitizes TNBC cells to Doxo and potentiates doxorubicin-induced elimination of the TNBC cancer stem cell-like phenotype.

  16. The impact of RSV, adenovirus, influenza, and parainfluenza infection in pediatric patients receiving stem cell transplant, solid organ transplant, or cancer chemotherapy.

    PubMed

    Lo, Mindy S; Lee, Grace M; Gunawardane, Nilanthi; Burchett, Sandra K; Lachenauer, Catherine S; Lehmann, Leslie E

    2013-03-01

    RVIs are a significant cause of morbidity and mortality in immunocompromised children. We analyzed the characteristics and outcomes of infection by four respiratory viruses (RSV, adenovirus, influenza, and parainfluenza) treated at a pediatric tertiary care hospital in a retrospective cohort of patients who had received cancer chemotherapy, hematopoietic stem cell, or SOT. A total of 208 infections were studied among 166 unique patients over a time period of 1993-2006 for transplant recipients, and 2000-2005 for patients with cancer. RSV was the most common respiratory virus identified. There were 17 (10% of all patients) deaths overall, of which 12 were at least partly attributed to the presence of a RVI. In multivariate models, LRT symptoms in the absence of upper respiratory symptoms on presentation (OR 10.2 [2.3, 45.7], p = 0.002) and adenoviral infection (OR 3.7 [1.1, 12.6], p = 0.034) were significantly associated with poor outcome, defined as death or disability related to RVI. All of the deaths occurred in patients who had received either solid organ or HSCT. There were no infections resulting in death or disability in the cancer chemotherapy group.

  17. Prostate cancer staging

    MedlinePlus

    ... test. A faster increase could show a more aggressive tumor. A prostate biopsy is done in your ... suggest the cancer is slow growing and not aggressive. Higher numbers indicate a faster growing cancer that ...

  18. Estimation of the tumor size at cure threshold among aggressive non-small cell lung cancers (NSCLCs): evidence from the surveillance, epidemiology, and end results (SEER) program and the national lung screening trial (NLST).

    PubMed

    Goldwasser, Deborah L

    2017-03-15

    The National Lung Screening Trial (NLST) demonstrated that non-small cell lung cancer (NSCLC) mortality can be reduced by a program of annual CT screening in high-risk individuals. However, CT screening regimens and adherence vary, potentially impacting the lung cancer mortality benefit. We defined the NSCLC cure threshold as the maximum tumor size at which a given NSCLC would be curable due to early detection. We obtained data from 518,234 NSCLCs documented in the U.S. SEER cancer registry between 1988 and 2012 and 1769 NSCLCs detected in the NLST. We demonstrated mathematically that the distribution function governing the cure threshold for the most aggressive NSCLCs, G(x|Φ = 1), was embedded in the probability function governing detection of SEER-documented NSCLCs. We determined the resulting probability functions governing detection over a range of G(x|Φ = 1) scenarios and compared them with their expected functional forms. We constructed a simulation framework to determine the cure threshold models most consistent with tumor sizes and outcomes documented in SEER and the NLST. Whereas the median tumor size for lethal NSCLCs documented in SEER is 43 mm (males) and 40 mm (females), a simulation model in which the median cure threshold for the most aggressive NSCLCs is 10 mm (males) and 15 mm (females) best fit the SEER and NLST data. The majority of NSCLCs in the NLST were treated at sizes greater than our median cure threshold estimates. New technology is needed to better distinguish and treat the most aggressive NSCLCs when they are small (i.e., 5-15 mm).

  19. Pediatric Sarcomas.

    PubMed

    Williams, Regan F; Fernandez-Pineda, Israel; Gosain, Ankush

    2016-10-01

    Pediatric sarcomas are a heterogeneous group of tumors accounting for approximately 10% of childhood solid tumors. Treatment is focused on multimodality therapy, which has improved the prognosis over the past two decades. Current regimens focus on decreasing treatment for low-risk patients to decrease the long-term side effects while maximizing therapy for patients with metastatic disease to improve survival. Pediatric sarcomas can be divided into soft tissue sarcomas and osseous tumors. Soft tissue sarcomas are further delineated into rhabdomyosarcomas, which affect young children and nonrhabdomyosarcomas, which are most common in adolescents. The most common bone sarcomas are osteosarcomas and Ewing's sarcoma.

  20. Effective Prevention and Management of Tumor Lysis Syndrome in Children With Cancer: The Important Contributions of Pediatric Oncology Nurses.

    PubMed

    Li, Ho Cheung William; Chung, Oi Kwan Joyce; Tam, Ching Janice; Chiu, Sau Ying

    2015-01-01

    The practice guidelines aimed to identify appropriate nursing management for the prevention and treatment of tumor lysis syndrome, in line with the current evidence-based medical guidelines. Using a systematic approach, 15 relevant articles were identified for the review. The evaluation of patient risk factors for tumor lysis syndrome and the appropriate medical and nursing assessment were identified. The treatment algorithms for the prevention of tumor lysis syndrome from both the medical and nursing perspectives have been established. In particular, the guidelines highlight the importance of pediatric oncology nurses in contributing to the prevention and management of tumor lysis syndrome.

  1. TIMP-1 is under regulation of the EGF signaling axis and promotes an aggressive phenotype in KRAS-mutated colorectal cancer cells: A potential novel approach to the treatment of metastatic colorectal cancer

    PubMed Central

    Christensen, Ib J.; Nordgaard, Cathrine; Noer, Julie; Guren, Tormod K.; Glimelius, Bengt; Sorbye, Halfdan; Ikdahl, Tone; Kure, Elin H.; Tveit, Kjell M.; Nielsen, Hans J.

    2016-01-01

    It is now widely accepted that therapeutic antibodies targeting epidermal growth factor receptor (EGFR) can have efficacy in KRAS wild-type advanced colorectal cancer (CRC) patients. What remains to be ascertained is whether a subgroup of KRAS-mutated CRC patients might not also derive benefit from EGFR inhibitors. Metalloproteinase inhibitor 1 (TIMP-1) is a pleiotropic factor predictive of survival outcome of CRC patients. Levels of TIMP-1 were measured in pre-treatment plasma samples (n = 426) of metastatic CRC patients randomized to Nordic FLOX (5-fluorouracil and oxaliplatin) +/− cetuximab (NORDIC VII study). Multivariate analysis demonstrated a significant interaction between plasma TIMP-1 protein levels, KRAS status and treatment with patients bearing KRAS mutated tumors and high TIMP-1 plasma level (> 3rd quartile) showing a significantly longer overall survival if treated with cetuximab (HR, 0.48; 95% CI, 0.25 to 0.93). To gain mechanistic insights into this association we analyzed a set of five different CRC cell lines. We show here that EGFR signaling induces TIMP-1 expression in CRC cells, and that TIMP-1 promotes a more aggressive behavior, specifically in KRAS mutated cells. The two sets of data, clinical and in vitro, are complementary and support each other, lending strength to our contention that TIMP- 1 plasma levels can identify a subset of patients with KRAS-mutated metastatic CRC that will have benefit from EGFR-inhibition therapy. PMID:27509063

  2. MO-E-17A-09: Has Cancer Risk for Pediatric CT Increased Or Decreased? An Analysis of Cohort Data From 2004-2013

    SciTech Connect

    Brady, S; Kaufman, R

    2014-06-15

    Purpose: To analyze CT radiation dosimetry trends in a pediatric population imaged with modern (2004-2013) CT technology Methods: The institutional review board approved this retrospective review. Two cohorts of pediatric patients that received CT scans for treatment or surveillance for Wilms tumor (n=73) or Neuroblastoma (n=74) from 2004–2013 were included in this study. Patients were scanned during this time period on a GE Ultra (8 slice; 2004–2007), a GE VCT (2008–2011), or a GE VCT-XTe (2011–2013). Each patient's individual or combined chest, abdomen, and pelvic CT exams (n=4138) were loaded onto a PACS workstation (Intelerad, Canada) and measured to calculate their effective diameter and SSDE. Patient SSDE was used to estimate patient organ dosimetry based on previously published data. Patient's organ dosimetry were sorted by gender, weight, age, scan protocol (i.e., chest, abdomen, or pelvis), and CT scanner technology and averaged accordingly to calculate population averaged absolute and effective dose values. Results: Patient radiation dose burden calculated for all genders, weights, and ages decreased at a rate of 0.2 mSv/year (4.2 mGy/year; average organ dose) from 2004–2013; overall levels decreased by 50% from 3.0 mSv (60.0 mGy) to 1.5 mSv (25.9 mGy). Patient dose decreased at equal rates for both male and female, and for individual scan protocols. The greatest dose savings was found for patients between 0–4 years old (65%) followed by 5-9 years old (45%), 10–14 years old (30%), and > 14 years old (21%). Conclusion: Assuming a linear-nothreshold model, there always will be potential risk of cancer induction from CT. However, as demonstrated among these patient populations, effective and organ dose has decreased over the last decade; thus, potential risk of long-term side effects from pediatric CT examinations has also been reduced.

  3. SU-F-BRD-12: When Does Pencil Beam Scanning Become Superior to Passive Scattered Proton Therapy for Pediatric Head and Neck Cancers?

    SciTech Connect

    Moteabbed, M; Depauw, N; Kooy, H; Yock, T; Paganetti, H

    2015-06-15

    Purpose: To investigate the dosimetric benefits of pencil beam scanning (PBS) compared with passive scattered (PS) proton therapy for treatment of pediatric head&neck patients as a function of the PBS spot size and explore the advantages of using apertures in PBS. Methods: Ten pediatric patients with head&neck cancers treated by PS proton therapy at our institution were retrospectively selected. The histologies included rhabdomyosarcoma, ependymoma, astrocytoma, craniopharyngioma and germinoma. The prescribed dose ranged from 36 to 54 Gy(RBE). Five PBS plans were created for each patient using variable spot size (average sigma at isocenter) and choice of beam specific apertures: (1) 10mm spots, (2) 10mm spots with apertures, (3) 6mm spots, (4) 6mm spots with apertures, and (5) 3mm spots. The plans were optimized for intensity modulated proton therapy (IMPT) with no single beam uniformity constraints. Dose volume indices as well as equivalent uniform dose (EUD) were compared between PS and PBS plans. Results: Although target coverage was clinically adequate for all cases, the plans with largest (10mm) spots provide inferior quality compared with PS in terms of dose to organs-at-risk (OAR). However, adding apertures to these plans ensured lower OAR dose than PS. The average EUD difference between PBS and PS plans over all patients and organs at risk were (1) 2.5%, (2) −5.1%, (3) -5%, (4) −7.8%, and (5) −9.5%. As the spot size decreased, more conformal plans were achieved that offered similar target coverage but lower dose to the neighboring healthy organs, while alleviating the need for using apertures. Conclusion: The application of PBS does not always translate to better plan qualities compared to PS depending on the available beam spot size. We recommend that institutions with spot size larger than ∼6mm at isocenter consider using apertures to guarantee clinically comparable or superior dosimetric efficacy to PS treatments.

  4. Improving Pediatric Cancer Care Disparities Across the United States-Mexico Border: Lessons Learned from a Transcultural Partnership between San Diego and Tijuana.

    PubMed

    Aristizabal, Paula; Fuller, Spencer; Rivera, Rebeca; Beyda, David; Ribeiro, Raul C; Roberts, William

    2015-01-01

    In 2007, the 5-year survival rate for children with acute leukemia in Baja California, Mexico was estimated at 10% (vs. 88% in the United States). In response, stakeholders at St. Jude Children's Research Hospital, Rady Children's Hospital San Diego, and the Hospital General de Tijuana (HGT) implemented a transcultural partnership to establish a pediatric oncology program. The aim was to improve clinical outcomes and overall survival for children in Baja California. An initial needs assessment evaluation was performed and a culturally sensitive, comprehensive, 5-year plan was designed and implemented. After six years, healthcare system accomplishments include the establishment of a fully functional pediatric oncology unit with 60 new healthcare providers (vs. five in 2007). Patient outcome improvements include a rise in 5-year survival for leukemia from 10 to 43%, a rise in new cases diagnosed per year from 21 to 70, a reduction in the treatment abandonment rate from 10% to 2%, and a 45% decrease in the infection rate. More than 600 patients have benefited from this program. Knowledge sharing has taken place between teams at the HGT and Rady Children's Hospital San Diego. Further, one of the most significant outcomes is that the HGT has transitioned into a regional referral center and now mentors other hospitals in Mexico. Our results show that collaborative initiatives that implement long-term partnerships along the United States-Mexico border can effectively build local capacity and reduce the survival gap between children with cancer in the two nations. Long-term collaborative partnerships should be encouraged across other disciplines in medicine to further reduce health disparities across the United States-Mexico border.

  5. Improving Pediatric Cancer Care Disparities Across the United States–Mexico Border: Lessons Learned from a Transcultural Partnership between San Diego and Tijuana

    PubMed Central

    Aristizabal, Paula; Fuller, Spencer; Rivera, Rebeca; Beyda, David; Ribeiro, Raul C.; Roberts, William

    2015-01-01

    In 2007, the 5-year survival rate for children with acute leukemia in Baja California, Mexico was estimated at 10% (vs. 88% in the United States). In response, stakeholders at St. Jude Children’s Research Hospital, Rady Children’s Hospital San Diego, and the Hospital General de Tijuana (HGT) implemented a transcultural partnership to establish a pediatric oncology program. The aim was to improve clinical outcomes and overall survival for children in Baja California. An initial needs assessment evaluation was performed and a culturally sensitive, comprehensive, 5-year plan was designed and implemented. After six years, healthcare system accomplishments include the establishment of a fully functional pediatric oncology unit with 60 new healthcare providers (vs. five in 2007). Patient outcome improvements include a rise in 5-year survival for leukemia from 10 to 43%, a rise in new cases diagnosed per year from 21 to 70, a reduction in the treatment abandonment rate from 10% to 2%, and a 45% decrease in the infection rate. More than 600 patients have benefited from this program. Knowledge sharing has taken place between teams at the HGT and Rady Children’s Hospital San Diego. Further, one of the most significant outcomes is that the HGT has transitioned into a regional referral center and now mentors other hospitals in Mexico. Our results show that collaborative initiatives that implement long-term partnerships along the United States–Mexico border can effectively build local capacity and reduce the survival gap between children with cancer in the two nations. Long-term collaborative partnerships should be encouraged across other disciplines in medicine to further reduce health disparities across the United States–Mexico border. PMID:26157788

  6. Moral Distress in Pediatric Healthcare Providers.

    PubMed

    Trotochaud, Karen; Coleman, Joyce Ramsey; Krawiecki, Nicolas; McCracken, Courtney

    2015-01-01

    Pediatric providers across professions and clinical settings experience moral distress. Higher moral distress correlates with intent to leave for all professionals. Physicians as professional group had the highest moral distress. Intensive care nurses had the highest moral distress for nurses. While all providers describe distressing scenarios as disturbing, physicians report situations as occurring more frequently. The most distressing situations include requests for aggressive treatments not in child's best interest, poor team communication and lack of provider continuity. Understanding moral distress as experienced by all pediatric providers is needed to create interventions with a goal of reducing provider turnover.

  7. Myocarditis - pediatric

    MedlinePlus

    ... enable JavaScript. Pediatric myocarditis is inflammation of the heart muscle in an infant or young child. Causes Myocarditis is rare in ... the infection. This can lead to symptoms of heart failure. ... to detect. However, in newborns and infants, symptoms may sometimes appear suddenly. Symptoms may include: ...

  8. Pediatric ultrasonography

    SciTech Connect

    Hayden, C.K. Jr.; Swischuk, L.E.

    1987-01-01

    Two leading experts explore the benefits and limitations of pediatric ultrasonography, explaining the latest techniques for optimal imaging of specific body regions: the head, chest, abdomen, pelvis, extremities, and soft tissues. Numerous illustrations emphasize significant points and combine with the text to show specifically what to look for when imaging children.

  9. Pediatric Dermatology

    PubMed Central

    McMahon, Patrick

    2017-01-01

    Skin changes are common in children. Common concerns are birthmarks (e.g., hemangiomas and port wine stains), atopic and contact dermatitis, acne, and alopecia areata. The authors review advances in common and not so common skin changes in pediatric patients. PMID:28360970

  10. Pediatric Sinusitis

    MedlinePlus

    ... Your child’s sinuses are not fully developed until late in the teen years. Although small, the maxillary (behind the cheek) and ethmoid (between the eyes) sinuses are present at birth. Unlike in adults, pediatric sinusitis is difficult to ...

  11. Eyelid Cancer

    MedlinePlus

    ... Content ASCO Conquer Cancer Foundation Journal of Clinical Oncology Journal of Oncology Practice ASCO University Donate eNEWS SIGNUP f Cancer. ... of medical, surgical, radiation, gynecologic, and pediatric oncologists, oncology nurses, physician assistants, social workers, and patient advocates. ...

  12. Appendix Cancer

    MedlinePlus

    ... Content ASCO Conquer Cancer Foundation Journal of Clinical Oncology Journal of Oncology Practice ASCO University Donate eNEWS SIGNUP f Cancer. ... of medical, surgical, radiation, gynecologic, and pediatric oncologists, oncology nurses, physician assistants, social workers, and patient advocates. ...

  13. Anal Cancer

    MedlinePlus

    ... Content ASCO Conquer Cancer Foundation Journal of Clinical Oncology Journal of Oncology Practice ASCO University Donate eNEWS SIGNUP f Cancer. ... of medical, surgical, radiation, gynecologic, and pediatric oncologists, oncology nurses, physician assistants, social workers, and patient advocates. ...

  14. Development of a Pediatric Adverse Events Terminology

    PubMed Central

    Gipson, Debbie S.; Kirkendall, Eric S.; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A.; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M.; Haber, Margaret; Hirschfeld, Steven

    2017-01-01

    In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute’s Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute’s Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization. PMID:28028203

  15. Development of a Pediatric Adverse Events Terminology.

    PubMed

    Gipson, Debbie S; Kirkendall, Eric S; Gumbs-Petty, Brenda; Quinn, Theresa; Steen, A; Hicks, Amanda; McMahon, Ann; Nicholas, Savian; Zhao-Wong, Anna; Taylor-Zapata, Perdita; Turner, Mark; Herreshoff, Emily; Jones, Charlotte; Davis, Jonathan M; Haber, Margaret; Hirschfeld, Steven

    2017-01-01

    In 2009, the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) established the Pediatric Terminology Harmonization Initiative to establish a core library of terms to facilitate the acquisition and sharing of knowledge between pediatric clinical research, practice, and safety reporting. A coalition of partners established a Pediatric Terminology Adverse Event Working Group in 2013 to develop a specific terminology relevant to international pediatric adverse event (AE) reporting. Pediatric specialists with backgrounds in clinical care, research, safety reporting, or informatics, supported by biomedical terminology experts from the National Cancer Institute's Enterprise Vocabulary Services participated. The multinational group developed a working definition of AEs and reviewed concepts (terms, synonyms, and definitions) from 16 pediatric clinical domains. The resulting AE terminology contains >1000 pediatric diseases, disorders, or clinical findings. The terms were tested for proof of concept use in 2 different settings: hospital readmissions and the NICU. The advantages of the AE terminology include ease of adoption due to integration with well-established and internationally accepted biomedical terminologies, a uniquely temporal focus on pediatric health and disease from conception through adolescence, and terms that could be used in both well- and underresourced environments. The AE terminology is available for use without restriction through the National Cancer Institute's Enterprise Vocabulary Services and is fully compatible with, and represented in, the Medical Dictionary for Regulatory Activities. The terminology is intended to mature with use, user feedback, and optimization.

  16. Testosterone and Aggression.

    ERIC Educational Resources Information Center

    Archer, John

    1994-01-01

    Studies comparing aggressive and nonaggressive prisoners show higher testosterone levels among the former. While there is limited evidence for a strong association between aggressiveness and testosterone during adolescence, other studies indicate that testosterone levels are responsive to influences from the social environment, particularly those…

  17. Social Aggression among Girls.

    ERIC Educational Resources Information Center

    Underwood, Marion K.

    Noting recent interest in girls' social or "relational" aggression, this volume offers a balanced, scholarly analysis of scientific knowledge in this area. The book integrates current research on emotion regulation, gender, and peer relations, to examine how girls are socialized to experience and express anger and aggression from infancy…

  18. Neuropsychiatry of Aggression

    PubMed Central

    Lane, Scott D.; Kjome, Kimberly L.; Moeller, F. Gerard

    2010-01-01

    Synopsis Aggression is a serious medical problem that can place both the patient and the health care provider at risk. Aggression can result from medical, neurologic and or psychiatric disorders. A comprehensive patient evaluation is needed. Treatment options include pharmacotherapy as well as non-pharmacologic interventions, both need to be individualized to the patient. PMID:21172570

  19. Humor, Aggression, and Aging.

    ERIC Educational Resources Information Center

    Barrick, Ann Louise; And Others

    Although humor is an important phenomenon in human interactions, it has rarely been studied in the elderly. An understanding of responses to humor in aggressive cartoons as a function of advancing age would provide information regarding both the development of humor and the negative (aggressive) emotional experiences of the elderly. This study was…

  20. Serotonin and Aggression.

    ERIC Educational Resources Information Center

    Brown, Serena-Lynn; And Others

    1994-01-01

    Decreased serotonin function has consistently been shown to be highly correlated with impulsive aggression across a number of different experimental paradigms. Such lowered serotonergic indices appear to correlate with the dimension of aggression dyscontrol and/or impulsivity rather than with psychiatric diagnostic categories per se. Implications…

  1. 4-Acetylantroquinonol B suppresses autophagic flux and improves cisplatin sensitivity in highly aggressive epithelial cancer through the PI3K/Akt/mTOR/p70S6K signaling pathway.

    PubMed

    Liu, Mingche; Bamodu, Oluwaseun Adebayo; Huang, Wen-Chien; Zucha, Muhammad Ary; Lin, Yen-Kuang; Wu, Alexander T H; Huang, Chun-Chih; Lee, Wei-Hwa; Yuan, Chiou-Chung; Hsiao, M; Deng, Li; Tzeng, Yew-Min; Yeh, Chi-Tai

    2017-04-10

    Targeting residual self-renewing, chemoresistant cancerous cells may represent the key to overcoming therapy resistance. The entry of these quiescent cells into an activated state is associated with high metabolic demand and autophagic flux. Therefore, modulating the autophagy pathway in aggressive carcinomas may be beneficial as a therapeutic modality. In this study, we evaluated the anti-tumor activities of 4-acetylantroquinonol B (4-AAQB) in chemoresistant ovarian cancer cells, particularly its ability to modulate autophagy through autophagy-related genes (Atg). Atg-5 was overexpressed in invasive ovarian cancer cell lines and tissue (OR: 5.133; P=0.027) and depleting Atg-5 in ES-2 cell lines significantly induced apoptosis. 4-AAQB effectively suppressed viability of various subtypes of ovarian cancer. Cells with higher cisplatin-resistance were more responsive to 4-AAQB. For the first time, we demonstrate that 4-AAQB significantly suppress Atg-5 and Atg-7 expression with decreased autophagic flux in ovarian cancer cells via inhibition of the PI3K/Akt/mTOR/p70S6K signaling pathway. Similar to Atg-5 silencing, 4-AAQB-induced autophagy inhibition significantly enhanced cell death in vitro. These results are comparable to those of hydroxychloroquine (HCQ). In addition, 4-AAQB/cisplatin synergistically induced apoptosis in ovarian cancer cells. In vivo, 4-AAQB/cisplatin also significantly induced apoptosis and autophagy in an ES-2 mouse xenografts model. This is the first report demonstrating the efficacy of 4-AAQB alone or in combination with cisplatin on the suppression of ovarian cancer via Atg-5-dependent autophagy. We believe these findings will be beneficial in the development of a novel anti-ovarian cancer therapeutic strategy.

  2. Improving outcomes for children with cancer in low-income countries in Latin America: a report on the recent meetings of the Monza International School of Pediatric Hematology/Oncology (MISPHO)-Part I.

    PubMed

    Howard, Scott C; Marinoni, Marco; Castillo, Luis; Bonilla, Miguel; Tognoni, Gianni; Luna-Fineman, Sandra; Antillon, Federico; Valsecchi, Maria Grazia; Pui, Ching-Hon; Ribeiro, Raul C; Sala, Alessandra; Barr, Ronald D; Masera, Giuseppe

    2007-03-01

    The difference in survival for children diagnosed with cancer between high- and low-income countries (LIC) continues to widen as curative therapies are developed in the former but not implemented in the latter. In 1996, the Monza International School of Pediatric Hematology/Oncology (MISPHO) was founded in an attempt to narrow this survival gap. During its sixth and seventh meetings, members recognized the problem of lack of affordability of essential drugs to treat childhood cancer in many LIC, and initiated an advocacy program. In 1998, MISPHO spawned a collaboration of Central American pediatric oncology centers: the Asociación de Hemato-Oncología Pediátrica Centroamericana (AHOPCA). AHOPCA members reported preliminary findings from several of the 10 cooperative protocols that are currently in progress. In 2003, a second regional collaborative group was formed that includes seven centers in South America. Twinning programs between MISPHO centers and centers in high-income countries (HIC) have proven invaluable to harness the resources of these centers to improve pediatric oncology care in LIC. MISPHO educational efforts include oncology nursing, supportive care, cancer-specific updates, epidemiology, and clinical research methods. Educational efforts are facilitated by educational content and online conferencing via www.cure4kids.org. Identifying preventable causes of abandonment of therapy and documenting the nutritional status of patients treated at MISPHO centers are areas of active research.

  3. Pediatric solid tumor genomics and developmental pliancy.

    PubMed

    Chen, X; Pappo, A; Dyer, M A

    2015-10-08

    Pediatric solid tumors are remarkably diverse in their cellular origins, developmental timing and clinical features. Over the last 5 years, there have been significant advances in our understanding of the genetic lesions that contribute to the initiation and progression of pediatric solid tumors. To date, over 1000 pediatric solid tumors have been analyzed by Next-Generation Sequencing. These genomic data provide the foundation to launch new research efforts to address one of the fundamental questions in cancer biology-why are some cells more susceptible to malignant transformation by particular genetic lesions at discrete developmental stages than others? Because of their developmental, molecular, cellular and genetic diversity, pediatric solid tumors provide an ideal platform to begin to answer this question. In this review, we highlight the diversity of pediatric solid tumors and provide a new framework for studying the cellular and developmental origins of pediatric cancer. We also introduce a new unifying concept called cellular pliancy as a possible explanation for susceptibility to cancer and the developmental origins of pediatric solid tumors.

  4. Biopsy: Types of Biopsy Procedures Used to Diagnose Cancer

    MedlinePlus

    ... A biopsy also helps your doctor determine how aggressive your cancer is — the cancer's grade. The grade ... grade (grade 1) cancers are generally the least aggressive and high-grade (grade 4) cancers are generally ...

  5. Pediatric sleep apnea

    MedlinePlus

    Sleep apnea - pediatric; Apnea - pediatric sleep apnea syndrome; Sleep-disordered breathing - pediatric ... During sleep, all of the muscles in the body become more relaxed. This includes the muscles that help keep ...

  6. Children's (Pediatric) Nuclear Medicine

    MedlinePlus Videos and Cool Tools

    ... Professions Site Index A-Z Children's (Pediatric) Nuclear Medicine Children’s (pediatric) nuclear medicine imaging uses small amounts ... Children's Nuclear Medicine? What is Children's (Pediatric) Nuclear Medicine? Nuclear medicine is a branch of medical imaging ...

  7. Pediatric tracheostomy.

    PubMed

    Campisi, Paolo; Forte, Vito

    2016-06-01

    Tracheotomy refers to a surgical incision made into a trachea. Tracheostomy, on the other hand, refers to a surgical procedure whereby the tracheal lumen is positioned in close proximity to the skin surface. Tracheostomy is an uncommon procedure in the pediatric population. When required tracheostomy is typically performed as an open surgical procedure under general anesthesia with the patient intubated. However, it may need to be performed under local anesthesia or over a rigid bronchoscope in the patient with a precarious airway. Over the past half century, the primary indication for pediatric tracheostomy has shifted from acute infectious airway compromise to the need for prolonged ventilatory support in neurologically compromised children. The surgical technique, choice of tracheostomy tube, and post-operative care requires a nuanced approach in infants and young children. This article will review these topics in a comprehensive fashion.

  8. Pediatric parasomnias.

    PubMed

    Mason, Thornton B A; Pack, Allan I

    2007-02-01

    Parasomnias in childhood are common, and often more frequent than in adults. The large number of parasomnias underscore that sleep is not simply a quiescent state, but can involve complex episodes of movement, ranging from subtle to dramatic and complex. Clinicians should be aware that many pediatric parasomnias are benign, self-limited, and may not persist into late childhood or adolescence. Importantly, parasomnias in childhood often differ in type from adults. Nevertheless, parasomnias across ages can be classified as: 1) disorders of arousal (from non-rapid eye movement, or NREM, sleep); 2) parasomnias usually associated with REM sleep; and 3) other parasomnias. We detail here issues in the clinical diagosis, evaluation, and management of multiple pediatric parasomnias. The further study of parasomnias in children may help elucidate the multi-factorial etiologies of these fascinating conditions, shedding light on the potential genetic bases as well as environmental contributions.

  9. The proteomics of pediatric brain tumors.

    PubMed

    Anagnostopoulos, Athanasios K; Tsangaris, George T

    2014-10-01

    Pediatric tumors of the CNS are the leading cause of cancer-related mortality in children. In pediatric pathology, brain tumors constitute the most frequent solid malignancy. An unparalleled outburst of information in pediatric neuro-oncology research has been witnessed over the last few years, largely due to increased use of high-throughput technologies such as genomics, proteomics and meta-analysis tools. Input from these technologies gives scientists the advantage of early prognosis assessment, more accurate diagnosis and prospective curative intent in the pediatric brain tumor clinical setting. The present review aims to summarize current knowledge on research applying proteomics techniques or proteomics-based approaches performed on pediatric brain tumors. Proteins that can be used as potential disease markers or molecular targets, and their biological significance, are herein listed and discussed. Furthermore, future perspectives that proteomics technologies may offer regarding this devastating disorder are presented.

  10. Pediatric stridor.

    PubMed

    Ida, Jonathan B; Thompson, Dana Mara

    2014-10-01

    Pediatric stridor is an important symptom of upper airway obstruction, and must be recognized early by evaluating physicians. Proper evaluation and management, both acutely and chronically, can provide improved outcomes and better quality of life for patients. This article discusses the physiology of stridor and its intimate relation to airway anatomy, the work-up of the stridorous child, and recent advances in treatment, and provides illustrative examples of common lesions.

  11. Pediatric nutrition.

    PubMed

    Greco, Deborah S

    2014-03-01

    This article discusses pediatric nutrition in puppies and kittens. Supplementation of basic nutrients such as fat, protein, minerals, vitamins, and essential fatty acids of the bitch is essential for the proper growth and development of puppies during the lactation period. Milk replacers are compared for use in puppies and kittens. Supplements such as colostrum and probiotics for promotion of a healthy immune system and prevention or treatment of stress-induced and weaning diarrhea are also discussed.

  12. Pediatric Virology

    PubMed Central

    Portnoy, Bernard

    1965-01-01

    Pediatric virology is not an isolàted discipline. Rather, the syndromes associated with viral infection are modified by the unique characteristics of infancy and childhood. Fortunately for the pediatrician, and certainly for children, viral infections in childhood are rarely fatal, and are almost never serious. Future efforts of the pediatrician and virologist should be directed toward increased fetal salvage as with rubella and the prevention of severe, viral lower respiratory tract disease. PMID:14298871

  13. Pediatric sialendoscopy.

    PubMed

    Bruch, Jean M; Setlur, Jennifer

    2012-01-01

    Sialendoscopy was introduced in the early 1990s as a minimally invasive alternative to standard methods for diagnosis and treatment of inflammatory and obstructive salivary gland disease. The technique was pioneered in adults; however, advances in instrumentation have allowed this to be adapted to the smaller salivary ductal anatomy found in the pediatric population. In this chapter, the technique of sialendoscopy for parotid and submandibular glands is described.

  14. Aggression and sport.

    PubMed

    Burton, Robert W

    2005-10-01

    Viewing aggression in its healthy form, in contrast to its extreme and inappropriate versions, and sport as a health-promoting exercise in psychological development and maturation may allow participants and spectators alike to retain an interest in aggression and sport and derive further enjoyment from them. In addition, it will benefit all involved with sport to have a broader understanding of human aggression. Physicians, mental health professionals, and other health care providers can be influential in this process, and should be willing to get involved and speak out when issues and problems arise.

  15. Development and implementation of a pediatric palliative care program.

    PubMed

    Pelant, Diane; McCaffrey, Terri; Beckel, Jean

    2012-08-01

    Palliative care, long-used in the adult setting, is new to the pediatric setting. Research indicates that palliative care reduces length of stay and use of aggressive end-of-life interventions, improves quality of life, and provides hope. It balances provision of coordinated care with building of family memories and preparation for the child's death with celebration of the child's life. We advocate implementation of pediatric palliative care in any hospital that cares for children. This article provides a model outlining critical steps and considerations for establishing a successful pediatric palliative care program.

  16. Identification of a novel BET bromodomain inhibitor-sensitive, gene regulatory circuit that controls Rituximab response and tumour growth in aggressive lymphoid cancers

    PubMed Central

    Emadali, Anouk; Rousseaux, Sophie; Bruder-Costa, Juliana; Rome, Claire; Duley, Samuel; Hamaidia, Sieme; Betton, Patricia; Debernardi, Alexandra; Leroux, Dominique; Bernay, Benoit; Kieffer-Jaquinod, Sylvie; Combes, Florence; Ferri, Elena; McKenna, Charles E; Petosa, Carlo; Bruley, Christophe; Garin, Jérôme; Ferro, Myriam; Gressin, Rémy; Callanan, Mary B; Khochbin, Saadi

    2013-01-01

    Immuno-chemotherapy elicit high response rates in B-cell non-Hodgkin lymphoma but heterogeneity in response duration is observed, with some patients achieving cure and others showing refractory disease or relapse. Using a transcriptome-powered targeted proteomics screen, we discovered a gene regulatory circuit involving the nuclear factor CYCLON which characterizes aggressive disease and resistance to the anti-CD20 monoclonal antibody, Rituximab, in high-risk B-cell lymphoma. CYCLON knockdown was found to inhibit the aggressivity of MYC-overexpressing tumours in mice and to modulate gene expression programs of biological relevance to lymphoma. Furthermore, CYCLON knockdown increased the sensitivity of human lymphoma B cells to Rituximab in vitro and in vivo. Strikingly, this effect could be mimicked by in vitro treatment of lymphoma B cells with a small molecule inhibitor for BET bromodomain proteins (JQ1). In summary, this work has identified CYCLON as a new MYC cooperating factor that autonomously drives aggressive tumour growth and Rituximab resistance in lymphoma. This resistance mechanism is amenable to next-generation epigenetic therapy by BET bromodomain inhibition, thereby providing a new combination therapy rationale for high-risk lymphoma. The nuclear factor CYCLON is a new MYC cooperating factor that drives tumor growth and Rituximab resistance in lymphoma. This resistance mechanism can be targeted by next-generation epigenetic therapy by BET bromodomain inhibition downstream of MYC. PMID:23828858

  17. Pediatric radiation oncology

    SciTech Connect

    Halperin, E.C.; Kun, L.E.; Constine, L.S.; Tarbell, N.J.

    1989-01-01

    This text covers all aspects of radiation therapy for treatment of pediatric cancer. The book describes the proper use of irradiation in each of the malignancies of childhood, including tumors that are rarely encountered in adult practice. These include acute leukemia; supratentorial brain tumors; tumors of the posterior fossa of the brain and spinal canal; retinoblastoma and optic nerve glioma; neuroblastoma; Hodgkin's disease; malignant lymphoma; Ewing's sarcoma; osteosarcoma; rhabdomyosarcoma; Desmoid tumor; Wilms' tumor; liver and biliary tumors; germ cell and stromal cell tumors of the gonads; endocrine, aerodigestive tract, and breast tumors; Langerhans' cell histiocytosis; and skin cancer and hemangiomas. For each type of malignancy, the authors describe the epidemiology, common presenting signs and symptoms, staging, and proper diagnostic workup. Particular attention is given to the indications for radiation therapy and the planning of a course of radiotherapy, including the optimal radiation dose, field size, and technique.

  18. Aggression in Pretend Play and Aggressive Behavior in the Classroom

    ERIC Educational Resources Information Center

    Fehr, Karla K.; Russ, Sandra W.

    2013-01-01

    Research Findings: Pretend play is an essential part of child development and adjustment. However, parents, teachers, and researchers debate the function of aggression in pretend play. Different models of aggression predict that the expression of aggression in play could either increase or decrease actual aggressive behavior. The current study…

  19. Pediatric oncology in Morocco: achievements and challenges.

    PubMed

    Hessissen, Laila; Madani, Abdellah

    2012-03-01

    Cancer in children is quickly becoming one of the leading causes of non traumatic death among children. In pediatric oncology, palliative care is a primary component of the cancer control plan. In low income countries also known as emerging nations or developing countries access to adequate care remains a challenge for most pediatric oncology patients. In Morocco the situation has dramatically improved in the last few years as both the government and NGOs have become more aware of the importance and urgency of the issue. The incidence of cancer in patients under 15 years of age in Morocco is estimated to be 1000 new cases per year and the incidence of leukemia to be 100 new cases diagnosed per year. Pediatric cancer patients are mostly managed by public hospitals. Thus they are highly influenced by the Moroccan public health system, which is now considering cancer management a priority. Since health cover is very limited, most chemotherapy drugs were purchased by local parent associations. Recently, a new large Moroccan NGO (ALSC) provides anti-cancer drugs to all government-run oncology units. Despite all the progress, Morocco has witnessed in the pediatric oncology field, the palliative aspect of the care is not yet organized. Pediatric oncology is supported by the work of the National Society of Pediatric Oncolgy. The opioide therapy is available. However its use is strongly limited by the current restrictive and obsolete legislation which represents a major barrier to care. Despite the latest progress, pediatric oncology in Morocco still needs to improve in order to achieve performances comparable to those of the developed world. These improvements include better survival rates, less treatment abandonment, developing new techniques, improving quality of life and creating data collection teams. In order for this action to succeed all the stakeholders (government, NGOs, medical societies, oncology teams) must work together and coordinate their efforts.

  20. ¹⁸F-FDG PET/CT in the early prediction of pathological response in aggressive subtypes of breast cancer: review of the literature and recommendations for use in clinical trials.

    PubMed

    Groheux, David; Mankoff, David; Espié, Marc; Hindié, Elif

    2016-05-01

    Early assessment of response to neoadjuvant chemotherapy (NAC) might be helpful in avoiding the toxicity of ineffective chemotherapy and allowing refinement of treatment. We conducted a review of the literature regarding the applicability of (18)F-FDG PET/CT to the prediction of an early pathological response in different subgroups of breast cancer. Clinical research in this field has intensified in the last few years. Early studies by various groups have shown the potential of (18)F-FDG PET/CT in the early assessment of response to NAC. However, interim PET/CT in breast cancer has not yet gained wide acceptance compared to its use in other settings such as lymphomas. This is in part due to a lack of consensus that early evaluation of response can be used to direct change in therapy in the neoadjuvant breast cancer setting, and only limited data showing that response-adaptive therapy leads to improved outcomes. However, one major element that has hampered the use of (18)F-FDG PET/CT in directing neoadjuvant therapy is its evaluation in populations with mixed subtypes of breast cancer. However, major improvements have occurred in recent years. Pilot studies have highlighted the need for considering breast cancer subtype and the type of treatment, and have offered criteria for the use of PET/CT for the early prediction of response in specific settings. (18)F-FDG PET/CT has considerable potential for the early prediction of pathological complete response to NAC in aggressive subtypes such as triple-negative or HER2-positive breast cancers. The results of a multicentre trial that used early metabolic response on (18)F-FDG PET/CT as a means to select poor responders to adapt neoadjuvant treatment have recently been published. Other trials are ongoing or being planned.

  1. Pediatric soft tissue tumor pathology: A happy morpho-molecular union.

    PubMed

    O'Sullivan, Maureen

    2016-11-01

    Since its foundation by remarkably talented and insightful individuals, prominently including Pepper Dehner, pediatric soft tissue tumor pathology has developed at an immense rate. The morphologic classification of tumoral entities has extensively been corroborated, but has also evolved with refinement or realignment of these classifications, through accruing molecular data, with many derivative ancillary diagnostic assays now already well-established. Tumors of unclear histogenesis, classically morphologically undifferentiated, are prominent amongst pediatric sarcomas, however, the classes of undifferentiated round- or spindle-cell-tumors-not-otherwise-specified are being dismantled gradually with the identification of their molecular underpinnings. Within recent years, for example, numerous subcategories of 'Ewing-like' round cell sarcoma have emerged. Such advances have provided the basis for novel diagnostic and prognostic sub-classifications. Efforts at defining cell- or lineage-of-origin for several tumor types have produced interesting insights especially for rhabdomyosarcoma. The remarkably early onset of pediatric sarcomas defies the theory necessitating stochastic accumulation of several somatic mutations for cancer development and indeed, these tumors may be remarkably genomically stable, often belying their aggressive nature. Much is coming to light recently regarding the role of epigenetic modifications in the evolution of these sarcomas. Indeed the morphologic features of embryonal tumors generally (not just sarcomas) may be highly reminiscent of arrested differentiation, and given the tight epigenetic regulation of cell fate determination and cell identity maintenance, a theory of epigenetically-driven oncogenesis sits easily with these tumors. The age-delimited distinct biologies of 'pediatric' and adult GIST are intriguing, particularly, the SDH-deficient 'pediatric' form, driven by a metabolic defect, but resulting in epigenetic dysregulation with

  2. Predictors of Aggressive Inflammatory Bowel Disease

    PubMed Central

    Yarur, Andres J.; Strobel, Sebastian G.; Deshpande, Amar R.

    2011-01-01

    Inflammatory bowel disease comprises a group of conditions characterized by idiopathic inflammation of the gastrointestinal tract. The natural course of disease can range from an indolent course with prolonged periods of remission to aggressive, incapacitating disease. Predicting which patients are more susceptible to developing severe disease is important, especially when choosing therapeutic agents and treatment strategies. This paper reviews current evidence on the main demographic, clinical, endoscopic, histologic, serologic, and genetic markers that predict aggressive inflammatory bowel disease. In ulcerative colitis, we considered disease to be aggressive when patients had a high relapse rate, need for admission and/or surgery, development of colon cancer, or extraintestinal manifestations. We defined aggressive Crohn's disease as having a high relapse rate, development of penetrating disease, need for repeat surgery, or multiple admissions for flares. In Crohn's disease, involvement of the upper gastrointestinal tract and ileum, penetrating disease, early age at diagnosis, smoking, extensive ulceration of the mucosa, high titers of serum antibodies, and mutations of the NOD2 gene are markers of aggressive disease. In ulcerative colitis, patients with more extensive involvement of the colon (pancolitis) have more symptomatology and are at higher risk for needing a colectomy and developing colon cancer. Also, plasmocytic infiltration of the colonic mucosa and crypt atrophy predict treatment failure. As with diagnosis, no single method can predict disease aggressiveness. Multiple serologic and genetic tests are being developed to refine the accuracy of prediction. Endoscopic findings can also predict the future course of disease. At present, clinical manifestations are the most useful way to make therapeutic decisions. PMID:22298958

  3. Pediatric vitiligo.

    PubMed

    Silverberg, Nanette B

    2014-04-01

    Vitiligo is a disease of pigment loss. Most investigators currently consider vitiligo to be a disorder that occurs as a result of autoimmune destruction of melanocytes, supported by identification of antimelanocyte antibodies in many patients, and the presence of comorbid autoimmune disease in patients with and family members of individuals with vitiligo. One-half of vitiligo cases are of childhood onset. This article presents a current overview of pediatric vitiligo including comorbidities of general health, psychological factors, therapeutic options, and long-term health considerations.

  4. Pediatric Appendicitis.

    PubMed

    Rentea, Rebecca M; St Peter, Shawn D

    2017-02-01

    Appendicitis is one of the most common surgical pathologies in children. It can present with right lower quadrant pain. Scoring systems in combination with selective imaging and surgical examination will diagnose most children with appendicitis. Clinical pathways should be used. Most surgical interventions for appendicitis are now almost exclusively laparoscopic, with trials demonstrating better outcomes for children who undergo index hospitalization appendectomies when perforated. Nonoperative management has a role in the treatment of both uncomplicated and complicated appendicitis. This article discusses the workup and management, modes of treatment, and continued areas of controversy in pediatric appendicitis.

  5. Pediatric urticaria.

    PubMed

    Tsakok, Teresa; Du Toit, George; Flohr, Carsten

    2014-02-01

    Although urticaria is not a life-threatening disease, its impact on quality of life in children should not be overlooked. A systematic search of online databases, including Medline, was performed to inform a review aiming to equip clinicians with an evidence-based approach to all aspects of pediatric urticaria. This review hinges on an illustrative case and includes a summary table of studies pertaining to disease management in children. The multiple issues faced by patients, their families, and treating clinicians are highlighted, and the current literature on the presentation, natural history, investigation, and management of this poorly understood condition is assessed.

  6. Pediatric vasculitis.

    PubMed

    Weiss, Pamela F

    2012-04-01

    Childhood vasculitis is a challenging and complex group of conditions that are multisystem in nature and often require integrated care from multiple subspecialties, including rheumatology, dermatology, cardiology, nephrology, neurology, and gastroenterology. Vasculitis is defined as the presence of inflammation in the blood vessel wall. The site of vessel involvement, size of the affected vessels, extent of vascular injury, and underlying pathology determine the disease phenotype and severity. This article explores the classification and general features of pediatric vasculitis, as well as the clinical presentation, diagnostic evaluation, and therapeutic options for the most common vasculitides.

  7. Oral and Dental Considerations in Pediatric Leukemic Patient

    PubMed Central

    Padmini, Chiyadu; Bai, K. Yellamma

    2014-01-01

    Throughout the world, there have been drastic decline in mortality rate in pediatric leukemic population due to early diagnosis and improvements in oncology treatment. The pediatric dentist plays an important role in the prevention, stabilization, and treatment of oral and dental problems that can compromise the child's health and quality of life during, and follow up of the cancer treatment. This manuscript discusses recommendations and promotes dental care of the pediatric leukemic patients. PMID:24724033

  8. Pediatric considerations in chemical exposures: are we prepared?

    PubMed

    Lynch, Elizabeth Lea; Thomas, Tamara L

    2004-03-01

    Manmade disasters have risen over the past decaFde. Specifically, chemical weapons used in acts of aggression pose an increasing threat to our society. These potential disaster situations raise concerns regarding preparedness for both adults and children. This article's purpose is to review general principles of chemical exposure and treatment of specific chemical agents, and to identify specific pediatric considerations involved.

  9. Pediatric Rhinosinusitis.

    PubMed

    Badr, Dana T; Gaffin, Jonathan M; Phipatanakul, Wanda

    2016-09-01

    Rhinosinusitis, is defined as an inflammation of the paranasal and nasal sinus mucosae. Chronic rhinosinusitis (CRS)is a common problem in the pediatric age group and the diagnosis and treatment are challenging due to the chronicity and similarity of symptoms with allergic rhinitis and adenoid hypertrophy. Although it is less common than acute rhinosinusitis, CRS is becoming more frequent and significantly affects the quality of life in children and can substantially impair daily function. CRS is characterized by sinus symptoms lasting more than 3 months despite medical therapy. Many factors are involved in the pathogenesis of this disease and include a primary insult with a virus followed bybacterial infection and mucosal inflammation, along with predisposition to allergies. The standard treatment of pediatricacute bacterial rhinosinusitis (ABRS) is nasal irrigation and antibiotic use. Medical treatment of pediatric CRS includes avoidance of allergens in allergic patients (environmental or food) and therapy with nasal irrigation, nasal corticosteroids sprays, nasal decongestants, and antibiotics directed at the most common sinonasalorganisms (Haemophilusinfluenzae, Streptococcus pneumoniae, and Moraxella catarrhalis). Surgical therapy is rarely needed after appropriate medical therapy. Referral to an otolaryngologist and allergy specialist is recommended in case of failure of medical treatment.

  10. Results of a nurse-led intervention: connecting pediatric cancer patients from the hospital to the school using videoconferencing technologies.

    PubMed

    Ellis, Sarah J; Drew, Donna; Wakefield, Claire E; Saikal, Samra L; Punch, Deborah; Cohn, Richard J

    2013-01-01

    The objectives of this study were to assess the feasibility and perceived academic/psychosocial outcomes of a pilot program using videoconferencing facilities to connect children with cancer to their home school. Eight parents, three patients, and five teachers (n = 16) participated in semistructured interviews evaluating the efficacy/feasibility of this program. Results were analyzed using the qualitative framework of Miles and Huberman. Parents reported that videoconferencing provided the family with a sense of normalcy and connection to the outside world (4/8), often boosting patients' mood (6/8). Further benefits included stronger relationships with classmates and teachers (15/16) and improved peer acceptance and school reintegration. There were no notable impacts on patients' academic progression. Reported barriers included: costs, time commitments, bureaucratic hurdles, and technical and logistical difficulties. Videoconferencing technologies provide an important tool to connect childhood cancer patients to their classrooms; however, further solution-based investigation is warranted to overcome existing barriers.

  11. Microarray analysis revealed dysregulation of multiple genes associated with chemoresistance to As(2)O(3) and increased tumor aggressiveness in a newly established arsenic-resistant ovarian cancer cell line, OVCAR-3/AsR.

    PubMed

    Ong, Pei-Shi; Chan, Sui-Yung; Ho, Paul C

    2012-02-14

    The potential of arsenic trioxide (As(2)O(3)) for use as a novel therapy for ovarian cancer treatment has been increasingly recognized. In this study, we developed an arsenic-resistant OVCAR-3 subline (OVCAR-3/AsR) and aimed to identify the molecular mechanisms and signaling pathways contributing to the development of acquired arsenic chemoresistance in ovarian cancer. OVCAR-3/AsR cells were obtained following continual exposure of parental OVCAR-3 cells to low dose As(2)O(3) for 12months. Cytotoxicity of OVCAR-3/AsR cells to As(2)O(3), paclitaxel and cisplatin was investigated. Cell apoptosis and cell cycle distribution following As(2)O(3) treatment of OVCAR-3/AsR cells was also analyzed using flow cytometry. Subsequently, cDNA microarray analysis was performed from the RNA samples of OVCAR-3 and OVCAR-3/AsR cells in duplicate experiments. Microarray data were analyzed using Genespring® and Pathway Studio® Softwares. OVCAR-3/AsR cells showed 9-fold greater resistance to As(2)O(3) and lack of collateral resistance to cisplatin and paclitaxel. Compared with parental OVCAR-3 cells, OVCAR-3/AsR had significantly lower apoptotic rates following As(2)O(3) treatment. These cells were also arrested at both the S phase and G(2)/M phase of the cell cycle after exposure to high concentrations of As(2)O(3). Gene expression profiling revealed significant differences in expression levels of 397 genes between OVCAR-3/AsR and OVCAR-3 cells. The differentially regulated transcripts genes have functional ontologies related to continued cancer cell growth, cell survival, tumor metastasis and tumor aggressiveness. Additionally, numerous gene targets of the nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor showed elevated expression in OVCAR-3/AsR cells. Subsequent pathway analysis further revealed a gene network involving interleukin 1-alpha (IL1A) in mediating the arsenic-resistant phenotype. These results showed that changes in multiple genes and an

  12. Personalized Assessment of kV Cone Beam Computed Tomography Doses in Image-guided Radiotherapy of Pediatric Cancer Patients

    SciTech Connect

    Zhang Yibao; Yan Yulong; Nath, Ravinder; Bao Shanglian; Deng Jun

    2012-08-01

    Purpose: To develop a quantitative method for the estimation of kV cone beam computed tomography (kVCBCT) doses in pediatric patients undergoing image-guided radiotherapy. Methods and Materials: Forty-two children were retrospectively analyzed in subgroups of different scanned regions: one group in the head-and-neck and the other group in the pelvis. Critical structures in planning CT images were delineated on an Eclipse treatment planning system before being converted into CT phantoms for Monte Carlo simulations. A benchmarked EGS4 Monte Carlo code was used to calculate three-dimensional dose distributions of kVCBCT scans with full-fan high-quality head or half-fan pelvis protocols predefined by the manufacturer. Based on planning CT images and structures exported in DICOM RT format, occipital-frontal circumferences (OFC) were calculated for head-and-neck patients using DICOMan software. Similarly, hip circumferences (HIP) were acquired for the pelvic group. Correlations between mean organ doses and age, weight, OFC, and HIP values were analyzed with SigmaPlot software suite, where regression performances were analyzed with relative dose differences (RDD) and coefficients of determination (R{sup 2}). Results: kVCBCT-contributed mean doses to all critical structures decreased monotonically with studied parameters, with a steeper decrease in the pelvis than in the head. Empirical functions have been developed for a dose estimation of the major organs at risk in the head and pelvis, respectively. If evaluated with physical parameters other than age, a mean RDD of up to 7.9% was observed for all the structures in our population of 42 patients. Conclusions: kVCBCT doses are highly correlated with patient size. According to this study, weight can be used as a primary index for dose assessment in both head and pelvis scans, while OFC and HIP may serve as secondary indices for dose estimation in corresponding regions. With the proposed empirical functions, it is possible

  13. 77 FR 65002 - Best Pharmaceuticals for Children Act (BPCA) Priority List of Needs in Pediatric Therapeutics

    Federal Register 2010, 2011, 2012, 2013, 2014

    2012-10-24

    ... Table 5: Bio-defense Research Priorities Table 6: Pediatric Cancer Priorities Table 7: Psychiatric...: Gastrointestinal Disease Priorities Table 15: Renal Disease Priorities Table 16: Rheumatologic Disease...

  14. Pediatric Hypovitaminosis D

    PubMed Central

    Ariganjoye, Rafiu

    2017-01-01

    Vitamin D, a secosteroid, is essential for the development and maintenance of healthy bone in both the adult and pediatric populations. Low level of 25-hydroxy vitamin D (25-(OH)-D) is highly prevalent in children worldwide and has been linked to various adverse health outcomes including rickets, osteomalacia, osteomalacic myopathy, sarcopenia, and weakness, growth retardation, hypocalcemia, seizure and tetany, autism, cardiovascular diseases, diabetes mellitus, cancers (prostate, colon, breast), infectious diseases (viral, tuberculosis), and autoimmune diseases, such as multiple sclerosis and Hashimoto’s thyroiditis. Risk factors for hypovitaminosis D are people with darker skin pigmentation, use of sunscreen, insufficient ultraviolet B exposure, prematurity, living in northern latitudes, malnutrition, obesity, exclusive breastfeeding, low maternal vitamin D level, certain medications, drinking unfortified cow’s milk, liver failure, chronic renal insufficiency, cystic fibrosis, asthma, and sickle cell hemoglobinopathy. This review highlights and summarizes the molecular perspectives of vitamin D deficiency and its potential adverse health outcomes in pediatric age groups. The recommended treatment regimen is beyond the scope of this review. PMID:28229097

  15. Reactivity with A monoclonal antibody to Epstein-Barr virus (EBV) nuclear antigen 1 defines a subset of aggressive breast cancers in the absence of the EBV genome.

    PubMed

    Murray, Paul G; Lissauer, David; Junying, Jia; Davies, Gillian; Moore, Sukhjinder; Bell, Andrew; Timms, Judith; Rowlands, David; McConkey, Christopher; Reynolds, Gary M; Ghataura, Suk; England, David; Caroll, Rebecca; Young, Lawrence S

    2003-05-01

    Previous studies have suggested that common breast cancers are associated with EBV. We used a highly sensitive quantitative real-time PCR method to screen whole tumor sections of breast cancers for the presence of the EBV genome. EBV DNA was detected in 19 of 92 (21%) tumors, but viral load was very low in positive samples (mean = 1.1 copy EBV/1000 cells, maximum = 7.1 copies EBV/1000 cells). Importantly, quantitative real-time PCR failed to detect the EBV genome in microdissected tumor cells from any case. Using a monoclonal antibody (2B4-1) reactive against the EBV nuclear antigen-1, we noted strong staining of tumor nuclei in a proportion of those breast cancers that had tested negative for the presence of the EBV genome. Because nuclear staining with the 2B4-1 antibody was previously observed more frequently in poor prognosis breast cancers, we examined a larger series of breast cancers with complete clinical follow-up. Strong punctate staining of tumor cell nuclei was observed in 47 of 153 (31%) breast cancers; 2B4-1-positive tumors were significantly more likely to be ER-negative (P < 0.0001), to be of higher grade (P = 0.001) and larger (P = 0.03), to involve more regional lymph nodes (P = 0.01), and to have higher Nottingham Prognostic Index scores (P = 0.0003). Conclusions are: (a) EBV can be regularly detected in whole sections of breast cancers but viral copy number is very low; (b) in these cases, tumor cells do not harbor virus; and (c) reactivity with the monoclonal antibody 2B4-1 is detectable in the absence of the EBV genome and is strongly associated with ER-negative breast tumors and with prognostically unfavorable disease. Additional studies should be directed to the identification of this protein and to elucidation of its role in breast cancer.

  16. MicroRNA-378-mediated suppression of Runx1 alleviates the aggressive phenotype of triple negative MDA-MB-231 human breast cancer cells

    PubMed Central

    Browne, Gillian; Dragon, Julie A.; Hong, Deli; Messier, Terri L.; Gordon, Jonathan A. R.; Farina, Nicholas H.; Boyd, Joseph R.; VanOudenhove, Jennifer J.; Perez, Andrew W.; Zaidi, Sayyed K.; Stein, Janet L.; Stein, Gary S.; Lian, Jane B.

    2016-01-01

    The Runx1 transcription factor, known for its essential role normal hematopoiesis, was reported in limited studies to be mutated or associated with human breast tumor tissues. Runx 1 increases concomitant with disease progression in the MMTV-PyMT transgenic mouse model of breast cancer. Compelling questions relate to mechanisms that regulate Runx1 expression in breast cancer. Here, we tested the hypothesis that dysregulation of Runx1-targeting microRNAs (miRNAs) allows for pathologic increase of Runx1 during breast cancer progression. Microarray profiling of the MMTV-PyMT model revealed significant down-regulation of numerous miRNAs predicted to target Runx1. One of these, miR-378, was inversely correlated with Runx1 expression during breast cancer progression in mouse, and in human breast cancer cell lines MCF7 and triple negative MDA-MB-231 that represent early and late stage disease, respectively. MiR-378 is nearly absent in MDA-MB-231 cells. Luciferase reporter assays revealed that miR-378 binds the Runx1 3′UTR and inhibits Runx1 expression. Functionally, we demonstrated that ectopic expression of miR-378 in MDA-MB-231 cells inhibited Runx1 and suppressed migration and invasion; while inhibition of miR-378 in MCF7 cells increased Runx1 levels and cell migration. Depletion of Runx1 in late stage breast cancer cells resulted in increased expression of both the miR-378 host gene PPARGC1B and pre-miR-378, suggesting a feedback loop. Taken together, our study identifies a novel and clinically relevant mechanism for regulation of Runx1 in breast cancer that is mediated by a PPARGC1B-miR-378-Runx1 regulatory pathway. Our results highlight the translational potential of miRNA replacement therapy for inhibiting Runx1 in breast cancer. PMID:26749280

  17. Pediatric tracheomalacia.

    PubMed

    Fraga, Jose Carlos; Jennings, Russell W; Kim, Peter C W

    2016-06-01

    Tracheomalacia (TM) is defined as an increased collapsibility of the trachea due to structural anomalies of the tracheal cartilage and/or posterior membrane. Tracheomalacia has a wide range of etiologies but is most commonly present in children born with esophageal atresia and tracheal esophageal fistula. Clinical symptoms can range from minor expiratory stridor with typical barking cough to severe respiratory distress episodes to acute life-threatening events (ALTE). Although the majority of children have mild-to-moderate symptoms and will not need surgical intervention, some will need life-changing surgical treatment. This article examines the published pediatric literature on TM, discusses the details of clinical presentation, evaluation, diagnosis, and a variety of treatments.

  18. Impulsive Aggression as a Comorbidity of Attention-Deficit/Hyperactivity Disorder in Children and Adolescents

    PubMed Central

    Amann, Birgit H.

    2016-01-01

    Abstract Objective: This article examines the characteristics of impulsive aggression (IA) as a comorbidity in children and adolescents with attention-deficit/hyperactivity disorder (ADHD), focusing on its incidence, impact on ADHD outcomes, need for timely intervention, and limitations of current treatment practices. Methods: Relevant literature was retrieved with electronic searches in PubMed and PsycINFO using the search strategy of “ADHD OR attention deficit hyperactivity disorder” AND “impulsive aggression OR reactive aggression OR hostile aggression OR overt aggression” AND “pediatric OR childhood OR children OR pre-adolescent OR adolescent” with separate searches using review OR clinical trial as search limits. Key articles published before the 2007 Expert Consensus Report on IA were identified using citation analysis. Results: More than 50% of preadolescents with ADHD combined subtype reportedly display clinically significant aggression, with impulsive aggression being the predominant subtype. Impulsive aggression is strongly predictive of a highly unfavorable developmental trajectory characterized by the potential for persistent ADHD, increasing psychosocial burden, accumulating comorbidities, serious lifelong functional deficits across a broad range of domains, delinquency/criminality, and adult antisocial behavior. Impulsive aggression, which triggers peer rejection and a vicious cycle of escalating dysfunction, may be a key factor in unfavorable psychosocial outcomes attributed to ADHD. Because severe aggressive behavior does not remit in many children when treated with primary ADHD therapy (i.e., stimulants and behavioral therapy), a common practice is to add medication of a different class to specifically target aggressive behavior. Conclusions: Impulsive aggression in children and adolescents with ADHD is a serious clinical and public health problem. Although adjunctive therapy with an aggression-targeted agent is widely recommended when

  19. Stability of Aggressive Behavior.

    ERIC Educational Resources Information Center

    Eron, Leonard D.; Huesmann, L. Rowell

    As indicated by multiple measures (including overt criminal behavior), stability of aggressive behavior was investigated across 22 years for males and females in a variety of situations. Originally, subjects included the entire population enrolled in the third grade in a semi-rural county in New York State. The sample included approximately 870…

  20. Aggressiveness and Disobedience

    ERIC Educational Resources Information Center

    Vaaland, Grete Sorensen; Idsoe, Thormod; Roland, Erling

    2011-01-01

    This study aims to conceptualize disobedient pupil behavior within the more general framework of antisocial behavior and to reveal how two forms of aggressiveness are related to disobedience. Disobedience, in the context of this article, covers disruptive pupil behavior or discipline problems when the pupil is aware of breaking a standard set by…

  1. Intellectual Competence and Aggression.

    ERIC Educational Resources Information Center

    Huesmann, L. Rowell; Yarmel, Patty Warnick

    Using data from a broader longitudinal study, this investigation explores within-subject and cross-generational stability of intellectual competence and the relationship of such stability to aggressive behavior. Data were gathered three times (when subjects' modal age was 8, 19, and 30 years). Initially, subjects included the entire population…

  2. Relational Aggression among Students

    ERIC Educational Resources Information Center

    Young, Ellie L.; Nelson, David A.; Hottle, America B.; Warburton, Brittney; Young, Bryan K.

    2011-01-01

    "Relational aggression" refers to harm within relationships caused by covert bullying or manipulative behavior. Examples include isolating a youth from his or her group of friends (social exclusion), threatening to stop talking to a friend (the silent treatment), or spreading gossip and rumors by email. This type of bullying tends to be…

  3. Neuroimaging and Aggression.

    ERIC Educational Resources Information Center

    Mills, Shari; Raine, Adrian

    1994-01-01

    Brain imaging research allows direct assessment of structural and functional brain abnormalities, and thereby provides an improved methodology for studying neurobiological factors predisposing to violent and aggressive behavior. This paper reviews 20 brain imaging studies using four different types of neuroimaging techniques that were conducted in…

  4. Human Aggression and Suicide

    ERIC Educational Resources Information Center

    Brown, Gerald L.; Goodwin, Frederick K

    1986-01-01

    The central nervous system transmitter serontonin may be altered in aggressive/impulsive and suicidal behaviors in humans. These reports are largely consistent with animal data, and constitute one of the most highly replicated set of findings in biological psychiatry. Suggests that some suicidal behavior may be a special kind of aggressive…

  5. Establishment of a novel human medulloblastoma cell line characterized by highly aggressive stem-like cells.

    PubMed

    Silva, Patrícia Benites Gonçalves da; Rodini, Carolina Oliveira; Kaid, Carolini; Nakahata, Adriana Miti; Pereira, Márcia Cristina Leite; Matushita, Hamilton; Costa, Silvia Souza da; Okamoto, Oswaldo Keith

    2016-08-01

    Medulloblastoma is a highly aggressive brain tumor and one of the leading causes of morbidity and mortality related to childhood cancer. These tumors display differential ability to metastasize and respond to treatment, which reflects their high degree of heterogeneity at the genetic and molecular levels. Such heterogeneity of medulloblastoma brings an additional challenge to the understanding of its physiopathology and impacts the development of new therapeutic strategies. This translational effort has been the focus of most pre-clinical studies which invariably employ experimental models using human tumor cell lines. Nonetheless, compared to other cancers, relatively few cell lines of human medulloblastoma are available in central repositories, partly due to the rarity of these tumors and to the intrinsic difficulties in establishing continuous cell lines from pediatric brain tumors. Here, we report the establishment of a new human medulloblastoma cell line which, in comparison with the commonly used and well-established cell line Daoy, is characterized by enhanced proliferation and invasion capabilities, stem cell properties, increased chemoresistance, tumorigenicity in an orthotopic metastatic model, replication of original medulloblastoma behavior in vivo, strong chromosome structural instability and deregulation of genes involved in neural development. These features are advantageous for designing biologically relevant experimental models in clinically oriented studies, making this novel cell line, named USP-13-Med, instrumental for the study of medulloblastoma biology and treatment.

  6. Introduction to Pediatric Sepsis.

    PubMed

    Wheeler, Derek S

    2011-10-07

    Sepsis is a significant health problem in both critically ill children and adults. While the mortality rate from sepsis is much lower in children, sepsis is directly responsible for over 4,000 childhood deaths per year in the United States alone. At face value, this number suggests that more children die per year in the United States from sepsis as the primary cause than from cancer. Unfortunately, there are few studies on the epidemiology, pathophysiology, and management of sepsis in children. Moreover, extrapolation of adult data to critically ill children is probably not appropriate due to several key developmental differences in the host response to infection and response to therapy. Therefore, additional studies targeting sepsis in the pediatric population are urgently required.

  7. Tyrosine kinome sequencing of pediatric acute lymphoblastic leukemia: a report from the Children's Oncology Group TARGET Project | Office of Cancer Genomics

    Cancer.gov

    TARGET researchers sequenced the tyrosine kinome and downstream signaling genes in 45 high-risk pediatric ALL cases with activated kinase signaling, including Ph-like ALL, to establish the incidence of tyrosine kinase mutations in this cohort. The study confirmed previously identified somatic mutations in JAK and FLT3, but did not find novel alterations in any additional tyrosine kinases or downstream genes. The mechanism of kinase signaling activation in this high-risk subgroup of pediatric ALL remains largely unknown.

  8. Parents' Aggressive Influences and Children's Aggressive Problem Solutions with Peers

    ERIC Educational Resources Information Center

    Duman, Sarah; Margolin, Gayla

    2007-01-01

    This study examined children's aggressive and assertive solutions to hypothetical peer scenarios in relation to parents' responses to similar hypothetical social scenarios and parents' actual marital aggression. The study included 118 children ages 9 to 10 years old and their mothers and fathers. Children's aggressive solutions correlated with…

  9. Relational Aggression and Physical Aggression among Adolescent Cook Islands Students

    ERIC Educational Resources Information Center

    Page, Angela; Smith, Lisa F.

    2016-01-01

    Both physical and relational aggression are characterised by the intent to harm another. Physical aggression includes direct behaviours such as hitting or kicking; relational aggression involves behaviours designed to damage relationships, such as excluding others, spreading rumours, and delivering threats and verbal abuse. This study extended…

  10. A cross-sectional study to determine the prevalence of calcium metabolic disorder in malignant childhood cancers in patients admitted to the pediatric ward of Vali-Asr Hospital.

    PubMed

    Moayeri, Heshmat; Oloomi, Zohreh; Sambo, Saudatu A

    2011-01-01

    Calcium metabolic disorders, such as hypercalcemia is a potentially life-threatening disorder especially when coupled with an already compromised condition. The aim of this study was to determine the prevalence of metabolic calcium disorders in childhood cancers of patients admitted to the pediatric ward of Vali-Asr Hospital from the year 2001-2008. The study was carried out by reviewing hospital records of these patients from the hospital archives. Range of age was between 1 and 18 years. Inclusion criteria for the study population were the presence of total serum calcium evaluated at least once; and for the hypercalcemia subgroup, at least two occasions of elevated calcium levels. The prevalence of hypercalcemia and other metabolic abnormalities of phosphorus, alkaline phosphatase, urea and creatinine; the prevalence of parameters such as age, gender, type and duration of cancer were determined within these groups. Median of elevated calcium levels was also determined to classify hypercalcemia into moderate and severe hypercalcemia. Median was 11.7 mg/dl, therefore, severe hypercalcemia was ≥11.7 mg/dl and moderate hypercalcemia, a range between the upper limit of normal, 10.8 and 10.2 mg/dl for the child and adolescent respectively, and 11.7 mg/dl. Relationship between hypercalcemia and the other metabolic disorders and parameters were analyzed by the SPSS V.17 program. The population of study consisted of 148 cases. Hypercalcemia was found in 8 (5.4%) patients. Half of the cases were associated with severe hypercalcemia and acute lymphoblastic leukemia (ALL). Out of 148 cases, there were 92 (62%) boys and 56 (38%) girls. Mean and median ages were 10.9 and 11 years respectively. Mean duration of cancer was 12.8 and median 6 months. There were 57 (38.5%) cases of leukemia and 91 (61.5%) cases of solid tumors. The most common cancers were ALL, 44 cases (29.7%) followed by brain tumors, 19 cases (12.8%); non-Hodgkin's lymphoma, 16 cases (10.8%); 13 cases of acute

  11. Nuclear Medicine in Thyroid Diseases in Pediatric and Adolescent Patients

    PubMed Central

    Volkan-Salancı, Bilge; Özgen Kıratlı, Pınar

    2015-01-01

    Both benign and malignant diseases of the thyroid are rare in the pediatric and adolescent population, except congenital hypothyroidism. Nuclear medicine plays a major role, both in the diagnosis and therapy of thyroid pathologies. Use of radioactivity in pediatric population is strictly controlled due to possible side effects such as secondary cancers; therefore, management of pediatric patients requires detailed literature knowledge. This article aims to overview current algorithms in the management of thyroid diseases and use of radionuclide therapy in pediatric and adolescent population. PMID:26316469

  12. Loss of Secreted Frizzled-Related Protein 4 Correlates with an Aggressive Phenotype and Predicts Poor Outcome in Ovarian Cancer Patients

    PubMed Central

    Nixdorf, Sheri; Ford, Caroline E.; Olivier, Jake; Caduff, Rosmarie; Scurry, James P.; Guertler, Rea; Hornung, Daniela; Mueller, Renato; Fink, Daniel A.; Hacker, Neville F.; Heinzelmann-Schwarz, Viola A.

    2012-01-01

    Background Activation of the Wnt signaling pathway is implicated in aberrant cellular proliferation in various cancers. In 40% of endometrioid ovarian cancers, constitutive activation of the pathway is due to oncogenic mutations in β-catenin or other inactivating mutations in key negative regulators. Secreted frizzled-related protein 4 (SFRP4) has been proposed to have inhibitory activity through binding and sequestering Wnt ligands. Methodology/Principal Findings We performed RT-qPCR and Western-blotting in primary cultures and ovarian cell lines for SFRP4 and its key downstream regulators activated β-catenin, β-catenin and GSK3β. SFRP4 was then examined by immunohistochemistry in a cohort of 721 patients and due to its proposed secretory function, in plasma, presenting the first ELISA for SFRP4. SFRP4 was most highly expressed in tubal epithelium and decreased with malignant transformation, both on RNA and on protein level, where it was even more profound in the membrane fraction (p<0.0001). SFRP4 was expressed on the protein level in all histotypes of ovarian cancer but was decreased from borderline tumors to cancers and with loss of cellular differentiation. Loss of membrane expression was an independent predictor of poor survival in ovarian cancer patients (p = 0.02 unadjusted; p = 0.089 adjusted), which increased the risk of a patient to die from this disease by the factor 1.8. Conclusions/Significance Our results support a role for SFRP4 as a tumor suppressor gene in ovarian cancers via inhibition of the Wnt signaling pathway. This has not only predictive implications but could also facilitate a therapeutic role using epigenetic targets. PMID:22363760

  13. Acrp30 inhibits leptin-induced metastasis by downregulating the JAK/STAT3 pathway via AMPK activation in aggressive SPEC-2 endometrial cancer cells.

    PubMed

    Wu, Xiaomei; Yan, Qin; Zhang, Zhenbo; Du, Guiqiang; Wan, Xiaoping

    2012-05-01

    Obesity is a well-established risk factor for endometrial cancer, due in part to the adipokines generated by adipose tissue, such as adiponectin (also known as Acrp30) and leptin, which are associated with many endocrine-related cancers. Recent reports suggested that Acrp30 inhibits leptin-stimulated cell proliferation in HEC-1A and RL95-2 endometrial cancer cell lines, and that the serum leptin/Acrp30 ratio plays an important role in endometrial cancer development. We explored whether Acrp30 could reverse the leptin-induced metastasis phenotype in the SPEC-2 endometrial cancer cell line. Transcripts for Acrp30 receptors (AdipoR1 and AdipoR2) and leptin receptor (Ob-Rb) were detected by quantitative real-time RT-PCR (qRT-PCR) in six endometrial cancer cell lines. Leptin (1 µg/ml) treatment stimulated SPEC-2 cell proliferation by inducing cell cycle arrest and apoptosis, while Acrp30 (10 µg/ml) treatment inhibited the growth of SPEC-2 cells. Importantly, Acrp30 was able to inhibit leptin-induced SPEC-2 cell proliferation. Leptin promoted SPEC-2 cell invasion in a Matrigel transwell assay, while Acrp30 partly suppressed the invasion stimulated by leptin. To investigate the molecular mechanism underlying this phenomenon, we monitored the AMPK and JAK/STAT3 signaling pathways by western blotting and cell immunofluorescence. Acrp30 reduced leptin-induced STAT3 phosphorylation and nuclear translocation via activation of the MAPK pathway. AG490 (JAK/STAT3 inhibitor) reduced MMP-2 and MMP-9 protein levels in cells treated with leptin, while IL-6 (JAK/STAT3 stimulator) and Compound C (AMPK inhibitor) elevated MMP-2 and MMP-9 protein levels in cells treated with Acrp30. In conclusion, we demonstrated that Acrp30 effectively reversed the invasion stimulated by leptin, and AMPK and JAK/STAT3 pathways mediated the invasive phenotype of SPEC-2 cells.

  14. Prostate cancer risk and aggressiveness associated with the CYP1B1 4326C/G (Leu432Val) polymorphism: a meta-analysis of 2788 cases and 2968 controls

    PubMed Central

    Yang, Jie; Xu, Dong-Liang; Lu, Qiang; Han, Zhi-Jian; Tao, Jun; Lu, Pei; Wang, Chao; Di, Xiao-Ke; Gu, Min

    2012-01-01

    To derive a precise estimation of the associations between the cytochrome P450 1B1 (CYP1B1) 4326C/G variants and prostate cancer (PCa) risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYP1B1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians (OR=1.52, 95% CI: 1.20–1.92), and significant associations were also observed in a heterozygote comparison (OR=1.40, 95% CI: 1.03–1.89), a homozygote comparison (OR=2.38, 95% CI: 1.31–4.33) and in a dominant genetic model (OR=1.52, 95% CI: 1.14–2.01). Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa (OR=1.13, 95% CI: 1.04–1.24), and significant associations were observed in a heterozygote comparison (OR=1.16, 95% CI: 1.02–1.33), a homozygote comparison (OR=1.24, 95% CI: 1.03–1.49) and a dominant genetic model (OR=1.19, 95% CI: 1.05–1.34). The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYP1B1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases. PMID:22504876

  15. Prostate cancer risk and aggressiveness associated with the CYP1B1 4326C/G (Leu432Val) polymorphism: a meta-analysis of 2788 cases and 2968 controls.

    PubMed

    Yang, Jie; Xu, Dong-Liang; Lu, Qiang; Han, Zhi-Jian; Tao, Jun; Lu, Pei; Wang, Chao; Di, Xiao-Ke; Gu, Min

    2012-07-01

    To derive a precise estimation of the associations between the cytochrome P450 1B1 (CYP1B1) 4326C/G variants and prostate cancer (PCa) risk or aggressiveness, a meta-analysis was performed using all eligible published studies. Odds ratios (ORs) with 95% confidence intervals (CIs) were estimated to assess the association in seven literature studies with 2788 cases and 2968 controls. In the overall analysis, no significant association was found between the CYP1B1 4326C/G polymorphism and PCa risk, but ethnicity subgroup analyses and a case-source analysis revealed significant associations. The 4326G allele showed a significant association with increased PCa risk in Asians (OR=1.52, 95% CI: 1.20-1.92), and significant associations were also observed in a heterozygote comparison (OR=1.40, 95% CI: 1.03-1.89), a homozygote comparison (OR=2.38, 95% CI: 1.31-4.33) and in a dominant genetic model (OR=1.52, 95% CI: 1.14-2.01). Moreover, the 4326G allele was also significantly correlated with an increased risk of sporadic PCa (OR=1.13, 95% CI: 1.04-1.24), and significant associations were observed in a heterozygote comparison (OR=1.16, 95% CI: 1.02-1.33), a homozygote comparison (OR=1.24, 95% CI: 1.03-1.49) and a dominant genetic model (OR=1.19, 95% CI: 1.05-1.34). The overall analyses and all subgroup analyses showed no significant association between the 4326C/G polymorphism and PCa aggressiveness. Our meta-analysis showed that CYP1B1 4326G allele is significantly associated with an increased PCa risk in Asians and in sporadic PCa cases.

  16. The Treatment of Differentiated Thyroid Cancer in Children: Emphasis on Surgical Approach and Radioactive Iodine Therapy

    PubMed Central

    Mazzaferri, Ernest L.; Verburg, Frederik A.; Reiners, Christoph; Luster, Markus; Breuer, Christopher K.; Dinauer, Catherine A.; Udelsman, Robert

    2011-01-01

    Pediatric thyroid cancer is a rare disease with an excellent prognosis. Compared with adults, epithelial-derived differentiated thyroid cancer (DTC), which includes papillary and follicular thyroid cancer, presents at more advanced stages in children and is associated with higher rates of recurrence. Because of its uncommon occurrence, randomized trials have not been applied to test best-care options in children. Even in adults that have a 10-fold or higher incidence of thyroid cancer than children, few prospective trials have been executed to compare treatment approaches. We recognize that treatment recommendations have changed over the past few decades and will continue to do so. Respecting the aggressiveness of pediatric thyroid cancer, high recurrence rates, and the problems associated with decades of long-term follow-up, a premium should be placed on treatments that minimize risk of recurrence and the adverse effects of treatments and facilitate follow-up. We recommend that total thyroidectomy and central compartment lymph node dissection is the surgical procedure of choice for children with DTC if it can be performed by a high-volume thyroid surgeon. We recommend radioactive iodine therapy for remnant ablation or residual disease for most children with DTC. We recommend long-term follow-up because disease can recur decades after initial diagnosis and therapy. Considering the complexity of DTC management and the potential complications associated with therapy, it is essential that pediatric DTC be managed by physicians with expertise in this area. PMID:21880704

  17. Breast Cancer Types: What Your Type Means

    MedlinePlus

    ... the most different looking and considered the most aggressive. Some breast cancers are sensitive to your body's ... which cancers will spread and which may need aggressive treatments. That way, women with relatively low-risk ...

  18. Serotonin and Aggressiveness in Chickens

    Technology Transfer Automated Retrieval System (TEKTRAN)

    Serotonin (5-HT) regulates aggressive behavior in animals. This study examined if 5-HT regulation of aggressiveness is gene-dependent. Chickens from two divergently selected lines KGB and MBB (Kind Gentle Birds and Mean Bad Birds displaying low and high aggressiveness, respectively) and DXL (Dekalb ...

  19. Initial resuscitation and management of pediatric septic shock

    PubMed Central

    Martin, Kelly; Weiss, Scott L.

    2015-01-01

    The pediatric sepsis syndrome remains a common cause of morbidity, mortality, and health care utilization costs worldwide. The initial resuscitation and management of pediatric sepsis is focused on 1) rapid recognition of abnormal tissue perfusion and restoration of adequate cardiovascular function, 2) eradication of the inciting invasive infection, including prompt administration of empiric broad-spectrum antimicrobial medications, and 3) supportive care of organ system dysfunction. Efforts to improve early and aggressive initial resuscitation and ongoing management strategies have improved outcomes in pediatric severe sepsis and septic shock, though many questions still remain as to the optimal therapeutic strategies for many patients. In this article, we will briefly review the definitions, epidemiology, clinical manifestations, and pathophysiology of sepsis and provide an extensive overview of both current and novel therapeutic strategies used to resuscitate and manage pediatric patients with severe sepsis and septic shock. PMID:25604591

  20. Minimizing and communicating radiation risk in pediatric nuclear medicine.

    PubMed

    Fahey, Frederic H; Treves, S Ted; Adelstein, S James

    2011-08-01

    The value of pediatric nuclear medicine is well established. Pediatric patients are referred to nuclear medicine from nearly all pediatric specialties including urology, oncology, cardiology, gastroenterology, and orthopedics. Radiation exposure is associated with a potential, small, risk of inducing cancer in the patient later in life and is higher in younger patients. Recently, there has been enhanced interest in exposure to radiation from medical imaging. Thus, it is incumbent on practitioners of pediatric nuclear medicine to have an understanding of dosimetry and radiation risk to communicate effectively with their patients and their families. This article reviews radiation dosimetry for radiopharmaceuticals and also CT given the recent proliferation of PET/CT and SPECT/CT. It also describes the scientific basis for radiation risk estimation in the context of pediatric nuclear medicine. Approaches for effective communication of risk to patients' families are discussed. Lastly, radiation dose reduction in pediatric nuclear medicine is explicated.

  1. Minimizing and communicating radiation risk in pediatric nuclear medicine.

    PubMed

    Fahey, Frederic H; Treves, S Ted; Adelstein, S James

    2012-03-01

    The value of pediatric nuclear medicine is well established. Pediatric patients are referred to nuclear medicine from nearly all pediatric specialties including urology, oncology, cardiology, gastroenterology, and orthopedics. Radiation exposure is associated with a potential, small, risk of inducing cancer in the patient later in life and is higher in younger patients. Recently, there has been enhanced interest in exposure to radiation from medical imaging. Thus, it is incumbent on practitioners of pediatric nuclear medicine to have an understanding of dosimetry and radiation risk to communicate effectively with their patients and their families. This article reviews radiation dosimetry for radiopharmaceuticals and also CT given the recent proliferation of PET/CT and SPECT/CT. It also describes the scientific basis for radiation risk estimation in the context of pediatric nuclear medicine. Approaches for effective communication of risk to patients' families are discussed. Lastly, radiation dose reduction in pediatric nuclear medicine is explicated.

  2. The risk of radiation-induced second cancers in the high to medium dose region: a comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors

    NASA Astrophysics Data System (ADS)

    Moteabbed, Maryam; Yock, Torunn I.; Paganetti, Harald

    2014-06-01

    The incidence of second malignant tumors is a clinically observed adverse late effect of radiation therapy, especially in organs close to the treatment site, receiving medium to high doses (>2.5 Gy). For pediatric patients, choosing the least toxic radiation modality is of utmost importance, due to their high radiosensitivity and small size. This study aims to evaluate the risk of second cancer incidence in the vicinity of the primary radiation field, for pediatric patients with brain/head and neck tumors and compare four treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). For a cohort of six pediatric patients originally treated with PPT, additional PBS, IMRT and VMAT plans were created. Dose distributions from these plans were used to calculate the excess absolute risk (EAR) and lifetime attributable risk (LAR) for developing a second tumor in soft tissue and skull. A widely used risk assessment formalism was employed and compared with a linear model based on recent clinical findings. In general, LAR was found to range between 0.01%-2.8% for PPT/PBS and 0.04%-4.9% for IMRT/VMAT. PBS was associated with the lowest risk for most patients using carcinoma and sarcoma models, whereas IMRT and VMAT risks were comparable and the highest among all modalities. The LAR for IMRT/VMAT relative to PPT ranged from 1.3-4.6 for soft tissue and from 3.5-9.5 for skull. Larger absolute LAR was observed for younger patients and using linear risk models. The number of fields used in proton therapy and IMRT had minimal effect on the risk. When planning treatments and deciding on the treatment modality, the probability of second cancer incidence should be carefully examined and weighed against the possibility of developing acute side effects for each patient individually.

  3. The risk of radiation-induced second cancers in the high to medium dose region: a comparison between passive and scanned proton therapy, IMRT and VMAT for pediatric patients with brain tumors.

    PubMed

    Moteabbed, Maryam; Yock, Torunn I; Paganetti, Harald

    2014-06-21

    The incidence of second malignant tumors is a clinically observed adverse late effect of radiation therapy, especially in organs close to the treatment site, receiving medium to high doses (>2.5 Gy). For pediatric patients, choosing the least toxic radiation modality is of utmost importance, due to their high radiosensitivity and small size. This study aims to evaluate the risk of second cancer incidence in the vicinity of the primary radiation field, for pediatric patients with brain/head and neck tumors and compare four treatment modalities: passive scattering and pencil beam scanning proton therapy (PPT and PBS), intensity modulated radiation therapy (IMRT) and volumetric modulated arc therapy (VMAT). For a cohort of six pediatric patients originally treated with PPT, additional PBS, IMRT and VMAT plans were created. Dose distributions from these plans were used to calculate the excess absolute risk (EAR) and lifetime attributable risk (LAR) for developing a second tumor in soft tissue and skull. A widely used risk assessment formalism was employed and compared with a linear model based on recent clinical findings. In general, LAR was found to range between 0.01%-2.8% for PPT/PBS and 0.04%-4.9% for IMRT/VMAT. PBS was associated with the lowest risk for most patients using carcinoma and sarcoma models, whereas IMRT and VMAT risks were comparable and the highest among all modalities. The LAR for IMRT/VMAT relative to PPT ranged from 1.3-4.6 for soft tissue and from 3.5-9.5 for skull. Larger absolute LAR was observed for younger patients and using linear risk models. The number of fields used in proton therapy and IMRT had minimal effect on the risk. When planning treatments and deciding on the treatment modality, the probability of second cancer incidence should be carefully examined and weighed against the possibility of developing acute side effects for each patient individually.

  4. Pediatric Brain Tumor Foundation

    MedlinePlus

    ... you insights into your child's treatment. LEARN MORE Brain tumors and their treatment can be deadly so ... Pediatric Brain Tumor Foundation Board Read more >> Pediatric Brain Tumor Foundation 302 Ridgefield Court, Asheville, NC 28806 ...

  5. Pediatric Celiac Disease

    MedlinePlus

    ... of Pediatric Gastroenterology and Nutrition Nurses Print Share Celiac Disease Many kids have sensitivities to certain foods, ... protein found in wheat, rye, and barley. Pediatric Celiac Disease If your child has celiac disease, consuming ...

  6. Find a Pediatric Dentist

    MedlinePlus

    ... Litch's Law Log HIPAA Forms Practice Management and Marketing Newsletter Webinar Materials Member Resources 2017 General Assembly ... Archives Access Pediatric Dentistry Today Practice Management and Marketing Newsletter Pediatric Dentistry Journal Open Access Articles Policies & ...

  7. Pediatric diagnostic imaging

    SciTech Connect

    Gyll, C.; Blake, N.S.

    1986-01-01

    This book treats the practical problems of pediatric radiography and radiological procedures. Written jointly by a radiographer and a radiologist, it covers pediatric positioning and procedures. An extended chapter covers neonatal radiography and radiology.

  8. Nuances in pediatric trauma.

    PubMed

    Kenefake, Mary Ella; Swarm, Matthew; Walthall, Jennifer

    2013-08-01

    Pediatric trauma evaluation mimics adult stabilization in that it is best accomplished with a focused and systematic approach. Attention to developmental differences, anatomic and physiologic nuances, and patterns of injury equip emergency physicians to stabilize and manage pediatric injury.

  9. Deregulation of MYCN, LIN28B and LET7 in a Molecular Subtype of Aggressive High-Grade Serous Ovarian Cancers

    PubMed Central

    Cowin, Prue A.; Johnstone, Cameron N.; House, Colin M.; Sheppard, Karen E.; Etemadmoghadam, Dariush; Melnyk, Nataliya; Rustgi, Anil K.; Phillips, Wayne A.; Johnsen, Hilde; Holm, Ruth; Kristensen, Gunnar B.; Birrer, Michael J.; Pearson, Richard B.; Børresen-Dale, Anne-Lise; Huntsman, David G.; deFazio, Anna; Creighton, Chad J.; Smyth, Gordon K.; Bowtell, David D. L.

    2011-01-01

    Molecular subtypes of serous ovarian cancer have been recently described. Using data from independent datasets including over 900 primary tumour samples, we show that deregulation of the Let-7 pathway is specifically associated with the C5 molecular subtype of serous ovarian cancer. DNA copy number and gene expression of HMGA2, alleles of Let-7, LIN28, LIN28B, MYC, MYCN, DICER1, and RNASEN were measured using microarray and quantitative reverse transcriptase PCR. Immunohistochemistry was performed on 127 samples using tissue microarrays and anti-HMGA2 antibodies. Fluorescence in situ hybridisation of bacterial artificial chromosomes hybridized to 239 ovarian tumours was used to measure translocation at the LIN28B locus. Short interfering RNA knockdown in ovarian cell lines was used to test the functionality of associations observed. Four molecular subtypes (C1, C2, C4, C5) of high-grade serous ovarian cancers were robustly represented in each dataset and showed similar pattern of patient survival. We found highly specific activation of a pathway involving MYCN, LIN28B, Let-7 and HMGA2 in the C5 molecular subtype defined by MYCN amplification and over-expression, over-expression of MYCN targets including the Let-7 repressor LIN28B, loss of Let-7 expression and HMGA2 amplification and over-expression. DICER1, a known Let-7 target, and RNASEN were over-expressed in C5 tumours. We saw no evidence of translocation at the LIN28B locus in C5 tumours. The reported interaction between LIN28B and Let-7 was recapitulated by siRNA knockdown in ovarian cancer cell lines. Our results associate deregulation of MYCN and downstream targets, including Let-7 and oncofetal genes, with serous ovarian cancer. We define for the first time how elements of an oncogenic pathway, involving multiple genes that contribute to stem cell renewal, is specifically altered in a molecular subtype of serous ovarian cancer. By defining the drivers of a molecular subtype of serous ovarian cancers we

  10. Nuclear imaging in pediatrics

    SciTech Connect

    Siddiqui, A.R.

    1985-01-01

    The author's intent is to familiarize practicing radiologists with the technical aspects and interpretation of nuclear medicine procedures in children and to illustrate the indications for nuclear medicine procedures in pediatric problems. Pediatric doses, dosimetry, sedation, and injection techniques, organ systems, oncology and infection, testicular scanning and nuclear crystography, pediatric endocrine and skeletal systems, ventilation and perfusion imaging of both congenital and acquired pediatric disorders, cardiovascular problems, gastrointestinal, hepatobiliary, reticuloendothelial studies, and central nervous system are all topics which are included and discussed.

  11. Pediatric electrocardiographic imaging applications.

    PubMed

    Silva, Jennifer N A

    2015-03-01

    Noninvasive electrocardiographic imaging (ECGI) has been used in pediatric and congenital heart patients to better understand their electrophysiologic substrates. In this article we focus on the 4 subjects related to pediatric ECGI: (1) ECGI in patients with congenital heart disease and Wolff–Parkinson–White syndrome, (2) ECGI in patients with hypertrophic cardiomyopathy and preexcitation, (3) ECGI in pediatric patients with Wolff–Parkinson–White syndrome, and (4) ECGI for pediatric cardiac resynchronization therapy.

  12. Quo vadis pediatric nuclear medicine.

    PubMed

    Conway, James J

    2007-07-01

    What has happened to the nuclear medicine subspecialty since those earlier issues of the Seminars in Nuclear Medicine? The earliest issues in 1972 presented topics in vogue at the time that included brain "scanning," cisternography, whole body counting, and abdominal imaging with (99m)Tc pertechnetate. The second pediatric subspecialty issues in 1993 reflected a 21-year evolution of the subspecialty and included the topics of renal scintigraphy, labeled cells for abdominal imaging, metaiodobenzylguanidine imaging, single photon emission computed tomography, and bone scintigraphy for benign disorders. The current issues will address diverse topics that cover the spectrum of the current practice of pediatric nuclear medicine. They include radiation exposure and absorbed dose reduction, positron emission tomography/computed tomography in children, neuroblastoma and other neuroendocrine tumors, thyroid cancer and therapy, bone density studies and, of course, the most prevalent studies in children, renal and bone. Brain, heart, and lung studies complete the spectrum.

  13. Aggressive blood pressure control for chronic kidney disease unmasks moyamoya!

    PubMed Central

    Davis, T. Keefe; Halabi, Carmen M.; Siefken, Philp; Karmarkar, Swati; Leonard, Jeffrey

    2013-01-01

    Hypertensive crises in children or adolescents are rare, but chronic kidney disease (CKD) is a major risk factor for occurrence. Vesicoureteral reflux nephropathy is a common cause of pediatric renal failure and is associated with hypertension. Aggressive blood pressure (BP) control has been shown to delay progression of CKD and treatment is targeted for the 50th percentile for height when compared with a target below the 90th percentile for the general pediatric hypertensive patient. We present a case of an adolescent presenting with seizures and renal failure due to a hypertensive crisis. Hypertension was thought to be secondary to CKD as she had scarred echogenic kidneys due to known reflux nephropathy. However, aggressive BP treatment improved kidney function which is inconsistent with CKD from reflux nephropathy. Secondly, aggressive BP control caused transient neurological symptoms. Further imaging identified moyamoya disease. We present this case to highlight the consideration of moyamoya as a diagnosis in the setting of renal failure and hypertensive crisis. PMID:26064513

  14. Identification of a pivotal endocytosis motif in c-Met and selective modulation of HGF-dependent aggressiveness of cancer using the 16-mer endocytic peptide.

    PubMed

    Cho, K-W; Park, J H; Park, C-W; Lee, D; Lee, E; Kim, D J; Kim, K J; Yoon, S H; Park, Y; Kim, E; Cho, S; Jang, S; Park, B-C; Chi, S-W; Yoo, S H; Jang, M H; Kim, H N; Kim, E; Jo, K; Park, Y W

    2013-02-21

    Since c-Met has an important role in the development of cancer, it is considered as an attractive target for cancer therapy. Although molecular mechanisms for oncogenic property of c-Met have been actively investigated, regulatory elements for c-Met endocytosis and its effect on c-Met signaling remain unclear. In this study, we identified a pivotal endocytic motif in c-Met and tested it for selective modulation of HGF-induced c-Met response. Using various chimeric constructs with the cytoplasmic tail of c-Met, we were able to demonstrate that a dileucine motif located in the C-terminus of c-Met acts to regulate its endocytosis. Synthetic peptide Ant-3S, consisting of antennapedia-derived protein transduction domain (designated as Ant) and c-Met-derived 16 amino-acids (designated as 3S, spanning amino-acids 1378 to 1393), rapidly moved into cancer cells and disrupted c-Met trafficking. Importantly, an extension of c-Met retention time on the membrane by Ant-3S peptide significantly decreased phosphorylation-dependent c-Met signal transduction. Additionally, the peptide effectively inhibited HGF-induced cell growth, scattering and migration. The underlying molecular mechanism for these observations has been investigated and revealed that the dileucine motif interacts with endocytic machinery, including adaptin β and caveolin-1, for sustained and enhanced signal transduction. Finally, Ant-3S peptide specifically blocked internalization of interleukin-2 receptor α-subunit/3S chimeric protein, but not the other receptors, including Glut4, Glut8 and transferrin receptor. Such results indicate the presence of a selective endocytic assembly for c-Met. It also suggests a potential for c-Met-specific anti-cancer therapy using the identified endocytic motif in this study.

  15. Detection and imaging of aggressive cancer cells using an epidermal growth factor receptor (EGFR)-targeted filamentous plant virus-based nanoparticle.

    PubMed

    Chariou, Paul L; Lee, Karin L; Wen, Amy M; Gulati, Neetu M; Stewart, Phoebe L; Steinmetz, Nicole F

    2015-02-18

    Molecular imaging approaches and targeted drug delivery hold promise for earlier detection of diseases and treatment with higher efficacy while reducing side effects, therefore increasing survival rates and quality of life. Virus-based nanoparticles are a promising platform because their scaffold can be manipulated both genetically and chemically to simultaneously display targeting ligands while carrying payloads for diagnosis or therapeutic intervention. Here, we displayed a 12-amino-acid peptide ligand, GE11 (YHWYGYTPQNVI), on nanoscale filaments formed by the plant virus potato virus X (PVX). Bioconjugation was used to produce fluorescently labeled PVX-GE11 filaments targeted toward the epidermal growth factor receptor (EGFR). Cell detection and imaging was demonstrated using human skin epidermoid carcinoma, colorectal adenocarcinoma, and triple negative breast cancer cell lines (A-431, HT-29, MDA-MB-231), all of which upregulate EGFR to various degrees. Nonspecific uptake in ductal breast carcinoma (BT-474) cells was not observed. Furthermore, co-culture experiments with EGFR(+) cancer cells and macrophages indicate successful targeting and partitioning toward the cancer cells. This study lays a foundation for the development of EGFR-targeted filaments delivering contrast agents for imaging and diagnosis, and/or toxic payloads for targeted drug delivery.

  16. Motives in Sexual Aggression: The Chinese Context.

    ERIC Educational Resources Information Center

    Tang, Catherine So-Kum; And Others

    1993-01-01

    Compared sexual and aggressive motives for sexual aggression in Chinese college students. Male undergraduates (N=146) completed self-report measures. Results suggest that sex guilt and aggressive guilt acted as inhibitors for their respective drives and sexual aggression resulted from aggressive, rather than sexual, motives. Sexual aggression may…

  17. Radiation-induced osteosarcomas in the pediatric population

    SciTech Connect

    Koshy, Matthew; Paulino, Arnold C. . E-mail: apaulino@tmh.tmc.edu; Mai, Wei Y.; Teh, Bin S.

    2005-11-15

    Purpose: Radiation-induced osteosarcomas (R-OS) have historically been high-grade, locally invasive tumors with a poor prognosis. The purpose of this study was to perform a comprehensive literature review and analysis of reported cases dealing with R-OS in the pediatric population to identify the characteristics, prognostic factors, optimal treatment modalities, and overall survival of these patients. Methods and Materials: A MEDLINE/PubMed search of articles written in the English language dealing with OSs occurring after radiotherapy (RT) in the pediatric population yielded 30 studies from 1981 to 2004. Eligibility criteria included patients <21 years of age at the diagnosis of the primary cancer, cases satisfying the modified Cahan criteria, and information on treatment outcome. Factors analyzed included the type of primary cancer treated with RT, the radiation dose and beam energy, the latency period between RT and the development of R-OS, and the treatment, follow-up, and final outcome of R-OS. Results: The series included 109 patients with a median age at the diagnosis of primary cancer of 6 years (range, 0.08-21 years). The most common tumors treated with RT were Ewing's sarcoma (23.9%), rhabdomyosarcoma (17.4%), retinoblastoma (12.8%), Hodgkin's disease (9.2%), brain tumor (8.3%), and Wilms' tumor (6.4%). The median radiation dose was 47 Gy (range, 15-145 Gy). The median latency period from RT to the development of R-OS was 100 months (range, 36-636 months). The median follow-up after diagnosis of R-OS was 18 months (1-172 months). The 3- and 5-year cause-specific survival rate was 43.6% and 42.2%, respectively, and the 3- and 5-year overall survival rate was 41.7% and 40.2%, respectively. Variables, including age at RT, primary site, type of tumor treated with RT, total radiation dose, and latency period did not have a significant effect on survival. The 5-year cause-specific and overall survival rate for patients who received treatment for R-OS involving

  18. The art of pediatric oncology nursing practice.

    PubMed

    Cantrell, Mary Ann

    2007-01-01

    Pediatric oncology nursing practice must incorporate both the science and the art of the discipline to foster positive physical and psychosocial treatment outcomes for pediatric oncology patients, especially those outcomes related to their health-related quality of life. In this article, the art of nursing care is described within the context of scientifically based care, and the art of nursing practice is evident in the implementation of the scientific principles and standards for pediatric oncology nursing practice. The author proposes that the art of pediatric oncology nursing practice ought to be evident in care activities that the nurse provides within a therapeutic relationship that is steeped in nursing presence. Although the art of nursing care and the nature of an effective therapeutic relationship is tacit, valued knowledge among pediatric oncology nurses, as well as children and adolescents with cancer and their families, it is difficult to describe and challenging to quantify its effect on patient care outcomes. This article discusses the art of pediatric oncology nursing practice and its influence on treatment outcomes.

  19. Overexpression of collagen triple helix repeat containing 1 (CTHRC1) is associated with tumour aggressiveness and poor prognosis in human non-small cell lung cancer.

    PubMed

    Ke, Zunfu; He, Weiling; Lai, Yuanhui; Guo, Xuefeng; Chen, Sharon; Li, Shuhua; Wang, Yuefeng; Wang, Liantang

    2014-10-15

    Collagen triple helix repeat-containing 1 (CTHRC1), a novel oncogene, was identified to be aberrantly overexpressed in several malignant tumors. However, the expression profile of CTHRC1 and its clinical significance in non-small cell lung cancer (NSCLC) remain unknown. In this study, we showed that CTHRC1 was evidently overexpressed in human NSCLC tissues and NSCLC cell lines at the protein and mRNA level. Ectopic up-regulation of CTHRC1 in cancer cells resulted in elevated invasive and proliferative abilities, which were attenuated by the specific CTHRC1 siRNA. The biological effect of CTHRC1 on metastasis and proliferation was mediated by the activation of the Wnt/β-catenin pathway. Furthermore, CTHRC1 immunoreactivity was evidently overexpressed in paraffin-embedded NSCLC tissues (212/292, 72.60%) in comparison to corresponding adjacent non-cancerous tissues (6/66, 9.09%) (p<0.001). Clinicopathologic analysis showed that CTHRC1 expression was significantly correlated with differentiation degree (p<0.001), clinical stage (p<0.001), T classification (p<0.001), lymph node metastasis (p=0.013) and distant metastasis (p<0.001). Kaplan-Meier analysis revealed that patients with high CTHRC1 expression had poorer overall survival rates than those with low CTHRC1 expression. Multivariate analysis indicated that CTHRC1 expression was an independent prognostic factor for the overall survival of NSCLC patients. Collectively, CTHRC1 plays important roles in NSCLC progression, and the evaluation of CTHRC1 expression could serve as a potential marker for metastasis progression and prognosis in NSCLC patients.

  20. Salivary Gland Cancer

    MedlinePlus

    ... Content ASCO Conquer Cancer Foundation Journal of Clinical Oncology Journal of Oncology Practice ASCO University Donate eNEWS SIGNUP f Cancer. ... of medical, surgical, radiation, gynecologic, and pediatric oncologists, oncology nurses, physician assistants, social workers, and patient advocates. ...

  1. Cancer immunotherapy in children

    Cancer.gov

    More often than not, cancer immunotherapies that work in adults are used in modified ways in children. Seldom are new therapies developed just for children, primarily because of the small number of pediatric patients relative to the adult cancer patient

  2. Transperineal aggressive angiomyxoma.

    PubMed

    Pereira, Pedro; Melo Abreu, Elisa; Cunha, Teresa Margarida; Rolim, Inês

    2017-04-11

    A 45-year-old woman with a history of total hysterectomy with adnexal preservation for uterine leiomyomas presented to our hospital with a right gluteal palpable mass, which she first noticed 6 months before and had progressively enlarged since then.Radiological studies revealed a 14 cm lesion with translevator growth that displaced rather than invaded adjacent structures, with a peculiar whorled pattern on T2-weighted MRI, which enhanced following gadolinium administration. CT-guided biopsy was performed, and in conjunction with imaging features the diagnosis of an aggressive angiomyxoma was assumed and confirmed following surgical excision.

  3. Understanding Prostate Cancer: Newly Diagnosed

    MedlinePlus

    ... tumor cells. The higher the score, the more aggressive the tumor. The cells are scored on a ... Gleason scores (2 – 4) tend to be less aggressive, while cancers with higher Gleason scores (7 – 10) ...

  4. Quantitative Analysis of Prostate Multiparametric MR Images for Detection of Aggressive Prostate Cancer in the Peripheral Zone: A Multiple Imager Study.

    PubMed

    Hoang Dinh, Au; Melodelima, Christelle; Souchon, Rémi; Lehaire, Jérôme; Bratan, Flavie; Mège-Lechevallier, Florence; Ruffion, Alain; Crouzet, Sébastien; Colombel, Marc; Rouvière, Olivier

    2016-07-01

    Purpose To assess the intermanufacturer variability of quantitative models in discriminating cancers with a Gleason score of at least 7 among peripheral zone (PZ) lesions seen at 3-T multiparametric magnetic resonance (MR) imaging. Materials and Methods An institutional review board-approved prospective database of 257 patients who gave written consent and underwent T2-weighted, diffusion-weighted, and dynamic contrast material-enhanced imaging before prostatectomy was retrospectively reviewed. It contained outlined lesions found to be suspicious for malignancy by two independent radiologists and classified as malignant or benign after correlation with prostatectomy whole-mount specimens. One hundred six patients who underwent imaging with 3-T MR systems from two manufacturers were selected (data set A, n = 72; data set B, n = 34). Eleven parameters were calculated in PZ lesions: normalized T2-weighted signal intensity, skewness and kurtosis of T2-weighted signal intensity, T2 value, wash-in rate, washout rate, time to peak (TTP), mean apparent diffusion coefficient (ADC), 10th percentile of the ADC, and skewness and kurtosis of the histogram of the ADC values. Parameters were selected on the basis of their specificity for a sensitivity of 0.95 in diagnosing cancers with a Gleason score of at least 7, and the area under the receiver operating characteristic curve (AUC) for the models was calculated. Results The model of the 10th percentile of the ADC with TTP yielded the highest AUC in both data sets. In data set A, the AUC was 0.90 (95% confidence interval [CI]: 0.85, 0.95) or 0.89 (95% CI: 0.82, 0.94) when it was trained in data set A or B, respectively. In data set B, the AUC was 0.84 (95% CI: 0.74, 0.94) or 0.86 (95% CI: 0.76, 0.95) when it was trained in data set A or B, respectively. No third variable added significantly independent information in any data set. Conclusion The model of the 10th percentile of the ADC with TTP yielded accurate results in

  5. The nature of human aggression.

    PubMed

    Archer, John

    2009-01-01

    Human aggression is viewed from four explanatory perspectives, derived from the ethological tradition. The first consists of its adaptive value, which can be seen throughout the animal kingdom, involving resource competition and protection of the self and offspring, which has been viewed from a cost-benefit perspective. The second concerns the phylogenetic origin of aggression, which in humans involves brain mechanisms that are associated with anger and inhibition, the emotional expression of anger, and how aggressive actions are manifest. The third concerns the origin of aggression in development and its subsequent modification through experience. An evolutionary approach to development yields conclusions that are contrary to the influential social learning perspective, notably that physical aggression occurs early in life, and its subsequent development is characterized by learned inhibition. The fourth explanation concerns the motivational mechanisms controlling aggression: approached from an evolutionary background, these mechanisms range from the inflexible reflex-like responses to those incorporating rational decision-making.

  6. Aggression can be contagious: Longitudinal associations between proactive aggression and reactive aggression among young twins.

    PubMed

    Dickson, Daniel J; Richmond, Ashley D; Brendgen, Mara; Vitaro, Frank; Laursen, Brett; Dionne, Ginette; Boivin, Michel

    2015-01-01

    The present study examined sibling influence over reactive and proactive aggression in a sample of 452 same-sex twins (113 male dyads, 113 female dyads). Between and within siblings influence processes were examined as a function of relative levels of parental coercion and hostility to test the hypothesis that aggression contagion between twins occurs only among dyads who experience parental coerciveness. Teacher reports of reactive and proactive aggression were collected for each twin in kindergarten (M = 6.04 years; SD = 0.27) and in first grade (M = 7.08 years; SD = 0.27). Families were divided into relatively low, average, and relatively high parental coercion-hostility groups on the basis of maternal reports collected when the children were 5 years old. In families with relatively high levels of parental coercion-hostility, there was evidence of between-sibling influence, such that one twin's reactive aggression at age 6 predicted increases in the other twin's reactive aggression from ages 6 to 7, and one twin's proactive aggression at age 6 predicted increases in the other twin's proactive aggression from ages 6 to 7. There was also evidence of within-sibling influence such that a child's level of reactive aggression at age 6 predicted increases in the same child's proactive aggression at age 7, regardless of parental coercion-hostility. The findings provide new information about the etiology of reactive and proactive aggression and individual differences in their developmental interplay.

  7. Preclinical Testing of a New MR Imaging Approach to Distinguish Aggressive from Indolent Disease

    DTIC Science & Technology

    2015-08-01

    AWARD NUMBER: W81XWH-13-1-0128 TITLE: ““Preclinical Testing of a New MR Imaging Approach to Distinguish Aggressive from Indolent Disease...9 May 2015 4. TITLE AND SUBTITLE 5a. CONTRACT NUMBER “Preclinical Testing of a New MR Imaging Approach to Distinguish Aggressive from Indolent...13. SUPPLEMENTARY NOTES 14. ABSTRACT The aim of this project was to develop a new MRI approach to characterize aggressive prostate cancers and

  8. Clinical recommendation: pediatric lichen sclerosus.

    PubMed

    Bercaw-Pratt, Jennifer L; Boardman, Lori A; Simms-Cendan, Judith S

    2014-04-01

    Lichen sclerosus is a chronic inflammatory condition affecting the anogenital region that may present in the prepubertal or adolescent patient. Clinical presentations include significant pruritus, labial adhesions, and loss of pigmentation. Treatment includes topical anti-inflammatory agents and long-term follow-up as there is a high risk of recurrence and an increased risk of vulvar cancer in adult women with history of lichen sclerosus. These recommendations are intended for pediatricians, gynecologists, nurse practitioners and others who care for pediatric/adolescent girls in order to facilitate diagnosis and treatment.

  9. Television viewing, aggression, and ethnicity.

    PubMed

    Harris, M B

    1992-02-01

    For 416 college students, questioned about their experiences with aggression and television viewing, only very weak correlations between preference for violent shows and aggression were observed. Black males watched significantly more television than other respondents. These findings suggest that the frequently reported correlation between viewing televised violence and aggression may not appear when sex, ethnicity, and education are controlled in a sample of young adults.

  10. Pediatric medulloblastoma xenografts including molecular subgroup 3 and CD133+ and CD15+ cells are sensitive to killing by oncolytic herpes simplex viruses

    PubMed Central

    Friedman, Gregory K.; Moore, Blake P.; Nan, Li; Kelly, Virginia M.; Etminan, Tina; Langford, Catherine P.; Xu, Hui; Han, Xiaosi; Markert, James M.; Beierle, Elizabeth A.; Gillespie, G. Yancey

    2016-01-01

    Background Childhood medulloblastoma is associated with significant morbidity and mortality that is compounded by neurotoxicity for the developing brain caused by current therapies, including surgery, craniospinal radiation, and chemotherapy. Innate therapeutic resistance of some aggressive pediatric medulloblastoma has been attributed to a subpopulation of cells, termed cancer-initiating cells or cancer stemlike cells (CSCs), marked by the surface protein CD133 or CD15. Brain tumors characteristically contain areas of pathophysiologic hypoxia, which has been shown to drive the CSC phenotype leading to heightened invasiveness, angiogenesis, and metastasis. Novel therapies that target medulloblastoma CSCs are needed to improve outcomes and decrease toxicity. We hypothesized that oncolytic engineered herpes simplex virus (oHSV) therapy could effectively infect and kill pediatric medulloblastoma cells, including CSCs marked by CD133 or CD15. Methods Using 4 human pediatric medulloblastoma xenografts, including 3 molecular subgroup 3 tumors, which portend worse patient outcomes, we determined the expression of CD133, CD15, and the primary HSV-1 entry molecule nectin-1 (CD111) by fluorescence activated cell sorting (FACS) analysis. Infectability and cytotoxicity of clinically relevant oHSVs (G207 and M002) were determined in vitro and in vivo by FACS, immunofluorescent staining, cytotoxicity assays, and murine survival studies. Results We demonstrate that hypoxia increased the CD133+ cell fraction, while having the opposite effect on CD15 expression. We established that all 4 xenografts, including the CSCs, expressed CD111 and were highly sensitive to killing by G207 or M002. Conclusions Pediatric medulloblastoma, including Group 3 tumors, may be an excellent target for oHSV virotherapy, and a clinical trial in medulloblastoma is warranted. PMID:26188016

  11. Psychopharmacology of aggression in children and adolescents with primary neuropsychiatric disorders: a review of current and potentially promising treatment options.

    PubMed

    Nevels, Robert M; Dehon, Erin E; Alexander, Katrina; Gontkovsky, Samuel T

    2010-04-01

    Research examining the role of pharmacological therapy in the treatment of children and adolescents with clinical disorders is growing. Clinical disorders that present with comorbid aggression can add a challenge to treatment. Child and adolescent neuropsychiatric disorders associated with aggression include attention-deficit hyperactivity disorder, various mood disorders and in particular bipolar disorders/pediatric mania, schizophrenia, mental retardation, oppositional defiant disorder, conduct disorder, and autism spectrum disorders. This review describes the psychopharmacy to treat these disorders and the aggression that often appears comorbidly. Existing literature regarding the efficacy and safety of psychotropics for youth with neuropsychiatric disorders also is discussed. In addition, general guidelines for psychopharmacy of aggression in children and adolescents are presented. Studies reviewed in this article provide evidence for the use of psychostimulants, alpha-2 agonists, beta blockers, lithium, anticonvulsant mood-stabilizers, atypical antipsychotics, traditional antipsychotics, and selective serotonin reuptake inhibitors in treating pediatric aggression with the choice of medication dependent on symptomology. Despite increased support for pediatric psychotropic use, there is a need for more long-term safety and efficacy studies of existing medications and newer, safer, and more effective agents with fewer side effects for the pharmacological treatment of all childhood disorders in which aggression is prominent.

  12. Comparison of the Luminex xTAG RVP Fast assay and the Idaho Technology FilmArray RP assay for detection of respiratory viruses in pediatric patients at a cancer hospital.

    PubMed

    Babady, N Esther; Mead, Peter; Stiles, Jeffrey; Brennan, Carrie; Li, Haijing; Shuptar, Susan; Stratton, Charles W; Tang, Yi-Wei; Kamboj, Mini

    2012-07-01

    Respiratory viruses are increasingly recognized as serious causes of morbidity and mortality in immunocompromised patients. The rapid and sensitive detection of respiratory viruses is essential for the early diagnosis and administration of appropriate antiviral therapy, as well as for the effective implementation of infection control measures. We compared the performance of two commercial assays, xTAG RVP Fast (Luminex Diagnostics, Toronto, Canada) and FilmArray RVP (FA RVP; Idaho Technology, Salt Lake City, UT), in pediatric patients at Memorial Sloan-Kettering Cancer Center. These assays detect the following viruses: respiratory syncytial virus; influenza A and B viruses; parainfluenza viruses 1, 2, 3, and 4; hu